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

• partners. The scope of the protocol was further expanded to a radical cyclization/aminocarbonylation cascade reaction yielding the bis-carbonylated α-keto amide 26h in 31% yield. 2.1.2 C(sp3)–X activation: The generation of alkyl radicals using alkyl halides as precursors proves very challenging due their

Photoredox catalysis enabling decarboxylative radical cyclization of γ,γ-dimethylallyltryptophan (DMAT) derivatives: formal synthesis of 6,7-secoagroclavine

• Alessio Regni,
• Francesca Bartoccini and
• Giovanni Piersanti

Beilstein J. Org. Chem. 2023, 19, 918–927, doi:10.3762/bjoc.19.70

• common synthetic route to ergot alkaloids, providing an advantageous synthetic method for this class of natural products. Further studies on the utility of the decarboxylative radical cyclization and their applications are currently being investigated in our laboratory. (a) Transformations of DMAT to

Synthesis of medium and large phostams, phostones, and phostines

• Jiaxi Xu

Beilstein J. Org. Chem. 2023, 19, 687–699, doi:10.3762/bjoc.19.50

• refluxing acetonitrile for 6 h. It underwent a radical cyclization in refluxing benzene for 20 h to give rise to a nine-membered phostone thieno[2,3-d]pyrimidine-fused 2-hydroxy-1,2-oxaphosphonane 2-oxide 46 as a potential inhibitor after the deprotection of the benzyl group in the presence of DABCO in

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

• construction of the 8-membered ring from an appropriate cyclopentane precursor. The proposed strategies include metathesis, Nozaki–Hiyama–Kishi (NHK) cyclization, Pd-mediated cyclization, radical cyclization, Pauson–Khand reaction, Lewis acid-promoted cyclization, rearrangement, cycloaddition and biocatalysis

• precursor. The proposed strategies include metathesis, Nozaki–Hiyama–Kishi (NHK) cyclization, Pd-mediated cyclization, radical cyclization (including SmI2), Pauson–Khand reaction, Lewis acid-promoted cyclization, rearrangement, cycloaddition, and biocatalysis. In particular, the purpose will focus on the

• by a vinyl ketone (compound 135) or a butenolide (compound 137) moiety dramatically influenced the outcome of the reaction and no cycloadduct was observed in both cases (Scheme 27). 4 Radical cyclization (including SmI2) Introduced by Kagan more than four decades ago, samarium diiodide (SmI2) has

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• polyene 14 (prepared in two steps) in multigram quantities [23]. The reaction employed a divided cell with substoichiometric amounts of magnesium(II) acetate (0.5 equiv) and catalytic copper(II) 3,5-diisopropylsalicylate (0.02 equiv) to allow the redox radical cyclization of polyene in 42% yield. A Tsuji

• and the aromatic moieties present in these natural products and provided the common synthetic intermediate 70 (Scheme 6). The diverse tetracycles were accessed either via an intramolecular radical cyclization of the reduced congener 73 or through a Heck reaction of intermediate 71. Reaction of 73 with

• cyclization (using Bu3SnH and AIBN) [46], led to the construction of the key bicyclo[3.2.1]octene carbocyclic core of jungermatrobrunin, which was further elaborated to 87 in up to 61% yield, after alkene cleavage by OsO4 and NaIO4. The described reductive radical cyclization can be scaled up to 2 g without

Total synthesis of grayanane natural products

• Nicolas Fay,
• Rémi Blieck,
• Cyrille Kouklovsky and
• Aurélien de la Torre

Beilstein J. Org. Chem. 2022, 18, 1707–1719, doi:10.3762/bjoc.18.181

• , obtaining excellent selectivity in all cases. Alternatively, the same year, the authors published a vinyl radical cyclization occurring in presence of n-Bu3SnH, providing a stereoselective access to the bicyclo[3.2.1]octane unit corresponding to the CD rings [25]. Newhouse’s synthesis of principinol D In

• [3.2.1]octane 67 was achieved by a radical cyclization using n-Bu3SnH in refluxing toluene. A sequence involving an ester reduction, Ley–Griffith oxidation and Seyferth–Gilbert homologation with Bestmann–Ohira reagent allowed to obtain the alkynyl bicylo[3.2.1]octane 69. On the other hand, the five

• radical cyclization of an alkynyl ketone as the key step. The synthesis started by a Cu-catalyzed conjugate addition of the vinyl Grignard reagent, followed by TMS α-propargylation under basic conditions, affording the TMS-alkynyl ketone 76 as the major diastereomer (Scheme 11). Originally a Au-catalyzed

