Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

Beilstein J. Org. Chem. 2021, 17, 58–82, doi:10.3762/bjoc.17.7

• . J. K. Taylor and co-workers reported the first total synthesis of inthomycin B ((+)-2) using a Stille coupling of a stannyl-diene with an oxazole vinyl iodide unit followed by a Kiyooka ketene acetal/amino acid-derived oxazaborolidinone procedure as its cornerstones (Scheme 4) [43]. In the beginning

• by oxidation of the resulting alcohol using the Ley-Griffith TPAP procedure [47][48]. Treatment of aldehyde 57 with the Ando phenoxy phosphonate 58a [49] gave the desired (Z,Z)-diene 59 as the major product (59/60 = 87:13). DIBAL-H reduction of 59 allowed the isolation of (Z,Z)-isomeric alcohol

• )-diene 66 (E/Z = 19:1, separable) using the standard (E)-selective Horner–Wadsworth–Emmons (HWE) reaction. DIBAL-H reduction of ester 66 followed by MnO2 oxidation produced aldehyde (E,E)-67 stereoselectively. Unfortunately, attempted enantioselective aldol reactions of (E,E)-67 with silylketene acetal

Pentannulation of N-heterocycles by a tandem gold-catalyzed [3,3]-rearrangement/Nazarov reaction of propargyl ester derivatives: a computational study on the crucial role of the nitrogen atom

• Giovanna Zanella,
• Martina Petrović,
• Dina Scarpi,
• Ernesto G. Occhiato and
• Enrique Gómez-Bengoa

Beilstein J. Org. Chem. 2020, 16, 3059–3068, doi:10.3762/bjoc.16.255

• being higher in energy than TS6. As mentioned before, after the slow cyclization step in TS3, we focused our analysis on the transformation of the bicyclic intermediate IV to the final diene product. Basically, the final steps have to include a deprotonation, protodeauration, and in some cases acetate

• believe that the higher thermodynamic stability of XV (4.4 kcal⋅mol−1 lower than for XII), which is due to the conjugation of the nitrogen atom and the diene system, accounts for the preferential formation and the consequent formation of 15. It cannot be overlooked that the formation of the intermediates

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

• 60% yield (74% yield, brsm). A two-step synthesis from 127 produced diene 128, which was subjected to ring-closing metathesis and subsequent Dess–Martin oxidation to give 129 in 63% yield over two steps. Tetracycle 130, which was prepared from 129 in one step, was converted to lycojaponicumin C (18

• of aldehyde 163 and isoprene (164) with Ni(acac)2 and diethylzinc [78] and then Dess–Martin oxidation gave a diene (not shown, 94% yield over two steps), which was subjected to ring-closing metathesis to give enone 165 in 85% yield. Isomerization of the freshly prepared 165 to more stable α,β

Ring-closing metathesis of prochiral oxaenediynes to racemic 4-alkenyl-2-alkynyl-3,6-dihydro-2H-pyrans

• Viola Kolaříková,
• Markéta Rybáčková,
• Martin Svoboda and
• Jaroslav Kvíčala

Beilstein J. Org. Chem. 2020, 16, 2757–2768, doi:10.3762/bjoc.16.226

• (Scheme 2). This effect was explained to be caused not by an improved activation of the ruthenium precatalyst, but either by the participation in the second metathesis cycle releasing the diene product and returning methyleneruthenium complex to the catalytic cycle [22], or by preventing the catalytic

• alkenyl dialkynylphosphinates (Scheme 4) [31]. Thus, the possibility to perform a desymmetrizing RCEYM of oxaenediynes, which should lead to chiral compounds bearing both alkyne and conjugated diene systems, seemed highly appealing to us. Before addressing the enantioselective RCEYM, we report in this

• dihydropyrans 12 obtained by the RCEYM of oxaenediynes 2 contain both a triple bond and a conjugated diene system. We were interested in the possible orthogonal transformation of the products and hence carried out the Diels–Alder reaction of the dihydropyran 12b with N-phenylmaleimide (13) as described in [41

Synthesis of novel fluorinated building blocks via halofluorination and related reactions

• Attila Márió Remete,
• Tamás T. Novák,
• Melinda Nonn,
• Matti Haukka,
• Ferenc Fülöp and
• Loránd Kiss

