Search results
Search for "molecular complexity" in Full Text gives 47 result(s) in Beilstein Journal of Organic Chemistry.
Latest development in the synthesis of ursodeoxycholic acid (UDCA): a critical review
- Fabio Tonin and
- Isabel W. C. E. Arends
Beilstein J. Org. Chem. 2018, 14, 470–483, doi:10.3762/bjoc.14.33
- ) in the treatment against biliary calculus, since it possesses high efficacy and total absence of side effects [11]. UDCA is commonly produced by transformation of cholic acid (CA), which is the most abundant and least expensive bile acid available. Because of the molecular complexity of bile acids
Graphical Abstract
Figure 1: Chemical structure of UDCA.
Figure 2: Chemical structures of bile acids and salts.
Figure 3: Comparison between Wolff–Kishner and Mozingo reduction. Notably the overall chemical reaction is th...
Figure 4: Reaction catalysed by the 12α-HSDH; the 12-OH group of CA or UCA is oxidized yielding 12-oxo-CDCA o...
Figure 5: Epimerization reaction catalysed by the 7α-HSDH and 7β-HSDH; the 7α-OH group of CA (R = OH) or CDCA...
Figure 6: Overview of the chemoenzymatic process for the production of UDCA from CA: The oxidation, reduction...
Figure 7: Schematic representation of the flow reactor for the continuous conversion of CDCA to UDCA [93].
Figure 8: Chemoenzymatic pathways for the formation of UDCA from CA that profit by the C7 hydroxylation activ...
Framing major prebiotic transitions as stages of protocell development: three challenges for origins-of-life research
- Ben Shirt-Ediss,
- Sara Murillo-Sánchez and
- Kepa Ruiz-Mirazo
Beilstein J. Org. Chem. 2017, 13, 1388–1395, doi:10.3762/bjoc.13.135
- compartmentalised chemistries run by poly-nucleotides (e.g., the ‘ribocell’ model), protocell systems with molecular components of much lower molecular complexity should be investigated as units of pre-Darwinian evolution. The overarching question then becomes: how can far-from-equilibrium chemical assemblies that
Figure 1: Protocells as the main units of prebiotic evolution: three hypothetical stages of development towar...
Synthesis of polyhydroxylated decalins via two consecutive one-pot reactions: 1,4-addition/aldol reaction followed by RCM/syn-dihydroxylation
- Michał Malik and
- Sławomir Jarosz
Beilstein J. Org. Chem. 2016, 12, 2602–2608, doi:10.3762/bjoc.12.255
- ]. Although this approach is challenging in terms of diastereoselectivity (up to eight possible diastereoisomers), it enables a rapid increase of molecular complexity. The major diastereoisomer of 11 can be then subjected to the assisted tandem catalytic sequence: RCM reaction, followed by the reuse of the
- efficient way for the preparation of highly oxygenated trans-decalins. It offers a possibility to significantly increase molecular complexity in just two steps. General structures of mono- and bicyclic carbasugars. Possible course of the syn-dihydroxylation leading to 27, 28, and 29. Approach to the
Graphical Abstract
Figure 1: General structures of mono- and bicyclic carbasugars.
Scheme 1: Approach to the synthesis of bicyclic carbasugars based on the use of sugar allyltins (previous wor...
Scheme 2: Approach to the synthesis of bicyclic decalins based on a 1,4-addition/aldol reaction followed by R...
Scheme 3: Reagents and conditions: (a) i. Zn, MeOH/H2O, 60 °C, 2 h, ii. Jones reagent, acetone, rt, 1 h, iii....
Scheme 4: Reagents and conditions: (a) i. BzCl, DCM, Et3N, DMAP, rt, 24 h, ii. HCl, MeOH/H2O, rt, 24 h, 55% (...
Scheme 5: Reagents and conditions: (a) TBAF∙3H2O, THF, rt, 24 h, 96% (19) or 94% (23); (b) i. BzCl, DCM, Et3N...
Scheme 6: Reagents and conditions: (a) vinyl-MgBr, CuBr∙Me2S, THF, −45 °C, 15 min, then (S)- or (R)-10, −45 °...
Scheme 7: Reagents and conditions: (a) Hoveyda–Grubbs II cat. (5 mol %), toluene, 50 °C, 2 h, then evaporatio...
Figure 2: Possible course of the syn-dihydroxylation leading to 27, 28, and 29.
Scheme 8: Reagents and conditions: (a) NaBH(OAc)3, MeCN/THF/AcOH, rt, 24 h, 67% (30, dr >99:1) or 74% (31 + 32...
Application of heterocyclic aldehydes as components in Ugi–Smiles couplings
- Katelynn M. Mason,
- Michael S. Meyers,
- Abbie M. Fox and
- Sarah B. Luesse
Beilstein J. Org. Chem. 2016, 12, 2032–2037, doi:10.3762/bjoc.12.191
- nitrogen-containing heterocyclic systems [11][12][13]. Multicomponent coupling reactions (MCRs) have been combined with IMDA approaches to efficiently increase molecular complexity [14] and prepare complex molecular scaffolds for the synthesis of natural products [15][16]. While the Ugi–Smiles condensation
Graphical Abstract
Scheme 1: N-Arylepoxyisoindolines via tandem Ugi–Smiles/IMDA reaction.
Scheme 2: Reaction monitoring by 1H NMR for production of 1b.
Scheme 3: Use of a thienyl-substituted aldehyde for Ugi–Smiles couplings.
(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers
- Giorgos Koutoulogenis,
- Nikolaos Kaplaneris and
- Christoforos G. Kokotos
Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48
- in the production of 93 and 94 in moderate to excellent enantioselectivities, considering the high molecular complexity achieved in only one step. Recently, Bugaut, Constantieux and co-workers described the enantioselective organocatalytic multicomponent synthesis of 2,6-diazabicyclo[2.2.2]octanones
- good yield and stereoselectivity, given the high molecular complexity that is being achieved in one step (Scheme 64). The researchers suggested that diketone 204 and benzaldehyde 205 reacts through Knoevenagel condensation, to produce 2-arylidene-1,3-indanediones, which is subsequently attacked by the
- tertiary chiral amine-thioureas, or a combination of catalysts. Products were obtained in one-pot or step-economic domino processes, achieving high increase of molecular complexity in step-economy transformations. There is no doubt that this scientific field will grow in the near future, providing more
Graphical Abstract
Scheme 1: Activation of carbonyl compounds via enamine and iminium intermediates [2].
Scheme 2: Electronic and steric interactions present in enamine activation mode [2].
Scheme 3: Electrophilic activation of carbonyl compounds by a thiourea moiety.
Scheme 4: Asymmetric synthesis of dihydro-2H-pyran-6-carboxylate 3 using organocatalyst 4 [16].
Scheme 5: Possible hydrogen-bonding for the reaction of (E)-methyl 2-oxo-4-phenylbut-3-enoate [16].
Scheme 6: Asymmetric desymmetrization of 4,4-cyclohexadienones using the Michael addition reaction with malon...
Scheme 7: The enantioselective synthesis of α,α-disubstituted cycloalkanones using catalyst 11 [18].
Scheme 8: The enantioselective synthesis of indolo- and benzoquinolidine compounds through aza-Diels–Alder re...
Scheme 9: Enantioselective [5 + 2] cycloaddition [20].
Scheme 10: Asymmetric synthesis of oxazine derivatives 26 [21].
Scheme 11: Asymmetric synthesis of bicyclo[3.3.1]nonadienone, core 30 present in (−)-huperzine [22].
Scheme 12: Asymmetric inverse electron-demand Diels-Alder reaction catalyzed by amine-thiourea 34 [23].
Scheme 13: Asymmetric entry to morphan skeletons, catalyzed by amine-thiourea 37 [24].
Scheme 14: Asymmetric transformation of (E)-2-nitroallyl acetate [25].
Scheme 15: Proposed way of activation.
Scheme 16: Asymmetric synthesis of nitrobicyclo[3.2.1]octan-2-one derivatives [26].
Scheme 17: Asymmetric tandem Michael–Henry reaction catalyzed by 50 [27].
Scheme 18: Asymmetric Diels–Alder reactions of 3-vinylindoles 51 [29].
Scheme 19: Proposed transition state and activation mode of the asymmetric Diels–Alder reactions of 3-vinylind...
Scheme 20: Desymmetrization of meso-anhydrides by Chin, Song and co-workers [30].
Scheme 21: Desymmetrization of meso-anhydrides by Connon and co-workers [31].
