Search results
Search for "cyclopentene" in Full Text gives 71 result(s) in Beilstein Journal of Organic Chemistry.
Recent advances in total synthesis of illisimonin A
- Juan Huang and
- Ming Yang
Beilstein J. Org. Chem. 2025, 21, 2571–2583, doi:10.3762/bjoc.21.199
- introduce another side chain, affording a diene intermediate. A subsequent ring-closing metathesis (RCM) reaction formed the cyclopentene ring, and one pot protection of both carbonyl groups with ethylene glycol provided bis-ketal 55. Notably, due to steric hindrance, only one carbonyl group could be
- protected prior to the RCM step. Oxidative cleavage of the cyclopentene followed by Pinnick oxidation of the resulting aldehyde to the carboxylic acid and esterification yielded ketoester 56. Dieckmann condensation of 56, esterification of the resulting enolate with 57, and subsequent one-pot partial
Graphical Abstract
Figure 1: The categorization of Illicium sesquiterpenes and representative natural products.
Figure 2: The original assigned (−)-illisimonin A, revised (−)-illisimonin A, and their different draws.
Scheme 1: Proposed biosynthetic pathway of illisimonin A by Yu et al.
Scheme 2: Rychnovsky’s racemic synthesis of illisimonin A (1).
Scheme 3: The absolute configuration revision of (−)-illisimonin A.
Scheme 4: Kalesse’s asymmetric synthesis of (−)-illisimonin A.
Scheme 5: Yang group proposed biosynthetic pathway of illisimonin A.
Scheme 6: Yang’s bioinspired synthesis of illisimonin A.
Scheme 7: Dai’s asymmetric synthesis of (–)-illisimonin A.
Scheme 8: Lu’s total synthesis of illisimonin A.
Scheme 9: Initial efforts toward the total synthesis of illisimonin A by the Lu Group.
Scheme 10: Suzuki’s synthetic effort towards illisimonin A.
Synthesis of the tetracyclic skeleton of Aspidosperma alkaloids via PET-initiated cationic radical-derived interrupted [2 + 2]/retro-Mannich reaction
- Ru-Dong Liu,
- Jian-Yu Long,
- Zhi-Lin Song,
- Zhen Yang and
- Zhong-Chao Zhang
Beilstein J. Org. Chem. 2025, 21, 2470–2478, doi:10.3762/bjoc.21.189
- -substituted cyclobutenones 9a–n were prepared and reacted under the optimal conditions. The results are shown in Scheme 1. Substrate 9a, which contains a spiro-cyclopentene moiety, delivered the best result and gave 10a in 86% isolated yield. When C15 or C16 was substituted with a chlorine atom, 10b and 10c
- synthesis; d) naturally occurring Aspidosperma alkaloids; e) ring strain energy of cyclopentene, bicyclo[3.2.0]heptane, cycloheptane, cyclobutene, bicyclo[2.2.0]hexane and cyclohexane. Computational study. a) Energy profiles from IN1 to IN3 and spin density of TS2 (isovalue = 0.004), solvated (SMD) Gibbs
Graphical Abstract
Figure 1: Synthetic plan. a) General model of cyclobutenone bond cleavage; b) our previously reported method;...
Scheme 1: Substrate scope.
Figure 2: Computational study. a) Energy profiles from IN1 to IN3 and spin density of TS2 (isovalue = 0.004),...
Transformation of the cyclohexane ring to the cyclopentane fragment of biologically active compounds
- Natalya Akhmetdinova,
- Ilgiz Biktagirov and
- Liliya Kh. Faizullina
Beilstein J. Org. Chem. 2025, 21, 2416–2446, doi:10.3762/bjoc.21.185
- and Favorskii reaction), using oxidants based on thallium and iodine, with a focus on recent works published in the period from 2014 to 2024. Review 1 Recyclization A common method for converting cyclohexene 1 into cyclopentene 2 is the ozonolytic cleavage of the double bond followed by intramolecular
Graphical Abstract
Scheme 1: Ozonolysis–cyclization sequence in the synthesis of echinopine A (3).
Scheme 2: Ozonolysis–cyclization sequence in the synthesis of taiwaniaquinoids 7–12.
Figure 1: Iridoid skeleton.
Scheme 3: Ozonolysis–cyclization sequence in the synthesis of compounds 17a,b, 18 and 19 with iridoid topolog...
Scheme 4: Oxidation–aldol condensation sequence in the synthesis of compounds 21 and 23 with iridoid topology....
Scheme 5: Oxidation–aldol condensation sequence in the synthesis of compounds 29 and 30 with iridoid topology....
Scheme 6: Method for ring contraction in the absence of a double bond in a six-membered ring of triterpenoids....
Scheme 7: Oxidation–Dieckmann cyclization sequence in the synthesis of a new nortriterpenoid 39.
Scheme 8: Oxidation–Dieckmann cyclization sequence in the synthesis of 18,19-di-nor-cholesterol (40).
Scheme 9: Oxidation–cyclization sequence in the synthesis of 3-ethyl-substituted betulinic acid derivatives 49...
Scheme 10: Benzilic acid-type rearrangement in the synthesis of 4β-acetoxyprobotryane-9β,15α-diol (52).
Scheme 11: Benzilic acid-type rearrangement in the synthesis of (−)-taiwaniaquinone H (11).
Scheme 12: Benzilic acid-type rearrangement in the synthesis of dactylicapnosines A (63) and B (64).
Scheme 13: Aza-benzilic acid-type rearrangement in the synthesis of (+)-stephadiamine (71).
Scheme 14: α-Ketol rearrangement in the synthesis of saffloneoside (73).
Scheme 15: Conversion of (−)-preaustinoid A (80) to (−)-preaustinoid B (81) via α-ketol rearrangement.
Scheme 16: α-Ketol rearrangement in the synthesis of 2,8-oxymethano-bridged diquinane 90.
Scheme 17: Oxidative ring contraction during the synthesis of (+)-cuparene (91) and (+)-tochuinylacetate (92).
Scheme 18: Semipinacol rearrangement in the synthesis of diterpenoids 97–100.
Scheme 19: Co-catalyzed homoallyl-type rearrangement in the syntheses of meroterpenes 106–109.
Scheme 20: Ring contraction reaction promoted by TTN·3H2O and HTIB in the synthesis of indanes.
Scheme 21: Rearrangement involving a hypervalent iodine compound in the synthesis of derivative 120.
Scheme 22: Wolff rearrangement in the synthesis of taiwaniaquinones A (7), F (8), taiwaniaquinols B (10), D (1...
Scheme 23: Wolff rearrangement in the synthesis of cheloviolene C (128), seconorrisolide B (129), and seconorr...
Scheme 24: Wolff rearrangement in the synthesis of (−)-pavidolide B (134).
Scheme 25: Wolff rearrangement in the synthesis of presilphiperfolan-8-ol (141).
Scheme 26: Photochemical rearrangement in the synthesis of cyclopentane derivatives 147a,b.
Scheme 27: Synthesis of cyclopentane derivatives 147a and 151.
Scheme 28: Photochemical rearrangement in the synthesis of cyclopentane derivative 153.
Scheme 29: Photochemical rearrangement in the synthesis of tricyclic ketones 155, 156.
Scheme 30: Photochemical rearrangement in the synthesis of cis/trans salts 160.
Figure 2: Scope of the photoinduced carboborative ring contraction of steroids. Reaction conditions: steroid ...
Scheme 31: Photoinduced carboborative ring contraction in the synthesis of artalbic acid (180).
Scheme 32: Synthetic versatility of the photoinduced carboborative ring contraction.
Scheme 33: Methods of disclosure of epoxide 189.
Scheme 34: Methods of disclosure of epoxide 190.
Scheme 35: Rearrangement of α,β-epoxy ketone 197.
Scheme 36: Acid-induced rearrangement in the synthesis of perhydrindane ketones 202 and 205.
Scheme 37: Rearrangement of epoxyketone 208 in the synthesis of huperzine Q (206).
Scheme 38: Rearrangement of epoxide 212 under the action of Grignard reagent.
Scheme 39: Semipinacol rearrangement of epoxide 220 in the synthesis of (−)-citrinadin A (217) and (+)-citrina...
Scheme 40: Semipinacol rearrangement of epoxide 225 in the synthesis of hamigeran G (223).
Scheme 41: Semipinacol rearrangement of epoxide 231 in the synthesis of (−)-spirochensilide A (228).
Scheme 42: Wagner–Meerwein rearrangement in the synthesis of compound 234 with iridoid topology.
Scheme 43: Wagner–Meerwein rearrangement in the synthesis of compound 238 with iridoid topology.
Scheme 44: Wagner–Meerwein rearrangement in the synthesis of compound 241 with iridoid topology.
Scheme 45: Wagner–Meerwein rearrangement in the synthesis of lupane derivatives 245, 246, 248, and 249.
Scheme 46: Wagner–Meerwein rearrangement in the synthesis of weisaconitine D (252) and cardiopetaline (255).
Scheme 47: Wagner–Meerwein rearrangement in the synthesis of cardiopetaline (255).
Synthetic study toward vibralactone
- Liang Shi,
- Jiayi Song,
- Yiqing Li,
- Jia-Chen Li,
- Shuqi Li,
- Li Ren,
- Zhi-Yun Liu and
- Hong-Dong Hao
Beilstein J. Org. Chem. 2025, 21, 2376–2382, doi:10.3762/bjoc.21.182
- vibralactone, a potent inhibitor of pancreatic lipase, is reported. The synthesis of the challenging all-carbon quaternary center within the cyclopentene ring was achieved through intramolecular alkylidene carbene C–H insertion. Keywords: alkylidene carbene; C–H insertion; total synthesis; vibralactone
- cyclopentene ring containing an all-carbon quaternary center [14], and inhibits pancreatic lipase with an IC50 of 0.4 µg/mL. Several congeners with varying oxidation state, as well as related β-hydroxy acids or esters have also been isolated from the culture broth of the basidiomycete [15][16][17][18][19][20
- lactone 13 through allylic oxidation and cross metathesis. For the construction of the cyclopentene ring, an alkylidene carbene-mediated C–H insertion would be applied [35]. The synthetic route could be traced back to β-lactone 14, which contains two continuous stereogenic centers with trans configuration
Graphical Abstract
Figure 1: Selected representative natural products and derivatives with β-lactone moiety.
Scheme 1: Previous syntheses of vibralactone (6).
Scheme 2: Retrosynthetic analysis of vibralactone (6).
Scheme 3: Synthetic study toward vibralactone (6) in the present of β-lactone.
Scheme 4: C–H insertion utilizing linear precursor 19.
Scheme 5: Construction the bicyclic skeleton of vibralactone (6) through C–H insertion.
Understanding the origin of stereoselectivity in the photochemical denitrogenation of 2,3-diazabicyclo[2.2.1]heptene and its derivatives with non-adiabatic molecular dynamics
- Leticia A. Gomes and
- Steven A. Lopez
Beilstein J. Org. Chem. 2025, 21, 2007–2020, doi:10.3762/bjoc.21.156
- starting materials for different types of reactions including thermal isomerization to cyclopentenes [36][37][38] and 1,4-pentadienes [37][38], chemical electron-transfer oxidations to cyclopentene [39] and cycloaddition reactions with electron-deficient alkenes and alkynes [38][40][41] (Scheme 1b
Graphical Abstract
Scheme 1: Applications of bicyclo[1.1.0]butane (a) and bicyclo[2.1.0]pentane (b). Molecules with biological a...
Scheme 2: Diastereoselectivity in the direct photolysis of 2,3-diazabicyclo[2.2.1]hept-2-enes.
Scheme 3: Mechanism for the photodenitrogenation of DBH proposed in the literature.
Figure 1: CASSCF(8,9) active space of 1 with average electron occupancies. Orbitals were calculated at the SA...
Figure 2: Absorption spectra and geometric overlays corresponding to Wigner-sampled geometries of 1 (a), 3 (b...
Figure 3: Minimum energy path using XMS-CASPT2(8,9)/ANO-S-VDZP for 1 (a), 3 (b), and 5 (c). The dots on the g...