Beilstein J. Org. Chem. 2020, 16, 2562–2575, doi:10.3762/bjoc.16.208

• uncovered, too. The oxidation of (rac)-31 under basic conditions delivered the conjugated diene (rac)-34, possibly through a deselenation/E1cB elimination sequence similar to the one shown in Scheme 22. Conclusion In conclusion, novel fluorine-containing, functionalized small-molecular scaffolds have been

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

• to allenes 80 to give complex bicyclic products 81 in moderate yields and good enantioselectivities (20 examples, up to 92:8 er) (Scheme 9b) [47]. The Bach group recently developed an enantioselective synthesis of cyclobutane 82 from enal 83 and diene 84 (Scheme 11a) [48]. Most of the examples

• . With an electron-rich alkene, the reaction is proposed to proceed via a reductive quenching cycle to generate chiral ion pair 262•+ and TP•. Subsequent enantioselective cycloaddition with a diene results in ion pair 266•+, which is then reduced by TP• to complete the catalytic cycle and affords the

Hierarchically assembled helicates as reaction platform – from stoichiometric Diels–Alder reactions to enamine catalysis

• David Van Craen,
• Jenny Begall,
• Johannes Großkurth,
• Leonard Himmel,
• Oliver Linnenberg,
• Elisabeth Isaak and
• Markus Albrecht

Beilstein J. Org. Chem. 2020, 16, 2338–2345, doi:10.3762/bjoc.16.195

• ][17][18][19][20]. Enantioselectivities up to 25% ee at elevated temperature (32% ee at 0 °C) depending on the substrate were achieved in a Diels–Alder reaction by introducing two different substituted catechol ester ligands during the complex formation: (1) A diene-substituted ligand 1-H2 for the

• auxiliary, Lewis acid or catalyst. In the previously reported system two different induction pathways were conceivable: (1) A chiral ligand is located close to the diene and controls the stereochemistry of the cycloaddition. (2) The chiral ligand controls the helicity of the helicate (ΔΔ or ΛΛ) and the

• helix induces the stereoselectivity of the Diels–Alder reaction. To find out which of the induction pathways takes over the control of the Diels–Alder reaction in the periphery of the helicates, a specific helicity was induced at an achiral diene bearing helicate. It has been described before that an

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

• reacts with cyclopentadiene in two different ways: concerted [4 + 2] cycloaddition and a stepwise [2 + 2] cycloaddition via an allenyl-cyclopentenyl cation (which could be trapped with OH−) [54][55]. Styrene structural moieties are also present in (E,E)-1,4-diphenylbuta-1,3-diene. Therefore, it was of

• interest to know whether it would react with propyn-1-iminium salts 1 as a styrene or a 1,3-diene. With 3-(4-bromophenyl)propyn-1-iminium salt 1c in acetonitrile, no reaction was observed at 20 °C, but within two hours at 45 °C, an unclean reaction took place, which became evident by a multitude of 19F NMR

• + 2] cycloaddition of 1c and the diene component, which is probably a two-step process as shown in Scheme 5. Cyclobutene 20 is prone to a thermally induced conrotatory electrocyclic ring-opening, which yields iminium-substituted triene 21. In a similar reaction, an α-phenyliminium salt structurally

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

Beilstein J. Org. Chem. 2020, 16, 1991–2006, doi:10.3762/bjoc.16.166

• -methyl-3-buten-1-yl tosylate in the presence of Grubbs’ 2nd generation catalyst yielded 59, which, upon elimination with potassium tert-butoxide led to the diene 50. The reductive amination of 50 afforded an inseparable mixture of the C-14 amines (6:1 ratio). However, the amidation of this mixture with

• ] was followed by a 3-O-vinylation. A thermal 3,3-sigmatropic Claisen rearrangement of 62 gave the cis-2,6-disubstituted dihydropyran 63, which upon sequential Wittig olefination with 2-(triphenylphosporanylidene)propanal and then methylenetriphenylphosphorane yielded the diene 64. The removal of the di