Scheme 22: Asymmetric intramolecular Michael reaction [32].
Scheme 23: Asymmetric addition of malonate to 3-nitro-2H-chromenes 67 [33].
Scheme 24: Intramolecular desymmetrization through an intramolecular aza-Michael reaction [34].
Scheme 25: Enantioselective synthesis of (−)-mesembrine [34].
Scheme 26: A novel asymmetric Michael–Michael reaction [35].
Scheme 27: Asymmetric three-component reaction catalyzed by Takemoto’s catalyst 77 [46].
Scheme 28: Asymmetric domino Michael–Henry reaction [47].
Scheme 29: Asymmetric domino Michael–Henry reaction [48].
Scheme 30: Enantioselective synthesis of derivatives of 3,4-dihydro-2H-pyran 89 [49].
Scheme 31: Asymmetric addition of α,α-dicyano olefins 90 to 3-nitro-2H-chromenes 91 [50].
Scheme 32: Asymmetric three-component reaction producing 2,6-diazabicyclo[2.2.2]octanones 95 [51].
Scheme 33: Asymmetric double Michael reaction producing substituted chromans 99 [52].
Scheme 34: Enantioselective synthesis of multi-functionalized spiro oxindole dienes 106 [53].
Scheme 35: Organocatalyzed Michael aldol cyclization [54].
Scheme 36: Asymmetric synthesis of dihydrocoumarins [55].
Scheme 37: Asymmetric double Michael reaction en route to tetrasubstituted cyclohexenols [56].
Scheme 38: Asymmetric synthesis of α-trifluoromethyl-dihydropyrans 121 [58].
Scheme 39: Tyrosine-derived tertiary amino-thiourea 123 catalyzed Michael hemiaketalization reaction [59].
Scheme 40: Enantioselective entry to bicyclo[3.2.1]octane unit [60].
Scheme 41: Asymmetric synthesis of spiro[4-cyclohexanone-1,3’-oxindoline] 126 [61].
Scheme 42: Kinetic resolution of 3-nitro-2H-chromene 130 [62].
Scheme 43: Asymmetric synthesis of chromanes 136 [63].
Scheme 44: Wang’s utilization of β-unsaturated α-ketoesters 87 [64,65].
Scheme 45: Asymmetric entry to trifluoromethyl-substituted dihydropyrans 144 [66].
Scheme 46: Phenylalanine-derived thiourea-catalyzed domino Michael hemiaketalization reaction [67].
Scheme 47: Asymmetric synthesis of α-trichloromethyldihydropyrans 149 [68].
Scheme 48: Takemoto’s thiourea-catalyzed domino Michael hemiaketalization reaction [69].
Scheme 49: Asymmetric synthesis of densely substituted cyclohexanes [70].
Scheme 50: Enantioselective synthesis of polysubstituted chromeno [4,3-b]pyrrolidine derivatines 157 [71].
Scheme 51: Enantioselective synthesis of spiro-fused cyclohexanone/5-oxazolone scaffolds 162 [72].
Scheme 52: Utilizing 2-mercaptobenzaldehydes 163 in cascade processes [73,74].
Scheme 53: Proposed transition state of the initial sulfa-Michael step [74].
Scheme 54: Asymmetric thiochroman synthesis via dynamic kinetic resolution [75].
Scheme 55: Enantioselective synthesis of thiochromans [76].
Scheme 56: Enantioselective synthesis of chromans and thiochromans synthesis [77].
Scheme 57: Enantioselective sulfa-Michael aldol reaction en route to spiro compounds [78].
Scheme 58: Enantioselective synthesis of 4-aminobenzo(thio)pyrans 179 [79].
Scheme 59: Asymmetric synthesis of tetrahydroquinolines [80].
Scheme 60: Novel asymmetric Mannich–Michael sequence producing tetrahydroquinolines 186 [81].
Scheme 61: Enantioselective synthesis of biologically interesting chromanes 190 and 191 [82].
Scheme 62: Asymmetric tandem Henry–Michael reaction [83].
Scheme 63: An asymmetric synthesis of substituted cyclohexanes via a dynamic kinetic resolution [84].
Scheme 64: Three component-organocascade initiated by Knoevenagel reaction [85].
Scheme 65: Asymmetric Michael reaction catalyzed by catalysts 57 and 211 [86].
Scheme 66: Proposed mechanism for the asymmetric Michael reaction catalyzed by catalysts 57 and 211 [86].
Scheme 67: Asymmetric facile synthesis of hexasubstituted cyclohexanes [87].
Scheme 68: Dual activation catalytic mechanism [87].
Scheme 69: Asymmetric Michael–Michael/aldol reaction catalyzed by catalysts 57, 219 and 214 [88].
Scheme 70: Asymmetric synthesis of substituted cyclohexane derivatives, using catalysts 57 and 223 [89].
Scheme 71: Asymmetric synthesis of substituted piperidine derivatives, using catalysts 223 and 228 [90].
Scheme 72: Asymmetric synthesis of endo-exo spiro-dihydropyran-oxindole derivatives catalyzed by catalyst 232 [91]....
Scheme 73: Asymmetric synthesis of carbazole spiroxindole derivatives, using catalyst 236 [92].
Scheme 74: Enantioselective formal [2 + 2] cycloaddition of enal 209 with nitroalkene 210, using catalysts 23 ...
Scheme 75: Asymmetric synthesis of polycyclized hydroxylactams derivatives, using catalyst 242 [94].
Scheme 76: Asymmetric synthesis of product 243, using catalyst 246 [95].
Scheme 77: Formation of the α-stereoselective acetals 248 from the corresponding enol ether 247, using catalys...
Scheme 78: Selective glycosidation, catalyzed by Shreiner’s catalyst 23 [97].
Tandem cross enyne metathesis (CEYM)–intramolecular Diels–Alder reaction (IMDAR). An easy entry to linear bicyclic scaffolds
- Javier Miró,
- María Sánchez-Roselló,
- Álvaro Sanz,
- Fernando Rabasa,
- Carlos del Pozo and
- Santos Fustero
Beilstein J. Org. Chem. 2015, 11, 1486–1493, doi:10.3762/bjoc.11.161
- multiple carbon–carbon bonds can be generated in a single operation, therefore increasing molecular complexity in a quite simple manner [10]. While examples of ring-closing enyne metathesis (RCEYM) reactions are widespread in the literature [11], the development of the intermolecular version, i.e., the
Graphical Abstract
Scheme 1: Tandem cross enyne metathesis–intramolecular Diels–Alder reaction.
Scheme 2: Stereochemical outcome of the IMDAR.
Scheme 3: Preparation of starting materials 8.
Figure 1: Determination of the relative stereochemistry on compounds 10b.
Triazol-substituted titanocenes by strain-driven 1,3-dipolar cycloadditions
- Andreas Gansäuer,
- Andreas Okkel,
- Lukas Schwach,
- Laura Wagner,
- Anja Selig and
- Aram Prokop
Beilstein J. Org. Chem. 2014, 10, 1630–1637, doi:10.3762/bjoc.10.169
- functions. An especially attractive approach is the use of already functionalized building blocks as starting materials in diversity oriented synthesis that increases the molecular complexity. Any synthetic methodology used in this context must take into account the sensitivity of the titanocene towards
Graphical Abstract
Scheme 1: Modular titanocene synthesis via acylation reactions [24].
Figure 1: Carboxylates employed as titanocene starting materials for azide-substituted complexes.
Figure 2: Azides employed in this study and conditions for their synthesis.
Figure 3: Most active titanocenes of this study and their AC50 values.
Rational design of cyclopropane-based chiral PHOX ligands for intermolecular asymmetric Heck reaction
- Marina Rubina,
- William M. Sherrill,
- Alexey Yu. Barkov and
- Michael Rubin
Beilstein J. Org. Chem. 2014, 10, 1536–1548, doi:10.3762/bjoc.10.158
- installation of tertiary and quaternary chiral centres leading to a rapid increase of molecular complexity [3][4][5]. To date, various modes of this transformation are being successfully employed in the synthesis of complex organic molecules [6][7][8][9][10][11][12][13][14]. Considerable achievements have also
Graphical Abstract
Scheme 1: Intermolecular asymmetric Heck reaction by Hayashi [16].
Scheme 2: Mechanistic rationale of asymmetric Heck reaction.
Figure 1: Chiral diphosphine ligands used for intermolecular asymmetric Heck reaction.
Figure 2: Chiral phosphanyl-oxazoline (PHOX) ligands used for intermolecular asymmetric Heck reaction.
