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

• (III) and iodine(III), and Wolff rearrangement. 2.1 Benzilic acid and semipinacol-type rearrangements The strategy of ring contraction using the benzilic acid-type rearrangement was used by Zhang et al. [38] for the asymmetric synthesis of 4β-acetoxyprobotryane-9β,15α-diol (52). This compound contains

• 30% and a selectivity of 70% at −100 °C (Scheme 21). 2.3 Wolff rearrangement The Wolff rearrangement is the transformation of α-diazoketones into acids or their derivatives through heating, catalysis, or UV irradiation in the presence of water, alcohols, ammonia, amines, etc. The Wolff rearrangement

• 6,5,6-abeoabietane scaffold and impressive antitumor activity. α-Diazoketone 124 was synthesized from commercially available 1,2,4-trimethoxybenzene (123) [64] by a series of synthetic transformations, and converted by Wolff rearrangement to esters 125 and 126 with a trans-fused 6,5,6-ring system

Harnessing the versatility of hydrazones through electrosynthetic oxidative transformations

• Aurélie Claraz

Beilstein J. Org. Chem. 2024, 20, 1988–2004, doi:10.3762/bjoc.20.175

• ’-dimethoxybenzilhydrazone (X = H, Cl). In these cases, the diazo compounds directly underwent both Wolff rearrangement and overoxidations to yield a mixture of the corresponding diphenyl acetal and benzil dimethyl acetal (akin to the conversion of 132 into 133 in Scheme 27), respectively (Scheme 29) [78]. Using a similar

Access to 2-oxoazetidine-3-carboxylic acid derivatives via thermal microwave-assisted Wolff rearrangement of 3-diazotetramic acids in the presence of nucleophiles

• Ivan Lyutin,
• Vasilisa Krivovicheva,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 1894–1899, doi:10.3762/bjoc.20.164

• 191036, Russian Federation 10.3762/bjoc.20.164 Abstract In this work, we report an efficient approach to 2-oxoazetidine-3-carboxylic acid derivatives based on a thermally promoted Wolff rearrangement of diazotetramic acids in the presence of nucleophiles. The method allows easy variation of the

• well as a wide range of nucleophiles provides access to a structural diversity of medically relevant 2-oxoazetidine-3-carboxylic acid amides and esters. Keywords: β-lactams; diazotetramic acids; nucleophiles; spirocycles; thermolysis; Wolff rearrangement; Introduction The importance of the β-lactam

• ketenes 2 generated by a thermally promoted Wolff rearrangement [3]. The interaction of such ketenes with nucleophiles of different nature could serve as a source of libraries of structurally diverse 2-oxoazetidine-3-carboxylic acid derivatives 3 (Scheme 1). The 2-oxoazetidine-3-carboxylic acid

(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• planarity. Brown and co-workers prepared the [2]-ladderanes via a multistep sequence from diene 147 including an intramolecular [2 + 2] cycloaddition (to (±)-148) and a Wolff rearrangement (to (±)-150) (Scheme 16A) [63]. This approach yielded predominantly the endo diastereomer of trans-[2]-ladderanes 150

Efficient synthesis of ethyl 2-(oxazolin-2-yl)alkanoates via ethoxycarbonylketene-induced electrophilic ring expansion of aziridines

• Yelong Lei and
• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 70–76, doi:10.3762/bjoc.18.6

• heating, diazo esters 1 undergo a Wolff rearrangement to generate ethoxycarbonylketenes A by loss of nitrogen. The nucleophilic attack of 2-arylaziridine 2 on the ketene moiety produces zwitterionic intermediates B, in which the aziridinium is opened to form the benzylic carbocation stabilized through the

Novel photochemical reactions of carbocyclic diazodiketones without elimination of nitrogen – a suitable way to N-hydrazonation of C–H-bonds

• Liudmila L. Rodina,
• Xenia V. Azarova,
• Jury J. Medvedev,
• Dmitrij V. Semenok and
• Valerij A. Nikolaev

Beilstein J. Org. Chem. 2018, 14, 2250–2258, doi:10.3762/bjoc.14.200

• %. Further irradiation of hydrazones derived from furan-fused tricyclic diazocyclopentanediones culminates in the cycloelimination of furans to yield 2-N-(alkyl)hydrazone of cyclopentene-1,2,3-trione. By contrast, the direct photolysis of carbocyclic diazodiketones gives only Wolff rearrangement products

• with up to 90–97% yield. Keywords: C–H insertion; diazo compounds; excited state; photochemistry; Wolff rearrangement; Introduction Photochemical reactions of diazocarbonyl compounds are well-known transformations in the synthesis of the diversified acyclic, carbo- and heterocyclic structures [1][2

• nucleophilic reagents (H2O, MeOH) or C–H-bonds at С5 or С6 atoms in 1 [26][42][43][44][45] were detected in the reaction mixtures. Thus, it was experimentally shown that the direct photolysis of diazodiketones 1а–c employing UV light with λ > 210 nm produces only Wolff rearrangement products in high yields

