P(NMe₂)₃-Mediated Umpolung Alkylation and Nonylidic Olefination of α-Keto Esters

Abstract

A commercial phosphorus-based reagent (P-(NMe2)3) mediates umpolung alkylation of methyl aroylformates with benzylic and allylic bromides, leading to either Barbier-type addition or ylide-free olefination products upon workup. The reaction sequence is initiated by a two-electron redox addition of the tricoordinate phosphorus reagent with an α-keto ester compound (Kukhtin–Ramirez addition). A mechanistic rationale is offered for the chemoselectivity upon which the success of this nonmetal mediated C–C bond forming strategy is based.

Mass Efficiency of Alkene Syntheses with Tri- and Tetrasubstituted Double Bonds

“…Further examples for the utilization of mass metrics (and approaches to consider health, safety, and environment aspects) can be found not only in the professional literature (e.g., bromination reactions, ,, photochemical transformations, ,, methylating agents, , cross-metathesis, , esterifications, , substitution reactions, , reduction reactions, ,, oxidation reactions, , asymmetric ,,, /biocatalytic , syntheses, azidation, deprotection, total synthesis, flash chromatography as method and other ,,− ) but also in chemical didactics. ,− Further references − …”

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.…”

“…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.…”

“…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 ).…”