Carbonylative synthesis and functionalization of indoles

• Alex De Salvo,
• Raffaella Mancuso and
• Xiao-Feng Wu

Beilstein J. Org. Chem. 2024, 20, 973–1000, doi:10.3762/bjoc.20.87

• reductive elimination and the generated Pd(0) species gets oxidated by the oxygen to the active Pd(II) species (Scheme 7). Synthesis of indoles by metal-catalyzed reductive cyclization reaction of organic nitro compounds with carbon monoxide as reductant In the last 60 years, the metal-catalyzed

• determined by 1H NMR spectroscopy (Scheme 15). More recently, in 2016, still in Söderberg’s group, the synthesis of 2,2′-bi-1H-indoles, 2,3′-bi-1H-indoles, 3,3′-bi-1H-indoles, indolo[3,2-b]indoles, and indolo[2,3-b]indoles via reductive cyclization Pd-catalyzed was developed [36]. The reaction was possible

• -catalyzed reductive cyclization of 1,2-bis(2-nitrophenyl)ethene and 1,1-bis(2-nitrophenyl)ethene derivatives. Flow synthesis of 2-substituted indoles by reductive carbonylation. Pd-catalyzed synthesis of variously substituted 3H-indoles from nitrostyrenes by using Mo(CO)6 as CO source. Synthesis of indoles

Beyond n-dopants for organic semiconductors: use of bibenzo[d]imidazoles in UV-promoted dehalogenation reactions of organic halides

• Kan Tang,
• Megan R. Brown,
• Chad Risko,
• Melissa K. Gish,
• Garry Rumbles,
• Phuc H. Pham,
• Oana R. Luca,
• Stephen Barlow and
• Seth R. Marder

Beilstein J. Org. Chem. 2023, 19, 1912–1922, doi:10.3762/bjoc.19.142

• either dimerization of 2R• or by a second reduction of R• to R− (as invoked in the reductive cyclization of (2-halophenyl)propanoic esters [2]) which then acts as a nucleophile towards a second molecule of RX. However, addition of Me3SiCl to a photoirradiated BnBr/(N-DMBI)2 reaction mixture did not lead

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

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

• (Scheme 30). 4.3 Nickel-catalyzed reductive cyclization: mutilin and pleuromutilin C12-epimers access In view of maximizing the scope of accessible pleuromutilin epimers from one single synthetic pathway, Herzon’s group reported a modular and convergent route, where the eight-membered ring was built

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

• allowed the delivery of trans-decalin 85 in a gram-scale quantity. Birch reduction of the electron-rich aromatic ring, followed by propargylic addition and functional group interconversion (FGI) provided dienyne 86. Compound 86, under the previously developed radical reductive cyclization for 1,6-dienyne

• reduction of the amide using Wilkinson’s catalyst provided diastereoisomeric indole 131. Careful manipulation of the nitrile and alcohol side chains allowed selective cyclizations to the nitrogen atom of the indole core to conclude the total syntheses of 132–134. Samarium diiodide-mediated reductive

• cyclization of aldehyde 135, obtained also from 131, provided the pentacyclic core of (−)-strempeliopine (136) as a single diastereoisomer in 65% yield. Then, Barton’s radical deoxygenation resulted in the total synthesis of 136. Further, FGI of both diastereoisomers of 130 allowed the formal synthesis of

Rhodium-catalyzed intramolecular reductive aldol-type cyclization: Application for the synthesis of a chiral necic acid lactone

• Motoyuki Isoda,
• Kazuyuki Sato,
• Kenta Kameda,
• Kana Wakabayashi,
• Ryota Sato,
• Hideki Minami,
• Yukiko Karuo,
• Atsushi Tarui,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2022, 18, 1642–1648, doi:10.3762/bjoc.18.176

• development of a rhodium-catalyzed intramolecular reductive cyclization, we found that using [RhCl(cod)]2 improved the diastereomeric ratio of the products compared with other Rh catalysts. It seems that using [RhCl(cod)]2 leads to milder reaction conditions that lead to highly improved diastereomeric ratios