Scheme 3: Synthetic scheme for preparation of PHOX ligands with chiral cyclopropyl backbone.
Figure 3: PHOX ligands with chiral cyclopropyl backbone employed in this study.
Scheme 4: Conformational equilibrium in cationic arylpalladium(II) complexes with chiral ligand L1.
Figure 4: X-ray structures of complexes (L1)PdCl2 (left) and (L4)PdCl2 (right). These structures were origina...
Scheme 5: For discussion on asymmetric induction imparted by chiral ligands L1 and L2 (originally published i...
Scheme 6: For discussion on asymmetric induction imparted by chiral ligands L3 (originally published in [64]).
Scheme 7: Conformational equilibrium in cationic arylpalladium(II) complexes with chiral ligand L4.
Scheme 8: For discussion on asymmetric induction imparted by chiral ligands L4 (originally published in [64]).
Scheme 9: Mechanism of migration of C=C double bond leading to isomerization of product 3 into product 4.
Scheme 10: For discussion on isomerization 3→4 imparted by Pd/L1 complex (originally published in [64]).
Scheme 11: For discussion on isomerization 3→4 imparted by Pd/L4 complex (originally published in [64]).
Cyclization–endoperoxidation cascade reactions of dienes mediated by a pyrylium photoredox catalyst
- Nathan J. Gesmundo and
- David A. Nicewicz
Beilstein J. Org. Chem. 2014, 10, 1272–1281, doi:10.3762/bjoc.10.128
- reactions of peroxyquinols [11]. While these extant methods are effective at installing the endoperoxide functional group, our interest lay in developing strategies that simultaneously forged both the cyclic peroxide as well as the carbon framework to rapidly build molecular complexity. For this reason, we
Graphical Abstract
Figure 1: Selected examples of endoperoxide-containing natural products.
Scheme 1: Endoperoxide formation via cation radicals. In both examples, single electron oxidation is followed...
Scheme 2: Diversification strategy for endoperoxide synthesis by single electron transfer. E*red vs SCE [20].
Figure 2: ORTEP of 3a.
Scheme 3: Proposed mechanism for endoperoxide synthesis from tethered dienes.
Scheme 4: Competing formal [3,3] pathway.
Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics
- Gijs Koopmanschap,
- Eelco Ruijter and
- Romano V.A. Orru
Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50
- structural diversity and molecular complexity in only one step. Among the MCRs, the isocyanide-based multicomponent reactions (IMCRs) are most relevant for the synthesis of peptidomimetics because they provide peptide-like products. However, these IMCRs usually give linear products and in order to obtain
Graphical Abstract
Scheme 1: The proposed mechanism of the Passerini reaction.
Scheme 2: The PADAM-strategy to α-hydroxy-β-amino amide derivatives 7. An additional oxidation provides α-ket...
Scheme 3: The general accepted Ugi-mechanism.
Scheme 4: Three commonly applied Ugi/cyclization approaches. a) UDC-process, b) UAC-sequence, c) UDAC-combina...
Scheme 5: Ugi reaction that involves the condensation of Armstrong’s convertible isocyanide.
Scheme 6: Mechanism of the U-4C-3CR towards bicyclic β-lactams.
Scheme 7: The Ugi 4C-3CR towards oxabicyclo β-lactams.
Scheme 8: Ugi MCR between an enantiopure monoterpene based β-amino acid, aldehyde and isocyanide resulting in...
Scheme 9: General MCR for β-lactams in water.
Scheme 10: a) Ugi reaction for β-lactam-linked peptidomimetics. b) Varying the β-amino acid resulted in β-lact...
Scheme 11: Ugi-4CR followed by a Pd-catalyzed Sn2 cyclization.
Scheme 12: Ugi-3CR of dipeptide mimics from 2-substituted pyrrolines.
Scheme 13: Joullié–Ugi reaction towards 2,5-disubstituted pyrrolidines.
Scheme 14: Further elaboration of the Ugi-scaffold towards bicyclic systems.
Scheme 15: Dihydroxyproline derivatives from an Ugi reaction.
Scheme 16: Diastereoselective Ugi reaction described by Banfi and co-workers.
Scheme 17: Similar Ugi reaction as in Scheme 16 but with different acids and two chiral isocyanides.
Scheme 18: Highly diastereoselective synthesis of pyrrolidine-dipeptoids via a MAO-N/MCR-procedure.
Scheme 19: MAO-N/MCR-approach towards the hepatitis C drug telaprevir.
Scheme 20: Enantioselective MAO-U-3CR procedure starting from chiral pyrroline 64.
Scheme 21: Synthesis of γ-lactams via an UDC-sequence.
Scheme 22: Utilizing bifunctional groups to provide bicyclic γ-lactam-ketopiperazines.
Scheme 23: The Ugi reaction provided both γ- as δ-lactams depending on which inputs were used.
Scheme 24: The sequential Ugi/RCM with olefinic substrates provided bicyclic lactams.
Scheme 25: a) The structural and dipole similarities of the triazole unit with the amide bond. b) The copper-c...
Scheme 26: The Ugi/Click sequence provided triazole based peptidomimetics.
Scheme 27: The Ugi/Click reaction as described by Nanajdenko.
Scheme 28: The Ugi/Click-approach by Pramitha and Bahulayan.
Scheme 29: The Ugi/Click-combination by Niu et al.
Scheme 30: Triazole linked peptidomimetics obtained from two separate MCRs and a sequential Click reaction.
Scheme 31: Copper-free synthesis of triazoles via two MCRs in one-pot.
Scheme 32: The sequential Ugi/Paal–Knorr reaction to afford pyrazoles.
Scheme 33: An intramolecular Paal–Knorr condensation provided under basic conditions pyrazolones.
Scheme 34: Similar cyclization performed under acidic conditions provided pyrazolones without the trifluoroace...
Scheme 35: The Ugi-4CR towards 2,4-disubstituted thiazoles.
Scheme 36: Solid phase approach towards thiazoles.
Scheme 37: Reaction mechanism of formation of thiazole peptidomimetics containing an additional β-lactam moiet...
Scheme 38: The synthesis of the trisubstituted thiazoles could be either performed via an Ugi reaction with pr...
Scheme 39: Performing the Ugi reaction with DMB-protected isocyanide gave access to either oxazoles or thiazol...
Scheme 40: Ugi/cyclization-approach towards 2,5-disubstituted thiazoles. The Ugi reaction was performed with d...
Scheme 41: Further derivatization of the thiazole scaffold.
Scheme 42: Three-step procedure towards the natural product bacillamide C.
Scheme 43: Ugi-4CR to oxazoles reported by Zhu and co-workers.
Scheme 44: Ugi-based synthesis of oxazole-containing peptidomimetics.
Scheme 45: TMNS3 based Ugi reaction for peptidomimics containing a tetrazole.
Scheme 46: Catalytic cycle of the enantioselective Passerini reaction towards tetrazole-based peptidomimetics.
Scheme 47: Tetrazole-based peptidomimetics via an Ugi reaction and a subsequent sigmatropic rearrangement.
Scheme 48: Resin-bound Ugi-approach towards tetrazole-based peptidomimetics.
Scheme 49: Ugi/cyclization approach towards γ/δ/ε-lactam tetrazoles.
Scheme 50: Ugi-3CR to pipecolic acid-based peptidomimetics.
Scheme 51: Staudinger–Aza-Wittig/Ugi-approach towards pipecolic acid peptidomimetics.
Figure 1: The three structural isomers of diketopiperazines. The 2,5-DKP isomer is most common.
Scheme 52: UDC-approach to obtain 2,5-DKPs, either using Armstrong’s isocyanide or via ethylglyoxalate.
Scheme 53: a) Ugi reaction in water gave either 2,5-DKP structures or spiro compounds. b) The Ugi reaction in ...
Scheme 54: Solid-phase approach towards diketopiperazines.
Scheme 55: UDAC-approach towards DKPs.
Scheme 56: The intermediate amide is activated as leaving group by acid and microwave assisted organic synthes...
Scheme 57: UDC-procedure towards active oxytocin inhibitors.
Scheme 58: An improved stereoselective MCR-approach towards the oxytocin inhibitor.
Scheme 59: The less common Ugi reaction towards DKPs, involving a Sn2-substitution.
Figure 2: Spatial similarities between a natural β-turn conformation and a DKP based β-turn mimetic [158].
Scheme 60: Ugi-based syntheses of bicyclic DKPs. The amine component is derived from a coupling between (R)-N-...
