α,γ-Dioxygenated amides via tandem Brook rearrangement/radical oxygenation reactions and their application to syntheses of γ-lactams

• Mikhail K. Klychnikov,
• Radek Pohl,
• Ivana Císařová and
• Ullrich Jahn

Beilstein J. Org. Chem. 2021, 17, 688–704, doi:10.3762/bjoc.17.58

• defined combinations of chiral epoxides and chiral amides. This represents a very rare example of an oxidative geminal C–C/C–O difunctionalization next to carbonyl groups. The resulting dioxygenated allylic amides are subsequently subjected to persistent radical effect-based 5-exo-trig radical cyclization

• thermal radical cyclization reactions according to the persistent radical effect [79][80] forming functionalized cyclopentanes 6 (Scheme 1B). Based on this sequence various other reaction pathways can be envisaged. Among them we hypothesized that the nucleophilic ring opening of simple epoxides 7 by N

• results indicate negligible asymmetric inductions from the chiral centers, both at the exocyclic hydroxy substituent in the C3 side chain (Table 3, entry 8) and/or of the 1-arylethyl group during the radical cyclization under the reaction conditions (Table 3, entries 9–11). The size of the arylethyl

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• -difluorocyclopropanecarboxylic acid derivatives 58 by the Michael addition of ester and amide enolates to 2,4,6-trimethylphenyl 4-bromo-4,4-difluorocrotonate (57) followed by an Et3B-initiated radical cyclization (Scheme 24) [68]. Furthermore, when the sodium salt of dimethyl malonate was used as the Michael donor the

• isomeric methylenecyclobutane derivatives 102 and 103 by a radical cyclization (Scheme 47). The minor product 102 underwent a fast rearrangement to produce the major product 103. An alternative pathway, that involved the cleavage of the C4–C5 bond in 101, also led to the product 103. 2.2 Ring opening of

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

• catalytic amount of tributylstannane [40] led to a radical cyclization, in which the resultant alkyl radical formed was trapped by AIBN to give a proposed nitrogen-centered radical 70. An 1,4-hydrogen abstraction of the nitrogen-centered radical on 70 produced carbon-centered radical 71, which underwent

• authors mentioned that the employment of the previously reported conditions for the radical cyclization in the synthesis of marcfortine B (8) led to the decomposition of the starting material. It was suggested that the MOM group of 80 may contribute to undesired side reactions. Synthesis of marcfortine C

• -membered carbocycles. These reactions have been applied successfully in the synthesis of complex natural products. In 2011, Curran and co-workers reported the synthesis of meloscine (158) featuring a tandem radical cyclization of a divinylcyclopropane [70] (Scheme 13A). Slow addition of tributylstannane

A complementary approach to conjugated N-acyliminium formation through photoredox-catalyzed intermolecular radical addition to allenamides and allencarbamates

• Olusesan K. Koleoso,
• Matthew Turner,
• Felix Plasser and
• Marc C. Kimber

Beilstein J. Org. Chem. 2020, 16, 1983–1990, doi:10.3762/bjoc.16.165

• radical cyclization of allenamides have been reported by Hsung and co-workers, where the radical adds principally to the central carbon of the allene (10) [45]; and (iii) the photoredox-catalyzed addition of radicals to enamides reported by Masson [46][47][48][49], and more recently by our own laboratory

Metal-free synthesis of phosphinoylchroman-4-ones via a radical phosphinoylation–cyclization cascade mediated by K₂S₂O₈

• Qiang Liu,
• Weibang Lu,
• Guanqun Xie and
• Xiaoxia Wang

Beilstein J. Org. Chem. 2020, 16, 1974–1982, doi:10.3762/bjoc.16.164

• afforded the title compounds in moderate yields. Keywords: chroman-4-ones; diphenylphosphine oxide; metal-free; potassium persulfate; radical cyclization; Introduction The chroman-4-one framework is a privileged structural motif found in numerous natural products and pharmaceuticals with extraordinary

