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. 2014 Apr 7;53(15):3877-80.
doi: 10.1002/anie.201310517. Epub 2014 Mar 6.

Regio- and stereoselective 1,2-dihydropyridine alkylation/addition sequence for the synthesis of piperidines with quaternary centers

Simon Duttwyler  1 , Shuming Chen, Colin Lu, Brandon Q Mercado, Robert G Bergman, Jonathan A Ellman
Affiliations

Regio- and stereoselective 1,2-dihydropyridine alkylation/addition sequence for the synthesis of piperidines with quaternary centers

Simon Duttwyler et al. Angew Chem Int Ed Engl. .

Abstract

The first example of C alkylation of 1,2-dihydropyridines with alkyl triflates and Michael acceptors was developed to introduce quaternary carbon centers with high regio- and diastereoselectivity. Hydride or carbon nucleophile addition to the resultant iminium ion also proceeded with high diastereoselectivity. Carbon nucleophile addition results in an unprecedented level of substitution to provide piperidine rings with adjacent tetrasubstituted carbon atoms.

Keywords: alkylation; diastereoselectivity; heterocycles; reduction; synthetic methods.

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Figures

Scheme 1
Scheme 1
a) Previously reported 1,2-dihydropyridine protonation and nucleophilic addition sequence. b) Transformation developed in this study: Reaction with carbon electrophiles (R+) followed by addition of hydride or carbon nucleophiles.
Scheme 2
Scheme 2
Michael addition of dihydropyridines to methyl acrylate.
See this image and copyright information in PMC

References

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