Catalytic Staudinger/Aza‐Wittig Sequence by in situ Phosphane Oxide Reduction

Abstract

A Staudinger/aza‐Wittig reaction sequence is described that is catalytic in phosphorus. Towards this end, the phosphane oxide is reduced in situ by diphenylsilane, which allows for substoichiometric amounts of the catalyst 5‐phenyldibenzophosphole to be used. The substrate scope is investigated and benzoxazoles, benzodiazepine imidates and a 2‐methoxypyrrole were successfully synthesized. These investigations show that a fast aza‐Wittig reaction is required to obtain high yields.

Catalytic Wittig Reactions of Semi‐ and Nonstabilized Ylides Enabled by Ylide Tuning

“…Indeed, a recent life cycle analysis by Huijbregts and co‐workers has shown that the CWR offers a clear reduction in both cumulative energy demand and greenhouse gas emissions compared to the stoichiometric Wittig reaction 5. In addition, other research groups have applied our reduction strategy to the Appel, aza‐Wittig, and Staudinger reactions 6c,e,g,h. Moreover, related organophosphorus catalysis has also seen significant advancement 6.…”

Convergent Synthesis of Polysubstituted Furans via Catalytic Phosphine Mediated Multicomponent Reactions

“…nBu 3 P=O (20 mol%) instead of nBu 3 P; 51% yield nBu 3 P=O (100 mol%) instead of nBu 3 P; 58% yield without nBu Control experiments.Based on the results of this work and previous reports[59][60][61][62][63][64][65][66][67][68][69][70][71][72][73][74][75]97], a multiple domino process is proposed to rationalize the formation of tetra-substituted furans 3 (Scheme 5, left). The catalytic cycle starts with the nucleophilic addition of nBu3P to an activate alkene 1 like acrylates, the resulting intermediate undergoes a C-acylation reaction with acyl chloride 2 to give a phosphonium enolate A.…”

“…Under the reported conditions, various reducible functional groups such as ketones, aldehydes, olefins, nitriles, and esters were well tolerated. Based on these encouraging findings, a number of important stoichiometric phosphine-involved reactions, including (aza-)Wittig [59][60][61][62][63][64][65][66][67][68][69][70][71][72][73][74][75], Mitsunobu [76][77][78], Staudinger [79][80][81][82][83][84], Appel [85,86], Cadogan [87], and others [88][89][90][91][92][93] have been successfully developed into the catalytic phosphine mediated ones.…”

Catalytic Wittig and aza-Wittig reactions

“…Subsequently they extended such reactions to include aza-Wittig reactions using diphenylsilane as the reducing reagent [35]. For example, starting materials 64 could be converted into benzoxazoles 48 in overall net transformations that were similar as to those discussed above by Marsden (Scheme 14).…”