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. 2018 Oct 19;20(20):6453-6456.
doi: 10.1021/acs.orglett.8b02766. Epub 2018 Oct 11.

Synthesis of Phthalans Via Copper-Catalyzed Enantioselective Cyclization/Carboetherification of 2-Vinylbenzyl Alcohols

Dake Chen  1 , Sherry R Chemler  1
Affiliations

Synthesis of Phthalans Via Copper-Catalyzed Enantioselective Cyclization/Carboetherification of 2-Vinylbenzyl Alcohols

Dake Chen et al. Org Lett. .

Abstract

Enantiomerically enriched phthalans were synthesized efficiently via an enantioselective copper-catalyzed alkene carboetherification reaction. In this reaction, 2-vinylbenzyl alcohols enantioselectively cyclize then couple with vinylarenes. The utility of the method was demonstrated by the enantioselective synthesis of ( R)-fluspidine, a σ1 receptor ligand.

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Figures

Figure 1.
Figure 1.
Bioactive phthalides and phthalans.
Scheme 1.
Scheme 1.
Phthalides and Phthalans from 2-Vinylbenzyl Alcohols and 2-Vinylbenzoic Acids
Scheme 2.
Scheme 2.
Proposed Copper-Catalyzed Carboetherification Mechanism
Scheme 3.
Scheme 3.
Scope with Respect to 2-Vinylbenzyl Alcohol or 2-Vinylbenzoic Acida
Scheme 4.
Scheme 4.
Scope of the Alkene Coupling Partnera
Scheme 5.
Scheme 5.
Enantioselective Synthesis of (R)-Fluspidine
See this image and copyright information in PMC

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