Synthesis, Stereochemical, and Conformational Studies of Selected 3,7-Diheterabicyclo[3.3.1]nonan-9-ols: X-Ray Diffraction Analyses of 7-Benzyl-9-phenyl-3-oxa-7-azabicyclo[3.3.1]nonan-9-ol and 7-Benzyl-9-(4- N,N′ -dimethylaminophenyl)-3-thia-7-azabicyclo[3.3.1]nonan-9-ol, a Rare Stable Chair–Boat Form With Trigonal Nitrogen

Abstract

A systematic study of 1,2-additions to 3,7-diheterabicyclo[3.3.1]nonan-9-ones (3,7-DHBCN-9-ONES) by symmetrically substituted aryl Grignard reagents in anhydrous THF or ether has been conducted. 1,2-Additions of aryl Grignard reagents to the carbonyl group at C-9 in 7-benzyl-3-oxa-7-azabicyclo[3.3.1]nonan-9-one and 7-benzyl-3-thia-7-azabicyclo[3.3.1]nonan-9-one resulted in the formation of tertiary alcohols with the aryl group “syn” to the oxygen or sulfur atoms in the respective rings. The X-ray analyses demonstrated that the solid, bicyclic, oxygen-containing alcohol was in chair–chair form while the solid, bicyclic, sulfur-containing alcohol existed in chair–boat form. A tentative mechanism is that the Grignard reagent may coordinate with the oxygen atom and / or sulfur atom in a boat conformer of the bicyclic system prior to the attack from the “oxygen or sulfur sides.”