Scheme 61: Ugi-based synthesis of β-turn and γ-turn mimetics.
Figure 3: Isocyanide substituted 3,4-dihydropyridin-2-ones, dihydropyridines and the Freidinger lactams. Bio-...
Scheme 62: The mechanism of the 4-CR towards 3,4-dihydropyridine-2-ones 212.
Scheme 63: a) Multiple MCR-approach to provide DHP-peptidomimetic in two-steps. b) A one-pot 6-CR providing th...
Scheme 64: The MCR–alkylation–MCR procedure to obtain either tetrapeptoids or depsipeptides.
Scheme 65: U-3CR/cyclization employing semicarbazone as imine component gave triazine based peptidomimetics.
Scheme 66: 4CR towards triazinane-diones.
Scheme 67: The MCR–alkylation–IMCR-sequence described by our group towards triazinane dione-based peptidomimet...
Scheme 68: Ugi-4CR approaches followed by a cyclization to thiomorpholin-ones (a) and pyrrolidines (b).
Scheme 69: UDC-approach for benzodiazepinones.
Scheme 70: Ugi/Mitsunobu sequence to BDPs.
Scheme 71: A UDAC-approach to BDPs with convertible isocyanides. The corresponding amide is cleaved by microwa...
Scheme 72: microwave assisted post condensation Ugi reaction.
Scheme 73: Benzodiazepinones synthesized via the post-condensation Ugi/ Staudinger–Aza-Wittig cyclization.
Scheme 74: Two Ugi/cyclization approaches utilizing chiral carboxylic acids. Reaction (a) provided the product...
Scheme 75: The mechanism of the Gewald-3CR includes three base-catalysed steps involving first a Knoevnagel–Co...
Scheme 76: Two structural 1,4-thienodiazepine-2,5-dione isomers by U-4CR/cyclization.
Scheme 77: Tetrazole-based diazepinones by UDC-procedure.
Scheme 78: Tetrazole-based BDPs via a sequential Ugi/hydrolysis/coupling.
Scheme 79: MCR synthesis of three different tricyclic BPDs.
Scheme 80: Two similar approaches both involving an Ugi reaction and a Mitsunobu cyclization.
Scheme 81: Mitsunobu–Ugi-approach towards dihydro-1,4-benzoxazepines.
Scheme 82: Ugi reaction towards hetero-aryl fused 5-oxo-1,4-oxazepines.
Scheme 83: a) Ugi/RCM-approach towards nine-membered peptidomimetics b) Sequential peptide-coupling, deprotect...
Scheme 84: Ugi-based synthesis towards cyclic RGD-pentapeptides.
Scheme 85: Ugi/MCR-approach towards 12–15 membered macrocycles.
Scheme 86: Stereoselective Ugi/RCM approach towards 16-membered macrocycles.
Scheme 87: Passerini/RCM-sequence to 22-membered macrocycles.
Scheme 88: UDAC-approach towards 12–18-membered depsipeptides.
Figure 4: Enopeptin A with its more active derivative ADEP-4.
Scheme 89: a) The Joullié–Ugi-approach towards ADEP-4 derivatives b) Ugi-approach for the α,α-dimethylated der...
Scheme 90: Ugi–Click-strategy for 15-membered macrocyclic glyco-peptidomimetics.
Scheme 91: Ugi/Click combinations provided macrocycles containing both a triazole and an oxazole moiety.
Scheme 92: a) A solution-phase procedure towards macrocycles. b) Alternative solid-phase synthesis as was repo...
Scheme 93: Ugi/cyclization towards cyclophane based macrocycles.
Scheme 94: PADAM-strategy towards eurystatin A.
Scheme 95: PADAM-approach for cyclotheanamide.
Scheme 96: A triple MCR-approach affording RGD-pentapeptoids.
Scheme 97: Ugi-MiBs-approach towards peptoid macrocycles.
Scheme 98: Passerini-based MiB approaches towards macrocycles 345 and 346.
Scheme 99: Macrocyclic peptide formation by the use of amphoteric aziridine-based aldehydes.
Silver and gold-catalyzed multicomponent reactions
- Giorgio Abbiati and
- Elisabetta Rossi
Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46
- transformation, i.e., [3 + 2] cycloaddition (Scheme 9). Another application of an A3-MCR for the improvement of molecular complexity was published by Kokezu and Srinivas [39]. The authors suggested a straightforward AuBr3-catalyzed route to 2-, 3-, or 5-propargylamine substituted indoles 9. The reactions were
Graphical Abstract
Scheme 1: General reaction mechanism for Ag(I)-catalyzed A3-coupling reactions.
Scheme 2: A3-coupling reaction catalyzed by polystyrene-supported NHC–silver halides.
Figure 1: Various NHC–Ag(I) complexes used as catalysts for A3-coupling.
Scheme 3: Proposed reaction mechanism for NHC–AgCl catalyzed A3-coupling reactions.
Scheme 4: Liu’s synthesis of pyrrole-2-carboxaldehydes 4.
Scheme 5: Proposed reaction mechanism for Liu’s synthesis of pyrrole-2-carboxaldehydes 4.
Scheme 6: Gold-catalyzed synthesis of propargylamines 1.
Scheme 7: A3-coupling catalyzed by phosphinamidic Au(III) metallacycle 6.
Scheme 8: Gold-catalyzed KA2-coupling.
Scheme 9: A3-coupling applied to aldehyde-containing oligosaccharides 8.
Scheme 10: A3-MCR for the preparation of propargylamine-substituted indoles 9.
Scheme 11: A3-coupling interceded synthesis of furans 12.
Scheme 12: A3/KA2-coupling mediated synthesis of functionalized dihydropyrazoles 13 and polycyclic dihydropyra...
Scheme 13: Au(I)-catalyzed entry to cyclic carbamimidates 17 via an A3-coupling-type approach.
Scheme 14: Proposed reaction mechanism for the Au(I)-catalyzed synthesis of cyclic carbamimidates 17.
Figure 2: Chiral trans-1-diphenylphosphino-2-aminocyclohexane–Au(I) complex 20.
Scheme 15: A3-coupling-type synthesis of oxazoles 21 catalyzed by Au(III)–salen complex.
Scheme 16: Proposed reaction mechanism for the synthesis of oxazoles 21.
Scheme 17: Synthesis of propargyl ethyl ethers 24 by an A3-coupling-type reaction.
Scheme 18: General mechanism of Ag(I)-catalyzed MCRs of 2-alkynylbenzaldehydes, amines and nucleophiles.
Scheme 19: General synthetic pathway to 1,3-disubstituted-1,2-dihydroisoquinolines.
Scheme 20: Synthesis of 1,3-disubstituted-1,2-dihydroisoquinolines 29.
Scheme 21: Synthesis of 1,3-disubstituted-1,2-dihydroisoquinolines 35 and 36.
Scheme 22: Rh(II)/Ag(I) co-catalyzed synthesis of 1,3-disubstituted-1,2-dihydroisoquinolines 40.
Scheme 23: General synthetic pathway to 2-amino-1,2-dihydroquinolines.
Scheme 24: Synthesis of 2-amino-1,2-dihydroquinolines 47.
Scheme 25: Synthesis of tricyclic H-pyrazolo[5,1-a]isoquinoline 48.
Scheme 26: Synthesis of tricyclic H-pyrazolo[5,1-a]isoquinolines 48.
Scheme 27: Cu(II)/Ag(I) catalyzed synthesis of H-pyrazolo[5,1-a]isoquinolines 48.
Scheme 28: Synthesis of 2-aminopyrazolo[5,1-a]isoquinolines 53.
Scheme 29: Synthesis of 1-(isoquinolin-1-yl)guanidines 55.
Scheme 30: Ag(I)/Cu(I) catalyzed synthesis of 2-amino-H-pyrazolo[5,1-a]isoquinolines 58.
Scheme 31: Ag(I)/Ni(II) co-catalyzed synthesis of 3,4-dihydro-1H-pyridazino[6,1-a]isoquinoline-1,1-dicarboxyla...
Scheme 32: Ag(I) promoted activation of the α-carbon atom of the isocyanide group.
Scheme 33: Synthesis of dihydroimidazoles 65.
Scheme 34: Synthesis of oxazoles 68.
Scheme 35: Stereoselective synthesis of chiral butenolides 71.
Scheme 36: Proposed reaction mechanism for the synthesis of butenolides 71.
Scheme 37: Stereoselective three-component approach to pirrolidines 77 by means of a chiral auxiliary.
