(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

• in moderate to good yields, employing 2,7-dimethoxythioxanthone (2,2’-OMeTX) as a triplet sensitizer for BCB excitation (Scheme 3A) [38]. Starting from BCB 24, alkenes including styrene derivatives, enol ethers, and vinyl boronates could be incorporated to give 1,2-BCHs (±)-25a–d. Brown and co

• alkenes including acrylates, vinyl sulfones, and acrylamides could all be incorporated and the number of accessible bifunctional 1,2-BCHs was increased further by chemical transformation (Scheme 3D) [35]. Among the reported transformations were reduction of the ketone (to (±)-34), hydrolysis of the

• substituted ortho-benzene. Stephenson and co-workers accessed 1,2-BCHeps 79a–c by insertion of alkenes into BCPs 78, and proposed the 1,2-BCHeps as isosteres of ortho-benzenes (Scheme 7A) [46]. The reaction proceeded via homolytic cleavage of a C–C bond adjacent to the imine functionality and stepwise alkene

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• Daniel S. Muller Univ. Rennes, CNRS, ISCR (Institut des Sciences Chimiques de Rennes) – UMR 6226, 263 Avenue du Général Leclerc, F-35000 Rennes, France 10.3762/bjoc.20.72 Abstract The hydrochlorination of alkenes has been extensively studied in research and is commonly featured in organic

• chemistry textbooks as an exemplification of the Markovnikov rule. However, the application of this reaction is typically limited to specific alkenes, such as highly substituted ones, styrenes, or strained systems. Conversely, monosubstituted or 1,2-disubstituted alkenes do not readily react with HCl gas or

• solutions of HCl gas at practical rates. The challenges associated with hydrochlorination reactions for these "non-activated" alkenes have spurred considerable research efforts over the past 30 years, which constitute the primary focus of this review. The discussion begins with classical polar

SOMOphilic alkyne vs radical-polar crossover approaches: The full story of the azido-alkynylation of alkenes

• Julien Borrel and
• Jerome Waser

Beilstein J. Org. Chem. 2024, 20, 701–713, doi:10.3762/bjoc.20.64

• discovery and development of the synthesis of homopropargylic azides by the azido-alkynylation of alkenes. Initially, a strategy involving SOMOphilic alkynes was adopted, but only resulted in a 29% yield of the desired product. By switching to a radical-polar crossover approach and after optimization, a

• terminal azide, despite its implication in the synthesis of complex molecules [3][6]. Therefore, the development of a straightforward reaction to synthesize homopropargylic azides would be of general interest. The azido-alkynylation of alkenes would allow to generate the desired motif in a single step

• ]. Moreover, different azide sources are known to efficiently promote the diazidation of alkenes in the presence of a copper catalyst, often proceeding via a radical mechanism [24][29][30][31]. A second approach would involve SOMOphilic alkynes to trap the radical by a purely open-shell mechanism (Scheme 1B

Palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines

• Geng-Xin Liu,
• Xiao-Ting Jie,
• Ge-Jun Niu,
• Li-Sheng Yang,
• Xing-Lin Li,
• Jian Luo and
• Wen-Hao Hu

Beilstein J. Org. Chem. 2024, 20, 661–671, doi:10.3762/bjoc.20.59

• a highly emerging area of research and exhibit complementary reactivity to those well-developed carbene-mediated MCRs [30][31][32][33][34][35][36][37][38][39][40][41][42]. In the radical-mediated difunctionalization of alkenes, the carbon-centered radical species from a diazo compound can add to

• diverse alkenes followed by a diradical coupling or radical addition process to achieve the difunctionalization (Scheme 1b, middle) [32][33][34][35][36][37]. However, to the best of our knowledge, the methodology involving the addition of a carbon radical from a diazo compound onto the double bond of an

• reaction of diazo compounds mediated by visible light has been reported by the group of Gevorgyan, which achieves the monofunctionalization of alkenes [52]. Inspired by these collective studies, we considered diazo compounds could be a competent activated alkyl halide equivalent to overcome the synthetic

Ligand effects, solvent cooperation, and large kinetic solvent deuterium isotope effects in gold(I)-catalyzed intramolecular alkene hydroamination

• Ruichen Lan,
• Brock Yager,
• Yoonsun Jee,
• Cynthia S. Day and
• Amanda C. Jones

Beilstein J. Org. Chem. 2024, 20, 479–496, doi:10.3762/bjoc.20.43

• of alkenes remains challenging. Advances in asymmetric catalysis [2][3][4][5][6][7][8][9][10], C–N [11][12][13][14][15][16][17] and C–C functionalization [18][19] reveal opportunities, but harsh conditions and limited substrate scope present problems. Intramolecular reactions almost invariably