Photocatalyzed syntheses of phenanthrenes and their aza-analogues. A review

• Alessandra Del Tito,
• Havall Othman Abdulla,
• Davide Ravelli,
• Stefano Protti and
• Maurizio Fagnoni

Beilstein J. Org. Chem. 2020, 16, 1476–1488, doi:10.3762/bjoc.16.123

• 10.1a–e generated the corresponding imidoyl radicals 10.2·a–e that, upon intramolecular radical cyclization, afforded 6-(trifluoromethyl)phenanthridines 10.3a–e in very good yields [72]. A complementary approach in the synthesis of 6-arylphenanthridines started from N-(2-aminoaryl)benzoimine 11.1 and

• quenching of the excited photocatalyst, in turn triggering the formation of radicals 12.2·a–d. These smoothly underwent radical cyclization to give the corresponding methyl 5,6-dihydrophenanthridine-6-carboxylates and then the desired phenanthridine 6-carboxylates 12.3a–d in good yields. Noteworthy, the

• derivatives 3.3a–d upon rearomatization. Notably, the process offers a wide substrate scope and the products are obtained with complete regioselectivity [43]. 2 Synthesis of phenanthridines or related azaarenes Under photocatalyzed conditions, phenanthridines are mostly obtained via an intramolecular radical

An overview on disulfide-catalyzed and -cocatalyzed photoreactions

• Yeersen Patehebieke

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

• -substituted cation 19 favors the radical cyclization path because the stabilization by an α-substituent makes its cation center more stable and less reactive. In contrast, the non-α-substituted cation 19 prefers the cationic cyclization. However, the two cyclization processes form the intermediates 20 and 21

• -ylidene·borane (diMe–Imd–BH3) as the initiator [20]. Thiyl radicals formed by diphenyl disulfide under light can further generate the active HAT catalyst thiophenol in situ. The yield of the reductive dehalogenation or dehalogenative radical cyclization could reach up to 40–98% (Scheme 14). The introduction of

• compounds. Disulfide-catalyzed oxidation of allyl alcohols. Disulfide-catalyzed diboration of alkynes. Dehalogenative radical cyclization catalyzed by disulfide. Hydrodifluoroacetamidation of alkenes catalyzed by disulfide. Plausible mechanism of the hydrodifluoroacetamidation of alkenes catalyzed by

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

• started to develop extensively only after 2010. The oxidation of β,γ- and γ,δ-unsaturated oximes (103 and 104, respectively) using the TEMPO/DEAD system or only DEAD (diethyl azodicarboxylate) afforded 5-exo-trig radical cyclization [124] with the formation of the corresponding isoxazolines 105 and 106 or

Photocatalysis with organic dyes: facile access to reactive intermediates for synthesis

• Stephanie G. E. Amos,
• Marion Garreau,
• Luca Buzzetti and
• Jerome Waser

Beilstein J. Org. Chem. 2020, 16, 1163–1187, doi:10.3762/bjoc.16.103

• oxidation of 29.1 was achieved using Mes-Acr-Me+ (OD2) and a cobalt cocatalyst, ensuring an efficient dehydrogenation. Various N-heterocycles 29.3 were accessed via a radical cyclization cascade with the alkyne derivatives 29.2. Amidyl radical generation The oxidation of amides is more difficult compared to

Cascade trifluoromethylthiolation and cyclization of N-[(3-aryl)propioloyl]indoles

• Ming-Xi Bi,
• Shuai Liu,
• Yangen Huang,
• Xiu-Hua Xu and
• Feng-Ling Qing

Beilstein J. Org. Chem. 2020, 16, 657–662, doi:10.3762/bjoc.16.62

• strategy in the synthesis of a series of CH2SCF3-substituted heterocycles. For the construction of SCF3-substituted cyclic compounds, normally proper alkynes are chosen as the substrates for cascade reactions [28][29][30][31][32]. In 2015, Wang developed an oxidative radical cyclization of aryl alkynoate