Scheme 38: Stereoselective three-component approach to pyrrolidines 81 and 82 by means of a chiral catalyst.
Scheme 39: Synthesis of substituted five-membered carbocyles 86.
Scheme 40: Synthesis of regioisomeric arylnaphthalene lactones.
Scheme 41: Enantioselective synthesis of spiroacetals 96 by Fañanás and Rodríguez [105].
Scheme 42: Enantioselective synthesis of spiroacetals 101 by Gong [106].
Scheme 43: Synthesis of polyfunctionalized fused bicyclic ketals 103 and bridged tricyclic ketals 104.
Scheme 44: Proposed reaction mechanism for the synthesis of ketals 103 and 104.
Scheme 45: Synthesis of β-alkoxyketones 108.
Scheme 46: Synthesis of N-methyl-1,4-dihydropyridines 112.
Scheme 47: Synthesis of tetrahydrocarbazoles 115–117.
Scheme 48: Plausible reaction mechanism for the synthesis of tetrahydrocarbazoles 115–117.
Scheme 49: Carboamination, carboalkoxylation and carbolactonization of terminal alkenes.
Scheme 50: Oxyarylation of alkenes with arylboronic acids and Selectfluor as reoxidant.
Scheme 51: Proposed reaction mechanism for oxyarylation of alkenes.
Scheme 52: Oxyarylation of alkenes with arylsilanes and Selectfluor as reoxidant.
Scheme 53: Oxyarylation of alkenes with arylsilanes and IBA as reoxidant.
Boron-substituted 1,3-dienes and heterodienes as key elements in multicomponent processes
- Ludovic Eberlin,
- Fabien Tripoteau,
- François Carreaux,
- Andrew Whiting and
- Bertrand Carboni
Beilstein J. Org. Chem. 2014, 10, 237–250, doi:10.3762/bjoc.10.19
- heterodienes presented herein in creating molecular complexity, the field of multicomponent reactions involving these versatile building blocks remains insufficiently explored. If Diels–Alder cycloadditions have been mainly employed as key steps in most of the reported processes, numerous other reactions can
Graphical Abstract
Scheme 1: 1-Boron-substituted 1,3-diene in a tandem cycloaddition [4 + 2]/allylboration sequence.
Scheme 2: Lewis acid catalyst in the tandem cycloaddition [4 + 2]/allylboration sequence.
Scheme 3: Synthesis of an advanced precursor of clerodin.
Scheme 4: Intramolecular Diels–Alder/allylboration sequence.
Scheme 5: Diastereoselective Diels–Alder reaction with N-phenylmaleimide and 4-phenyltriazoline-3,5-dione.
Scheme 6: Asymmetric synthesis of a α-hydroxyalkylcyclohexane.
Scheme 7: Tandem [4 + 2]-cycloaddition/allylboration of 3-silyloxy- and 4-alkoxy-dienyl boronates.
Scheme 8: Metal-mediated cycloisomerization/Diels–Alder reaction/allylboration sequence.
Scheme 9: Cobalt-catalyzed Diels–Alder/allylboration sequence.
Scheme 10: A two-step reaction sequence for the synthesis of tetrahydronaphthalenes 12.
Scheme 11: Tandem sequence based on the Petasis borono–Mannich reaction as first key step.
Scheme 12: One-pot tandem dimerization/allylboration reaction of 1,3-diene-2-boronate.
Scheme 13: Tandem Diels–Alder/cross-coupling reactions of trifluoroborates 15.
Scheme 14: Diels–Alder/cross-coupling reactions of 16.
Scheme 15: Metal catalyzed tandem Diels–Alder/hydrolysis reactions.
Scheme 16: Synthesis of anti-1,5-diols 18 by triple aldehyde addition.
Scheme 17: Catalytic enantioselective three-component hetero-[4 + 2]-cycloaddition/allylboration sequence.
Scheme 18: Synthesis of natural products using the catalytic enantioselective HDA/allylboration sequence.
Scheme 19: Total synthesis of a thiomarinol derivative.
Scheme 20: Synthesis of an advanced intermediate 27 for the east fragment of palmerolide A.
Scheme 21: Bicyclic piperidines from tandem aza-[4 + 2]-cycloaddition/allylboration.
Scheme 22: Hydrogenolysis reactions of hydrazinopiperidines.
Scheme 23: Tandem aza-[4 + 2]-cycloaddition/allylboration/retrosulfinyl-ene sequence.
Scheme 24: Boronated heterodendralene 32 in [4 + 2]-cycloadditions.
Scheme 25: Synthesis of tricyclic imides derivatives.
Scheme 26: Synthesis of 37 via a HDA/allylboration/DA sequence.
Scheme 27: Diels–Alder/allylboration sequence.
Stereoselectively fluorinated N-heterocycles: a brief survey
- Xiang-Guo Hu and
- Luke Hunter
Beilstein J. Org. Chem. 2013, 9, 2696–2708, doi:10.3762/bjoc.9.306
- for synthesising fluorinated analogues of the natural product brevianamide E [68] (65, Scheme 7). This synthesis was remarkable for its rapid generation of molecular complexity, which is a defining feature of the fluorocyclisation approach. Even more spectacular was the extension of this methodology
Graphical Abstract
Figure 1: Fluorination alters the reactivity of aziridines.
Scheme 1: Fluorination makes β-lactam derivatives more reactive towards lipase-catalysed methanolysis.
Figure 2: The ring pucker in azetidine derivatives can be influenced by a C–F…N+ charge–dipole interaction.
Figure 3: Fluorination ridifies the pyrrolidine rings of ligand 10, with several consequences for its G-quadr...
Figure 4: Proline 11 readily undergoes a ring-flip process, but (4R)-fluoroproline 12 is more rigid because o...
Scheme 2: Hyperconjugation rigidifies the ring pucker of a fluorinated organocatalyst 14, leading to higher e...
Figure 5: Fluorinated piperidines prefer the axial conformation, due to stabilising C–F…N+ interactions.
Figure 6: Fluorination can rigidify a substituted azepane, but only if it acts in synergy with the other subs...
Figure 7: The eight-membered N-heterocycle 24 prefers an axial orientation of the fluorine substituent, givin...
Figure 8: Some iminosugars are “privileged structures” that serve as valuable drug leads.
Figure 9: Fluorinated iminosugar analogues 32–34 illuminate the binding interactions of the α-glycosidase inh...
Figure 10: Fluorinated miglitol analogues, and their inhibitory activity towards yeast α-glycosidase.
Figure 11: Analogues of isofagomine (31) have different pKaH values, and therefore exhibit maximal β-glucosida...
Scheme 3: General strategy for the synthesis of fluorinated N-heterocycles via deoxyfluorination.
Figure 12: Late stage deoxyfluorination in the synthesis of multifunctional N-heterocycles.
Scheme 4: During the deoxyfluorination of N-heterocycles, neighbouring group participation can sometimes lead...
Scheme 5: A building block approach for the synthesis of fluorinated aziridines 2 and 3.
Scheme 6: Building block approach for the synthesis of a difluorinated analogue of calystegine B (63).
Scheme 7: Synthesis of fluorinated analogues of brevianamide E (65) and gypsetin (68) via electrophilic fluor...
Scheme 8: Organocatalysed enantioselective fluorocyclisation.
Scheme 9: Synthesis of 3-fluoroazetidine 73 via radical fluorination.
Scheme 10: Synthesis of 3,3-difluoropyrrolidine 78 via a radical cyclisation.
Scheme 11: Chemoenzymatic synthesis of fluorinated β-lactam 4b.
Quantification of N-acetylcysteamine activated methylmalonate incorporation into polyketide biosynthesis
- Stephan Klopries,
- Uschi Sundermann and
- Frank Schulz
Beilstein J. Org. Chem. 2013, 9, 664–674, doi:10.3762/bjoc.9.75
- widespread application in current medicine and agriculture. Polyketide synthases (PKS), giant multienzyme complexes, play a pivotal role in their biosynthesis. PKS generate molecular complexity and diversity through a number of stepwise condensations in analogy to fatty acid synthases but with optional and
Graphical Abstract
Figure 1: The most intensively studied PKS, deoxyerythronolide B synthase (DEBS), which catalyzes the key ste...
Scheme 1: Synthesis of SNAC-activated D3-methylmalonate. a: 2.1 equiv [(CH3)2CH]2NLi, 1 equiv CD3I, abs. THF,...
Figure 2: Structures of erythromycin (left) and rapamycin (right). In this experiment both compounds were lab...