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

• compound 267. Nitro compound 267 was also hydrogenated to produce 7-amino derivative 264. Diazoketone 265 was prepared from 264 with sodium nitrite in fluoroboric acid (HBF4) and its Wolff rearrangement under reflux conditions in water gave 1-hydroxy-2-naphthoic acid (266). Acetylation of 264 with sodium

Unusual reactions of diazocarbonyl compounds with α,β-unsaturated δ-amino esters: Rh(II)-catalyzed Wolff rearrangement and oxidative cleavage of N–H-insertion products

• Valerij A. Nikolaev,
• Jury J. Medvedev,
• Olesia S. Galkina,
• Ksenia V. Azarova and
• Christoph Schneider

Beilstein J. Org. Chem. 2016, 12, 1904–1910, doi:10.3762/bjoc.12.180

• .12.180 Abstract Rh(II)-сatalyzed reactions of aroyldiazomethanes, diazoketoesters and diazodiketones with α,β-unsaturated δ-aminoesters, in contrast to reactions of diazomalonates and other diazoesters, give rise to the Wolff rearrangement and/or oxidative cleavage of the initially formed N–H-insertion

• ; transition-metal-catalyzed reactions; Wolff rearrangement; Introduction Transition-metal-catalyzed reactions of diazocarbonyl compounds (DCC) with different organic substrates comprise a powerful tool of organic synthesis [1][2][3][4][5][6][7][8]. Of prime importance was found to be the ability of reactive

• as a consequence of the initial Wolff rearrangement of diazoketoesters 3a,b accompanied by acylation of the N–H-group of aminoester 1 with α-oxoketene formed. When passing from diazoketoesters 3a,b to dibenzoyldiazomethane 3с, the formation of N,N-disubstituted 2-oxo-2-phenylacetamide 7 was observed

The synthesis of functionalized bridged polycycles via C–H bond insertion

• Jiun-Le Shih,
• Po-An Chen and
• Jeremy A. May

Beilstein J. Org. Chem. 2016, 12, 985–999, doi:10.3762/bjoc.12.97

• [31]. Metal-catalyzed reactions Copper The earliest example to our knowledge of transition metal catalysis for the formation of bridged rings via C–H bond insertion was Wolff’s use of copper (Scheme 6) [32][33]. Silver was also examined as a possible catalyst, but then a Wolff rearrangement was the

• primary outcome. The major product with copper was insertion into the more electron-rich methine to give bicyclo[3.2.1]octane 29. The yields of both transannular C–H insertion products were increased relative to the Wolff rearrangement when a methyl group was present on the cyclohexyl carbon bearing the

Azirinium ylides from α-diazoketones and 2H-azirines on the route to 2H-1,4-oxazines: three-membered ring opening vs 1,5-cyclization

• Nikolai V. Rostovskii,
• Mikhail S. Novikov,
• Alexander F. Khlebnikov,
• Galina L. Starova and
• Margarita S. Avdontseva

Beilstein J. Org. Chem. 2015, 11, 302–312, doi:10.3762/bjoc.11.35

• active electrophilic trap in the reaction mixture. 3-Diazoacetylacetone under Rh(II)-catalysis gives, along with a Rh(II) carbenoid, a highly electrophilic acetyl(methyl)ketene (12) via Wolff rearrangement (Scheme 3). The nucleophilic attack of the azirenooxazole 10j nitrogen on the ketene sp-carbon

• presence of Rh2(Oct)4 (Scheme 5). We suggested that the azirenooxazole formed from the azirine and diazo compound 2d will be trapped by ketene 12 generated from diazoacetylacetone 2c via Wolff rearrangement. The 1H NMR and TLC analysis of the reaction mixture revealed, along with oxazines 4k, 4h and adduct

• -2-ene and/or 5,7-dioxa-1-azabicyclo[4.3.1]deca-3,8-diene-2-one derivatives. This reaction sequence partly occurs, when 3-aryl-2H-azirines and 3-diazoacetylacetone, which is able to produce acetyl(methyl)ketenes via Rh(II)-catalyzed Wolff rearrangement, are used as starting materials. According to

Domino reactions of 2H-azirines with acylketenes from furan-2,3-diones: Competition between the formation of ortho-fused and bridged heterocyclic systems

• Alexander F. Khlebnikov,
• Mikhail S. Novikov,
• Viktoriia V. Pakalnis,
• Roman O. Iakovenko and
• Dmitry S. Yufit

Beilstein J. Org. Chem. 2014, 10, 784–793, doi:10.3762/bjoc.10.74

• application of the reaction is the nonselective mode of the Wolff rearrangement of the unsymmetrical diazo compounds. This generates a mixture of isomeric oxoketenes [27][28][29] and, as a result, a complex mixture of products is formed [22]. Moreover not all diazo compounds give oxoketenes easily [27][28][29

Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

• Sebastian Krüger and
• Tanja Gaich

Beilstein J. Org. Chem. 2014, 10, 163–193, doi:10.3762/bjoc.10.14

• condition. Final reduction gave core skeleton 233. DVCPR in tandem reactions The group of Stoltz [196][197] succeeded in establishing a tandem Wolff rearrangement/divinylcyclopropane rearrangement strategy [198]. Readily accessible α-diazo ketone 234 (see Scheme 28) was shown to undergo Wolff rearrangement

Less reactive dipoles of diazodicarbonyl compounds in reaction with cycloaliphatic thioketones – First evidence for the 1,3-oxathiole–thiocarbonyl ylide interconversion

• Valerij A. Nikolaev,
• Alexey V. Ivanov,
• Ludmila L. Rodina and
• Grzegorz Mlostoń

Beilstein J. Org. Chem. 2013, 9, 2751–2761, doi:10.3762/bjoc.9.309

• . The formation of 1,3-oxathiinone 4b (in addition to 1,3-oxathiole 3b) in the reaction of diazo compound 2b with thioketone 1a at 80 °С is evidently caused by partial thermal decomposition and a Wolff rearrangement of diazodiketone 2b which gives rise to 2-oxoketene 12b [7][8][19][26]. The latter

• corresponding 1,3-oxathiole. Upon increasing the reaction temperature, the rate of the [2 + 3]-cycloaddition of the diazodicarbonyl compounds notably increases, but in the case of diazodiketone 2b simultaneous thermolysis followed by the Wolff rearrangement occurs. The in situ formed 2-oxoketene reacts as a

Total synthesis of (−)-epimyrtine by a gold-catalyzed hydroamination approach

• Thi Thanh Huyen Trinh,
• Khanh Hung Nguyen,
• Patricia de Aguiar Amaral and
• Nicolas Gouault

Beilstein J. Org. Chem. 2013, 9, 2042–2047, doi:10.3762/bjoc.9.242

• of the β-aminoynone 2 began with the Arndt–Eistert homologation [23] of N-Boc-protected D-alanine (Scheme 3). Thus, the N-Boc-D-alanine was treated with isobutyl chloroformate at 0 °C in THF/diethyl ether followed by the addition of diazomethane to afford the corresponding diazoketone. The Wolff

• rearrangement was then carried out by using silver nitrate in THF to give the intermediate ketene which was trapped with N,O-dimethylhydroxylamine to provide the corresponding Weinreb amide 1 in 84% yield over two steps. In the next step, the Weinreb amide 1 was added to a solution of O-protected 1-hexynol

Flow photochemistry: Old light through new windows

• Jonathan P. Knowles,
• Luke D. Elliott and
• Kevin I. Booker-Milburn

Beilstein J. Org. Chem. 2012, 8, 2025–2052, doi:10.3762/bjoc.8.229

Synthesis of trifunctional cyclo-β-tripeptide templates

• Frank Stein,
• Tahir Mehmood,
• Tilman Plass,
• Javid H. Zaidi and
• Ulf Diederichsen

Beilstein J. Org. Chem. 2012, 8, 1576–1583, doi:10.3762/bjoc.8.180

• prepared from the respective β-amino acids by Arndt–Eistert homologation [17][18][19]. The β-amino acids were transformed into the respective diazoketones with isobutyl chloroformate, triethylamine and diazomethane. The ketones were further converted into the β-amino acids by Wolff rearrangement using

• intermolecular stack of rings by backbone hydrogen bonding. β-Amino acids 1–3 with orthogonal side-chain protection obtained by Arndt–Eistert homologation followed by Wolff rearrangement; cyclo-β-tripeptide template 4 as obtained by coupling of amino acids 1–3 followed by cyclization. Functional units provided

Synthesis of glycosylated β³-homo-threonine conjugates for mucin-like glycopeptide antigen analogues

• Florian Karch and
• Anja Hoffmann-Röder

Beilstein J. Org. Chem. 2010, 6, No. 47, doi:10.3762/bjoc.6.47

• ). Without further purification, the latter was subjected to a silver-promoted Wolff-rearrangement, again using NMM as the base, providing the spectroscopically pure TN antigen analogue Fmoc-β3hThr(αAc3GalNAc)-OH (2a) in 60% yield over two steps after aqueous work-up. Compound 2a was also accessible from a

• . The organic layer was dried over Na2SO4, filtered, and the solvents were removed under reduced pressure. The resulting diazo ketones were used without further purification. General procedure (GP2) for the Wolff-rearrangement: The diazo ketone (1 equiv) was dissolved in a mixture of THF/H2O (9:1) and

Synthesis of highly substituted allenylsilanes by alkylidenation of silylketenes

• Stephen P. Marsden and
• Pascal C. Ducept

Beilstein J. Org. Chem. 2005, 1, No. 5, doi:10.1186/1860-5397-1-5

• functional group tolerant approach to substituted silylketenes based upon a rhodium-mediated formal Wolff rearrangement of silylated diazoketones.[23] Related photolytic approaches also hold some promise.[24][25][26][27] These methods allow access for the first time to a wide range of substituted