Visible‐Light‐Driven Aza‐ortho‐quinone Methide Generation for the Synthesis of Indoles in a Multicomponent Reaction

Abstract

Av isible-light-driven radical-mediated strategy for the in situ generation of aza-ortho-quinone methides from 2-vinyl-substituted anilines and alkylr adical precursors is described. This process enables an efficient multicomponent reaction of 2-vinylanilines,h alides,a nd sulfur ylides,a nd has aw ide substrate scope and good functional group tolerance. Treatment of the cycloaddition products with ab ase leads to densely functionalized indoles in as ingle-flask operation.Aza-ortho-quinone methides (aza-o-QMs) are highly reac-Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.

A Phosphorus(III)‐Mediated (4+1)‐Cycloaddition of 1,2‐Dicarbonyls and Aza‐o‐Quinone Methides to Access 2,3‐Dihydroindoles

“…Based on our current and previous findings, as well as those reported by Ramirez , Scheidt , Radosevich , and Xiao , our working mechanistic hypothesis addresses two possible competing pathways en route to dihydroindole formation ( Scheme ). Addition of P(NMe 2 ) 3 to formate 1a leads to an equilibrium between dioxaphospholene 11a and oxyphosphonium enolate 11b , of which the enolate is the presumptive reactive constitutional isomer.…”

“…[25 -29] Inspired by Scheidt and coworkers elegant enantioselective assembly of benzopiperidinones employing Supporting information for this article is available on the WWW under https://doi.org/10.1002/hlca.201900192 an NHC-catalyzed [4 + 2]-cycloaddition of in situ generated aza-o-quinone methides (aza-o-QM) and aliphatic carboxylic acids (Scheme 2,a), and building on our previous work toward dihydrobenzofurans (Scheme 2,b), we speculated that aza-o-QMs could serve as 1,3-heterodienes in the construction of 2,3-dihydroindoles employing readily accessible oxyphosphonium enolates as C 1 synthons. [25,27,[30][31][32][33][34][35][36][37][38] Herein, we report the successful development of a phosphorus(III)-mediated redox construction of 2,3-dihydroindoles resulting from the addition of 2-amino benzyl halides to 1,2dicarbonyls (Scheme 2,c). The resulting (4 + 1)-cycloaddition represents a complementary method for heterocycle assembly and adds to the growing ensemble of synthetic methods based on Kukhtin -Ramirez-like reactivity.…”

“…Inspired by Scheidt and coworkers elegant enantioselective assembly of benzopiperidinones employing an NHC‐catalyzed [4+2]‐cycloaddition of in situ generated aza‐ o ‐quinone methides (aza‐ o ‐QM) and aliphatic carboxylic acids ( Scheme ,a ), and building on our previous work toward dihydrobenzofurans ( Scheme ,b ), we speculated that aza‐ o ‐QMs could serve as 1,3‐heterodienes in the construction of 2,3‐dihydroindoles employing readily accessible oxyphosphonium enolates as C 1 synthons . Herein, we report the successful development of a phosphorus(III)‐mediated redox construction of 2,3‐dihydroindoles resulting from the addition of 2‐amino benzyl halides to 1,2‐dicarbonyls ( Scheme ,c ).…”

Shining Light on C−S Bonds: Recent Advances in C−C Bond Formation Reactions via C−S Bond Cleavage under Photoredox Catalysis

“…Laterly in 2017, Xiao and Chen group further developed a visible light driven multicomponent reaction for the synthesis of indoles via radical-mediated addition/cycloaddtion strategy, in which the aza-ortho-quinone was the key intermediate. [16] Interestingly, when using Umemoto's reagent 16 as the alkyl radical precursor, the multicomponent reaction of N-tosyl-2vinylanilines 36, sulfur ylide 37 and 16 could be achieved in the absence of any photocatalyst under blue LED irradiation with the formation of varous indole products 38 (Scheme 9a). On the other hand, when alkyl halides were used as the radical precursors, a metalic photocatalyst was necessary for the reaction of 36 a, 37 a and 39 to give the desired indole products 40 (Scheme 9b).…”

Transition‐Metal Free Catalytic Synthesis of Trifluoromethyl Indolines by [4+1] Cycloaddition of Trifluoromethyl Benzoxazinones with Sulfur Ylides

“…A wide variety of combinations of CF 3 ‐benzoxazinones and sulfur ylides were tolerated under those conditions to yield desired CF 3 ‐indolines in moderate to good yields. The key for this catalytic transformation is the dual nucleophilic attack of sulfur ylides in a reaction that proceeds through an aza‐ ortho ‐quinone methide intermediate [32–36] . While the reaction mechanism is entirely different from that of Pd‐catalysis, the outcome is almost the same as Pd‐catalysis.…”