• exocyclic epoxide prior to the formation of the C-6–C-9 conjugated diene was necessary in order to avoid the unwanted epoxidation of the C-6–C-7 olefin. Koide employed a unique strategy in which the exocyclic epoxide was generated as the initial stereocenter (Scheme 15) [12][13]. The Sharpless asymmetric

One-pot and metal-free synthesis of 3-arylated-4-nitrophenols via polyfunctionalized cyclohexanones from β-nitrostyrenes

• Haruyasu Asahara,
• Minami Hiraishi and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2020, 16, 1830–1836, doi:10.3762/bjoc.16.150

• School of Pharmaceutical Sciences, Osaka University, Yamadaoka 1-6, Suita, Osaka 565-0871, Japan 10.3762/bjoc.16.150 Abstract β-Nitrostyrenes underwent a Diels–Alder reaction with Danishefsky’s diene to afford cyclohexenes together with the corresponding hydrolyzed products, 3-arylated-5-methoxy-4

• with Danishefsky’s diene could be conducted in one pot to directly afford the corresponding nitrophenols. Moreover, a heteroaryl group, e.g., a thienyl group could be introduced into the nitrophenol framework. Keywords: 3-arylated-4-nitrophenol; Danishefsky’s diene; Diels–Alder reaction; nitroalkene

• reaction, a C2 unit possessing a nitro group and an aryl group at the vicinal position is incorporated into the products. This unique reactivity prompted us to probe the synthesis of the 3-arylated-4-nitrophenols 5 by the Diels–Alder reaction of nitrostyrenes 1 with Danishefsky’s diene (2, the

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• corresponding mesylate 38b proved sufficient for the synthesis of N-tethered substrates 37 (Z = NTs), through simple nucleophilic substitution (via c). It is noteworthy that under standard PK reaction conditions, fluoroenyne 39 evolves to diene 40. The formation of compound 40 is possible by elimination of HF

An overview on disulfide-catalyzed and -cocatalyzed photoreactions

• Yeersen Patehebieke

Beilstein J. Org. Chem. 2020, 16, 1418–1435, doi:10.3762/bjoc.16.118

• applications in total synthesis, medium- and large-ring syntheses, and conjugate diene isomerization processes. In 2006, Crimmins successfully used this isomerization method in the syntheses of ophirin B and astrogorgin (Scheme 25) [31]. In the reaction, the intermediate 70 reacts with

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

• ] cycloadditions of N-methyldithiosuccinimides 223 and N-methyldithiophthalimide (225) with alkenes 215 and a conjugated diene 226, generating spirothietanes 224, 227–229, 231, 232, and 234. In some cases, the reverse [2 + 2] cycloaddition occurred with the loss of a molecule of thioacetone [70] (Scheme 44). The

Highly selective Diels–Alder and Heck arylation reactions in a divergent synthesis of isoindolo- and pyrrolo-fused polycyclic indoles from 2-formylpyrrole

• Carlos H. Escalante,
• Eder I. Martínez-Mora,
• Carlos Espinoza-Hicks,
• Alejandro A. Camacho-Dávila,
• Fernando R. Ramos-Morales,
• Francisco Delgado and
• Joaquín Tamariz

Beilstein J. Org. Chem. 2020, 16, 1320–1334, doi:10.3762/bjoc.16.113

• . Accordingly, the R2 substituent in the diene would play an important role in directing the endo/exo orientation of the approach to the maleimide at the transition state (TS). Therefore, the endo diastereoselectivity is apparently not controlled by the presence or the absence of the substituent bonded to the

• nitrogen atom of the heterocycle. Since it is not clear what factors favor this relevant selectivity, the geometry and energy of the TSs were calculated for some of the diene–dienophile pairs depicted in Table 2 (vide infra). Cyclization via an intramolecular Heck arylation reaction Before attempting the

• . Firstly, the geometry and energy of the TSs and the associated minima along the reaction coordinates of the N-substituted diene 8g with maleimide 7c were calculated at the M06-2X/6-31+G(d,p) level of theory [48][49][50][51] on the Gaussian 09 program [52]. For each stationary point of the Diels–Alder

Oxime radicals: generation, properties and application in organic synthesis

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Alexander S. Budnikov and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2020, 16, 1234–1276, doi:10.3762/bjoc.16.107

