PBu₃-Mediated Vinylogous Wittig Reaction of α-Methyl Allenoates with Aldehydes and Mechanistic Investigations

Abstract

A highly stereoselective PBu(3)-mediated vinylogous Wittig olefination between α-methyl allenoates and a variety of aldehydes is presented as the first example of a practical and synthetically useful vinylogous Wittig reaction. Mechanistic experiments including deuterium-labeling, intermediate entrapment, and NMR monitoring have been deliberately conducted. On the basis of mechanistic investigations, a reliable mechanism for the vinylogous Wittig reaction is proposed, which features a water/phosphine-coassisted allylic phosphorus ylide 1,3-rearrangement pathway, rather than previous retro-Diels-Alder ones. It is noteworthy that mechanistic findings in this work also provide supportive evidence for typical mechanisms of important phosphine-mediated reactions of allenoates.

Recent advances in stoichiometric phosphine-mediated organic synthetic reactions

“…This reaction was previously observed independently by He 24 and Kwon 25 with triarylphosphines used as the mediator. Further studies by He 26 disclosed that the vinylogous Wittig reaction mediated by strongly nucleophilic PBu 3 was superior to the precedents with regard to yield, stereoselectivity and substrate scope, providing an efficient synthesis of trisubstituted 1,3-dienes.…”

“…Based on a series of in-depth mechanistic studies including deuterium-labeling, intermediate entrapment, and NMR monitoring, a novel mechanism was proposed to rationalize the vinylogous Wittig reaction (Scheme 15). 26 Initially, the nucleophilic attack of PBu 3 at allenoate 29e forms a zwitterionic intermediate 36, which converts into allylic phosphorus ylide 37 through a water-aided stepwise hydrogen shift. Subsequent protonation with adventitious water yields an allylic phosphonium salt 38.…”

Reaction Mechanism of Phosphane‐Catalyzed [4+2] Annulations between α‐Alkylallenoates and Activated Alkenes: A Computational Study

“…Yu and co-workers [10] have demonstrated the feasibility of water-aided [1,4]-H transfer in their computational and experimental study. Recently, He and coworkers [25] reported the results of a deuterium-labeling ex-periments that showed water-aided (or protic acid aided) [1,4]-H transfer.…”

Phosphine-Catalyzed (4 + 1) Annulation of o-Hydroxyphenyl and o-Aminophenyl Ketones with Allylic Carbonates: Syntheses and Transformations of 3-Hydroxy-2,3-Disubstituted Dihydrobenzofurans and Indolines

“… Huang et al first reported the phosphine-catalyzed (4 + 1) annulation reactions of salicyl N -thiophosphinyl imines with allenoates and allylic carbonates, respectively, leading to highly diastereoselective synthesis of 3-amino dihydrobenzofurans. , Most recently, Guo et al unveiled an effective and diastereoselective synthesis of 2,3-disubstituted indolines via the phosphine-catalyzed (4 + 1) annulation of 2-tosyl­amino­chalcones with allenoates . In our continuous exploration on the reactivity of in situ generated allylic phosphorus ylides from tertiary phosphines and allylic carbonates or allenoates with carbonyl compounds, we found that such formed allylic phosphorus ylides tend to undertake the phosphine stoichiometric Wittig olefinations with various aldehydes including salicylaldehydes, although a couple of phosphine-catalyzed reactions have also been realized from aldehydes in our laboratory . Under the same conditions, common ketones are usually inert in those olefinations. , Considering the reactivity bias of the allylic phosphorus ylides between aldehydes and ketones, recently we investigated the reactions of o -hydroxyphenyl and o -aminophenyl ketones with allylic carbonates under the mediation of tertiary phosphines in order to devise an organocatalytic phosphorus ylide-initiated synthesis of 3-hydroxy dihydrobenzofuran and 3-hydroxy indoline motifs .…”