Tosylhydrazine-promoted self-conjugate reduction–Michael/aldol reaction of 3-phenacylideneoxindoles towards dispirocyclopentanebisoxindole derivatives

• Sayan Pramanik and
• Chhanda Mukhopadhyay

Beilstein J. Org. Chem. 2022, 18, 469–478, doi:10.3762/bjoc.18.49

• and operational simplicity through one pot reaction. Keywords: chemoselective conjugate reduction; dispirocyclopentanebisoxindole scaffolds; metal-free; one-pot operation; reductive cyclization; Introduction There is a vast demand of the structurally complex spirooxindole scaffold which is an

• the In(III)-catalyzed reductive cyclization of isatylidene malononitriles using the Hantzsch ester as reducing agent for the synthesis of dispirocyclopentanebisoxindole. Our work utilizes tosylhydrazine as chemoselective reducing agent for 3-phenacylideneoxindoles and thereafter base-catalyzed

• were well acted for this reductive cyclization, among the bases screening, Et3N was the most effective when employed with a particular solvent (Table 1). In order to improve the yield of the reaction we optimized the reaction temperature and it was found that the reaction at 60 °C gave a satisfying

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

• cyclization of the mono-substituted anion to provide the cyclization product 3a. In addition, the hydromonomeric product 4 was also formed as a byproduct. Although Degrand et al. [27] could successfully obtain the piperidine derivatives by this reductive cyclization; a toxic mercury pool cathode was used in

• derivative 3c was not obtained at all by the reductive cyclization of 1 and 2e. LSV experiments revealed that the reduction of 2e occurred at a slightly lower potential than the reduction of 1 (Supporting Information File 1, Figure S14). Therefore, in this case, the competitive reduction of 2e would inhibit

• American Chemical Society. This content is not subject to CC BY 4.0. Yield of 3a for each fraction sample in the continuous flow reductive cyclization. Conventional synthetic routes for piperidine derivatives. Synthesis of 1,2-diphenylpiperidine (3a) by the electroreductive cyclization mechanism. Effect of

Heterogeneous photocatalytic cyanomethylarylation of alkenes with acetonitrile: synthesis of diverse nitrogenous heterocyclic compounds

• Guanglong Pan,
• Qian Yang,
• Wentao Wang,
• Yurong Tang and
• Yunfei Cai

Beilstein J. Org. Chem. 2021, 17, 1171–1180, doi:10.3762/bjoc.17.89

• in 41% yield (Scheme 6c). Furthermore, the tricyclic indoline 14, a structural motif in diverse natural products [4], could be obtained in 60% yield through a reductive cyclization reaction (Scheme 6d). To investigate the mechanism of the cyanomethylarylation of alkenes, a series of control

Synthesis and characterization of S,N-heterotetracenes

• Astrid Vogt,
• Florian Henne,
• Christoph Wetzel,
• Elena Mena-Osteritz and
• Peter Bäuerle

Beilstein J. Org. Chem. 2020, 16, 2636–2644, doi:10.3762/bjoc.16.214

• derivatives by Cadogan reaction of nitro-substituted precursors. Another possibility for the preparation of fused pyrrole rings is established by the Cadogan reaction [40]. Well-known examples are the reductive cyclization of 2-nitro-1,1’-biphenyls with triethyl phosphite or phosphanes as reducing agent to

• -heterotetracenes and related derivatives from nitro-substituted thiophene-based precursors. First of all, the reductive cyclization of nitrothienyl-substituted thienothiophene 16 to H-SN4 13 was investigated. For this purpose, 2-stannylthienothiophene 14, which was obtained from thienothiophene 1, was converted in

Convenient access to pyrrolidin-3-ylphosphonic acids and tetrahydro-2H-pyran-3-ylphosphonates with multiple contiguous stereocenters from nonracemic adducts of a Ni(II)-catalyzed Michael reaction

