Chiral oxime ethers in asymmetric synthesis. Part 5. Asymmetric synthesis of 2-substituted 5- to 8-membered nitrogen heterocycles by oxime addition–ring-closing metathesis

Abstract

Addition of organometallic reagents to chiral oxime ethers 1 derived from an unsaturated aldehyde, or addition of an alkene containing organometallic to chiral aldoxime ethers 2 results in highly stereoselective formation of the hydroxylamines 6. N-Allylation gives the dienes 7 which undergo ring-closing metathesis (RCM) reaction to give the 5-, 6-, and 7-membered nitrogen heterocycles 8. Likewise, the benzyl carbamates 9, also prepared by stereoselective addition to oxime ethers, were converted into dienes 10, which underwent RCM to give the 5- to 8-membered azacycles 11. The oxime addition–RCM protocol is thus a versatile method for the asymmetric synthesis of nitrogen heterocycles, further exemplified by the conversion of the unsaturated heterocycles into chiral piperidines, including the alkaloid (−)-coniine.