Polymer and small molecule mechanochemistry: closer than ever

• José G. Hernández

Beilstein J. Org. Chem. 2022, 18, 1225–1235, doi:10.3762/bjoc.18.128

• a collision between the ball and a particle of a chitin sample and (b) mechanical treatment of a particle of a lignin sample in a ring-and-puck mill. (a) Ultrasound-induced ATRP using piezoelectric BaTiO3 and (b) mechanochemical atom transfer radical cyclization (ATRC) using BaTiO3 by ball milling

Synthesis of piperidine and pyrrolidine derivatives by electroreductive cyclization of imine with terminal dihaloalkanes in a flow microreactor

• Yuki Naito,
• Naoki Shida and
• Mahito Atobe

Beilstein J. Org. Chem. 2022, 18, 350–359, doi:10.3762/bjoc.18.39

• ]. Conventional synthetic methods for piperidine derivatives include nucleophilic substitution (route (1) in Scheme 1), reductive amination (route (2)), intramolecular cyclization of amines and alkenes (route (3)), the Diels–Alder reaction and subsequent reduction (route (4)), and the radical cyclization reaction

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• [56][57][58]. The authors investigated the effect of alkenyl substitution on the reaction to better understand mechanistic details. On inspection of the results, it is clear the radical cyclization pathway precedes the cross-coupling pathway. Moreover, no dehalogenation or β-hydride elimination

• ]. The group expanded the reaction to include 1,6-dienes 24 leading to 25 via the formation of three C–C bonds through a radical cyclization/arylation cascade, like that reported by Kang et al. (Scheme 3). The authors hypothesized the alkyl halide could react with aryl iron species 27 to form the alkyl

• , including kinetic isotope effects and radical trapping, suggested a radical mechanism. The hydroperoxide, in the presence of an iron catalyst, abstracts the hydrogen atom alpha to the heteroatom. The alkyl radical may attack the acrylamide; subsequent intramolecular radical cyclization with the aryl ring

Synthesis of highly substituted fluorenones via metal-free TBHP-promoted oxidative cyclization of 2-(aminomethyl)biphenyls. Application to the total synthesis of nobilone

• Ilya A. P. Jourjine,
• Lukas Zeisel,
• Jürgen Krauß and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2668–2679, doi:10.3762/bjoc.17.181

• gives only a low cyclization yield (Table 1, entry 12). It is unclear, if water is directly involved with this mechanism, but studies indicate that water may lower the activation barrier for the radical cyclization owing to its solvent effect, as has been previously reported for the radical synthesis of

• , TBHP-mediated radical cyclization is applicable to a wide variety of primary and secondary benzylamines bearing electron-donating and electron-withdrawing groups to synthesize fluorenones in poor to good yields, and utilized this method for the first total synthesis of the fluorenone natural product

Recent advances in the syntheses of anthracene derivatives

• Giovanni S. Baviera and
• Paulo M. Donate

Beilstein J. Org. Chem. 2021, 17, 2028–2050, doi:10.3762/bjoc.17.131

• sequential modifications [30], photocyclization of divinylterphenyl derivatives [31], tandem radical cyclization of (Z,Z)-1,4-bis(2-iodostyryl)benzene derivatives [32], and ring-closing olefin metathesis of tetravinylterphenyls [33] as the best-known synthetic routes. Herein, we have classified the synthetic

Free-radical cyclization approach to polyheterocycles containing pyrrole and pyridine rings

• Ivan P. Mosiagin,
• Olesya A. Tomashenko,
• Dar’ya V. Spiridonova,
• Mikhail S. Novikov,
• Sergey P. Tunik and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2021, 17, 1490–1498, doi:10.3762/bjoc.17.105

• skeletons that are inaccessible via Pd-catalyzed cyclization. Keywords: arylation; pyridine; pyrrole; radical cyclization; tris(trimethylsilyl)silane; Introduction Polycyclic heteroaromatic molecules, which have a tunable electronic structure and excellent self-assembling properties, are highly desirable

• , attempts to assemble this framework using Pd-catalyzed intramolecular arylation of compounds C' (X = Br, I) failed [17]. In this work, we report an effective method for the assembly of pyrido[2,1-a]pyrrolo[3,4-c]isoquinoline and related frameworks via a free radical cyclization of pyrrolylpyridinium salts

• . Results and Discussion Although the intramolecular free-radical cyclization is widely used for the synthesis of heteroaromatic compounds [23][24][25][26], only a few examples of the successful use of radical cyclization for the synthesis of pyrrole-containing fused heteroaromatics are known in the

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