• require geminal substitution or backbone heteroatoms, internal alkenes are often not tolerated, and intermolecular reactions require high temperatures which can lead to significant catalyst decomposition [20]. This is usually addressed by employing bulky or strong donor ligands [21][22]. Novel strategies

• ) protodeauration (Scheme 1), the depth of experimental mechanistic validation achieved for allenes and alkynes have not been reproduced with alkenes. In an important foundational study by Toste, the expected alkylgold intermediate from intramolecular alkene hydroamination was isolated, however, turnover

Nucleophilic functionalization of thianthrenium salts under basic conditions

• Xinting Fan,
• Duo Zhang,
• Xiangchuan Xiu,
• Bin Xu,
• Yu Yuan,
• Feng Chen and
• Pan Gao

Beilstein J. Org. Chem. 2024, 20, 257–263, doi:10.3762/bjoc.20.26

• -metal-catalyzed cross-coupling [32][33] and aminofunctionalization [34] of alkenes were achieved, benefiting from the unique reactivity of organothianthrenium species that are generated through the reaction of alkenes and thianthrene sulfoxide (TT=O) or thianthrene (TT) (Scheme 1b). Alcohols are widely

• generation of alkyl radicals [39]. After that, a series of methods for the modification of alkylthianthrenium salts have been developed, including the transition-metal-catalyzed cross-coupling with terminal alkynes [40], sulfonylation with DABCO·(SO2)2 [41][42][43], or alkylation of active alkenes [44][45

Catalytic multi-step domino and one-pot reactions

• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2024, 20, 254–256, doi:10.3762/bjoc.20.25

• advances in the field. A Review article by Pounder, Tam, and co-authors summarizes new transition-metal-catalyzed domino reactions of strained bicyclic alkenes, including both homo- and heterobicyclic alkenes highly useful for the construction of biologically significant compounds with multiple

Tandem Hock and Friedel–Crafts reactions allowing an expedient synthesis of a cyclolignan-type scaffold

• Viktoria A. Ikonnikova,
• Cristina Cheibas,
• Oscar Gayraud,
• Alexandra E. Bosnidou,
• Nicolas Casaretto,
• Gilles Frison and
• Bastien Nay

Beilstein J. Org. Chem. 2024, 20, 162–169, doi:10.3762/bjoc.20.15

• mention that allylic hydroperoxides are conveniently produced by the photooxygenation of alkene substrates [14][15][16]. Taking all these informations together, since alkenes can be easier intermediates than aldehydes to handle, we envisaged to use a prenyl (= 3-methyl-2-buten-1-yl) group as an aldehyde

Perspectives on push–pull chromophores derived from click-type [2 + 2] cycloaddition–retroelectrocyclization reactions of electron-rich alkynes and electron-deficient alkenes

• Michio Yamada

Beilstein J. Org. Chem. 2024, 20, 125–154, doi:10.3762/bjoc.20.13

• ) reactions involving diverse electron-rich alkynes and electron-deficient alkenes. In this review, a comprehensive investigation of the recent and noteworthy advancements in the research on push–pull chromophores prepared via the [2 + 2] CA–RE reaction is conducted. In particular, an overview of the

• optoelectronics) [1][2]. The synthesis of push–pull chromophores is often achieved through click-type reactions between electron-rich alkynes and electron-deficient alkenes, which is a reliable and atom-economical method. Diverse chromophores can be obtained via this method, depending upon the choice of alkynes

• and alkenes. The pioneering work by Bruce et al. in 1981 revealed that the cleavage of tetracyanoethylene (TCNE) under mild conditions via its reaction with metal acetylides yields metal complexes featuring the tetracyanobuta-1,3-diene (TCBD) structural motif [3]. Subsequently, numerous researchers

Synthetic approach to 2-alkyl-4-quinolones and 2-alkyl-4-quinolone-3-carboxamides based on common β-keto amide precursors

• Yordanka Mollova-Sapundzhieva,
• Plamen Angelov,
• Danail Georgiev and
• Pavel Yanev

Beilstein J. Org. Chem. 2023, 19, 1804–1810, doi:10.3762/bjoc.19.132

• -mediated domino reaction of chromone-3-carboxaldehydes and amines [41], Pd-catalyzed redox-neutral C–N coupling reaction of iminoquinones with electron-deficient alkenes [42], NH3 insertion into o‑haloarylynones [43], gold(III)-catalyzed azide-yne cyclization [44], Michael/Truce-Smiles rearrangement