Visible-light-induced addition of carboxymethanide to styrene from monochloroacetic acid

• Kaj M. van Vliet,
• Nicole S. van Leeuwen,
• Albert M. Brouwer and
• Bas de Bruin

Beilstein J. Org. Chem. 2020, 16, 398–408, doi:10.3762/bjoc.16.38

• useful for the formation of new C–C bonds. Previous works from our group presented cobalt-catalyzed radical cyclization and carbonylation reactions [12][13][14][15][16]. Photoredox catalysis provides a way to generate radical intermediates from simple organic molecules by single-electron redox processes

Bacterial terpene biosynthesis: challenges and opportunities for pathway engineering

• Eric J. N. Helfrich,
• Geng-Min Lin,
• Christopher A. Voigt and
• Jon Clardy

Beilstein J. Org. Chem. 2019, 15, 2889–2906, doi:10.3762/bjoc.15.283

• analogy to nature’s biosynthetic strategies outlined above, cationic, Diels–Alder, oxidative, and radical cyclization strategies have been successfully applied in total syntheses of terpenoids [53]. In addition, chemists are currently creatively exploring means to mimic classical terpene cyclases and

A review of the total syntheses of triptolide

• Xiang Zhang,
• Zaozao Xiao and
• Hongtao Xu

Beilstein J. Org. Chem. 2019, 15, 1984–1995, doi:10.3762/bjoc.15.194

• 88. Ester exchange of 88 with (+)-8-phenylmenthol gave the key cyclization precursor 16. Oxidative radical cyclization of 16 in the presence of Mn(OAc)3 and Yb(OTf)3·H2O afforded the major tricyclic diastereomer 89 (dr = 38:1). Then the construction of the unsaturated lactone was performed by

A diastereoselective approach to axially chiral biaryls via electrochemically enabled cyclization cascade

• Hong Yan,
• Zhong-Yi Mao,
• Zhong-Wei Hou,
• Jinshuai Song and
• Hai-Chao Xu

Beilstein J. Org. Chem. 2019, 15, 795–800, doi:10.3762/bjoc.15.76

• Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou 450001, People’s Republic of China 10.3762/bjoc.15.76 Abstract A diastereoselective approach to axially chiral imidazopyridine-containing biaryls has been developed. The reactions proceed through a radical cyclization cascade to construct

• ] have studied the reactions of electrochemically generated NCRs. Particularly, we have recently reported an electrochemical synthesis of imidazo-fused N-heteroaromatic compounds via a radical cyclization cascade [31]. Building on this work, we report herein an atroposelective synthesis of

• for the electrochemical synthesis of 3a. Computation investigation on the vinyl radical cyclization. DFT (M06-2X/6-31G*) calculated energetics (kcal mol−1) are Gibbs free energies in MeCN. Investigation on the effects of substituents on the diastereoselectivity.a Supporting Information Supporting

Dirhodium(II)-catalyzed [3 + 2] cycloaddition of N-arylaminocyclopropane with alkyne derivatives

• Wentong Liu,
• Yi Kuang,
• Zhifan Wang,
• Jin Zhu and
• Yuanhua Wang

Beilstein J. Org. Chem. 2019, 15, 542–550, doi:10.3762/bjoc.15.48

• generated distonic radical cation can be further trapped by an alkene, alkyne, or triplet oxygen to initiate radical cyclization (Scheme 1) [7][8][9][10][11][12][13][14][15]. Thus, as key synthons, this class of molecules may play an important role in organic synthesis during construction of a series of

Oxidative radical ring-opening/cyclization of cyclopropane derivatives

• Yu Liu,
• Qiao-Lin Wang,
• Zan Chen,
• Cong-Shan Zhou,
• Bi-Quan Xiong,
• Pan-Liang Zhang,
• Chang-An Yang and
• Quan Zhou