Figure 3: Relative incorporation of the D3-label into erythromycin (A) and rapamycin (B), depending on the fe...
Figure 4: ESI–MS spectra of feeding experiments with an erythromycin-producing culture of S. erythraea. The m...
Scheme 2: Incorporation of a propargylated malonic acid derivative into erythromycin through an active-site m...
Alternaric acid: formal synthesis and related studies
- Michael C. Slade and
- Jeffrey S. Johnson
Beilstein J. Org. Chem. 2013, 9, 166–172, doi:10.3762/bjoc.9.19
- complex molecule synthesis. Keywords: formal synthesis; multicomponent coupling; natural products; silyl glyoxylates; Introduction The rapid development of molecular complexity from simple starting materials is an important goal in modern synthetic organic chemistry. In this context, streamlined one-pot
- build-up of molecular complexity. Alternaric acid (2) [21][22][23] is an antifungal and phytotoxic natural product, which bears a substituted glycolic acid in the functionally and stereochemically dense core of the molecule; the potential application of silyl glyoxylate technology emerged as an
- a single step. In particular, this underscores the unique utility of silyl glyoxylates to serve as crucial linchpins for the coupling of a variety of nucleophile/electrophile pairs at a glycolic acid junction for the rapid development of molecular complexity. (A) Silyl glyoxylates as versatile
Graphical Abstract
Scheme 1: (A) Silyl glyoxylates as versatile reagents for three-component coupling reactions: representative ...
Scheme 2: Potential applications of silyl glyoxylate couplings and precedent synthetic intermediates toward t...
Scheme 3: Three-component coupling with a vinyl nucleophile and elaboration to Ichihara’s aldehyde.
Scheme 4: Modified Julia olefination as a step-efficient alternative endgame strategy.
Scheme 5: Three-component coupling with an allyl nucleophile and demonstration of successful ruthenium-cataly...
Scheme 6: Approaches considered to address the stereochemical issue.
Scheme 7: Use of a dithiane moiety to excert stereochemical control in the three-component coupling reaction ...
Scheme 8: Synthesis of a vinyl iodide for nucleophile generation and its use in a three-component coupling re...
The chemistry of bisallenes
- Henning Hopf and
- Georgios Markopoulos
Beilstein J. Org. Chem. 2012, 8, 1936–1998, doi:10.3762/bjoc.8.225
- -containing tethers. Preparatively the bisallenes are especially useful in isomerization and cycloaddition reactions of all kinds leading to the respective target molecules with high atom economy and often in high yield. Bisallenes are hence substrates for generating molecular complexity in a small number of
- steps (high step economy). Keywords: alicyclic; bisallenes; cyclic; cycloadditions; cycloisomerization; isomerization; molecular complexity; step economy; Table of Contents Introduction Review Acyclic conjugated bisallenes 1.1 Synthesis of hydrocarbons 1.2 Synthesis of functionalized systems 1.3
Graphical Abstract
Figure 1: Loschmidt’s structure proposal for benzene (1) (Scheme 181 from [3]) and the corresponding modern stru...
Figure 2: The first isolated bisallenes.
Figure 3: Carbon skeletons of selected bisallenes discussed in this review.
Scheme 1: The preparation of 1,2,4,5-hexatetraene (2).
Scheme 2: The preparation of a conjugated bisallene by the DMS-protocol.
Scheme 3: Preparation of the 3-deuterio- and 3,4-dideuterio derivatives of 24.
Scheme 4: A versatile method to prepare alkylated conjugated bisallenes and other allenes.
Scheme 5: A preparation of 3,4-dimethyl-1,2,4,5-hexatetraene (38).
Scheme 6: A (C6 + 0)-approach to 1,2,4,5-hexatetraene (2).
Scheme 7: The preparation of a fully alkylated bisallenes from a 2,4-hexadiyne-1,6-diol diacetate.
Scheme 8: The preparation of the first phenyl-substituted conjugated bisallenes 3 and 4.
Scheme 9: Selective hydrogenation of [5]cumulenes to conjugated bisallenes: another (C6 + 0)-route.
Scheme 10: Aryl-substituted conjugated bisallenes by a (C3 + C3)-approach.
Scheme 11: Hexaphenyl-1,2,4,5-hexatetraene (59) by a (C3 + C3)-approach.
Scheme 12: An allenation route to conjugated bisallenes.
Scheme 13: The preparation of 3,4-difunctionalized conjugated bisallenes.
Scheme 14: Problems during the preparation of sulfur-substituted conjugated bisallenes.
Scheme 15: The preparation of 3,4-dibromo bisallenes.
Scheme 16: Generation of allenolates by an oxy-Cope rearrangement.
Scheme 17: A linear trimerization of alkynes to conjugated bisallenes: a (C2 + C2 + C2)-protocol.
Scheme 18: Preparation of a TMS-substituted conjugated bisallene by a C3-dimerization route.
Scheme 19: A bis(trimethylsilyl)bisallene by a C3-coupling protocol.
Scheme 20: The rearrangement of highly substituted benzene derivatives into their conjugated bisallenic isomer...
Scheme 21: From fully substituted benzene derivatives to fully substituted bisallenes.
Scheme 22: From a bicyclopropenyl to a conjugated bisallene derivative.
Scheme 23: The conversion of a bismethylenecyclobutene into a conjugated bisallene.
Scheme 24: The preparation of monofunctionalized bisallenes.
Scheme 25: Preparation of bisallene diols and their cyclization to dihydrofurans.
Scheme 26: A 3,4-difunctionalized conjugated bisallene by a C3-coupling process.
Scheme 27: Preparation of a bisallenic diketone by a coupling reaction.
Scheme 28: Sulfur and selenium-substituted bisallenes by a [2.3]sigmatropic rearrangement.
Scheme 29: The biallenylation of azetidinones.
Scheme 30: The preparation of a fully ferrocenylated conjugated bisallene.
Scheme 31: The first isomerization of a 1,5-hexadiyne to a 1,2,4,5-hexatetraene.
Scheme 32: The preparation of alkynyl-substituted bisallenes by a C3-dimerization protocol.
Scheme 33: Preparation of another completely ferrocenylated bisallene.
Scheme 34: The cyclization of 1,5-hexadiyne (129) to 3,4-bismethylenecyclobutene (130) via 1,2,4,5-hexatetraen...
Scheme 35: Stereochemistry of the thermal cyclization of bisallenes to bismethylenecyclobutenes.
Scheme 36: Bisallene→bismethylenecyclobutene ring closures in the solid state.
Scheme 37: A bisallene cyclization/dimerization reaction.
Scheme 38: A selection of Diels–Alder additions of 1,2,4,5-hexatetraene with various double-bond dienophiles.
Scheme 39: The stereochemistry of the [2 + 4] cycloaddition to conjugated bisallenes.
Scheme 40: Preparation of azetidinone derivatives from conjugated bisallenes.
Scheme 41: Cycloaddition of heterodienophiles to a conjugated bisallene.
Scheme 42: Addition of triple-bond dienophiles to conjugated bisallenes.
Scheme 43: Sulfur dioxide addition to conjugated bisallenes.
Scheme 44: The addition of a germylene to a conjugated bisallene.
Scheme 45: Trapping of conjugated bisallenes with phosphinidenes.
Scheme 46: The cyclopropanantion of 1,2,4,5-hexatetraene (2).
Scheme 47: Photochemical reactions involving conjugated bisallenes.
Scheme 48: Base-catalyzed isomerizations of conjugated bisallenes.
Scheme 49: Ionic additions to a conjugated bisallene.
Scheme 50: Oxidation reactions of a conjugated bisallene.
Scheme 51: The mechanism of oxidation of the bisallene 24.
Scheme 52: CuCl-catalyzed cyclization of 1,2,4,5-hexatetraene (2).
Scheme 53: The conversion of conjugated bisallenes into cyclopentenones.
Scheme 54: Oligomerization of a conjugated bisallene by nickel catalysts.
Scheme 55: Generation of 1,2,5,6-heptatetraene (229) as a reaction intermediate.
Scheme 56: The preparation of a stable derivative of 1,2,5,6-heptatetraene.
Scheme 57: A bisallene with a carbonyl group as a spacer element.
Scheme 58: The first preparation of 1,2,6,7-octatetraene (242).
Scheme 59: Preparation of 1,2,6,7-octatetraenes by (C4 + C4)-coupling of enynes.
Scheme 60: Preparation of 1,2,6,7-octatetraenes by (C4 + C4)-coupling of homoallenyl bromides.
