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. 2011 Jun 3;13(11):2932-5.
doi: 10.1021/ol2009895. Epub 2011 May 10.

Enantioconvergent synthesis of (+)-aphanorphine via asymmetric Pd-catalyzed alkene carboamination

Duy N Mai  1 , Brandon R Rosen, John P Wolfe
Affiliations

Enantioconvergent synthesis of (+)-aphanorphine via asymmetric Pd-catalyzed alkene carboamination

Duy N Mai et al. Org Lett. .

Abstract

A concise asymmetric synthesis of (+)-aphanorphine has been achieved via a new enantioconvergent strategy. A racemic γ-aminoalkene derivative is transformed into a 1:1 mixture of enantiomerically enriched diastereomers using an asymmetric Pd-catalyzed carboamination. This mixture is then converted to an enantiomerically enriched protected aphanorphine derivative by a Friedel-Crafts reaction, which generates a quaternary all-carbon stereocenter. The natural product is obtained in three additional steps.

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Figures

Figure 1
Figure 1
Benzomorphane Alkaloids
Scheme 1
Scheme 1
Asymmetric Carboamination/Friedel-Crafts Alkylation Strategy
Scheme 2
Scheme 2
Synthesis of Carboamination Substrate
Scheme 3
Scheme 3
Pd-Catalyzed Carboamination of 5 and Conversion to 13.
Scheme 4
Scheme 4
Completion of the Synthesis
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