Kobayashi Y, Taniguchi Y, Hayama N, Inokuma T, Takemoto Y * Kyoto University, Japan
A Powerful Hydrogen-Bond-Donating Organocatalyst for the Enantioselective Intramolecular Oxa-Michael Reaction of α,β-Unsaturated Amides and Esters.
Angew. Chem. Int. Ed. 2013;
52: 11114-11118
Key words
atorvastatin - enantioselectivity - oxa-Michael reaction - organocatalysis
Significance
The key step in this formal synthesis of atorvastatin (Lipitor®) is the enantioselective intramolecular oxa-Michael reaction of A mediated by 10 mol% of benzothiadiazine catalyst B. Methods for converting G and its relatives into atorvastatin have been summarized by Y. Kawato et al. (Chem. Eur. J. 2013, 19, 3802; see also references therein).
Comment
For the conversion of N-nitrosamides into esters (e.g., D → E), see: D. T. Glatzhofer, R. R. Roy, K. N. Cossey Org. Lett. 2002, 4, 2349. Phenolic nucleophiles (14 examples) also participate in the oxa-Michael reaction, and in the case of H only 1 mol% of catalyst I is required.
