The Formal Synthesis of Chiral Etodolac Using Chiral 1,2-Di(alkylcarbonyl)oxypentan-3-one as Chiral Building Block

A stereoselective synthesis of (+)- and (-)-(1,8-diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indol-1-yl)-1-ethanols (31) and (32), the key intermediates for chiral etodolac was executed in seven steps starting from the asymmetric cyclization of (2R)-1,2-di(acetyloxypentan)-3-one (5) or (2R)-1,2-di(propionyloxypentan)-3-one (6) and 7-ethyltryptophol (7). Some unexpected transformations are also described.