A Nonmetal Approach to α‐Heterofunctionalized Carbonyl Derivatives by Formal Reductive XH Insertion

Abstract

Rein organisch: Die direkte reduktive Kupplung leicht zugänglicher und beständiger α‐Ketoester mit protischen Pronucleophile zur Bildung von α‐Alkoxy‐ und α‐Aminoester‐Derivaten (siehe Schema; X=OR, NR2) bietet eine bequeme metallfreie Alternative zur X‐H‐Insertion unter Zersetzung von Diazoverbindungen.

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

“…[39,40] While epoxide 7 is a common self-condensation product in Kukhtin-Ramirez-like functionalizations, the formation of α-chloro ester 6 presumably arises from the addition of HCl across the oxyphosphonium enolate intermediate in a fashion commensurate with Radosevich's 2015 study. [25] The formation of 4a and 6 in a 1:1 ratio supports a mechanism wherein the presumptive aza-o-QM intermediate arises from a 1,4elimination of the benzyl chloride in 1a by a sacrificial equivalent of oxyphosphonium enolate that is then converted to the α-chloro ester through phosphine oxide displacement. Based on this mechanistic hypothesis, we surmised that by employing a strong, exogenous base in a polar, aprotic solvent, we could reduce the formation of α-chloro ester 6 and epoxide 7.…”

“…For this study, we chose to utilize a Kukhtin–Ramirez ‐like redox neutral condensation to exploit the biphilic nature of oxyphosphonium enolates as C 1 subunits . Recent work by Radosevich , He , and our own group have demonstrated the versatility of this approach in providing direct access to C−C and C−X bonds …”

“…[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.…”

Addition reactions of a phosphorus triamide to nitrosoarenes and acylpyridines

“…Selected bond lengths (Å) and angles (°) of P-O(1) 1.47(0), P(1)-N(1) 1.67 2, P(1)-N(2) 1.68 3 On the basis of prior literature which supports the formation of nitrene or nitrenoid reactive intermediates by deoxygenation of nitro-and nitrosoarenes, [26,[38][39][40] deoxygenation is extensively supported in the literature. [2,23,24,[42][43][44]…”

“…σ 5 ,λ 5 Dioxophospholenes with 1-to-1 stoichiometry are formed via formal [4+1] addition to 1,2-dicarbonyl compounds. [23,24] The synthetic importance of these intermediates are underscored by the numerous reports in which the addition of phosphine to carbonyl or nitroso substrates leads to net deoxygenation with transfer of a carbene or nitrene equivalent, respectively. [19,[25][26][27] We have recently been investigating the reactivity of bicyclic phosphorus triamide 1.…”