Recent advancements in iodide/phosphine-mediated photoredox radical reactions

• Tinglan Liu,
• Yu Zhou,
• Junhong Tang and
• Chengming Wang

Beilstein J. Org. Chem. 2023, 19, 1785–1803, doi:10.3762/bjoc.19.131

• urgent need to develop diverse monofluoromethylation methods. In this context, Chen and his colleagues recently developed a concise photocatalytic procedure for achieving monofluoromethylation, as well as di- and trifluoromethylation of various alkenes (Scheme 25) [50]. The synthetic method also

• and γ,σ-unsaturated N-(acyloxy)phthalimides. Proposed mechanism for the decarboxylative [3 + 2]/[4 + 2] annulation. Decarboxylative cascade annulation of alkenes/1,6-enynes with N-hydroxyphthalimide esters. Decarboxylative radical cascade cyclization of N-arylacrylamides. NaI/PPh3-driven

Decarboxylative 1,3-dipolar cycloaddition of amino acids for the synthesis of heterocyclic compounds

• Xiaofeng Zhang,
• Xiaoming Ma and
• Wei Zhang

Beilstein J. Org. Chem. 2023, 19, 1677–1693, doi:10.3762/bjoc.19.123

• anionic charge on the α-carbon connecting to the EWG. They are popular AMYs for 1,3-diploar [3 + 2] cycloaddition reactions with alkenes to generate pyrrolidines 1a–d with high regio- and stereoselectivities. They have been reported in a huge number (1,000+) of publications [18][19][20][21][22][23][24][25

• ][56][57][58]. The [3 + 2] cycloadditions of AMYs B1–B4 with alkenes lead to the formation of cycloaddition products 3a–d with attenuated regio- and stereoselectivity, since the Ar group is not strong enough to fully localize the negative charge on the carbon connecting to Ar in the 1,3-dipoles. Both

• ][50][51]. However, to the best of our knowledge, there are only few examples on the reactions of N–H-type semi-stabilized AMYs B3 or B4 which were either derived from special carbonyl compounds (such as isatin) [52][53][54][55] or the AMYs were reacted with uncommon alkenes as the 1,3-dipolarophiles

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• reactivity than electron-withdrawing groups, and the thiolation occurred mainly at the para position to the hydroxy group in phenols. In 2016, the azidoarylthiation of various alkenes 9 by trimethylsilyl azide (10) and N-(organothio)succinimide 1 to the corresponding products containing ortho-sited azide and

• chlorinated product 21 was detected, which with POCl3 gave the cyclized product 22. Also, the synthesis of benzo[b]thieno[2,3-c]quinolone 24 as an anticancer molecule was demonstrated in this approach (Scheme 13). An intermolecular sulfenoamination of alkenes 9 with sulfonamides 25 as the nitrogen source and

• N-thiosuccinimides 1 as the sulfur source was reported by Gao and Liu et al. (Scheme 14) [52]. Highly regio- and diastereoselective β-sulfonylamino sulfides 26 were obtained from alkenes 9, N-thiosuccinimides 1, and sulfonamides 25 in the presence of 20 mol % BF3·Et2O. While the transformation in

Cyclization of 1-aryl-4,4,4-trichlorobut-2-en-1-ones into 3-trichloromethylindan-1-ones in triflic acid

• Vladislav A. Sokolov,
• Andrei A. Golushko,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2023, 19, 1460–1470, doi:10.3762/bjoc.19.105

• ). The second protonation of the C=C bond is hampered due to a strong acceptor character of the substituents, contrary to other more donating enones. As a continuation of the research on the electrophilic activation of electron-poor alkenes bearing two electron-withdrawing substituents at the C=C bond

α-(Aminomethyl)acrylates as acceptors in radical–polar crossover 1,4-additions of dialkylzincs: insights into enolate formation and trapping

• Angel Palillero-Cisneros,
• Paola G. Gordillo-Guerra,
• Fernando García-Alvarez,
• Olivier Jackowski,
• Franck Ferreira,
• Fabrice Chemla,
• Joel L. Terán and
• Alejandro Perez-Luna

Beilstein J. Org. Chem. 2023, 19, 1443–1451, doi:10.3762/bjoc.19.103

• wherein the intermediate enoxyl radical II arising from the addition step evolves via intramolecular addition to tethered alkenes [16][17] or alkynes [18]. We wondered if, in the absence of the pending radical acceptor, the presence of the β-nitrogen atom could nevertheless promote zinc enolate formation

Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in organic synthesis: a review