• Alexander N. Reznikov,
• Dmitry S. Nikerov,
• Anastasiya E. Sibiryakova,
• Victor B. Rybakov,
• Evgeniy V. Golovin and
• Yuri N. Klimochkin

Beilstein J. Org. Chem. 2020, 16, 2073–2079, doi:10.3762/bjoc.16.174

• conjugated nitroolefins in the presence of a chiral Ni(II) complex to give nitro keto phosphonates with two stereocenters with excellent enantioselectivity and moderate to high diastereoselectivity. These products were used for a reductive cyclization leading to pyrrolidin-3-ylphosphonic acid and for

• addition of β-keto phosphonates to nitroolefins and subsequent reductive cyclization of enantioenriched, diastereomerically pure Michael adducts was developed. The present study also demonstrates that the diastereoselective cascade Henry/acetalyzation reaction with keto nitro phosphonates and aldehydes

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

• oxidative [66] and reductive cyclizations [67] have been described. The reductive cyclization reaction is particularly noteworthy, as the reduction and cyclization step are catalyzed by two distinct enzymes [67]. These examples show that the classical division of terpene biosynthesis into a cyclization and

Oxidative and reductive cyclization in stiff dithienylethenes

• Michael Kleinwächter,
• Ellen Teichmann,
• Lutz Grubert,
• Martin Herder and
• Stefan Hecht

Beilstein J. Org. Chem. 2018, 14, 2812–2821, doi:10.3762/bjoc.14.259

• substituents with different electronic properties (Scheme 2). Interestingly, we found that oxidative cyclization can occur from both double bond isomers. In addition, a reductive cyclization was discovered in bis(benzonitrile)-substituted DTEs and also in a DTE with an extended π-system. Results and Discussion

• closed isomer, determined in a separate experiment, was observed. Likewise, in a second cycle (Figure S24, Supporting Information File 1), the reduction wave of the closed isomer at Epc = −1.920 V appeared, clearly indicating reductive cyclization. The reductive formation of C-sDTE66-PhCN was

• cyclization product was formed (Figure 4a). Note that, however, both open isomers undergo oxidative cyclization (Figure S19b and Figure S20b, Supporting Information File 1). To investigate the generality of reductive cyclization mediated by cyano groups, we subjected the cyclopentene-bridged DTE with

Catalytic asymmetric synthesis of biologically important 3-hydroxyoxindoles: an update

• Bin Yu,
• Hui Xing,
• De-Quan Yu and
• Hong-Min Liu

Beilstein J. Org. Chem. 2016, 12, 1000–1039, doi:10.3762/bjoc.12.98

• ), which have been widely used as versatile intermediates for synthesizing biologically important indole containing compounds. The method was also successfully applied to the construction of the tetracyclic core that exists in natural azonazine through a reductive cyclization/MnO2-mediated intramolecular

Study on the synthesis of the cyclopenta[f]indole core of raputindole A

• Nils Marsch,
• Mario Kock and
• Thomas Lindel

Beilstein J. Org. Chem. 2016, 12, 334–342, doi:10.3762/bjoc.12.36

• °C had induced Nazarov cyclization affording a mixture of regioisomeric cyclopenta[f]- and -[g]indolones [34]. Kern and coworkers had obtained an indanone under the same conditions [38]. Other attempts to cyclize 8 also failed. We turned to Pd-catalyzed reductive cyclization. As precursor, a 5

A new and convenient synthetic way to 2-substituted thieno[2,3-b]indoles

• Roman A. Irgashev,
• Arseny A. Karmatsky,
• Gennady L. Rusinov and
• Valery N. Charushin

Beilstein J. Org. Chem. 2015, 11, 1000–1007, doi:10.3762/bjoc.11.112

• , including oxidative cyclization of indolin-2-thiones 1 [20], radical or palladium catalyzed cyclization of 3-(2-bromoindol-3-yl)acrylonitriles 2 [21][22], intramolecular CH/NH-coupling in benzo[b]thiophenes 3 [23], AlCl3 catalyzed recyclization of 2-(2-isothiocyanatophenyl)furanes 4 [24], reductive