Scheme 61: Preparation of 1,2,6,7-octatetraenes by alkylation of propargylic substrates.
Scheme 62: Preparation of two highly functionalized 1,2,6,7-octatetraenes.
Scheme 63: Preparation of several higher α,ω-bisallenes.
Scheme 64: Preparation of different alkyl derivatives of α,ω-bisallenes.
Scheme 65: The preparation of functionalized 1,2,7,8-nonatetraene derivatives.
Scheme 66: Preparation of functionalized α,ω-bisallenes.
Scheme 67: The preparation of an α,ω-bisallene by direct homologation of an α,ω-bisalkyne.
Scheme 68: The gas-phase pyrolysis of 4,4-dimethyl-1,2,5,6-heptatetraene (237).
Scheme 69: Gas-phase pyrolysis of 1,2,6,7-octatetraene (242).
Scheme 70: The cyclopropanation of 1,2,6,7-octatetraene (242).
Scheme 71: Intramolecular cyclization of 1,2,6,7-octatetraene derivatives.
Scheme 72: The gas-phase pyrolysis of 1,2,7,8-nonatetraene (265) and 1,2,8,9-decatetraene (266).
Scheme 73: Rh-catalyzed cyclization of a functionalized 1,2,7,8-nonatetraene.
Scheme 74: A triple cyclization involving two different allenic substrates.
Scheme 75: Bicyclization of keto derivatives of 1,2,7,8-nonatetraene.
Scheme 76: The preparation of complex organic compounds from functionalized bisallenes.
Scheme 77: Cycloisomerization of an α,ω-bisallene containing a C9 tether.
Scheme 78: Organoborane polymers from α,ω-bisallenes.
Scheme 79: Preparation of trans- (337) and cis-1,2,4,6,7-octapentaene (341).
Scheme 80: The preparation of 4-methylene-1,2,5,6-heptatetraene (349).
Scheme 81: The preparation of acetylenic bisallenes.
Scheme 82: The preparation of derivatives of hydrocarbon 351.
Scheme 83: The construction of macrocyclic alleno-acetylenes.
Scheme 84: Preparation and reactions of 4,5-bismethylene-1,2,6,7-octatetraene (365).
Scheme 85: Preparation of 1,2-bis(propadienyl)benzene (370).
Scheme 86: The preparation of 1,4-bis(propadienyl)benzene (376).
Scheme 87: The preparation of aromatic and heteroaromatic bisallenes by metal-mediated coupling reactions.
Scheme 88: Double cyclization of an aromatic bisallene.
Scheme 89: Preparation of an allenic [15]paracyclophane by a ring-closing metathesis reaction of an aromatic α...
Scheme 90: Preparation of a macrocyclic ring system containing 1,4-bis(propadienyl)benzene units.
Scheme 91: Preparation of copolymers from 1,4-bis(propadienyl)benzene (376).
Scheme 92: A boration/copolymerization sequence of an aromatic bisallene and an aromatic bisacetylene.
Scheme 93: Formation of a layered aromatic bisallene.
Figure 4: The first members of the semicyclic bisallene series.
Scheme 94: Preparation of the first bis(vinylidene)cyclobutane derivative.
Scheme 95: Dimerization of strain-activated cumulenes to bis(vinylidene)cyclobutanes.
Scheme 96: Photodimerization of two fully substituted butatrienes in the solid state.
Scheme 97: Preparation of the two parent bis(vinylidene)cyclobutanes.
Scheme 98: The preparation of 1,3-bis(vinylidene)cyclopentane and its thermal isomerization.
Scheme 99: The preparation of the isomeric bis(vinylidene)cyclohexanes.
Scheme 100: Bi- and tricyclic conjugated bisallenes.
Scheme 101: A selection of polycyclic bisallenes.
Scheme 102: The first endocyclic bisallenes.
Figure 5: The stereochemistry of 1,2,6,7-cyclodecatetraene.
Scheme 103: The preparation of several endocyclic bisallenes.
Scheme 104: Synthesis of diastereomeric derivatives of 1,2,6,7-cyclodecatetraene.
Scheme 105: Preparation of a derivative of 1,2,8,9-cyclotetradecatetraene.
Scheme 106: The preparation of keto derivatives of cyclic bisallenes.
Scheme 107: The preparation of cyclic biscumulenic ring systems.
Scheme 108: Cyclic bisallenes in natural- and non-natural-product chemistry.
Scheme 109: The preparation of iron carbonyl complexes from cyclic bisallenes.
Figure 6: A selection of unknown exocyclic bisallenes that should have interesting chemical properties.
Scheme 110: The thermal isomerization of 1,2-diethynylcyclopropanes and -cyclobutanes.
Scheme 111: Intermediate generation of a cyclooctapentaene.
Scheme 112: Attempted preparation of a cyclodecahexaene.
Scheme 113: The thermal isomerization of 1,5,9-cyclododecatriyne (511) into [6]radialene (514).
Scheme 114: An isomerization involving a diketone derived from a conjugated bisallene.
Scheme 115: Typical reaction modes of heteroorganic bisallenes.
Scheme 116: Generation and thermal behavior of acyclic hetero-organic bisallenes.
Scheme 117: Generation of bis(propadienyl)thioether.
Scheme 118: The preparation of a bisallenic sulfone and its thermal isomerization.
Scheme 119: Bromination of the bisallenic sulfone 535.
Scheme 120: Metalation/hydrolysis of the bisallenic sulfone 535.
Scheme 121: Aromatic compounds from hetero bisallenes.
Scheme 122: Isomerization/cyclization of bispropargylic ethers.
Scheme 123: The preparation of novel aromatic systems by base-catalyzed isomerization of bispropargyl ethers.
Scheme 124: The isomerization of bisacetylenic thioethers to bicyclic thiophenes.
Scheme 125: Aromatization of macrocyclic bispropargylic sulfides.
Scheme 126: Preparation of ansa-compounds from macrocyclic bispropargyl thioethers.
Scheme 127: Alternate route for cyclization of a heterorganic bisallene.
Scheme 128: Multiple isomerization/cyclization of “double” bispropargylic thioethers.
Scheme 129: Preparation of a bisallenyl disulfide and its subsequent bicyclization.
Scheme 130: Thermal cyclization of a bisallenyl thiosulfonate.
Scheme 131: Some reactions of heteroorganic bisallenes with two sulfur atoms.
Scheme 132: Further methods for the preparation of heteroorganic bisallenes.
Scheme 133: Cyclization reactions of heteroorganic bisallenes.
Scheme 134: Thermal cycloadditions of bisallenic tertiary amines.
Scheme 135: Cyclization of a bisallenic tertiary amine in the presence of a transition-metal catalyst.
Scheme 136: A Pauson–Khand reaction of a bisallenic ether.
Scheme 137: Formation of a 2:1adduct from two allenic substrates.
Scheme 138: A ring-forming silastannylation of a bisallenic tertiary amine.
Scheme 139: A three-component cyclization involving a heterorganic bisallene.
Scheme 140: Atom-economic construction of a complex organic framework from a heterorganic α,ω-bisallene.
Organocatalytic asymmetric allylic amination of Morita–Baylis–Hillman carbonates of isatins
- Hang Zhang,
- Shan-Jun Zhang,
- Qing-Qing Zhou,
- Lin Dong and
- Ying-Chun Chen
Beilstein J. Org. Chem. 2012, 8, 1241–1245, doi:10.3762/bjoc.8.139
- provides an electrophilic process to 3-amino-2-oxindoles with a C3-quaternary chiral center. A range of products with high molecular complexity were obtained with good to excellent enantioselectivity (up to 94% ee) and high yields (up to 97%). Currently, more studies on the catalytic asymmetric
Graphical Abstract
Scheme 1: Allylic amination of MBH carbonates of isatins to access 3-amino-2-oxindoles.
Scheme 2: Synthetic transformations of multifunctional product 4d.
Two-directional synthesis as a tool for diversity-oriented synthesis: Synthesis of alkaloid scaffolds
- Kieron M. G. O’Connell,
- Monica Díaz-Gavilán,
- Warren R. J. D. Galloway and
- David R. Spring
Beilstein J. Org. Chem. 2012, 8, 850–860, doi:10.3762/bjoc.8.95
- number of synthetic steps. Two-directional synthesis [9][10][11][12] offers a powerful method for the synthesis of such substrates, because each synthetic transformation has the potential to provide twice as much molecular complexity compared to standard approaches. We have recently reported a strategy
- (Scheme 3b). It seems in our case that, under the correct conditions, a Dieckmann reaction can be made to occur in tandem with the Boc-deprotection and double-conjugate addition processes. This one-pot, four-step reaction process is extremely interesting for the amount of molecular complexity generated in
Graphical Abstract
Figure 1: Overview of the DOS strategy.
