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Cyanomethylation of β‐Alkoxyaldehydes: Toward a Short Synthesis of Atorvastatin
Author(s) -
Tak Raj Kumar,
Noda Hidetoshi,
Shibasaki Masakatsu
Publication year - 2020
Publication title -
asian journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.846
H-Index - 44
eISSN - 2193-5815
pISSN - 2193-5807
DOI - 10.1002/ajoc.201900595
Subject(s) - chemistry , chemoselectivity , atorvastatin , combinatorial chemistry , reductive elimination , active ingredient , stereochemistry , organic chemistry , pharmacology , catalysis , medicine
The cyanomethylation of β‐alkoxyaldehydes is described. These elimination‐prone substrates pose a chemoselectivity issue due to the competing elimination and addition pathways. While many commonly used strong Brønsted bases favor elimination, n BuLi effectively promotes the addition of an α‐cyanocarbanion and suppresses the undesired elimination. The cyanomethylated product can be converted to a known intermediate for the synthesis of atorvastatin, an active pharmaceutical ingredient of Lipitor, showcasing the synthetic potential of the current transformation.