Figure 4: (a) The bond lengths we calculated are depicted. σCN bonds plotted against each other for 1 (b), 3 ...
Figure 5: (a) Geometrical parameters. Plots show trajectories for a 1 ps NAMD simulation with CASSCF (8,9)/AN...
Figure 6: (a) Geometrical parameters. H–C–C–C dihedral angles plotted against each other for S1-to-S0 hopping...
Figure 7: The minimum energy conical intersection geometries are shown for the partially inverted hopping poi...
Aryl iodane-induced cascade arylation–1,2-silyl shift–heterocyclization of propargylsilanes under copper catalysis
- Rasma Kroņkalne,
- Rūdolfs Beļaunieks,
- Armands Sebris,
- Anatoly Mishnev and
- Māris Turks
Beilstein J. Org. Chem. 2025, 21, 1984–1994, doi:10.3762/bjoc.21.154
- ), more interesting reaction patterns can be observed. For example, branched aliphatic chain-containing alkynes are arylated and carbocyclized into cyclopentene derivatives [12][13]. The triflate moiety of the diaryl-λ3-iodane may act as an external nucleophile, resulting in 1,2-carbotriflation products
Graphical Abstract
Scheme 1: Alkyne arylation with diaryl-λ3-iodanes in the context of 1,2-silyl shift and potential cyclization....
Scheme 2: Competing mechanistic pathways for diene 10 and indene 11 formation.
Scheme 3: Reaction scope for the synthesis of arylated tetrahydrofurans 8. Conditions: All reactions were per...
Scheme 4: Synthesis of lactone and pyrrolidine derivatives. Conditions: ac7e = 0.1 mmol/mL. bReaction conditi...
Scheme 5: Proposed arylation–heterocyclization mechanism for internal nucleophile-containing silanes 7.
Scheme 6: Arylation of C5-chain containing acylamides 16a–c. aThe reaction was performed under modified condi...
A multicomponent reaction-initiated synthesis of imidazopyridine-fused isoquinolinones
- Ashutosh Nath,
- John Mark Awad and
- Wei Zhang
Beilstein J. Org. Chem. 2025, 21, 1161–1169, doi:10.3762/bjoc.21.92
- formation of 8a,h,l,m,n and 8r (68–85%), R3 = phenyl resulted in 8b,g and 8q in 78–82% yields, R3 = isopropyl and cyclopentene gave 8c,f,p and 8d in greater than 70% yields, and R3 = 2-morpholinoethyl gave 8e,i and 8s in 60–76% yields. The energy status for the transformation of compound 6a to 8a was
Graphical Abstract
Figure 1: Bioactive compounds bearing imidazopyridine (red) and isoquinolinone-kind (blue) rings.
Scheme 1: GBB-initiated synthesis of imidazopyridine-fused isoquinolinones.
Scheme 2: GBB reaction and N-acylation for the preparation of imidazo[1,2-a]pyridines 6.
Scheme 3: Substrate scope for IMDA and dehydrative aromatization in making 8. Reaction conditions: 6 and AlCl3...
Figure 2: Transition state analysis of IMDA reactions for 6a, 6j, 6h and 6r.
Figure 3: Relative energy diagram for the synthesis of 8a from 6a.
Scheme 4: Using thiophene-2-carbaldehyde for the synthesis of 8t.
Scheme 5: Proposed mechanisms for IMDA reaction and dehydration re-aromatization.
Recent total synthesis of natural products leveraging a strategy of enamide cyclization
- Chun-Yu Mi,
- Jia-Yuan Zhai and
- Xiao-Ming Zhang
Beilstein J. Org. Chem. 2025, 21, 999–1009, doi:10.3762/bjoc.21.81
- a fragmentation process for the total synthesis of (−)-phlegmariurine B. A one-pot epoxidation/nucleophilic epoxide opening introduced both a hydroxy group and a chloride across the cyclopentene, producing 14 in 57% yield. After oxidation of alcohol 14 to ketone 15, the Mukaiyama hydration then
Graphical Abstract
Figure 1: Reactivity of enamides and enamide cyclizations.
Scheme 1: Total synthesis of (−)-dihydrolycopodine and (−)-lycopodine.
Scheme 2: Collective total synthesis of fawcettimine-type alkaloids.
Scheme 3: Total syntheses of cephalotaxine and cephalezomine H.
Scheme 4: Collective total syntheses of Cephalotaxus alkaloids.
Scheme 5: Asymmetric tandem cyclization/Pictet–Spengler reaction of tertiary enamides.
Scheme 6: Tandem cyclization/Pictet–Spengler reaction for the synthesis of chiral tetracyclic compounds.
Scheme 7: Total synthesis of (−)-cephalocyclidin A.
Hydrogen-bond activation enables aziridination of unactivated olefins with simple iminoiodinanes
- Phong Thai,
- Lauv Patel,
- Diyasha Manna and
- David C. Powers
Beilstein J. Org. Chem. 2024, 20, 2305–2312, doi:10.3762/bjoc.20.197
- with PhINTs (Table 1, entry 12) [42][43]. With metal-free aziridination conditions in hand, we explored the scope and limitations of the HFIP-promoted aziridination of unactivated olefins (Scheme 2). For cyclic substrates, aziridination of cyclopentene, cyclohexene, and cycloheptene afforded the
- the generality of H-bond activation of iminoiodinanes for direct aziridination, albeit with modest efficiency for some substrates. The impact of the iminoiodinane structure on the efficiency of HFIP-promoted direct aziridination was next investigated (Scheme 3). For this purpose, cyclopentene was
- selected as it underwent efficient aziridination with PhINTs. A family of iminoiodinanes 2 was synthesized from PIDA and the corresponding sulfonamide derivative. Reaction of phenylsulfonamide-derived iminoiodinane with cyclopentene afforded N-phenylsulfonylaziridine 6b in 45% yield, while N-(p
Graphical Abstract
Scheme 1: a) Lewis acid activation of hypervalent iodine reagents can enhance the reactivity of these reagent...
Scheme 2: Scope and limitations of HFIP-promoted direct aziridination with iminoiodinane reagents. Conditions...
Scheme 3: Scope of nitrogen group transfer in the aziridination of aliphatic olefins. Conditions using synthe...
Scheme 4: a) The broadening of the hydroxide proton (denoted by asterisk *) of HFIP in the presence of iminoi...
Natural resorcylic lactones derived from alternariol
- Joachim Podlech
Beilstein J. Org. Chem. 2024, 20, 2171–2207, doi:10.3762/bjoc.20.187
Graphical Abstract
Figure 1: Examples of compounds covered in this review categorized in six sub-classes (see text).
Figure 2: Examples of compounds not covered in this review.
Figure 3: Wrongly assigned and thus obsolete structures (details will be discussed in the respective chapters...
Figure 4: Alternariol with the correct IUPAC numbering and an occasionally used numbering based on the biphen...
Figure 5: Alternariol O-methyl ethers.
Figure 6: Alternariol O-glycosides.
Figure 7: Alternariol O-acetates and O-sulfates.
Figure 8: 2-Hydroxy- and 4-hydroxy-substituted alternariol and its O-methyl ethers.
Figure 9: Chloro- and amino-substituted alternariol and its O-methyl ethers.
Figure 10: Presumed alternariol derivatives with non-canonical substitution pattern.
Figure 11: Alternariol derivatives with the 1-methyl group hydroxylated.
Figure 12: Verrulactones: pseudo-dimeric derivatives of altertenuol and related compounds.
Figure 13: Biaryls formed by reductive lactone opening and/or by decarboxylation.
Figure 14: Altenuene and its diastereomers.
Figure 15: 9-O-Demethylated altenuene diastereomers.
Figure 16: Acetylated and methylated altenuene diastereomers.
Figure 17: Altenuene diastereomers modified with lactic acid, pyruvic acid, or acetone.
Figure 18: Neoaltenuene and related compounds.
Figure 19: Dehydroaltenusin and its derivatives.
Scheme 1: Equilibrium of dehydroaltenusin in polar solvents [278].
Figure 20: Further quinoid derivatives.
Figure 21: Dehydroaltenuenes.
Figure 22: Complex aggregates containing dehydroaltenuene substructures and related compounds.
Figure 23: Dihydroaltenuenes.
Figure 24: Altenuic acids and related compounds.
Figure 25: Cyclopentane- and cyclopentene-fused derivatives.
Figure 26: Cyclopentenone-fused derivatives.
Figure 27: Spiro-fused derivatives and a related ring-opened derivative.
Figure 28: Lactones-fused and lactone-substituted derivatives.
Scheme 2: Biosynthesis of alternariol [324].
Scheme 3: Biosynthesis of alternariol and its immediate successors with the genes involved in the respective ...
Scheme 4: Presumed formation of altenuene and its diastereomers and of botrallin.
Scheme 5: Presumed formation of altenuic acids and related compounds.
Scheme 6: A selection of plausible biosynthetic paths to cyclopenta-fused metabolites. (No stereochemistry is...
Scheme 7: Biomimetic synthesis of alternariol (1) by Harris and Hay [66].
Scheme 8: Total synthesis of alternariol (1) by Subba Rao et al. using a Diels–Alder approach [34].
Scheme 9: Total synthesis of alternariol (1) using a Suzuki strategy by Koch and Podlech [62], improved by Kim et...
Scheme 10: Total synthesis of alternariol (1) using an intramolecular biaryl coupling by Abe et al. [63].
Scheme 11: Total synthesis of altenuene (54) and isoaltenuene (55) by Podlech et al. [249].
Scheme 12: Total synthesis of neoaltenuene (69) by Podlech et al. [35].
Scheme 13: Total synthesis of TMC-264 (79) by Tatsuta et al. [185].
Scheme 14: Total synthesis of cephalosol (99) by Koert et al. [304].
Enhanced reactivity of Li+@C60 toward thermal [2 + 2] cycloaddition by encapsulated Li+ Lewis acid
- Hiroshi Ueno,
- Yu Yamazaki,
- Hiroshi Okada,
- Fuminori Misaizu,
- Ken Kokubo and
- Hidehiro Sakurai
Beilstein J. Org. Chem. 2024, 20, 653–660, doi:10.3762/bjoc.20.58
- of N,N,N',N'-tetraethylethynediamine and 1-morpholino-1-cyclopentene with empty C60 has been reported [17][23], while electron-rich styrene derivatives 1 and 2 can react with empty C60 only through a photoinduced SET pathway [19][22]. From these results, the energy gap between the HOMO of the alkene
Graphical Abstract
Scheme 1: Reaction mechanisms of thermal and photoinduced [2 + 2] cycloaddition on C60 [19,22,23].
Figure 1: HOMO levels of unsaturated substrates and LUMO levels of fullerenes computed at the B3LYP/6-31G(d) ...
Scheme 2: Thermal [2 + 2] reaction of Li+@C60 TFSI− with substrates 1–4. a100 equiv for the reaction screenin...
Figure 2: HPLC profiles of themal [2 + 2]reaction of Li+@C60 with substrate 1 (a) and 2 (b) in o-dichlorobenz...
Figure 3: HPLC profiles of 5a (a) and 5b (b) before and after photoirradiation at room temperature.
Figure 4: 1H-1H 2D-NOESY NMR spectrum (600 MHz, CD2Cl2) of 5a (a) and NOE correlations between two protons. T...
Figure 5: Cyclic voltammograms of 5a, 5b, and Li+@C60 TFSI− with the potentials relative to the ferrocene/fer...
Exploring the role of halogen bonding in iodonium ylides: insights into unexpected reactivity and reaction control
- Carlee A. Montgomery and
- Graham K. Murphy
Beilstein J. Org. Chem. 2023, 19, 1171–1190, doi:10.3762/bjoc.19.86
- reductive elimination of iodobenzene to give 11 (Figure 5, left). This was also the pathway subsequently suggested by Gallos et al. [116] for the synthesis of 13/14 from 12. In 2003, Hadjiarapoglou further investigated the intermolecular reaction between 8 and cyclopentene under thermal, metal-free
Graphical Abstract
Figure 1: Generic representation of halogen bonding.
Figure 2: Quantitative evaluation of σ-holes in monovalent iodine-containing compounds; and, qualitative mole...