Beilstein J. Org. Chem. 2019, 15, 256–278, doi:10.3762/bjoc.15.23

• transformation. In 2017, Reddy and co-workers reported the first radical cyclization of propiolamides (131 and 133) with cyclopropanols 91 for the synthesis of azaspiro[4.5]deca-3,6,9-triene-2,8-diones 132 and 6,7-dihydro-3H-pyrrolo[2,1-j]quinoline-3,9(5H)-diones 134 (Scheme 35) [115]. Interestingly, this

• developed a novel ring-opening of cyclopropanols 91 with acrylamides 122 for the synthesis of oxindoles 123 (Scheme 30) [110]. A series of desired γ-carbonylalkyl-substituted oxindoles 123 were synthesized between N-phenyl acrylamides 122 and tertiary cyclopropanols 91 through Na2S2O8-promoted radical

• cyclization under transition-metal free conditions. With the addition of a radical scavenger such as TEMPO or BHT, the reaction was suppressed remarkably. In the same year, Dai’s group also reported the ring-opening-initiated tandem cyclization of cyclopropanols 91 with acrylamides 122 or 2-isocyanobiphenyls

Degenerative xanthate transfer to olefins under visible-light photocatalysis

• Atsushi Kaga,
• Xiangyang Wu,
• Joel Yi Jie Lim,
• Hirohito Hayashi,
• Yunpeng Lu,
• Edwin K. L. Yeow and
• Shunsuke Chiba

Beilstein J. Org. Chem. 2018, 14, 3047–3058, doi:10.3762/bjoc.14.283

• functionalized cyclopentane 3an and pyrrolidine 3ao, respectively, via 5-exo-trig radical cyclization (Table 2, entries 13 and 14). The present method was capable in functionalizing olefins 2p and 2q installed on steroid scaffolds with high efficiency (Table 2, entries 15 and 16). We next examined the reactions

Synthesis of spirocyclic scaffolds using hypervalent iodine reagents

• Fateh V. Singh,
• Priyanka B. Kole,
• Saeesh R. Mangaonkar and
• Samata E. Shetgaonkar

Beilstein J. Org. Chem. 2018, 14, 1778–1805, doi:10.3762/bjoc.14.152

• substrate for the synthesis of natural product (+)-biscarvacrol (157). Koag and Lee [140] reported the synthesis of a spiroketal by radical cyclization of a steroidal alkylamine in presence of PIDA (15) as oxidant and molecular iodine in dichloromethane at low temperature. It is an example of hypoiodite

• -mediated radical cyclization wherein the oxazaspiroketal moiety is formed which is further used as key intermediate for the synthesis of the natural product cephalostatin. Additionally, spiroketals 159 were also synthesised by enatioselective spirocyclization of ortho-substituted phenols 158 using similar

One-pot preparation of 4-aryl-3-bromocoumarins from 4-aryl-2-propynoic acids with diaryliodonium salts, TBAB, and Na₂S₂O₈

• Teppei Sasaki,
• Katsuhiko Moriyama and
• Hideo Togo

Beilstein J. Org. Chem. 2018, 14, 345–353, doi:10.3762/bjoc.14.22

• acid-catalyzed reaction of phenols and propynoic acids [22] and the (−)-riboflavin-catalyzed photochemical reaction of cinnamic acids [23] were reported recently. Moreover, the use of radical cyclization for the construction of the coumarin skeleton has become widespread. Examples include the radical

Conjugated nitrosoalkenes as Michael acceptors in carbon–carbon bond forming reactions: a review and perspective

• Yaroslav D. Boyko,
• Valentin S. Dorokhov,
• Alexey Yu. Sukhorukov and
• Sema L. Ioffe

Beilstein J. Org. Chem. 2017, 13, 2214–2234, doi:10.3762/bjoc.13.220

• addition of dicarbonyl compounds to a nitrosoalkene followed by a silver-mediated radical cyclization of the resulting oximes 6 to final isoxazolines 100. Importantly, the reaction is well-tolerated by various substituents both in halooxime and in dicarbonyl compounds producing isoxazolines 100 in moderate

