Sustainable Radical Cascades to Synthesize Difluoroalkylated Pyrrolo[1,2-<i>a</i>]indoles

Huang, Honggui; Yu, Menglin; Su, Xiaolong; Guo, Peng; Zhao, Jia; Zhou, Jiabing; Li, Yang

doi:10.1021/acs.joc.7b03017

Cited by 58 publications

(19 citation statements)

References 42 publications

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“…Several other general fluoroalkylation/cascade cyclization reactions were reported where BrCF 2 P(O)(OEt) 2 was used in the context of other fluoroalkylating reagents. These reports include phosphoryldifluoromethylation of 4‐phenylpent‐4‐enoic acid ( 9 ) (Pan, Han and co‐workers; [55] later extended to a series of ω‐unsaturated carboxylic acids by Yang and co‐workers [56] ), N ‐(but‐3‐enoyl)indole 11 (Li and co‐workers [57] ), and 2‐( N ‐trifluoroacetyl‐ N ‐benzylamino)phenylacetylene ( 13 ) (Zhong, Tong and co‐workers [58] ), as well as carboxylative phosphoryldifluoromethylation of N ‐benzyl‐2‐phenylallylamine ( 15 ) (Yu and co‐workers [59] ) with subsequent intramolecular cyclizations of the corresponding intermediate radical species yielding CF 2 ‐phosphonate‐containing γ‐butyrolactone 10 , pyrrolo[1,2‐a]indole 12 , dibenzazepine 14 and oxazolidinone 16 , respectively (Scheme 5). Interesting use of radical clock as a synthetic method was reported by Xu, Lan, and co‐workers.…”

Section: Synthetic Methodsmentioning

confidence: 99%

Recent Advances in Synthesis of Difluoromethylene Phosphonates for Biological Applications

et al. 2021

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For almost 40 years, difluoromethylene phosphonates have proven to be versatile molecular tools in biochemical studies owing to their close resemblance to naturally occurring phosphates and phosphonates. As bioisosteric, non‐hydrolyzable analogs of these essential molecules, difluoromethylene phosphonates can target the critical parts of the cellular machinery and therefore exhibit a diverse spectrum of biological activity. In the past ten years, there have appeared many new methods for the synthesis of difluoromethylene phosphonates. Most notably, photoredox catalysis has firmly entered the field, while cross‐coupling and nucleophilic strategies have met considerable elaboration and refinement, entirely in accord with the current trends in synthetic organic chemistry. Herein, we introduce difluoromethylene phosphonates as a distinct, high‐tech subclass of synthetic phosphonates resulting from the research efforts on the cross‐section of organophosphorus, organofluorine, and bioorganic chemistry. We then proceed to the discussion of general methods for the preparation of difluoromethylene phosphonates, comprehensively reviewing reactions developed in the past 15 years while providing the context of earlier works where appropriate. Finally, we present selected examples of molecules with high biological activity, their biological targets, and the synthetic steps employed for their preparation.

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Section: Synthetic Methodsmentioning

confidence: 99%

Recent Advances in Synthesis of Difluoromethylene Phosphonates for Biological Applications

et al. 2021

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“…A wide array of the substrate bearing electron‐donating groups as well as electron‐withdrawing groups were amendable with the reaction affording the corresponding products in good to excellent yields (Scheme 28). [100] Irradiated by visible light, the photocatalyst [Ir 3+ ] transfers to an excited state that is subsequently oxidized by BrCF 2 CO 2 Et to give the CF 2 CO 2 Et radical. The addition of radical to the double bond produces intermediate.…”

Section: Difluoroalkylation and Intramolecular Cyclization Reactionmentioning

confidence: 99%

Progress in Visible Light‐Induced Difluroalkylation of Olefins

Laishram¹,

Chen²,

Fan³

2020

The Chemical Record

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The incorporation of difluoromethylated (CF2) moiety into potentially useful parent molecules lead to significant changes in metabolic stability, lipophilicity, and solubility of the molecules. Over the past several years, with the advent of new difluoromethylating reagents, great progress has been made in the development of a protocol for the direct incorporation of the CF2H group into organic molecules. Among them, difluroalkylation induced by visible light has emerged as an efficient strategy over the past few years. In particular, this protocol provides a more sustainable alternative to other traditional radical‐triggered reactions in terms of environment, energy, step‐economy, health, and safety. The present review mainly focuses on the development of the photocatalytic difluoroalkylation to olefinic moiety using transition‐metal complexes, organic dyes as the photocatalyst; and some organic compounds as a medium of photocatalysis.

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“…[36][37][38][39][40][41] In 2018, the Li group demonstrated that difluoroalkylated pyrrolo [1,2-α]indoles with a quaternary carbon center can be efficiently synthesized via difluoroalkylation and cyclization cascade reaction of N-(but-2-enoyl)indoles with BrCF 2 R (Scheme 1). 42 In the presence of visible light, products with good to high yields were generated. A plausible reaction mechanism is outlined in Scheme 1.…”

Section: Introductionmentioning

confidence: 99%