Figure 3: Quantitative evaluation of σ-holes in hypervalent iodine-containing molecules; and, qualitative MEP...
Figure 4: Quantitative evaluation of σ-holes in iodonium ylides; and, qualitative MEP map of I-12 from −0.083...
Scheme 1: Outline of possible reaction pathways between iodonium ylides and Lewis basic nucleophiles (top); a...
Scheme 2: Metal-free cyclopropanations of iodonium ylides, either as intermolecular (a) or intramolecular pro...
Figure 5: Zwitterionic mechanism for intramolecular cyclopropanation of iodonium ylides (left); and, stepwise...
Scheme 3: Metal-free intramolecular cyclopropanation of iodonium ylides.
Figure 6: Concerted cycloaddition pathway for the metal-free, intramolecular cyclopropanation of iodonium yli...
Scheme 4: Reaction of ylide 6 with diphenylketene to form lactone 24 and 25.
Figure 7: Nucleophilic (top) and electrophilic (bottom) addition pathways proposed by Koser and Hadjiarapoglo...
Scheme 5: Indoline synthesis from acyclic iodonium ylide 31 and tertiary amines.
Scheme 6: N-Heterocycle synthesis from acyclic iodonium ylide 31 and secondary amines.
Figure 8: Proposed mechanism for the formation of 33a from iodonium ylides and amines, involving an initial h...
Scheme 7: Indoline synthesis from acyclic iodonium ylides 39 and tertiary amines under blue light photocataly...
Scheme 8: Metal-free cycloproponation of iodonium ylides under blue LED irradiation. aUsing trans-β-methylsty...
Figure 9: Proposed mechanism of the cyclopropanation between iodonium ylides and alkenes under blue LED irrad...
Scheme 9: Formal C–H alkylation of iodonium ylides by nucleophilic heterocycles under blue LED irradiation.
Figure 10: Proposed mechanism of the formal C–H insertion of pyrrole under blue LED irradiation.
Scheme 10: X–H insertions between iodonium ylides and carboxylic acids, phenols and thiophenols.
Figure 11: Mechanistic proposal for the X–H insertion reactions of iodonium ylides.
Scheme 11: Radiofluorination of biphenyl using iodonium ylides 54a–e derived from various β-dicarbonyl auxilia...
Scheme 12: Radiofluorination of arenes using spirocycle-derived iodonium ylides 56.
Scheme 13: Radiofluorination of arenes using SPIAd-derived iodonium ylides 58.
Figure 12: Calculated reaction coordinate for the radiofluorination of iodonium ylide 60.
Scheme 14: Radiofluorination of iodonium ylides possessing various ortho- and para-substituents on the iodoare...
Figure 13: Difference in Gibbs activation energy for ortho- or para-anisyl derived iodonium ylides 63a and 63b....
Figure 14: Proposed equilibration of intermediates to transit between 64a (the initial adduct formed between 6...
Scheme 15: Comparison of 31 and ortho-methoxy iodonium ylide 39 in rhodium-catalyzed cyclopropanation and cycl...
Figure 15: X-ray crystal structure of dimeric 39 [6], (CCDC# 893474) [143,144].
Scheme 16: Enaminone synthesis using diazonium and iodonium ylides.
Figure 16: Transition state calculations for enaminone synthesis from iodonium ylides and thioamides.
Scheme 17: The reaction between ylides 73a–f and N-methylpyrrole under 365 nm UV irradiation.
Figure 17: Crystal structures of 76c (top) and 76e (bottom) [101], (CCDC# 2104180 & 2104181) [143,144].
Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles
- Péter Kisszékelyi and
- Radovan Šebesta
Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44
- . presented their work on the asymmetric desymmetrization of cyclopentene-1,3-diones 5 (Scheme 3) [23]. Following the Cu(OTf)2-catalyzed conjugate addition of R2Zn, the enolate 6 was trapped by several aromatic aldehydes 7. These complex chiral cyclopentane derivatives 8 bearing all-carbon quaternary
Graphical Abstract
Scheme 1: General scheme depicting tandem reactions based on an asymmetric conjugate addition followed by an ...
Scheme 2: Cu-catalyzed tandem conjugate addition of R2Zn/aldol reaction with chiral acetals.
Scheme 3: Cu-catalyzed asymmetric desymmetrization of cyclopentene-1,3-diones using a tandem conjugate additi...
Scheme 4: Stereocontrolled assembly of dialkylzincs, cyclic enones, and sulfinylimines utilizing a Cu-catalyz...
Scheme 5: Cu-catalyzed tandem conjugate addition/Mannich reaction (A). Access to chiral isoindolinones and tr...
Scheme 6: Cu-catalyzed tandem conjugate addition/nitro-Mannich reaction (A) with syn–anti or syn–syn selectiv...
Figure 1: Various chiral ligands utilized for the tandem conjugate addition/Michael reaction sequences.
Scheme 7: Cu-catalyzed tandem conjugate addition/Michael reaction: side-product formation with chalcone (A) a...
Scheme 8: Zn enolate trapping using allyl iodides (A), Stork–Jung vinylsilane reagents (B), and allyl bromide...
Scheme 9: Cu-catalyzed tandem conjugate addition/acylation through Li R2Zn enolate (A). A four-component coup...
Scheme 10: Selected examples for the Cu-catalyzed tandem conjugate addition/trifluoromethylthiolation sequence....
Scheme 11: Zn enolates trapped by vinyloxiranes: synthesis of allylic alcohols.
Scheme 12: Stereoselective cyclopropanation of Mg enolates formed by ACA of Grignard reagents to chlorocrotona...
Scheme 13: Domino aldol reactions of Mg enolates formed from coumarin and chromone.
Scheme 14: Oxidative coupling of ACA-produced Mg enolates.
Scheme 15: Tandem ACA of Grignard reagents to enones and Mannich reaction.
Scheme 16: Diastereodivergent Mannich reaction of Mg enolates with differently N-protected imines.
Scheme 17: Tandem Grignard–ACA–Mannich using Taddol-based phosphine-phosphite ligands.
Scheme 18: Tandem reaction of Mg enolates with aminomethylating reagents.
Scheme 19: Tandem reaction composed of Grignard ACA to alkynyl enones.
Scheme 20: Rh/Cu-catalyzed tandem reaction of diazo enoates leading to cyclobutanes.
Scheme 21: Tandem Grignard-ACA of cyclopentenones and alkylation of enolates.
Scheme 22: Tandem ACA of Grignard reagents followed by enolate trapping reaction with onium compounds.
Scheme 23: Mg enolates generated from unsaturated lactones in reaction with activated alkenes.
Scheme 24: Lewis acid mediated ACA to amides and SN2 cyclization of a Br-appended enolate.
Scheme 25: Trapping reactions of aza-enolates with Michael acceptors.
Scheme 26: Si enolates generated by TMSOTf-mediated ACA of Grignard reagents and enolate trapping reaction wit...
Scheme 27: Trapping reactions of enolates generated from alkenyl heterocycles (A) and carboxylic acids (B) wit...
Scheme 28: Reactions of heterocyclic Mg enolates with onium compounds.
Scheme 29: Synthetic transformations of cycloheptatrienyl and benzodithiolyl substituents.
Scheme 30: Aminomethylation of Al enolates generated by ACA of trialkylaluminum reagents.
Scheme 31: Trapping reactions of enolates with activated alkenes.
Scheme 32: Alkynylation of racemic aluminum or magnesium enolates.
Scheme 33: Trapping reactions of Zr enolates generated by Cu-ACA of organozirconium reagents.
Scheme 34: Chloromethylation of Zr enolates using the Vilsmeier–Haack reagent.
Scheme 35: Tandem conjugate borylation with subsequent protonation or enolate trapping by an electrophile.
Scheme 36: Tandem conjugate borylation/aldol reaction of cyclohexenones.
Scheme 37: Selected examples for the tandem asymmetric borylation/intramolecular aldol reaction; synthesis of ...
Scheme 38: Cu-catalyzed tandem methylborylation of α,β-unsaturated phosphine oxide in the presence of (R,Sp)-J...
Scheme 39: Cu-catalyzed tandem transannular conjugated borylation/aldol cyclization of macrocycles containing ...
Scheme 40: Stereoselective tandem conjugate borylation/Mannich cyclization: selected examples (A) and a multi-...
Scheme 41: Some examples of Cu-catalyzed asymmetric tandem borylation/aldol cyclization (A). Application to di...
Scheme 42: Atropisomeric P,N-ligands used in tandem conjugate borylation/aldol cyclization sequence.
Scheme 43: Selected examples for the enantioselective Cu-catalyzed borylation/intramolecular Michael addition ...
Scheme 44: Selected examples for the preparation of enantioenriched spiroindanes using a Cu-catalyzed tandem c...
Scheme 45: Enantioselective conjugate borylation of cyclobutene-1-carboxylic acid diphenylmethyl ester 175 wit...
Scheme 46: Cu-catalyzed enantioselective tandem conjugate silylation of α,β-unsaturated ketones with subsequen...
Scheme 47: Cu-catalyzed enantioselective tandem conjugate silylation of α,β-unsaturated ketones with subsequen...
Scheme 48: Cu-catalyzed tandem conjugate silylation/aldol condensation. The diastereoselectivity is controlled...
Scheme 49: Chiral Ru-catalyzed three-component coupling reaction.
Scheme 50: Rh-Phebox complex-catalyzed reductive cyclization and subsequent reaction with Michael acceptors th...
Scheme 51: Rh-catalyzed tandem asymmetric conjugate alkynylation/aldol reaction (A) and subsequent spiro-cycli...
Scheme 52: Rh-bod complex-catalyzed tandem asymmetric conjugate arylation/intramolecular aldol addition (A). S...
Scheme 53: Co-catalyzed C–H-bond activation/asymmetric conjugate addition/aldol reaction.
Scheme 54: (Diisopinocampheyl)borane-promoted 1,4-hydroboration of α,β-unsaturated morpholine carboxamides and...
Figure 2: Some examples of total syntheses that have been recently reviewed.
Scheme 55: Stereoselective synthesis of antimalarial prodrug (+)-artemisinin utilizing a tandem conjugate addi...
Scheme 56: Amphilectane and serrulatane diterpenoids: preparation of chiral starting material via asymmetric t...
Scheme 57: Various asymmetric syntheses of pleuromutilin and related compounds based on a tandem conjugate add...
Scheme 58: Total synthesis of glaucocalyxin A utilizing a tandem conjugate addition/acylation reaction sequenc...
Scheme 59: Installation of the exocyclic double bond using a tandem conjugate addition/aminomethylation sequen...
Scheme 60: Synthesis of the taxol core using a tandem conjugate addition/enolate trapping sequence with Vilsme...
Scheme 61: Synthesis of the tricyclic core of 12-epi-JBIR-23/24 utilizing a Rh-catalyzed asymmetric conjugate ...
Scheme 62: Total synthesis of (−)-peyssonoside A utilizing a Cu-catalyzed enantioselective tandem conjugate ad...
Transition-metal-catalyzed domino reactions of strained bicyclic alkenes
- Austin Pounder,
- Eric Neufeld,
- Peter Myler and
- William Tam
Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38
- be shifted to the 1,4-addition producing a cyclopentene product leading to the conclusion that the substitution pattern on the boronate ester played a significant role in the selectivity between 1,6-addition and 1,4-addition. The mechanism proposed by the authors initially begins in the same manner
- vinylcyclopropane products 126 while dienylboronate esters bearing methyl groups at the δ or γ position resulted in cyclopentene products. In 2009, the Lautens lab continued investigating the reactions of bicyclic alkenes 130 with a novel range of heteroaromatic boronate esters 131 (Scheme 23) [69]. This has
Graphical Abstract
Figure 1: Ring-strain energies of homobicyclic and heterobicyclic alkenes in kcal mol−1. a) [2.2.1]-Bicyclic ...
Figure 2: a) Exo and endo face descriptions of bicyclic alkenes. b) Reactivity comparisons for different β-at...
Scheme 1: Ni-catalyzed ring-opening/cyclization cascade of heterobicyclic alkenes 1 with alkyl propiolates 2 ...
