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. 2018 Nov 21;140(46):15943-15949.
doi: 10.1021/jacs.8b10008. Epub 2018 Nov 5.

Allenoates in Enantioselective [2+2] Cycloadditions: From a Mechanistic Curiosity to a Stereospecific Transformation

Johannes M Wahl  1 , Michael L Conner  1 , M Kevin Brown  1
Affiliations

Allenoates in Enantioselective [2+2] Cycloadditions: From a Mechanistic Curiosity to a Stereospecific Transformation

Johannes M Wahl et al. J Am Chem Soc. .

Abstract

Identification of a novel catalyst-allenoate pair allows enantioselective [2+2] cycloaddition of α-methylstyrene. To understand the origin of selectivity, a detailed mechanistic investigation was conducted. Herein, two competing reaction pathways are proposed, which operate simultaneously and funnel the alkenes to the same axially chiral cyclobutanes. In agreement with the Woodward-Hoffmann rules, this mechanistic curiosity can be rationalized through a unique symmetry operation that was elucidated by deuteration experiments. In the case of 1,1-diarylalkenes, distal communication between the catalyst and alkene is achieved through subtle alteration of electronic properties and conformation. In this context, a Hammett study lends further credibility to a concerted mechanism. Thus, extended scope exploration, including β-substitution on the alkene to generate two adjacent stereocenters within the cyclobutane ring, is achieved in a highly stereospecific and enantioselective fashion (33 examples, up to >99:1 er).

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1.
Scheme 1.
Enantioselective Arylcyclobutane Synthesis
Scheme 2.
Scheme 2.
Model for Enantioselectivity
Scheme 3.
Scheme 3.
Distal Differentiation of 1,1-Biarylalkenes
Scheme 4.
Scheme 4.
1,1-Disubstituted Alkene Substrate Scope*
Scheme 5.
Scheme 5.
Catalyst Induced Periselectivity
Scheme 6.
Scheme 6.
Initial Study on Trisubstituted Alkenes
Scheme 7.
Scheme 7.
TS for E-Alkenes
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