Proposed Mechanism for the Enantioselective Alkynylation of an Aryl Trifluoromethyl Ketone, the Key Step in the Synthesis of Efavirenz

The rationalization of observations made during optimization of the zinc-mediated enantioselective addition of cyclopropylacetylene (2) to ketoaniline 8 in the presence of (1R,2S)-1-phenyl-2-(pyrrolidin-1-yl)­propan-1-ol (3) to afford amino alcohol 11 has enabled us to propose a mechanism for this t...

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Bibliographic Details
Published in:Organic process research & development 2016-04, Vol.20 (4), p.803-813
Main Authors: Griffiths, Gareth J, Warm, Aleksander
Format: Article
Language:English
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Summary:The rationalization of observations made during optimization of the zinc-mediated enantioselective addition of cyclopropylacetylene (2) to ketoaniline 8 in the presence of (1R,2S)-1-phenyl-2-(pyrrolidin-1-yl)­propan-1-ol (3) to afford amino alcohol 11 has enabled us to propose a mechanism for this transformation. The proposed mechanism has been used as the basis for the development of a spreadsheet-based mass-balance simulation, which has proved useful in predicting the effects of stoichiometry changes and in process troubleshooting.
ISSN:1083-6160
1520-586X
DOI:10.1021/acs.oprd.6b00058