Scheme 2: Ni-catalyzed ring-opening/cyclization cascade of heterobicyclic alkenes 8 with β-iodo-(Z)-propenoat...
Scheme 3: Ni-catalyzed two- and three-component difunctionalizations of norbornene derivatives 15 with alkyne...
Scheme 4: Ni-catalyzed intermolecular three-component difunctionalization of oxabicyclic alkenes 1 with alkyn...
Scheme 5: Ni-catalyzed intermolecular three-component carboacylation of norbornene derivatives 15.
Scheme 6: Photoredox/Ni dual-catalyzed coupling of 4-alkyl-1,4-dihydropyridines 31 with heterobicyclic alkene...
Scheme 7: Photoredox/Ni dual-catalyzed coupling of α-amino radicals with heterobicyclic alkenes 30.
Scheme 8: Cu-catalyzed rearrangement/allylic alkylation of 2,3-diazabicyclo[2.2.1]heptenes 47 with Grignard r...
Scheme 9: Cu-catalyzed aminoboration of bicyclic alkenes 1 with bis(pinacolato)diboron (B2pin2) (53) and O-be...
Scheme 10: Cu-catalyzed borylalkynylation of oxabenzonorbornadiene (30b) with B2pin2 (53) and bromoalkynes 62.
Scheme 11: Cu-catalyzed borylacylation of bicyclic alkenes 1.
Scheme 12: Cu-catalyzed diastereoselective 1,2-difunctionalization of oxabenzonorbornadienes 30 for the synthe...
Scheme 13: Fe-catalyzed carbozincation of heterobicyclic alkenes 1 with arylzinc reagents 74.
Scheme 14: Co-catalyzed addition of arylzinc reagents of norbornene derivatives 15.
Scheme 15: Co-catalyzed ring-opening/dehydration of oxabicyclic alkenes 30 via C–H activation of arenes.
Scheme 16: Co-catalyzed [3 + 2] annulation/ring-opening/dehydration domino reaction of oxabicyclic alkenes 1 w...
Scheme 17: Co-catalyzed enantioselective carboamination of bicyclic alkenes 1 via C–H functionalization.
Scheme 18: Ru-catalyzed cyclization of oxabenzonorbornene derivatives with propargylic alcohols for the synthe...
Scheme 19: Ru-catalyzed coupling of oxabenzonorbornene derivatives 30 with propargylic alcohols and ethers 106...
Scheme 20: Ru-catalyzed ring-opening/dehydration of oxabicyclic alkenes via the C–H activation of anilides.
Scheme 21: Ru-catalyzed of azabenzonorbornadiene derivatives with arylamides.
Scheme 22: Rh-catalyzed cyclization of bicyclic alkenes with arylboronate esters 118.
Scheme 23: Rh-catalyzed cyclization of bicyclic alkenes with dienyl- and heteroaromatic boronate esters.
Scheme 24: Rh-catalyzed domino lactonization of doubly bridgehead-substituted oxabicyclic alkenes with seconda...
Scheme 25: Rh-catalyzed domino carboannulation of diazabicyclic alkenes with 2-cyanophenylboronic acid and 2-f...
Scheme 26: Rh-catalyzed synthesis of oxazolidinone scaffolds 147 through a domino ARO/cyclization of oxabicycl...
Scheme 27: Rh-catalyzed oxidative coupling of salicylaldehyde derivatives 151 with diazabicyclic alkenes 130a.
Scheme 28: Rh-catalyzed reaction of O-acetyl ketoximes with bicyclic alkenes for the synthesis of isoquinoline...
Scheme 29: Rh-catalyzed domino coupling reaction of 2-phenylpyridines 165 with oxa- and azabicyclic alkenes 30....
Scheme 30: Rh-catalyzed domino dehydrative naphthylation of oxabenzonorbornadienes 30 with N-sulfonyl 2-aminob...
Scheme 31: Rh-catalyzed domino dehydrative naphthylation of oxabenzonorbornadienes 30 with arylphosphine deriv...
Scheme 32: Rh-catalyzed domino ring-opening coupling reaction of azaspirotricyclic alkenes using arylboronic a...
Scheme 33: Tandem Rh(III)/Sc(III)-catalyzed domino reaction of oxabenzonorbornadienes 30 with alkynols 184 dir...
Scheme 34: Rh-catalyzed asymmetric domino cyclization and addition reaction of 1,6-enynes 194 and oxa/azabenzo...
Scheme 35: Rh/Zn-catalyzed domino ARO/cyclization of oxabenzonorbornadienes 30 with phosphorus ylides 201.
Scheme 36: Rh-catalyzed domino ring opening/lactonization of oxabenzonorbornadienes 30 with 2-nitrobenzenesulf...
Scheme 37: Rh-catalyzed domino C–C/C–N bond formation of azabenzonorbornadienes 30 with aryl-2H-indazoles 210.
Scheme 38: Rh/Pd-catalyzed domino synthesis of indole derivatives with 2-(phenylethynyl)anilines 212 and oxabe...
Scheme 39: Rh-catalyzed domino carborhodation of heterobicyclic alkenes 30 with B2pin2 (53).
Scheme 40: Rh-catalyzed three-component 1,2-carboamidation reaction of bicyclic alkenes 30 with aromatic and h...
Scheme 41: Pd-catalyzed diarylation and dialkenylation reactions of norbornene derivatives.
Scheme 42: Three-component Pd-catalyzed arylalkynylation reactions of bicyclic alkenes.
Scheme 43: Three-component Pd-catalyzed arylalkynylation reactions of norbornene and DFT mechanistic study.
Scheme 44: Pd-catalyzed three-component coupling N-tosylhydrazones 236, aryl halides 66, and norbornene (15a).
Scheme 45: Pd-catalyzed arylboration and allylboration of bicyclic alkenes.
Scheme 46: Pd-catalyzed, three-component annulation of aryl iodides 66, alkenyl bromides 241, and bicyclic alk...
Scheme 47: Pd-catalyzed double insertion/annulation reaction for synthesizing tetrasubstituted olefins.
Scheme 48: Pd-catalyzed aminocyclopropanation of bicyclic alkenes 1 with 5-iodopent-4-enylamine derivatives 249...
Scheme 49: Pd-catalyzed, three-component coupling of alkynyl bromides 62 and norbornene derivatives 15 with el...
Scheme 50: Pd-catalyzed intramolecular cyclization/ring-opening reaction of heterobicyclic alkenes 30 with 2-i...
Scheme 51: Pd-catalyzed dimer- and trimerization of oxabenzonorbornadiene derivatives 30 with anhydrides 268.
Scheme 52: Pd-catalyzed Catellani-type annulation and retro-Diels–Alder of norbornadiene 15b yielding fused xa...
Scheme 53: Pd-catalyzed hydroarylation and heteroannulation of urea-derived bicyclic alkenes 158 and aryl iodi...
Scheme 54: Access to fused 8-membered sulfoximine heterocycles 284/285 via Pd-catalyzed Catellani annulation c...
Scheme 55: Pd-catalyzed 2,2-bifunctionalization of bicyclic alkenes 1 generating spirobicyclic xanthone deriva...
Scheme 56: Pd-catalyzed Catellani-type annulation and retro-Diels–Alder of norbornadiene (15b) producing subst...
Scheme 57: Pd-catalyzed [2 + 2 + 1] annulation furnishing bicyclic-fused indanes 281 and 283.
Scheme 58: Pd-catalyzed ring-opening/ring-closing cascade of diazabicyclic alkenes 130a.
Scheme 59: Pd-NHC-catalyzed cyclopentannulation of diazabicyclic alkenes 130a.
Scheme 60: Pd-catalyzed annulation cascade generating diazabicyclic-fused indanones 292 and indanols 294.
Scheme 61: Pd-catalyzed skeletal rearrangement of spirotricyclic alkenes 176 towards large polycyclic benzofur...
Scheme 62: Pd-catalyzed oxidative annulation of aromatic enamides 298 and diazabicyclic alkenes 130a.
Scheme 63: Accessing 3,4,5-trisubstituted cyclopentenes 300, 301, 302 via the Pd-catalyzed domino reaction of ...
Scheme 64: Palladacycle-catalyzed ring-expansion/cyclization domino reactions of terminal alkynes and bicyclic...
Scheme 65: Pd-catalyzed carboesterification of norbornene (15a) with alkynes, furnishing α-methylene γ-lactone...
Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series
- Cécile Alleman,
- Charlène Gadais,
- Laurent Legentil and
- François-Hugues Porée
Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23
- cyclopentane ring C formation. In the second strategy (strategy 2, Figure 3), both cyclopentane rings A and C are formed first, and the eight-membered ring B is introduced at a late stage. 1.1.1.1 Strategy 1: Successive introduction of rings B and C starting from cyclopentene via the [5-8] bicyclic structure
Graphical Abstract
Figure 1: Examples of terpenes containing a bicyclo[3.6.0]undecane motif.
Figure 2: Commercially available first and second generation Grubbs and Hoveyda–Grubbs catalysts.
Figure 3: Examples of strategies to access the fusicoccan and ophiobolin tricyclic core structure by RCM.
Scheme 1: Synthesis of bicyclic core structure 12 of ophiobolin M (13) and cycloaraneosene (14).
Scheme 2: Synthesis of the core structure 21 of ophiobolins and fusicoccanes.
Scheme 3: Ring-closing metathesis attempts starting from thioester 22.
Scheme 4: Total synthesis of ent-fusicoauritone (28).
Figure 4: General structure of ophiobolins and congeners.
Scheme 5: Total synthesis of (+)-ophiobolin A (8).
Scheme 6: Investigation of RCM for the synthesis of ophiobolin A (8). Path A) RCM with TBDPS-protected alcoho...
Scheme 7: Synthesis of the core structure of cotylenin A aglycon, cotylenol (50).
Scheme 8: Synthesis of tricyclic core structure of fusicoccans.
Scheme 9: Total synthesis of (−)-teubrevin G (59).
Scheme 10: Synthesis of the core skeleton 63 of the basmane family.
Scheme 11: Total synthesis of (±)-schindilactone A (68).
Scheme 12: Total synthesis of dactylol (72).
Scheme 13: Ring-closing metathesis for the total synthesis of (±)-asteriscanolide (2).
Scheme 14: Synthesis of the simplified skeleton of pleuromutilin (1).
Scheme 15: Total synthesis of (−)-nitidasin (93) using a ring-closing metathesis to construct the eight-member...
Scheme 16: Total synthesis of (±)-naupliolide (97).
Scheme 17: Synthesis of the A-B ring structure of fusicoccane (101).
Scheme 18: First attempts of TRCM of dienyne substrates.
Scheme 19: TRCM on optimized substrates towards the synthesis of ophiobolin A (8).
Scheme 20: Tandem ring-closing metathesis for the synthesis of variecolin intermediates 114 and 115.
Scheme 21: Synthesis of poitediol (118) using the allylsilane ring-closing metathesis.
Scheme 22: Access to scaffold 122 by a NHK coupling reaction.
Scheme 23: Key step to construct the [5-8] bicyclooctanone core of aquatolide (4).
Scheme 24: Initial strategy to access aquatolide (4).
Scheme 25: Synthetic plan to cotylenin A (130).
Scheme 26: [5-8] Bicyclic structure of brachialactone (7) constructed by a Mizoroki–Heck reaction.
Scheme 27: Influence of the replacement of the allylic alcohol moiety.
Scheme 28: Formation of variecolin intermediate 140 through a SmI2-mediated Barbier-type reaction.
Scheme 29: SmI2-mediated ketyl addition. Pleuromutilin (1) eight-membered ring closure via C5–C14 bond formati...
Scheme 30: SmI2-mediated dialdehyde cyclization cascade of [5-8-6] pleuromutilin scaffold 149.
Scheme 31: A) Modular synthetic route to mutilin and pleuromutilin family members by Herzon’s group. B) Scaffo...
Scheme 32: Photocatalyzed oxidative ring expansion in pleuromutilin (1) total synthesis.
Scheme 33: Reductive radical cascade cyclization route towards (−)-6-epi-ophiobolin N (168).
