Enantioselective Synthesis of 3‐Substituted Cyclobutenes by Catalytic Conjugate Addition/Trapping Strategies

Abstract

A copper‐catalyzed tandem process to generate chiral cyclobutene derivatives has been developed. It is based on an enantioselective conjugate addition or reduction of a cyclobutenone and sequential trapping with a chlorophosphate in a one‐pot process. These phosphates are stable under mildly acidic conditions and serve as good electrophiles in Negishi coupling reactions.

Catalytic enantioselective synthesis of benzocyclobutenols and cyclobutanols via a sequential reduction/C–H functionalization

“…Recently, the precision modification of four-membered ring skeletons to access enantioenriched cyclobutane derivatives has attracted emerging attention. Several strategies have been developed, including allylic alkylation, 8 α-functionalization, 9 conjugate addition 10 and C–H functionalization 11 of prochiral or racemic cyclobutane derivatives ( Scheme 2a ). 12 However, the enantioselective synthesis of chiral benzocyclobutene derivatives is still underdeveloped.…”

Synthesis of Functionalized Cyclobutenes and Spirocycles via Asymmetric P(III)/P(V) Redox Catalysis

“…Various metal‐catalyzed [2+2] cycloaddition reactions were developed between olefins and alkynyl sulfides, [4a,b] ynamides, [4c–e] electron‐poor [4f–h] or electron‐rich [4i,j] alkynes. Other strategies for the synthesis of cyclobutenes include a copper‐catalyzed 1,4‐addition/trapping reaction of cyclobutenones [5a] and an intermolecular Heck annulation with propargylic acetates [5b] . Besides these metal‐catalyzed methodologies, some enantioselective organocatalyzed processes appeared recently.…”

Enantioselective Functionalization of Prochiral Cyclobutanones and Cyclobutenones

“…We envisioned that a catalytic enantioselective addition of cyclobutenones would provide chiral enolate intermediates, which could be trapped with proper electrophiles to afford cyclobutenes (Scheme 10). 30 Scheme 10 Enantioselective addition/trapping strategy of cyclobutenones.…”

“…We envisioned that a catalytic enantioselective addition of cyclobutenones would provide chiral enolate intermediates, which could be trapped with proper electrophiles to afford cyclobutenes (Scheme 10). 30 CuH-catalyzed enantioselective hydrofunctionalization of carbonyl substrates and alkenes has viewed as a reliable and efficient strategy to assemble enantiomerically enriched products. 31 Therefore, we decided to utilize hydrofunctionalization strategy to study the reaction of cyclobutenones (Scheme 11).…”