Reversible P(III)/P(V) Redox: Catalytic Aza‐Wittig Reaction for the Synthesis of 4(3H)‐Quinazolinones and the Natural Product Vasicinone

Abstract

The catalytic aza‐Wittig reaction based on a phosphine/phosphine oxide catalytic cycle is reported. The by‐product triphenylphosphine oxide (Ph3PO) was reduced in situ to triphenylphosphine (Ph3P) with good chemselectivity so that the aza‐Wittig reaction can be accomplished by using merely a catalytic amount of triphenylphosphine. The reaction has been demonstrated in an efficient synthesis of 4(3H)‐quinazolinones and the natural product (S)‐vasicinone in high yields, by using a catalytic amount of triphenylphosphine (5%) and the tetramethyldisiloxane/titanium tetraisopropoxide [TMDS/Ti(O‐i‐Pr)4] reductant system (81–95% yields and >99% ee).magnified image

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

“…In their initial report regarding this strategy, they used 1 to catalyze intramolecular reactions that converted aryl azides 68 into 4(3 H )-quinazolinones 69 via intermediate iminophosphoranes 70 , using the combination of titanium tetraisopropoxide and tetramethyldisiloxane (TMDS) for the in situ reduction of byproduct 2 (Scheme 18) [36]. …”

Catalytic Intramolecular Wittig Reaction Based on a Phosphine/Phosphine Oxide Catalytic Cycle for the Synthesis of Heterocycles

“…Recently, catalytic Wittig, Appel, and Staudinger reactions, the reduction of silyl peroxides, and cyclization reactions between the Huisgen zwitterion and carbonyl substrates with a phosphine/phosphine oxide catalytic cycle have attracted significant attention. In 2009, the O'Brien group disclosed the first catalytic Wittig reaction in which Ph 2 SiH 2 was employed as a reductant .…”

“…However, the catalytic intramolecular Wittig reactions of carbonyl‐containing bromides have not been reported previously. We have disclosed a catalytic aza‐Wittig reaction, in which inexpensive tetramethyldisiloxane (TMDS, Me 2 HSi–O–SiMe 2 H) was used as the reductant, and its application in the preparation of 4(3 H )‐quinazolinones and the natural product vasicinone . Herein, we wish to report the catalytic intramolecular Wittig reactions of carbonyl‐containing bromides; the reaction is based on a phosphine/phosphine oxide catalytic cycle with the TMDS/Ti(O i Pr) 4 reductant system.…”