Scheme 34: Reductive radical cascade cyclization route towards (+)-6-epi-ophiobolin A (173).
Scheme 35: Radical 8-endo-trig-cyclization of a xanthate precursor.
Figure 5: Structural representations of hypoestin A (177), albolic acid (178), and ceroplastol II (179) beari...
Scheme 36: Synthesis of the common [5-8-5] tricyclic intermediate of hypoestin A (177), albolic acid (178), an...
Scheme 37: Asymmetric synthesis of hypoestin A (177), albolic acid (178), and ceroplastol II (179).
Figure 6: Scope of the Pauson–Khand reaction.
Scheme 38: Nazarov cyclization revealing the fusicoauritone core structure 192.
Scheme 39: Synthesis of fusicoauritone (28) through Nazarov cyclization.
Scheme 40: (+)-Epoxydictymene (5) synthesis through a Nicholas cyclization followed by a Pauson–Khand reaction...
Scheme 41: Synthesis of aquatolide (4) by a Mukaiyama-type aldolisation.
Scheme 42: Tandem Wolff/Cope rearrangement furnishing the A-B bicyclic moiety 204 of variecolin.
Scheme 43: Asymmetric synthesis of the A-B bicyclic core 205 and 206 of variecolin.
Scheme 44: Formation of [5-8]-fused rings by cyclization under thermal activation.
Scheme 45: Construction of the [5-8-6] tricyclic core structure of variecolin (3) by Diels–Alder reaction.
Scheme 46: Synthesis of the [6-4-8-5]-tetracyclic skeleton by palladium-mediated cyclization.
Scheme 47: Access to the [5-8] bicyclic core structure of asteriscanolide (227) through rhodium-catalyzed cycl...
Scheme 48: Total syntheses of asterisca-3(15),6-diene (230) and asteriscanolide (2) with a Rh-catalyzed cycliz...
Scheme 49: Photocyclization of 2-pyridones to access the [5-8-5] backbone of fusicoccanes.
Scheme 50: Total synthesis of (+)-asteriscunolide D (245) and (+)-aquatolide (4) through photocyclization.
Scheme 51: Biocatalysis pathway to construct the [5-8-5] tricyclic scaffold of brassicicenes.
Scheme 52: Influence of the CotB2 mutant over the cyclization’s outcome of GGDP.
Molecular diversity of the base-promoted reaction of phenacylmalononitriles with dialkyl but-2-ynedioates
- Hui Zheng,
- Ying Han,
- Jing Sun and
- Chao-Guo Yan
Beilstein J. Org. Chem. 2022, 18, 991–998, doi:10.3762/bjoc.18.99
- multifunctionalized carboxamide-bridged dicyclopentenes in moderate to good yields and with high diastereoselectivity. Keywords: carboxamide; cycloaddition; cyclopentene; electron-deficient alkyne; phenacylmalononitrile; Introduction Phenacylmalononitrile is one of the privileged functionalized compounds [1][2][3
- phenacylmalononitriles and allenoates for the tunable synthesis of multifunctionalized cyclopentene carboxamides and cyclopentenols [33] (reaction 3 in Scheme 1). Recently, Zhang and Ban reported a NaHCO3-promoted reaction of phenacylmalononitriles and N-alkylmaleimides to give the novel cyclopenta[c]pyrrole-4
- hours afforded the expected product 4d in 45% yield. This result clearly showed that the initially formed functionalized cyclopentene 3b could be smoothly transferred to the carboxamide-bridged dicyclopentene 4d, which also strongly supported the above proposed reaction mechanism. Conclusion In summary
Graphical Abstract
Scheme 1: Representative cycloaddition reactions of phenacylmalononitriles.
Figure 1: Single crystal structure of compound 3k.
Figure 2: Single crystal structure of compound 4a.
Figure 3: Single crystal structure of compound 4c.
Scheme 2: Proposed reaction mechanism for compounds 3, 4, and 5.
Figure 4: Single crystal structure of compound 5.
Scheme 3: Control experiment.
On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets
- Renato L. Carvalho,
- Amanda S. de Miranda,
- Mateus P. Nunes,
- Roberto S. Gomes,
- Guilherme A. M. Jardim and
- Eufrânio N. da Silva Júnior
Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126
- [158]. The synthesis started with a cyclopentene derivative, obtained after two steps from a diol via tosylation/displacement strategy with Me2CuLi·LiI. Then, after a Lewis acid-promoted cycloaddition, the alkylation of the α-carbon atom followed by regioselective Baeyer–Villiger oxidation provided the
Graphical Abstract
Scheme 1: Schematic overview of transition metals studied in C–H activation processes.
Scheme 2: (A) Known biological activities related to benzimidazole-based compounds; (B and C) an example of a...
Scheme 3: (A) Known biological activities related to quinoline-based compounds; (B and C) an example of a sca...
Scheme 4: (A) Known biological activities related to sulfur-containing compounds; (B and C) an example of a s...
Scheme 5: (A) Known biological activities related to aminoindane derivatives; (B and C) an example of a scand...
Scheme 6: (A) Known biological activities related to norbornane derivatives; (B and C) an example of a scandi...
Scheme 7: (A) Known biological activities related to aniline derivatives; (B and C) an example of a titanium-...
Scheme 8: (A) Known biological activities related to cyclohexylamine derivatives; (B) an example of an intram...
Scheme 9: (A) Known biologically active benzophenone derivatives; (B and C) photocatalytic oxidation of benzy...
Scheme 10: (A) Known bioactive fluorine-containing compounds; (B and C) vanadium-mediated C(sp3)–H fluorinatio...
Scheme 11: (A) Known biologically active Lythraceae alkaloids; (B) synthesis of (±)-decinine (30).
Scheme 12: (A) Synthesis of (R)- and (S)-boehmeriasin (31); (B) synthesis of phenanthroindolizidines by vanadi...
Scheme 13: (A) Known bioactive BINOL derivatives; (B and C) vanadium-mediated oxidative coupling of 2-naphthol...
Scheme 14: (A) Known antiplasmodial imidazopyridazines; (B) practical synthesis of 41.
Scheme 15: (A) Gold-catalyzed drug-release mechanism using 2-alkynylbenzamides; (B and C) chromium-mediated al...
Scheme 16: (A) Examples of anti-inflammatory benzaldehyde derivatives; (B and C) chromium-mediated difunctiona...
Scheme 17: (A and B) Manganese-catalyzed chemoselective intramolecular C(sp3)–H amination; (C) late-stage modi...
Scheme 18: (A and B) Manganese-catalyzed C(sp3)–H amination; (C) late-stage modification of a leelamine deriva...
Scheme 19: (A) Known bioactive compounds containing substituted N-heterocycles; (B and C) manganese-catalyzed ...
Scheme 20: (A) Known indoles that present GPR40 full agonist activity; (B and C) manganese-catalyzed C–H alkyl...
Scheme 21: (A) Examples of known biaryl-containing drugs; (B and C) manganese-catalyzed C–H arylation through ...
Scheme 22: (A) Known zidovudine derivatives with potent anti-HIV properties; (B and C) manganese-catalyzed C–H...
Scheme 23: (A and B) Manganese-catalyzed C–H organic photo-electrosynthesis; (C) late-stage modification.
Scheme 24: (A) Example of a known antibacterial silylated dendrimer; (B and C) manganese-catalyzed C–H silylat...
Scheme 25: (A and B) Fe-based small molecule catalyst applied for selective aliphatic C–H oxidations; (C) late...
Scheme 26: (A) Examples of naturally occurring gracilioethers; (B) the first total synthesis of gracilioether ...
Scheme 27: (A and B) Selective aliphatic C–H oxidation of amino acids; (C) late-stage modification of proline-...
Scheme 28: (A) Examples of Illicium sesquiterpenes; (B) first chemical synthesis of (+)-pseudoanisatin (80) in...
Scheme 29: (A and B) Fe-catalyzed deuteration; (C) late-stage modification of pharmaceuticals.
Scheme 30: (A and B) Biomimetic Fe-catalyzed aerobic oxidation of methylarenes to benzaldehydes (PMHS, polymet...
Scheme 31: (A) Known tetrahydroquinolines with potential biological activities; (B and C) redox-selective Fe c...
Scheme 32: (A) Known drugs containing a benzofuran unit; (B and C) Fe/Cu-catalyzed tandem O-arylation to acces...
Scheme 33: (A) Known azaindolines that act as M4 muscarinic acetylcholine receptor agonists; (B and C) intramo...
Scheme 34: (A) Known indolinones with anticholinesterase activity; (B and C) oxidative C(sp3)–H cross coupling...
Scheme 35: (A and B) Cobalt-catalyzed C–H alkenylation of C-3-peptide-containing indoles; (C) derivatization b...
Scheme 36: (A) Cobalt-Cp*-catalyzed C–H methylation of known drugs; (B and C) scope of the o-methylated deriva...
Scheme 37: (A) Known lasalocid A analogues; (B and C) three-component cobalt-catalyzed C–H bond addition; (D) ...
Scheme 38: (A and B) Cobalt-catalyzed C(sp2)–H amidation of thiostrepton.
Scheme 39: (A) Known 4H-benzo[d][1,3]oxazin-4-one derivatives with hypolipidemic activity; (B and C) cobalt-ca...
Scheme 40: (A and B) Cobalt-catalyzed C–H arylation of pyrrole derivatives; (C) application for the synthesis ...
Scheme 41: (A) Known 2-phenoxypyridine derivatives with potent herbicidal activity; (B and C) cobalt-catalyzed...
Scheme 42: (A) Natural cinnamic acid derivatives; (B and C) cobalt-catalyzed C–H carboxylation of terminal alk...
Scheme 43: (A and B) Cobalt-catalyzed C–H borylation; (C) application to the synthesis of flurbiprofen.
Scheme 44: (A) Benzothiazoles known to present anticonvulsant activities; (B and C) cobalt/ruthenium-catalyzed...
Scheme 45: (A and B) Cobalt-catalyzed oxygenation of methylene groups towards ketone synthesis; (C) synthesis ...
Scheme 46: (A) Known anticancer tetralone derivatives; (B and C) cobalt-catalyzed C–H difluoroalkylation of ar...
Scheme 47: (A and B) Cobalt-catalyzed C–H thiolation; (C) application in the synthesis of quetiapine (153).
Scheme 48: (A) Known benzoxazole derivatives with anticancer, antifungal, and antibacterial activities; (B and...
Scheme 49: (A and B) Cobalt-catalyzed C–H carbonylation of naphthylamides; (C) BET inhibitors 158 and 159 tota...
Scheme 50: (A) Known bioactive pyrrolo[1,2-a]quinoxalin-4(5H)-one derivatives; (B and C) cobalt-catalyzed C–H ...
Scheme 51: (A) Known antibacterial cyclic sulfonamides; (B and C) cobalt-catalyzed C–H amination of propargyli...
Scheme 52: (A and B) Cobalt-catalyzed intramolecular 1,5-C(sp3)–H amination; (C) late-stage functionalization ...
Scheme 53: (A and B) Cobalt-catalyzed C–H/C–H cross-coupling between benzamides and oximes; (C) late-state syn...
Scheme 54: (A) Known anticancer natural isoquinoline derivatives; (B and C) cobalt-catalyzed C(sp2)–H annulati...
Scheme 55: (A) Enantioselective intramolecular nickel-catalyzed C–H activation; (B) bioactive obtained motifs;...
Scheme 56: (A and B) Nickel-catalyzed α-C(sp3)–H arylation of ketones; (C) application of the method using kno...
Scheme 57: (A and B) Nickel-catalyzed C(sp3)–H acylation of pyrrolidine derivatives; (C) exploring the use of ...
Scheme 58: (A) Nickel-catalyzed C(sp3)–H arylation of dioxolane; (B) library of products obtained from biologi...
Scheme 59: (A) Intramolecular enantioselective nickel-catalyzed C–H cycloalkylation; (B) product examples, inc...
Scheme 60: (A and B) Nickel-catalyzed C–H deoxy-arylation of azole derivatives; (C) late-stage functionalizati...
Scheme 61: (A and B) Nickel-catalyzed decarbonylative C–H arylation of azole derivatives; (C) application of t...
