A Novel, Highly Enantioselective Ketone Alkynylation Reaction Mediated by Chiral Zinc Aminoalkoxides

✍ Scribed by Lushi Tan; Cheng-yi Chen; Richard D. Tillyer; Edward J. J. Grabowski; Paul J. Reider

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 87 KB
• Volume: 38
• Category: Article
• ISSN: 0044-8249
• DOI: 10.1002/(sici)1521-3773(19990301)38:5<711::aid-anie711>3.0.co;2-w

✦ Synopsis

Kilogram-scale synthesis of the HIV reverse transcriptase inhibitor efavirenz was achieved by means of a highly enantioselective alkynylation of prochiral ketones 1 with alkynyllithium or alkynylmagnesium reagents in the presence of chiral zinc aminoalkoxides as mediators. With the achiral auxiliary 2,2,2-trifluoroethanol (R =CF CH ), the efavirenz precursor 2 (R =H, R =cyclopropyl) was obtained with an ee of 99.2%.