• addition of 20 equivalents of cyclohexa-1,4-diene (CHD) as hydrogen atom donor (conditions B) led to methylisoxazolines 111. Both aromatic (examples 110a–c,f, 111a,b,f) and aliphatic (examples 110d,e and 111c–e) β,γ-unsaturated oximes undergo this cyclization. The conditions A were also applied for the

A cyclopeptide and three oligomycin-class polyketides produced by an underexplored actinomycete of the genus Pseudosporangium

• Shun Saito,
• Kota Atsumi,
• Tao Zhou,
• Keisuke Fukaya,
• Daisuke Urabe,
• Naoya Oku,
• Md. Rokon Ul Karim,
• Hisayuki Komaki and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 1100–1110, doi:10.3762/bjoc.16.97

• , C-9, and C-11) and two methyl and one ethyl substituents on the even-numbered carbons (C-4, C-6, and C-12). Furthermore, via the two-carbon fragment C-13/C-14, a COSY-defined six-carbon chain from C-15 to C-20, containing a conjugated diene, was connected to C-12. Another six-carbon chain from C-21

• -47 were assigned to constitute an (E)-2,3-dehydroadipic acid by COSY and HMBC analysis along with coupling constant analysis (JH-43,H-44 = 14.8 Hz), and the connection of this diacid portion to C-13 via an ester linkage completed the planar structure of compound 2. An E,E-diene configuration for the

Recent applications of porphyrins as photocatalysts in organic synthesis: batch and continuous flow approaches

• Rodrigo Costa e Silva,
• Luely Oliveira da Silva,
• Aloisio de Andrade Bartolomeu,
• Timothy John Brocksom and
• Kleber Thiago de Oliveira

Beilstein J. Org. Chem. 2020, 16, 917–955, doi:10.3762/bjoc.16.83

• conditions, a porphyrin-based protocol for endoperoxidation of the diene, followed by the Kornblum–DeLaMare rearrangement and further telescoped transformations. This protocol yields different classes of products such as furans, tropone, diketones and hydroxyenones, all of them starting from the

Diversity-oriented synthesis of 17-spirosteroids

• Benjamin Laroche,
• Thomas Bouvarel,
• Martin Louis-Sylvestre and
• Bastien Nay

Beilstein J. Org. Chem. 2020, 16, 880–887, doi:10.3762/bjoc.16.79

• Paris, Palaiseau Cedex, France 10.3762/bjoc.16.79 Abstract A diversity-oriented synthesis (DOS) approach has been used to functionalize 17-ethynyl-17-hydroxysteroids through a one-pot procedure involving a ring-closing enyne metathesis (RCEYM) and a Diels–Alder reaction on the resulting diene, under

• the propargylic alcohol, the resulting enyne is a good substrate for ring closing enyne metathesis (RCEYM) towards new diene substrates [40][41][42], which can be employed in Diels–Alder reactions with a variety of dienophiles (Figure 1) [43][44][45][46][47][48][49][50][51][52][53][54]. This strategy

• at 170 °C for 17-(4-penten-1-yloxy)steroids, for 1 h under microwave irradiation. The solvent was removed by evaporation, and the resulting crude material was purified by chromatography on silica gel (petroleum ether/EtOAc 99:1) to afford the spirocyclic diene. General procedure C for one-pot RCEYM

Aldehydes as powerful initiators for photochemical transformations

• Maria A. Theodoropoulou,
• Nikolaos F. Nikitas and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2020, 16, 833–857, doi:10.3762/bjoc.16.76

• (Scheme 15) [50]. Among the compounds tested, 1-naphthaldehyde (63) provided a photostationary mixture rich in the trans-diene (trans/cis ratio ≈ 13). A year later, the same group further studied the cis/trans isomerization of the piperylenes 61 and 62 utilizing energy transfer from the triplet states of

• state quencher, as well as by the lowered rate of the reaction in the presence of the triplet energy quencher 2,5-dimethylhexa-2,4-diene or pyridazines, additives with lower triplet state energies than 4-anisaldehyde (52). The fact that the solvent polarity did not affect the sensitivity of the process