• Nosheen Beig,
• Varsha Goyal and
• Raj K. Bansal

Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102

• aziridination of alkenes was also investigated [32]. Cazin and co-workers reported the preparation of linear neutral NHC–CuCl complexes from the reaction of imidazolium and imidazolinium chlorides with Cu2O. Initially, dichloromethane was used as the solvent. However, except in the case of IMes and SIPr, the

• alkynes with silanes/t-BuOH and HBP, respectively. The Cu(I) complexes of five-, six-, and seven-membered NHCs were prepared through protonolysis of NHC–CuMes with t-BuOH (Scheme 63). Increasing the size of the heterocyclic ring was accompanied by higher selectivity to give mainly (Z)-alkenes and α

• improvement in the enantiomeric purity of the product (>98% conv., 85.5:14.5 er) was achieved while using the naphthyl-substituted salt 163 (Scheme 64). Besides, a highly enantioselective catalytic hydroboration could be achieved from several exocyclic 1,1-disubstituted alkenes 164; in this transformation

Non-noble metal-catalyzed cross-dehydrogenation coupling (CDC) involving ether α-C(sp³)–H to construct C–C bonds

• Hui Yu and
• Feng Xu

Beilstein J. Org. Chem. 2023, 19, 1259–1288, doi:10.3762/bjoc.19.94

• alkylation of S,S-functionalized internal olefins was achieved by a C(sp2)–H/C(sp3)–H cross-coupling reaction using DTBP as oxidant and DABCO·6H2O as an additive in the presence of FeCl3 (Scheme 22) [83]. The reaction provides a convenient route to tetrasubstituted alkenes and proceeds via a typical radical

• -catalyzed CDC reaction of N-methylaniline with ethers. Fe-catalyzed CDC of C(sp3)–H/C(sp3)–H bonds. Fe-catalyzed hydroalkylation of α,β-unsaturated ketones with ethers. Solvent-free Fe(NO3)3-catalyzed CDC of C(sp3)–H/C(sp2)–H bonds. Alkylation of disulfide compounds to afford tetrasubstituted alkenes. Fe

Radical ligand transfer: a general strategy for radical functionalization

• David T. Nemoto Jr,
• Kang-Jie Bian,
• Shih-Chieh Kao and
• Julian G. West

Beilstein J. Org. Chem. 2023, 19, 1225–1233, doi:10.3762/bjoc.19.90

• achieved (Scheme 1), showing that photolysis of stoichiometric Cu(II) chloride in the presence of unactivated alkenes allows for direct formation of vicinal dichloride products. The mechanistic study implicated initial formation of a chlorine radical through homolysis of a Cu–Cl bond via ligand-to-metal

• addition to alkenes and radical decarboxylation, with many of these being driven by light energy. RLT in alkene functionalization Outside of the realm of C–H activation, RLT has been leveraged to afford complex medicinal scaffolds in alkene difunctionalization. A recent example can be found in the merger

• paradigm with photocatalytic ATRA to enable the modular difunctionalization of alkenes under reagent control (Scheme 3). In Stephenson’s photocatalytic ATRA reports, the C–X bond in the product was proposed to be formed through both direct quenching of a transient alkyl radical by halogen atom transfer

Exploring the role of halogen bonding in iodonium ylides: insights into unexpected reactivity and reaction control

• Carlee A. Montgomery and
• Graham K. Murphy

Beilstein J. Org. Chem. 2023, 19, 1171–1190, doi:10.3762/bjoc.19.86

• had occurred, which was attributed to halogen bond complex formation. In 2019, the Murphy group reported the first transformation induced by blue LED irradiation of cyclic and acyclic iodonium ylides (e.g., 6) and alkenes, which generated cyclopropanes 40 in yields up to 96% (Scheme 8) [125]. UV–vis

• EDA complexes between alkenes and iodonium ylides with blue light was believed to induce intramolecular iodocyclobutane formation, followed by cyclopropane formation. These reactions were believed to either involve 1,2-diradicals on the ylide, which could engage the complexed alkene, or to involve

• and Hadjiarapoglou for the cyclization of 6 with diphenylketene. Proposed mechanism for the formation of 33a from iodonium ylides and amines, involving an initial halogen bonded EDA complex 36. Proposed mechanism of the cyclopropanation between iodonium ylides and alkenes under blue LED irradiation

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

• hydroarylation of tert-butyl vinylcarbamate and unactivated alkenes like 1-octene and 3-buten-1-ol although the vinyl carbamate substrate (Epred = −2.2 V vs SCE) is significantly easier to reduce than most aryl chlorides. This selectivity, especially considering the need for an excess of the vinyl carbamate

