On the Diastereoselectivity of the Aqueous‐Acid‐Catalyzed Intramolecular Aldol Condensation of 3‐Oxocyclohexaneacetaldehydes

The factors responsible for the diastereoselective formation of the 6-endo-hydroxybicyclo[2.2.2]octan-2-one by acid-catalyzed intramolecular aldol reaction of 3-oxocyclohexaneacetaldehydes have been investigated. This study, carried out on (1SR,4RS,6RS)-6-hydroxybicyclo[2.2.2]octan-2-one 1a, (1SR,4RS,6SR)-6-hydroxybicyclo[2.2.2]octan-2-one 1b, and 3,3-(ethylenedioxy)cyclohexaneacetaldehyde 2a, allowed to demonstrate the absence of intramolecular H-bonding in 1a as a stabilizing factor, and to ascertain the presence of unfavorable steric interactions in 1b.