Scheme 62: (A and B) Another important example of nickel-catalyzed C–H arylation of azole derivatives; (C) app...
Scheme 63: (A and B) Another notable example of a nickel-catalyzed C–H arylation of azole derivatives; (C) lat...
Scheme 64: (A and B) Nickel-based metalorganic framework (MOF-74-Ni)-catalyzed C–H arylation of azole derivati...
Scheme 65: (A) Known commercially available benzothiophene-based drugs; (B and C) nickel-catalyzed C–H arylati...
Scheme 66: (A) Known natural tetrahydrofuran-containing substances; (B and C) nickel-catalyzed photoredox C(sp3...
Scheme 67: (A and B) Another notable example of a nickel-catalyzed photoredox C(sp3)–H alkylation/arylation; (...
Scheme 68: (A) Electrochemical/nickel-catalyzed C–H alkoxylation; (B) achieved scope, including three using na...
Scheme 69: (A) Enantioselective photoredox/nickel catalyzed C(sp3)–H arylation; (B) achieved scope, including ...
Scheme 70: (A) Known commercially available trifluoromethylated drugs; (B and C) nickel-catalyzed C–H trifluor...
Scheme 71: (A and B) Stereoselective nickel-catalyzed C–H difluoroalkylation; (C) late-stage functionalization...
Scheme 72: (A) Cu-mediated ortho-amination of oxalamides; (B) achieved scope, including derivatives obtained f...
Scheme 73: (A) Electro-oxidative copper-mediated amination of 8-aminoquinoline-derived amides; (B) achieved sc...
Scheme 74: (A and B) Cu(I)-mediated C–H amination with oximes; (C) derivatization using telmisartan (241) as s...
Scheme 75: (A and B) Cu-mediated amination of aryl amides using ammonia; (C) late-stage modification of proben...
Scheme 76: (A and B) Synthesis of purine nucleoside analogues using copper-mediated C(sp2)–H activation.
Scheme 77: (A) Copper-mediated annulation of acrylamide; (B) achieved scope, including the synthesis of the co...
Scheme 78: (A) Known bioactive compounds containing a naphthyl aryl ether motif; (B and C) copper-mediated eth...
Scheme 79: (A and B) Cu-mediated alkylation of N-oxide-heteroarenes; (C) late-stage modification.
Scheme 80: (A) Cu-mediated cross-dehydrogenative coupling of polyfluoroarenes and alkanes; (B) scope from know...
Scheme 81: (A) Known anticancer acrylonitrile compounds; (B and C) Copper-mediated cyanation of unactivated al...
Scheme 82: (A) Cu-mediated radiofluorination of 8-aminoquinoline-derived aryl amides; (B) achieved scope, incl...
Scheme 83: (A) Examples of natural β-carbolines; (B and C) an example of a zinc-catalyzed C–H functionalizatio...
Scheme 84: (A) Examples of anticancer α-aminophosphonic acid derivatives; (B and C) an example of a zinc-catal...
The preparation and properties of 1,1-difluorocyclopropane derivatives
- Kymbat S. Adekenova,
- Peter B. Wyatt and
- Sergazy M. Adekenov
Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25
- -difluorocyclopropanes (Scheme 40) [86]. Vinylcyclopropane rearrangements: O’Neal and Benson examined the influence of fluorine substituents on the kinetics of the vinylcyclopropane-to-cyclopentene rearrangement [87]. They noted the effect of an additional strain (approximately 5 kcal/mol per fluorine atom) in raising
- -isomer 91 (>6 kcal/mol), because of the need to attain a cisoid conformation prior to the rearrangement. The thermal vinylcyclopropane rearrangement of ethyl trans-3-(2,2-difluoro-3-phenylcyclopropyl)acrylate (93) proceeded at 100 °C, resulting in the difluorinated cyclopentene 94 with the substituents
- oriented trans to each other (Scheme 43) [89]. The cis-isomer 95 was unable to rearrange directly to a cyclopentene and first isomerized to give 93. Alkenyldifluorocyclopropanes that were derived from 2-siloxybutadienes underwent analogous rearrangements to afford 1-siloxy-5,5-difluorocyclopentenes [90
Graphical Abstract
Scheme 1: Synthesis of 1,1-difluoro-2,3-dimethylcyclopropane (2).
Scheme 2: Cyclopropanation via dehydrohalogenation of chlorodifluoromethane.
Scheme 3: Difluorocyclopropanation of methylstyrene 7 using dibromodifluoromethane and zinc.
Scheme 4: Synthesis of difluorocyclopropanes from the reaction of dibromodifluoromethane and triphenylphosphi...
Scheme 5: Generation of difluorocarbene in a catalytic two-phase system and its addition to tetramethylethyle...
Scheme 6: The reaction of methylstyrene 7 with chlorodifluoromethane (11) in the presence of a tetraarylarson...
Scheme 7: Pyrolysis of sodium chlorodifluoroacetate (12) in refluxing diglyme in the presence of alkene 13.
Scheme 8: Synthesis of boron-substituted gem-difluorocyclopropanes 16.
Scheme 9: Addition of sodium bromodifluoroacetate (17) to alkenes.
Scheme 10: Addition of sodium bromodifluoroacetate (17) to silyloxy-substituted cyclopropanes 20.
Scheme 11: Synthesis of difluorinated nucleosides.
Scheme 12: Addition of butyl acrylate (26) to difluorocarbene generated from TFDA (25).
Scheme 13: Addition of difluorocarbene to propargyl esters 27 and conversion of the difluorocyclopropenes 28 t...
Scheme 14: The generation of difluorocyclopropanes using MDFA 30.
Scheme 15: gem-Difluorocyclopropanation of styrene (32) using difluorocarbene generated from TMSCF3 (31) under...
Scheme 16: Synthesis of a gem-difluorocyclopropane derivative using HFPO (41) as a source of difluorocarbene.
Scheme 17: Cyclopropanation of (Z)-2-butene in the presence of difluorodiazirine (44).
Scheme 18: The cyclopropanation of 1-octene (46) using Seyferth's reagent (45) as a source of difluorocarbene.
Scheme 19: Alternative approaches for the difluorocarbene synthesis from trimethyl(trifluoromethyl)tin (48).
Scheme 20: Difluorocyclopropanation of cyclohexene (49).
Scheme 21: Synthesis of difluorocyclopropane derivative 53 using bis(trifluoromethyl)cadmium (51) as the diflu...
Scheme 22: Addition of difluorocarbene generated from tris(trifluoromethyl)bismuth (54).
Scheme 23: Addition of a stable (trifluoromethyl)zinc reagent to styrenes.
Scheme 24: The preparation of 2,2-difluorocyclopropanecarboxylic acids of type 58.
Scheme 25: Difluorocyclopropanation via Michael cyclization.
Scheme 26: Difluorocyclopropanation using N-acylimidazolidinone 60.
Scheme 27: Difluorocyclopropanation through the cyclization of phenylacetonitrile (61) and 1,2-dibromo-1,1-dif...
Scheme 28: gem-Difluoroolefins 64 for the synthesis of functionalized cyclopropanes 65.
Scheme 29: Preparation of aminocyclopropanes 70.
Scheme 30: Synthesis of fluorinated methylenecyclopropane 74 via selenoxide elimination.
Scheme 31: Reductive dehalogenation of (1R,3R)-75.
Scheme 32: Synthesis of chiral monoacetates by lipase catalysis.
Scheme 33: Transformation of (±)-trans-81 using Rhodococcus sp. AJ270.
Scheme 34: Transformation of (±)-trans-83 using Rhodococcus sp. AJ270.
Scheme 35: Hydrogenation of difluorocyclopropenes through enantioselective hydrocupration.
Scheme 36: Enantioselective transfer hydrogenation of difluorocyclopropenes with a Ru-based catalyst.
Scheme 37: The thermal transformation of trans-1,2-dichloro-3,3-difluorocyclopropane (84).
Scheme 38: cis–trans-Epimerization of 1,1-difluoro-2,3-dimethylcyclopropane.
Scheme 39: 2,2-Difluorotrimethylene diradical intermediate.
Scheme 40: Ring opening of stereoisomers 88 and 89.
Scheme 41: [1,3]-Rearrangement of alkenylcyclopropanes 90–92.
Scheme 42: Thermolytic rearrangement of 2,2-difluoro-1-vinylcyclopropane (90).
Scheme 43: Thermal rearrangement for ethyl 3-(2,2-difluoro)-3-phenylcyclopropyl)acrylates 93 and 95.
Scheme 44: Possible pathways of the ring opening of 1,1-difluoro-2-vinylcyclopropane.
Scheme 45: Equilibrium between 1,1-difluoro-2-methylenecyclopropane (96) and (difluoromethylene)cyclopropane 97...
Scheme 46: Ring opening of substituted 1,1-difluoro-2,2-dimethyl-3-methylenecyclopropane 98.
Scheme 47: 1,1-Difluorospiropentane rearrangement.
Scheme 48: Acetolysis of (2,2-difluorocyclopropyl)methyl tosylate (104) and (1,1-difluoro-2-methylcyclopropyl)...
Scheme 49: Ring opening of gem-difluorocyclopropyl ketones 106 and 108 by thiolate nucleophiles.
Scheme 50: Hydrolysis of gem-difluorocyclopropyl acetals 110.
Scheme 51: Ring-opening reaction of 2,2-difluorocyclopropyl ketones 113 in the presence of ionic liquid as a s...
Scheme 52: Ring opening of gem-difluorocyclopropyl ketones 113a by MgI2-initiated reaction with diarylimines 1...
Scheme 53: Ring-opening reaction of gem-difluorocyclopropylstannanes 117.
Scheme 54: Preparation of 1-fluorovinyl vinyl ketone 123 and the synthesis of 2-fluorocyclopentenone 124. TBAT...
Scheme 55: Iodine atom-transfer ring opening of 1,1-difluoro-2-(1-iodoalkyl)cyclopropanes 125a–c.
Scheme 56: Ring opening of bromomethyl gem-difluorocyclopropanes 130 and formation of gem-difluoromethylene-co...
Scheme 57: Ring-opening aerobic oxidation reaction of gem-difluorocyclopropanes 132.
Scheme 58: Dibrominative ring-opening functionalization of gem-difluorocyclopropanes 134.
Scheme 59: The selective formation of (E,E)- and (E,Z)-fluorodienals 136 and 137 from difluorocyclopropyl acet...
Scheme 60: Proposed mechanism for the reaction of difluoro(methylene)cyclopropane 139 with Br2.
Scheme 61: Thermal rearrangement of F2MCP 139 and iodine by CuI catalysis.
Scheme 62: Synthesis of 2-fluoropyrroles 142.
Scheme 63: Ring opening of gem-difluorocyclopropyl ketones 143 mediated by BX3.
Scheme 64: Lewis acid-promoted ring-opening reaction of 2,2-difluorocyclopropanecarbonyl chloride (148).
Scheme 65: Ring-opening reaction of the gem-difluorocyclopropyl ketone 106 by methanolic KOH.
Scheme 66: Hydrogenolysis of 1,1-difluoro-3-methyl-2-phenylcyclopropane (151).
Scheme 67: Synthesis of monofluoroalkenes 157.
Scheme 68: The stereoselective Ag-catalyzed defluorinative ring-opening diarylation of 1-trimethylsiloxy-2,2-d...
Scheme 69: Synthesis of 2-fluorinated allylic compounds 162.
Scheme 70: Pd-catalyzed cross-coupling reactions of gem-difluorinated cyclopropanes 161.
Scheme 71: The (Z)-selective Pd-catalyzed ring-opening sulfonylation of 2-(2,2-difluorocyclopropyl)naphthalene...
Figure 1: Structures of zosuquidar hydrochloride and PF-06700841.
Scheme 72: Synthesis of methylene-gem-difluorocyclopropane analogs of nucleosides.
Figure 2: Anthracene-difluorocyclopropane hybrid derivatives.
Figure 3: Further examples of difluorcyclopropanes in modern drug discovery.
