Phosphine-Catalyzed Asymmetric Synthesis of β-Lactones from Arylketoketenes and Aromatic Aldehydes

Abstract

In this paper, the development of a chiral phosphine-catalyzed formal [2 + 2] cycloaddition of aldehydes and ketoketenes that provides access to a variety of highly substituted beta-lactones (14 examples) is reported. The BINAPHANE catalytic system displays excellent enantioselectivity (seven examples with ee >or=90%) and high diastereoselectivity favoring formation of the trans-diastereomer (nine examples with dr >or=90:10).

Assembly of Dimethyl Acetylenedicarboxylate and Phosphanes with Aldehydes Leading to γ‐Lactones Bearing α‐Phosphorus Ylides as Wittig Reagents

“…[1] In this context, nucleophilic carbenoid species generated in situ from phosphanes and electron-deficient acetylenes have received considerable attention due to their application in the construction of heterocyclic molecules. [4] In recent years, versatile reactions using phosphane catalysis have also been demonstrated for the synthesis of useful heterocycles. [4] In recent years, versatile reactions using phosphane catalysis have also been demonstrated for the synthesis of useful heterocycles.…”

2.07 The Aldol Reaction: Organocatalysis Approach

“…236 The BINAPHANE 442 catalytic system displayed excellent enantioselectivity and high diastereoselectivity in generating trans-isomer 443. Two mechanisms have been suggested to rationalize the observed stereoselectivity (Scheme 82).…”

“…Two mechanisms have been suggested to rationalize the observed stereoselectivity (Scheme 82). 236 The first mechanism A involves an attack of BINAPHANE 442 to aldehyde 228 to give phosphonium alkoxide 444, which would then add to ketene 441 to generate enolate 445. Intramolecular S N 2 displacement would provide trans β-lactone 443 as the major product.…”

(R,R)-Binaphane

“…11 Although some success has been achieved in the cinchona-based nucleophile-catalyzed formal [2 + 2]-cycloaddition of ketenes and aldehydes, 12 a more general nucleophilic catalyst that can tolerate disubstituted ketenes and both alkyl and aromatic aldehydes is needed. 13 BINAPHANE was determined to be the optimal catalyst with respect to reactivity, diastereoselectivity, and enantioselectivity, when slowly added via a syringe pump to minimize ketene dimerization. For the studied model substrate, without addition, the axially chiral BINAPHANE gave good diastereoselectivity (93:7 dr) and moderate ee (64%) with 94% yield ( Table 5, entry 8).…”