• (ATRA) reactions with alkenes [92]. Since the ATRA mechanism involves radical chain propagation, minimal loadings of the PDI (0.05 mol %) could be employed as an initiator together with a sub-stoichiometric amount of sodium ascorbate for reductive quenching of PDI to generate PDI•−. While terminal

• pathways, respectively (Figure 20A). Both protocols were able to successfully engage perfluoroalkyl iodides and bromotrichloromethane in combination with a diverse scope of alkenes and alkynes (Figure 20B). Products of terminal alkenes and alkynes were generally obtained in good to excellent yields while

Copper-catalyzed N-arylation of amines with aryliodonium ylides in water

• Kasturi U. Nabar,
• Bhalchandra M. Bhanage and
• Sudam G. Dawande

Beilstein J. Org. Chem. 2023, 19, 1008–1014, doi:10.3762/bjoc.19.76

• , catalyzed by a copper catalyst [39]. Murphy and co-workers reported blue LED-mediated metal-free cyclopropanation of alkenes with iodonium ylides through a diradical intermediate [40]. However, iodonium ylides are relatively unexplored for the arylation of amines. So far only Spyroudis’s group reported N

Synthesis of tetrahydrofuro[3,2-c]pyridines via Pictet–Spengler reaction

• Elena Y. Mendogralo and
• Maxim G. Uchuskin

Beilstein J. Org. Chem. 2023, 19, 991–997, doi:10.3762/bjoc.19.74

• the use of 3-substituted furans. For example, the intramolecular Friedel–Crafts alkylation reaction (Scheme 1a) of alcohols [9][10][11], alkenes [12] or acetylenes [13] affords the desired tetrahydrofuro[3,2-c]pyridines. A related method is based on a Au(I)-catalyzed domino sequence dearomatization

• ][18] was described (Scheme 1c). The most studied variation of this cyclization is based on the generation of an acyliminium cation from the corresponding alcohols [19][20][21][22][23] or alkenes [24][25][26][27][28][29], subsequent attack of furan ring and the formation of annulated tetrahydrofuro[3,2

The unique reactivity of 5,6-unsubstituted 1,4-dihydropyridine in the Huisgen 1,4-diploar cycloaddition and formal [2 + 2] cycloaddition

• Xiu-Yu Chen,
• Hui Zheng,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 982–990, doi:10.3762/bjoc.19.73

• ; isoquinolino[1,2-f][1,6]naphthyridine; Introduction Among various well-known cycloaddition reactions such as the 1,3-dipolar cycloaddition reaction, Diels–Alder reaction, and the Povarov reaction, the cycloaddition reaction of Huisgen 1,4-dipoles with activated alkenes received increasing attention [1][2][3

• ][59][60][61][62][63][64], herein, we wish to report the use of 5,6-unsubstituted 1,4-dihydropyridines as electron-deficient alkenes in the Huisgen 1,4-diploar cycloaddition and as electron-rich alkenes in formal [2 + 2] cycloadditions for the efficient synthesis of isoquinolino[1,2-f][1,6

Synthesis of aliphatic nitriles from cyclobutanone oxime mediated by sulfuryl fluoride (SO₂F₂)

• Xian-Lin Chen and
• Hua-Li Qin

Beilstein J. Org. Chem. 2023, 19, 901–908, doi:10.3762/bjoc.19.68

• Xian-Lin Chen Hua-Li Qin School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, 205 Luoshi Road, Wuhan, 430070, PR China 10.3762/bjoc.19.68 Abstract A SO2F2-mediated ring-opening cross-coupling of cyclobutanone oxime derivatives with alkenes was developed for

• esters and adopted the pre-acylation activation strategies [39][40][41]. Up to now, only one report employed an oxime for the generation of iminyl radicals to obtain the similar products, in which, substrates were limited to the electron-rich alkenes (Scheme 2b) [42]. On the other hand, sulfuryl fluoride

• possessing representative functional groups was employed subsequently to evaluate the reaction scope and limitations (Scheme 3). Under the optimized conditions, alkenes 2b–e with varying steric effects underwent smooth reaction, yielding the corresponding products 3ab–ae in moderate to good yields (56–68

First synthesis of acylated nitrocyclopropanes

• Kento Iwai,
• Rikiya Kamidate,
• Khimiya Wada,
• Haruyasu Asahara and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2023, 19, 892–900, doi:10.3762/bjoc.19.67

• ). These structural features enable the construction of a five-membered ring upon treatment with alkenes [9], diazo compounds (reaction g) [10], and nitriles [11]. Several approaches are available for the synthesis of cyclopropanedicarboxylates 1a, which consist of three steps: 1) conjugate addition, 2