Brønsted acid-mediated cyclization–dehydrosulfonylation/reduction sequences: An easy access to pyrazinoisoquinolines and pyridopyrazines

• Ramana Sreenivasa Rao and
• Chinnasamy Ramaraj Ramanathan

Beilstein J. Org. Chem. 2017, 13, 428–440, doi:10.3762/bjoc.13.46

• for the synthesis of many alkaloids (Figure 1) [16]. To synthesize pyrazinoisoquinoline and its derivatives, various approaches such as the Ugi multicomponent reaction [17] amidoalkylation [18][19], N-acyliminium ion cyclization [20] and a radical cyclization [21] have been reported. To this end

Cp₂TiCl/D₂O/Mn, a formidable reagent for the deuteration of organic compounds

• Antonio Rosales and
• Ignacio Rodríguez-García

Beilstein J. Org. Chem. 2016, 12, 1585–1589, doi:10.3762/bjoc.12.154

• epoxides [2][27][37], ozonides [29], ketones [31][32], activated halides [30][31][32], alkenes and alkynes [33]. Several examples are presented in Scheme 3. The results show that the combination Cp2TiCl/D2O/Mn is able to promote and/or catalyze deuteration of organic compounds by reduction or radical

• cyclization using reagents that are cheap, abundant and environmentally friendly. Certainly, this new methodology of deuteration will contribute to the synthesis of new deuterated organic compounds with applications as internal standards, pharmaceutical drugs and new materials, among others. Conclusion In

Cascade alkylarylation of substituted N-allylbenzamides for the construction of dihydroisoquinolin-1(2H)-ones and isoquinoline-1,3(2H,4H)-diones

• Ping Qian,
• Bingnan Du,
• Wei Jiao,
• Haibo Mei,
• Jianlin Han and
• Yi Pan

Beilstein J. Org. Chem. 2016, 12, 301–308, doi:10.3762/bjoc.12.32

• , these cascade radical cyclization reactions are of general use for the preparation of 4-alkyldihydroisoquinolin-1(2H)-one derivatives 5. The substrates bearing methyl, methoxy, halo and trifluoromethyl groups on the aromatic ring all worked well in the reaction, providing the target products with 31–65

• corresponding products (5ae1–5ae5) with 42% total yield. To extend the synthetic utility of this radical cyclization reaction, N-methacryloyl-N-methylbenzamide derivatives 6 were then tried as substrates for this reaction (Scheme 4). It should be mentioned that only a few radical precursors, such as the TMSCF3

• (Scheme 5c). This discloses that the cleavage of the C(sp3)−H bond to form the radical may be involved in the turnover-limiting steps of this procedure. Based on the previous radical cyclization reactions [44][47][48] and the results obtained above, a plausible mechanism accounting for this cascade

Synthesis of Xenia diterpenoids and related metabolites isolated from marine organisms

• Tatjana Huber,
• Lara Weisheit and
• Thomas Magauer

Beilstein J. Org. Chem. 2015, 11, 2521–2539, doi:10.3762/bjoc.11.273

• plumisclerin A by Pauson–Khand annulation and SmI2-mediated radical cyclization [59]. The xenicane-related diterpenoid (isolated from the same marine organism as xenicin 116) possesses a complex ring system that is proposed to be biosynthetically derived from the xenicin diterpenoid 116 by an intramolecular [2

Pyridinoacridine alkaloids of marine origin: NMR and MS spectral data, synthesis, biosynthesis and biological activity

• Louis P. Sandjo,
• Victor Kuete and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2015, 11, 1667–1699, doi:10.3762/bjoc.11.183

• by treating the binicotinic acid with methanol and sulfuric acid. The resulting product was transformed into a 2-haloanilide under Weinreb conditions, namely trimethylaluminium and 2-haloaniline. Subarine (37) was subsequently obtained from the radical cyclization of the haloanilide derivative in the