All-carbon [3 + 2] cycloaddition in natural product synthesis
- Zhuo Wang and
- Junyang Liu
Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251
- (9) was accomplished from 81 in two steps. Phosphine-catalyzed [3 + 2] cycloaddition In 1995, Lu and co-workers reported a phosphine-catalyzed [3 + 2] cycloaddition, employing electron-deficient olefins and either 2,3-butadienoates or 2-butynoates to give a cyclopentene as product [17] (Scheme 5A
Graphical Abstract
Figure 1: Highly-substituted five-membered carbocycle in biologically significant natural products.
Figure 2: Natural product synthesis featuring the all-carbon [3 + 2] cycloaddition. (Quaternary carbon center...
Scheme 1: Representative natural product syntheses that feature the all-carbon [3 + 2] cyclization as the key...
Scheme 2: (A) An intramolecular trimethylenemethane diyl [3 + 2] cycloaddition with allenyl diazo compound 38...
Scheme 3: (A) Palladium-catalyzed intermolecular carboxylative TMM cycloaddition [36]. (B) The proposed mechanism....
Scheme 4: Natural product syntheses that make use of palladium-catalyzed intermolecular [3 + 2] cycloaddition...
Scheme 5: (A) Phosphine-catalyzed [3 + 2] cycloaddition [17]. (B) The proposed mechanism.
Scheme 6: Lu’s [3 + 2] cycloaddition in natural product synthesis. (A) Synthesis of longeracinphyllin A (10) [41]...
Scheme 7: (A) Phosphine-catalyzed [3 + 2] annulation of unsymmetric isoindigo 100 with allene in the preparat...
Scheme 8: (A) Rhodium-catalyzed intracmolecular [3 + 2] cycloaddition [49]. (B) The proposed catalytic cycle of t...
Scheme 9: Total synthesis of natural products reported by Yang and co-workers applying rhodium-catalyzed intr...
Scheme 10: (A) Platinum(II)-catalyzed intermolecular [3 + 2] cycloaddition of propargyl ether 139 and n-butyl ...
Scheme 11: (A) Platinum-catalyzed intramolecular [3 + 2] cycloaddition of propargylic ketal derivative 142 to ...
Scheme 12: (A) Synthesis of phyllocladanol (21) features a Lewis acid-catalyzed formal intramolecular [3 + 2] ...
Scheme 13: The recent advances of [3 + 2] annulation in natural product synthesis. (A) The preparation of melo...
Photosensitized direct C–H fluorination and trifluoromethylation in organic synthesis
- Shahboz Yakubov and
- Joshua P. Barham
Beilstein J. Org. Chem. 2020, 16, 2151–2192, doi:10.3762/bjoc.16.183
Graphical Abstract
Figure 1: Fluorine-containing drugs.
Figure 2: Fluorinated agrochemicals.
Scheme 1: Selectivity of fluorination reactions.
Scheme 2: Different mechanisms of photocatalytic activation. Sub = substrate.
Figure 3: Jablonski diagram showing visible-light-induced energy transfer pathways: a) absorption, b) IC, c) ...
Figure 4: Schematic illustration of TTET.
Figure 5: Organic triplet PSCats.
Figure 6: Additional organic triplet PSCats.
Figure 7: A) Further organic triplet PSCats and B) transition metal triplet PSCats.
Figure 8: Different fluorination reagents grouped by generation.
Scheme 3: Synthesis of Selectfluor®.
Scheme 4: General mechanism of PS TTET C(sp3)–H fluorination.
Scheme 5: Selective benzylic mono- and difluorination using 9-fluorenone and xanthone PSCats, respectively.
Scheme 6: Chen’s photosensitized monofluorination: reaction scope.
Scheme 7: Chen’s photosensitized benzylic difluorination reaction scope.
Scheme 8: Photosensitized monofluorination of ethylbenzene on a gram scale.
Scheme 9: Substrate scope of Tan’s AQN-photosensitized C(sp3)–H fluorination.
Scheme 10: AQN-photosensitized C–H fluorination reaction on a gram scale.
Scheme 11: Reaction mechanism of the AQN-assisted fluorination.
Figure 9: 3D structures of the singlet ground and triplet excited states of Selectfluor®.
Scheme 12: Associated transitions for the activation of acetophenone by violet light.
Scheme 13: Ethylbenzene C–H fluorination with various PSCats and conditions.
Scheme 14: Effect of different PSCats on the C(sp3)–H fluorination of cyclohexane (39).
Scheme 15: Reaction scope of Chen’s acetophenone-photosensitized C(sp3)–H fluorination reaction.
Figure 10: a) Site-selectivity of Chen’s acetophenone-photosensitized C–H fluorination reaction [201]. b) Site-sele...
Scheme 16: Formation of the AQN–Selectfluor® exciplex Int1.
Scheme 17: Generation of the C3 2° pentane radical and the Selectfluor® N-radical cation from the exciplex.
Scheme 18: Hydrogen atom abstraction by the Selectfluor® N-radical cation from pentane to give the C3 2° penta...
Scheme 19: Fluorine atom transfer from Selectfluor® to the C3 2° pentane radical to yield 3-fluoropentane and ...
Scheme 20: Barrierless fluorine atom transfer from Int1 to the C3 2° pentane radical to yield 3-fluoropentane,...
Scheme 21: Ketone-directed C(sp3)–H fluorination.
Scheme 22: Ketone-directed fluorination through a 5- and a 6-membered transition state, respectively.
Scheme 23: Effect of different PSCats on the photosensitized C(sp3)–H fluorination of 47.
Scheme 24: Substrate scope of benzil-photoassisted C(sp3)–H fluorinations.
Scheme 25: A) Benzil-photoassisted enone-directed C(sp3)–H fluorination. B) Classification of the reaction mod...
Scheme 26: A) Xanthone-photoassisted ketal-directed C(sp3)–H fluorination. B) Substrate scope. C) C–H fluorina...
Scheme 27: Rationale for the selective HAT at the C2 C–H bond of galactose acetonide.
Scheme 28: Photosensitized C(sp3)–H benzylic fluorination of a peptide using different PSCats.
Scheme 29: Peptide scope of 5-benzosuberenone-photoassisted C(sp3)–H fluorinations.
Scheme 30: Continuous flow PS TTET monofluorination of 72.
Scheme 31: Photosensitized C–H fluorination of N-butylphthalimide as a PSX.
Scheme 32: Substrate scope and limitations of the PSX C(sp3)–H monofluorination.
Scheme 33: Substrate crossover monofluorination experiment.
Scheme 34: PS TTET mechanism proposed by Hamashima and co-workers.
Scheme 35: Photosensitized TFM of 78 to afford α-trifluoromethylated ketone 80.
Scheme 36: Substrate scope for photosensitized styrene TFM to give α-trifluoromethylated ketones.
Scheme 37: Control reactions for photosensitized TFM of styrenes.
Scheme 38: Reaction mechanism for photosensitized TFM of styrenes to afford α-trifluoromethylated ketones.
Scheme 39: Reaction conditions for TFMs to yield the cis- and the trans-product, respectively.
Scheme 40: Substrate scope of trifluoromethylated (E)-styrenes.
Scheme 41: Strategies toward trifluoromethylated (Z)-styrenes.
Scheme 42: Substrate scope of trifluoromethylated (Z)-styrenes.
Scheme 43: Reaction mechanism for photosensitized TFM of styrenes to afford E- or Z-products.
Reactions of 3-aryl-1-(trifluoromethyl)prop-2-yn-1-iminium salts with 1,3-dienes and styrenes
- Thomas Schneider,
- Michael Keim,
- Bianca Seitz and
- Gerhard Maas
Beilstein J. Org. Chem. 2020, 16, 2064–2072, doi:10.3762/bjoc.16.173
- analogous to 21 could be isolated [56]. A cationic 1,5-cylization converts 21 into cyclopentene 22, from which fulvene 19 is formed by deprotonation and a formal 1,4-shift of the NMe2 group. The details of this rearrangement are not known, an N,N-dimethyldihydropyrrolium intermediate may be involved
Graphical Abstract
Scheme 1: Diels–Alder reaction of propyn-1-iminium salt 1a compared with the reported [29] reaction of 4-phenyl-1...
Scheme 2: Sequential Diels–Alder/intramolecular SE(Ar) reaction of propyn-1-iminium triflates 1a,b. Condition...
Scheme 3: Diels–Alder reaction of 1a and anthracene followed by an intramolecular SE(Ar) reaction.
Figure 1: Solid-state molecular structure of 11 (ORTEP plot).
Scheme 4: Reactions of propyn-1-iminium salt 1a with styrenes.
Figure 2: Solid-state molecular structure of 12c (ORTEP plot).
Figure 3: Solid-state molecular structure of 12d (ORTEP plot). Both the R and the S enantiomer are present in...
Scheme 5: A mechanistic proposal for the reaction of alkyne 1a with styrenes.
Scheme 6: Reaction of alkyne 1a with 1,2-dihydronaphthalene.
Scheme 7: Synthesis and solid-state molecular structure (ORTEP plot) of pentafulvene 19; selected bond distan...
Scheme 8: Proposed mechanistic pathway leading to fulvene 19.
Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules
- Valerian Dragutan,
- Ileana Dragutan,
- Albert Demonceau and
- Lionel Delaude
Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68
- of cyclopentene-1,4-diol that was obtained by the enzymatic desymmetrization of the corresponding diacetate, an enyne metathesis precursor was accessed by a Mitsunobu-type coupling reaction with propargylic amide. The ring-rearrangement metathesis (RRM) of this enyne precursor was carried out using
Graphical Abstract
Scheme 1: Intramolecular (A) and intermolecular (B) enyne metathesis reactions.
Scheme 2: Ene–yne and yne–ene mechanisms for intramolecular enyne metathesis reactions.
Scheme 3: Metallacarbene mechanism in intermolecular enyne metathesis.
Scheme 4: The Oguri strategy for accessing artemisinin analogs 1a–c through enyne metathesis.
Scheme 5: Access to the tetracyclic core of nanolobatolide (2) via tandem enyne metathesis followed by an Eu(...
Scheme 6: Synthesis of (−)-amphidinolide E (3) using an intermolecular enyne metathesis as the key step.
Scheme 7: Synthesis of amphidinolide K (4) by an enyne metathesis route.
Scheme 8: Trost synthesis of des-epoxy-amphidinolide N (5) [72].
Scheme 9: Enyne metathesis between the propargylic derivative and the allylic alcohol in the synthesis of the...
Scheme 10: Synthetic route to amphidinolide N (6a).
Scheme 11: Synthesis of the stereoisomeric precursors of amphidinolide V (7a and 7b) through alkyne ring-closi...
Scheme 12: Synthesis of the anthramycin precursor 8 from ʟ-methionine by a tandem enyne metathesis–cross metat...
Scheme 13: Synthesis of (−)‐clavukerin A (9) and (−)‐isoclavukerin A (10) by an enyne metathesis route startin...
Scheme 14: Synthesis of (−)-isoguaiene (11) through an enyne metathesis as the key step.
Scheme 15: Synthesis of erogorgiaene (12) by a tandem enyne metathesis/cross metathesis sequence using the sec...
Scheme 16: Synthesis of (−)-galanthamine (13) from isovanilin by an enyne metathesis.
Scheme 17: Application of enyne metathesis for the synthesis of kempene diterpenes 14a–c.
Scheme 18: Synthesis of the alkaloid (+)-lycoflexine (15) through enyne metathesis.
Scheme 19: Synthesis of the AB subunits of manzamine A (16a) and E (16b) by enyne metathesis.
Scheme 20: Jung's synthesis of rhodexin A (17) by enyne metathesis/cross metathesis reactions.
Scheme 21: Total synthesis of (−)-flueggine A (18) and (+)-virosaine B (19) from Weinreb amide by enyne metath...
Scheme 22: Access to virgidivarine (20) and virgiboidine (21) by an enyne metathesis route.
Scheme 23: Enyne metathesis approach to (−)-zenkequinone B (22).
Scheme 24: Access to C-aryl glycoside 23 by an intermolecular enyne metathesis/Diels–Alder cycloaddition.
Scheme 25: Synthesis of spiro-C-aryl glycoside 24 by a tandem intramolecular enyne metathesis/Diels–Alder reac...