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

• that enyne metatheses are atom economical processes driven by the enthalpic stability of the conjugated diene products. Depending on the steric requirements of the transition metal carbene and of the starting enyne, the intramolecular reaction can proceed either via ene–yne or yne–ene pathways to yield

• (Scheme 3 (c)) leads to the expected 1,3-diene (Scheme 3 (d–f)). A particular advantage of the enyne metathesis is that the stereoselectivity can be readily controlled by the intramolecular vs the intermolecular process. Among the vast array of bioactive organic molecules already synthesized through enyne

• key step, adding this protocol to the existing synthetic or hemisynthetic procedures. Along this line, Oguri et al. elaborated an excellent strategy for assembling the tricyclic diene scaffold of artemisinin and its analogs that combines classical transformations with tandem dienyne ring-closing

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

• yields (Scheme 48). They proposed a mechanism in which LCu(I)–Si coordinates first with the triple bond, which eventually forms a monosilylated diene. The resulting organocopper species then participates in a second catalytic cycle to furnish the disilylated products [86]. 2 Cu-catalyzed carbon–boron

Synthesis of disparlure and monachalure enantiomers from 2,3-butanediacetals

• Adam Drop,
• Hubert Wojtasek and
• Bożena Frąckowiak-Wojtasek

Beilstein J. Org. Chem. 2020, 16, 616–620, doi:10.3762/bjoc.16.57

• semiochemicals. They have been frequently found as pheromones in lepidopteran species of the families Noctuidae, Arctiidae, Lymantridae, Geometridae and Erebidae [1]. (3Z,9Z)-6S,7R-Epoxyheneicosa-3,9-diene, a constituent of the female sex pheromone of the moth Tetanolita mynesalis (Erebidae) [2] is a

Combination of multicomponent KA² and Pauson–Khand reactions: short synthesis of spirocyclic pyrrolocyclopentenones

• Riccardo Innocenti,
• Elena Lenci,
• Gloria Menchi and
• Andrea Trabocchi

Beilstein J. Org. Chem. 2020, 16, 200–211, doi:10.3762/bjoc.16.23

• presence of camphorsulfonic acid did not give the desired amine, supporting the hypothesis of steric hindrance at such position [57]. Similarly, Simmons–Smith cyclopropanation reaction [58] did not work, and so as for the cycloaddition reaction with Danishefsky’s diene, possibly due to steric hindrance

Rapid, two-pot procedure for the synthesis of dihydropyridinones; total synthesis of aza-goniothalamin

• Thomas J. Cogswell,
• Craig S. Donald and
• Rodolfo Marquez

Beilstein J. Org. Chem. 2020, 16, 135–139, doi:10.3762/bjoc.16.15

• Zealand 10.3762/bjoc.16.15 Abstract A fast, protecting-group-free synthesis of dihydropyridinones has been developed. Starting from commercially available aldehydes, a novel one-pot amidoallylation gave access to diene compounds in good yields. Ring-closing metathesis conditions were then employed to

• generate the desired product. This stepwise addition was successful in affording an improved 88% yield of diene 5 as well as significantly reducing the overall reaction time (Scheme 3). Treatment of diene 5 under ring-closing metathesis conditions, using Grubbs I catalyst, then proceeded to generate the

• described above. Rewardingly, Hosomi–Sakurai allylation of the conjugated imine intermediate proceeded to afford the desired diene 10 in working yield (35%). The formation of diene 10 is significant as the corresponding α,β-enones and α,β-enals undergo exclusive conjugate addition under Hosomi–Sakurai

Synthesis and optoelectronic properties of benzoquinone-based donor–acceptor compounds

• Daniel R. Sutherland,
• Nidhi Sharma,
• Georgina M. Rosair,
• Ifor D. W. Samuel,
• Ai-Lan Lee and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2019, 15, 2914–2921, doi:10.3762/bjoc.15.285

• for C36H22N2O2, 515.1760; found, 515.1760. 4,4''-Bis(diphenylamino)[1,1':4',1''-terphenyl]-2',5'-dione (5): To a Schlenk tube equipped with a magnetic stirring bar were added 2,5-dibromocyclohexa-2,5-diene-1,4-dione (251 mg, 0.94 mmol, 1 equiv), 4-(diphenylamino)phenylboronic acid (809 mg, 2.80 mmol