Scheme 1: Synthesis of linear cyclisation precursors 1–4.
Scheme 2: AlCl3 catalysed tandem Boc-removal/bicyclisation processes; the yields quoted refer to the isolated...
Scheme 3: (a) AlCl3 catalysed formation of tricyclic alkaloid 10 along with an X-ray crystal structure of 10;...
Scheme 4: (a) Optimal conditions to obtain trans-8 and 10 and the control experiments carried out to probe th...
Scheme 5: DOS of 5-5-6 and 5-6-6 tricyclic alkaloids 13 and 14.
Scheme 6: Total synthesis of myrrhine, epi-myrrhine and myrrhine-N-oxide.
Scheme 7: Use of nitromethane in DOS: Synthesis of meso-diphenylpyrrolidizine 17.
Scheme 8: Use of Tris as a substrate for DOS: Synthesis of decorated morpholines 22 and 23.
Synthetic applications of gold-catalyzed ring expansions
- David Garayalde and
- Cristina Nevado
Beilstein J. Org. Chem. 2011, 7, 767–780, doi:10.3762/bjoc.7.87
- ]-cycloadditions are just some of the relevant available methods employed by organic chemists to increase the molecular complexity of products originating from rather straightforward starting materials. In contrast to the vast number of precedents involving Rh-catalyzed [4 + 3]-cycloaddition reactions to form 7
- application of these methodologies into more complex settings, such as natural product synthesis. In summary, gold-catalyzed ring expansions of strained rings can now be considered a mature tool for the construction of molecular complexity and thus are to be incorporated in to the toolbox of the synthetic
Graphical Abstract
Scheme 1: Transition metal promoted rearrangements of bicyclo[1.1.0]butanes.
Scheme 2: Gold-catalyzed rearrangements of strained rings.
Scheme 3: Gold-catalyzed ring expansions of cyclopropanols and cyclobutanols.
Scheme 4: Mechanism of the cycloisomerization of alkynyl cyclopropanols and cyclobutanols.
Scheme 5: Proposed mechanism for the Au-catalyzed isomerization of alkynyl cyclobutanols.
Scheme 6: Gold-catalyzed cycloisomerization of 1-allenylcyclopropanols.
Scheme 7: Gold-catalyzed cycloisomerization of cyclopropylmethanols.
Scheme 8: Gold-catalyzed cycloisomerization of aryl alkyl epoxides.
Scheme 9: Gold-catalyzed synthesis of furans.
Scheme 10: Transformations of alkynyl oxiranes.
Scheme 11: Transformations of alkynyl oxiranes into ketals.
Scheme 12: Gold-catalyzed cycloisomerization of cyclopropyl alkynes.
Scheme 13: Gold-catalyzed synthesis of substituted furans.
Scheme 14: Proposed mechanism for the isomerization of alkynyl cyclopropyl ketones.
Scheme 15: Cycloisomerization of cyclobutylazides.
Scheme 16: Cycloisomerization of alkynyl aziridines.
Scheme 17: Gold-catalyzed synthesis of disubstituted cyclohexadienes.
Scheme 18: Gold-catalyzed synthesis of indenes.
Scheme 19: Gold-catalyzed [n + m] annulation processes.
Scheme 20: Gold-catalyzed generation of 1,4-dipoles.
Scheme 21: Gold-catalyzed synthesis of repraesentin F.
Scheme 22: Gold-catalyzed ring expansion of cyclopropyl 1,6-enynes.
Scheme 23: Gold-catalyzed synthesis of ventricos-7(13)-ene.
Scheme 24: 1,2- vs 1,3-Carboxylate migration.
Scheme 25: Gold-catalyzed cycloisomerization of vinyl alkynyl cyclopropanes.
Scheme 26: Proposed mechanism for the cycloisomerization of vinyl alkynyl cyclopropanes.
Scheme 27: Gold-catalyzed 1,2-acyloxy rearrangement/cyclopropanation/cycloisomerization cascades.
Scheme 28: Formal total synthesis of frondosin A.
Scheme 29: Gold-catalyzed rearrangement/cycloisomerization of cyclopropyl propargyl acetates.
Tandem catalysis of ring-closing metathesis/atom transfer radical reactions with homobimetallic ruthenium–arene complexes
- Yannick Borguet,
- Xavier Sauvage,
- Guillermo Zaragoza,
- Albert Demonceau and
- Lionel Delaude
Beilstein J. Org. Chem. 2010, 6, 1167–1173, doi:10.3762/bjoc.6.133
- (Scheme 2). This process, known as assisted tandem catalysis [6], presents significant advantages over multistep synthesis for increasing molecular complexity, particularly in terms of time- and cost-savings, atom economy, environmental friendliness, or applicability to diversity-oriented high-throughput
Graphical Abstract
Scheme 1: Reaction of homobimetallic ruthenium–indenylidene complex 1 with ethylene.
Scheme 2: Schematic illustration of tandem assisted catalysis with complexes 1 and 2.
Scheme 3: Tandem RCM/ATRC of 2,2,2-trichloro-N-(octa-1,7-dien-3-yl)acetamide (4) catalyzed by complex 1.
Scheme 4: Ruthenium catalyzed transformation of substrate 16.
A thermally-induced, tandem [3,3]-sigmatropic rearrangement/[2 + 2] cycloaddition approach to carbocyclic spirooxindoles
- Kay M. Brummond and
- Joshua M. Osbourn
Beilstein J. Org. Chem. 2010, 6, No. 33, doi:10.3762/bjoc.6.33
- ] cycloaddition reaction is that the reaction remains selective for the distal double bond of the allene even with densely functionalized allenes [29]. In addition, conversion of the propargylic acetate to the spirooxindole in one step provides a rapid and potentially stereoselective increase in molecular
- complexity. Furthermore, this approach includes a rare example of a thermal [3,3]-sigmatropic rearrangement of a propargylic acetate while metal catalyzed rearrangements of the propargyl acetates are common. Work is currently underway to expand the synthetic utility of this reaction. Experimental
Graphical Abstract
Figure 1: Heterocyclic and carbocyclic spirooxindoles.
Scheme 1: A thermal [2 + 2] cycloaddition reaction.
Figure 2: Access to vinylidene indolin-2-ones.
Scheme 2: A tandem [3,3]-sigmatropic rearrangement/[2 + 2] cycloaddition.
Figure 3: A tandem [3,3]-sigmatropic rearrangement/[2 + 2] cycloaddition.
Radical cascades using enantioenriched 7-azabenzonorbornenes and their applications in synthesis
- David M. Hodgson and
- Leonard H. Winning
Beilstein J. Org. Chem. 2008, 4, No. 38, doi:10.3762/bjoc.4.38
- for the rapid enhancement of molecular complexity. Furthermore, in the structurally similar system created by the formal fusion of the norbornenyl skeleton with an aromatic ring, the ‘nortricyclyl’ radical is delocalised in the originally aromatic π-system. Ring-opening of this ‘nortricyclyl’ radical
Graphical Abstract
Scheme 1: Cyclopropylmethyl–homoallyl and nortricyclyl–norbornenyl radical systems.
Scheme 2: Deoxygenation-rearrangement-electrophile trapping.
Figure 1: Radical SOMO/α-nitrogen lone-pair interaction in the rearranged radical 7.
Figure 2: Other products obtained from xanthate 5 by tandem deoxygenation–rearrangement–electrophile trapping....
Scheme 3: Asymmetric hydroboration–oxidation of alkenes 14, 16 and 18.
Scheme 4: Deoxygenation–rearrangement–isomerisation of xanthates 20 and 23.
Scheme 5: Deoxygenation–rearrangement–electrophile trapping of xanthates 20 and 23.
Scheme 6: 2-Azabenzonorbornene as a masked pyrrolidine.
Scheme 7: Ring-opening–hydration–oxidation of azacycle 8.
Scheme 8: Preparation of trisubstituted pyrrolidine (+)-36.
Scheme 9: Preparation of pyrrolidine diester (+)-35 from Vince’s lactam 37.
Scheme 10: Acid-catalysed ring-opening–oxidation of azacycle (+)-8.
Scheme 11: Birch reduction of (+)-8 and 10.