• cyclization of 3-(2-nirtophenyl)thiophenes 5 via nitrene intermediates [25][26], and condensation of 3-unsubstituted indolin-2-thione 6 with aliphatic α-bromoaldehydes, α-bromoketones [27] or 3-halochromones (Hlg = Cl, Br) [28] under basic conditions (Scheme 1). However, all synthetic methods mentioned above

Novel stereocontrolled syntheses of tashiromine and epitashiromine

• Loránd Kiss,
• Enikő Forró and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2015, 11, 596–603, doi:10.3762/bjoc.11.66

• hydrogenolysis, followed by reductive cyclization, to give the corresponding indolizidine ester (±)-9 in 40% yield. Finally, ester reduction with LiAlH4 in THF resulted in epitashiromine (±)-10 [32][34][39] in 53% yield after isolation by chromatography (Scheme 3). The stereochemistry of (±)-epitashiromine was

Syntheses of fluorooxindole and 2-fluoro-2-arylacetic acid derivatives from diethyl 2-fluoromalonate ester

• Antal Harsanyi,
• Graham Sandford,
• Dmitri S. Yufit and
• Judith A.K. Howard

Beilstein J. Org. Chem. 2014, 10, 1213–1219, doi:10.3762/bjoc.10.119

• competing decarboxylation, rather than esterification, reflects the greater stabilisation of the carbanion system formed upon decarboxylation for this system. Reductive cyclization of methyl esters 6a–e using sodium dithionite provided fluorooxindoles 8a–e in acceptable yield after isolation by column

A Wittig-olefination–Claisen-rearrangement approach to the 3-methylquinoline-4-carbaldehyde synthesis

• Mukund G. Kulkarni,
• Mayur P. Desai,
• Deekshaputra R. Birhade,
• Yunus B. Shaikh,
• Ajit N. Dhatrak and
• Ramesh Gannimani

Beilstein J. Org. Chem. 2012, 8, 1725–1729, doi:10.3762/bjoc.8.197

• underwent Claisen rearrangement to give 4-pentenals 3a–h. Protection of the aldehyde group of the 4-pentenals as acetals 4a–h and subsequent oxidative cleavage of the terminal olefin furnished nitroaldehydes 5a–h. Reductive cyclization of these nitroaldehydes yielded the required 3-methylquinoline-4

• unsuccessful. Subjecting these acetals to oxidative cleavage in aq THF furnished the aldehydes 5a–h in good yields (Table 1). The NMR of these aldehydes revealed them again to be a mixture of diastereomers, although they appeared to be homogeneous on TLC. Reductive cyclization of these nitroaldehydes furnished

• procedure for the reductive cyclization Aldehydes 5a–h (11 mmol) were dissolved in glacial acetic acid (20 mL) and heated under reflux with zinc dust (5 equiv) for 0.5 h (TLC, ethyl acetate/petroleum ether 1:9). Acetic acid was evaporated under vacuum, and chloroform was added to the residue. The solution

Prediction of reduction potentials from calculated electron affinities for metal-salen compounds

• Sarah B. Bateni,
• Kellie R. England,
• Anthony T. Galatti,
• Handeep Kaur,
• Victor A. Mendiola,
• Alexander R. Mitchell,
• Michael H. Vu,
• Benjamin F. Gherman and
• James A. Miranda

Beilstein J. Org. Chem. 2009, 5, No. 82, doi:10.3762/bjoc.5.82

• The electroreductive cyclization (ERC) reaction is a process in which an electron-deficient alkene that is tethered to an acceptor (e.g., an aldehyde or ketone) undergoes an electrochemically promoted reductive cyclization leading to the formation of a new sigma bond between the β-carbon of the alkene

Recent progress on the total synthesis of acetogenins from Annonaceae

• Nianguang Li,
• Zhihao Shi,
• Yuping Tang,
• Jianwei Chen and
• Xiang Li

Beilstein J. Org. Chem. 2008, 4, No. 48, doi:10.3762/bjoc.4.48