Scheme 26: Pathways to (−)-exiguolide (25) by Trost’s Ru-catalyzed enyne cross-coupling and cross-metathesis [94].
Recent advances in Cu-catalyzed C(sp3)–Si and C(sp3)–B bond formation
- Balaram S. Takale,
- Ruchita R. Thakore,
- Elham Etemadi-Davan and
- Bruce H. Lipshutz
Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67
- )boronates 320–322. High functional group tolerance and enantioselectivities are characteristics of this reaction. The stereoselective formation of a 3,3-disubstituted cyclopentene scaffold (e.g., 331), containing three contiguous asymmetric centers, was also developed starting from an achiral cyclic acetal
Graphical Abstract
Scheme 1: Pharmaceuticals possessing a silicon or boron atom.
Scheme 2: The first Cu-catalyzed C(sp3)–Si bond formation.
Scheme 3: Conversion of benzylic phosphate 6 to the corresponding silane.
Scheme 4: Conversion of alkyl triflates to alkylsilanes.
Scheme 5: Conversion of secondary alkyl triflates to alkylsilanes.
Scheme 6: Conversion of alkyl iodides to alkylsilanes.
Scheme 7: Trapping of intermediate radical through cascade reaction.
Scheme 8: Radical pathway for conversion of alkyl iodides to alkylsilanes.
Scheme 9: Conversion of alkyl ester of N-hydroxyphthalimide to alkylsilanes.
Scheme 10: Conversion of gem-dibromides to bis-silylalkanes.
Scheme 11: Conversion of imines to α-silylated amines (A) and the reaction pathway (B).
Scheme 12: Conversion of N-tosylimines to α-silylated amines.
Scheme 13: Screening of diamine ligands.
Scheme 14: Conversion of N-tert-butylsulfonylimines to α-silylated amines.
Scheme 15: Conversion of aldimines to nonracemic α-silylated amines.
Scheme 16: Conversion of N-tosylimines to α-silylated amines.
Scheme 17: Reaction pathway [A] and conversion of aldehydes to α-silylated alcohols [B].
Scheme 18: Conversion of aldehydes to benzhydryl silyl ethers.
Scheme 19: Conversion of ketones to 1,2-diols (A) and conversion of imines to 1,2-amino alcohols (B).
Scheme 20: Ligand screening (A) and conversion of aldehydes to α-silylated alcohols (B).
Scheme 21: Conversion of aldehydes to α-silylated alcohols.
Scheme 22: 1,4-Additions to α,β-unsaturated ketones.
Scheme 23: 1,4-Additions to unsaturated ketones to give β-silylated derivatives.
Scheme 24: Additions onto α,β-unsaturated lactones to give β-silylated lactones.
Scheme 25: Conversion of α,β-unsaturated to β-silylated lactams.
Scheme 26: Conversion of N-arylacrylamides to silylated oxindoles.
Scheme 27: Conversion of α,β-unsaturated carbonyl compounds to silylated tert-butylperoxides.
Scheme 28: Catalytic cycle for Cu(I) catalyzed α,β-unsaturated compounds.
Scheme 29: Conversion of p-quinone methides to benzylic silanes.
Scheme 30: Conversion of α,β-unsaturated ketimines to regio- and stereocontrolled allylic silanes.
Scheme 31: Conversion of α,β-unsaturated ketimines to enantioenriched allylic silanes.
Scheme 32: Regioselective conversion of dienedioates to allylic silanes.
Scheme 33: Conversion of alkenyl-substituted azaarenes to β-silylated adducts.
Scheme 34: Conversion of conjugated benzoxazoles to enantioenriched β-silylated adducts.
Scheme 35: Conversion of α,β-unsaturated carbonyl indoles to α-silylated N-alkylated indoles.
Scheme 36: Conversion of β-amidoacrylates to α-aminosilanes.
Scheme 37: Conversion of α,β-unsaturated ketones to enantioenriched β-silylated ketones, nitriles, and nitro d...
Scheme 38: Regio-divergent silacarboxylation of allenes.
Scheme 39: Silylation of diazocarbonyl compounds, (A) asymmetric and (B) racemic.
Scheme 40: Enantioselective hydrosilylation of alkenes.
Scheme 41: Conversion of 3-acylindoles to indolino-silanes.
Scheme 42: Proposed mechanism for the silylation of 3-acylindoles.
Scheme 43: Silyation of N-chlorosulfonamides.
Scheme 44: Conversion of acyl silanes to α-silyl alcohols.
Scheme 45: Conversion of N-tosylaziridines to β-silylated N-tosylamines.
Scheme 46: Conversion of N-tosylaziridines to silylated N-tosylamines.
Scheme 47: Conversion of 3,3-disubstituted cyclopropenes to silylated cyclopropanes.
Scheme 48: Conversion of conjugated enynes to 1,3-bis(silyl)propenes.
Scheme 49: Proposed sequence for the Cu-catalyzed borylation of substituted alkenes.
Scheme 50: Cu-catalyzed synthesis of nonracemic allylic boronates.
Scheme 51: Cu–NHC catalyzed synthesis of α-substituted allylboronates.
Scheme 52: Synthesis of α-chiral (γ-alkoxyallyl)boronates.
Scheme 53: Cu-mediated formation of nonracemic cis- or trans- 2-substituted cyclopropylboronates.
Scheme 54: Cu-catalyzed synthesis of γ,γ-gem-difluoroallylboronates.
Scheme 55: Cu-catalyzed hydrofunctionalization of internal alkenes and vinylarenes.
Scheme 56: Cu-catalyzed Markovnikov and anti-Markovnikov borylation of alkenes.
Scheme 57: Cu-catalyzed borylation/ortho-cyanation/Cope rearrangement.
Scheme 58: Borylfluoromethylation of alkenes.
Scheme 59: Cu-catalyzed synthesis of tertiary nonracemic alcohols.
Scheme 60: Synthesis of densely functionalized and synthetically versatile 1,2- or 4,3-borocyanated 1,3-butadi...
Scheme 61: Cu-catalyzed trifunctionalization of allenes.
Scheme 62: Cu-catalyzed selective arylborylation of arenes.
Scheme 63: Asymmetric borylative coupling between styrenes and imines.
Scheme 64: Regio-divergent aminoboration of unactivated terminal alkenes.
Scheme 65: Cu-catalyzed 1,4-borylation of α,β-unsaturated ketones.
Scheme 66: Cu-catalyzed protodeboronation of α,β-unsaturated ketones.
Scheme 67: Cu-catalyzed β-borylation of α,β-unsaturated imines.
Scheme 68: Cu-catalyzed synthesis of β-trifluoroborato carbonyl compounds.
Scheme 69: Asymmetric 1,4-borylation of α,β-unsaturated carbonyl compounds.
Scheme 70: Cu-catalyzed ACB and ACA reactions of α,β-unsaturated 2-acyl-N-methylimidazoles.
Scheme 71: Cu-catalyzed diborylation of aldehydes.
Scheme 72: Umpolung pathway for chiral, nonracemic tertiary alcohol synthesis (top) and proposed mechanism for...
Scheme 73: Cu-catalyzed synthesis of α-hydroxyboronates.
Scheme 74: Cu-catalyzed borylation of ketones.
Scheme 75: Cu-catalyzed borylation of unactivated alkyl halides.
Scheme 76: Cu-catalyzed borylation of allylic difluorides.
Scheme 77: Cu-catalyzed borylation of cyclic and acyclic alkyl halides.
Scheme 78: Cu-catalyzed borylation of unactivated alkyl chlorides and bromides.
Scheme 79: Cu-catalyzed decarboxylative borylation of carboxylic acids.
Scheme 80: Cu-catalyzed borylation of benzylic, allylic, and propargylic alcohols.
Photophysics and photochemistry of NIR absorbers derived from cyanines: key to new technologies based on chemistry 4.0
- Bernd Strehmel,
- Christian Schmitz,
- Ceren Kütahya,
- Yulian Pang,
- Anke Drewitz and
- Heinz Mustroph
Beilstein J. Org. Chem. 2020, 16, 415–444, doi:10.3762/bjoc.16.40
- ][33][34]. They exhibit a flexible chain (I–III) or bridged chain (IV, V) where the cyclopentene pattern keeps the system planar while the introduction of the non-planar cyclohexene moiety results in improvement of compatibility of the surrounding matrix [5]. Indolium, benzo[e]indolium, and benzo[c,d
Graphical Abstract
Scheme 1: Structural patterns of several symmetric cyanines relating to trimethines (I), pentamethines (II), ...
Scheme 2: 1-Substituted 2,3,3-trimethylindolium-, 2,3,3-benzo[e]indolium-, and 2,3,3-benzo[c,d]indolium salts...
Scheme 3: Substitution of the chlorine substituent at the meso-position by a stronger nucleophilic moiety B [68].
Scheme 4: Structure of alternative chain builders for synthesis of heptamethines.
Figure 1: Simplified process chart of photophysical processes occurring in NIR absorbers.
Scheme 5: Chemical structure of the electron acceptors that were from iodonium cations 88 and triazines 89.
Figure 2: Photoinduced electron transfer under different scenarios in which each example exhibits an intrinsi...
Scheme 6: Photoexcited absorber 33 results in reaction with an iodonium cation in the respective cation radic...
Scheme 7: Reaction scheme of absorbers comprising in the molecules center a five ring bridged moiety. This le...
Scheme 8: Structure of donor compounds used in a three component system.
Figure 3: Cationic photopolymerization of an epoxide (Epikote 828) initiated by excitation of the absorber 36...
Scheme 9: Different modes of photoinitiated ATRP using UV, visible and NIR light.
Scheme 10: The structure of Sens used in photo-ATRP.
Figure 4: Comparison of the GPC traces of precursor PMMA with a) chain extended PMMA and b) PMMA-b-PS. Condit...
Figure 5: Spectral changes of the solution of 48 in the presence of [Cu(L)]Br2 (L: tris(2-pyridylmethyl)amine...
Scheme 11: Photoinduced CuAAC reactions in which photochemical reactions result in formation of the Cu(I) cata...
Scheme 12: Model reaction between benzyl azide and phenyacetylene using the absorber 48 as NIR sensitizer at 7...
Figure 6: Block copolymerization of the precursors PS-N3 and Alkyne-PCL results in the block copolymer PS-b-P...
Figure 7: UV–vis–NIR absorption changes of the solution of 48 in the presence of PMDETA, phenylacetylene and ...
Scheme 13: Workflow to design and process new materials in a setup based on an intelligent DoE to develop tech...
Scheme 14: Illustration of the iDoE setting up experiments suggested and analyzed by the A.I. After defining t...
Scheme 15: Classification of the factors for the formation of polymer networks by NIR-photocuring depending on...
A photochemical determination of luminescence efficiency of upconverting nanoparticles
- Baptiste Amouroux,
- Clément Roux,
- Jean-Claude Micheau,
- Fabienne Gauffre and
- Christophe Coudret
Beilstein J. Org. Chem. 2019, 15, 2671–2677, doi:10.3762/bjoc.15.260
- green emission of NaYF4:Yb,Er nanoparticles. Using the recently calibrated actinometer 1,2-bis(2,4-dimethyl-5-phenyl-3-thienyl)-3,3,4,4,5,5-hexafluoro-1-cyclopentene operating in the green region of the visible spectra, we propose a simple photochemical experiment to get an accurate estimation of the
- reliability. Recently, an accurate determination of photochemical quantum yields (QY) [26] was achieved for a commercially available diarylethene 1,2-bis(2,4-dimethyl-5-phenylthien-3-yl)-3,3,4,4,5,5-hexafluoro-1-cyclopentene, labelled 1. Since then, this dye has been used as actinometer in the visible range
Graphical Abstract
Figure 1: Top: photoisomers of diarylethene 1, bottom: spectral overlaps between the 1-o (black line), 1-c (r...
Figure 2: UCNPs (black dots) are irradiated inside the cylindrical CW 976 nm laser beam. Absorbed laser power...
Figure 3: Kinetic trace at 650 nm under CW 976 nm laser at 4.71 W. Initial slope (red line) was determined on...
