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.”

Keywords:

• 1,2-additions of aryl Grignard reagents to selected 3,7-DHBCN-9-ONES
• chair-chair and chair-boat alcohols
• possible heteroatom mediation of the direction of attack

Acknowledgments

We (KDB, VKY) gratefully acknowledge support of this research by grants [KS2-445, KC2-2288, and KAXO-002720-AL-D6] from the U.S. Civilian Research and Development Foundation (CRDF) for the Independent States of the Former Soviet Union. This work is dedicated to the memory of Dr. Elizabeth M. Holt. We thank Dr. Feng Qui for initial work on the 600 MHz NMR spectral analysis. One (KDB) of us is grateful to the College of Arts and Sciences of Oklahoma State University for support in the form of salary. RH gratefully acknowledges partial support by the Welch Foundation, Grant # AO-0001. We are pleased for partial funding for both the Varian Inova 400 MHz NMR spectrometer and the Varian Unity Inova 600 NMR spectrometer in the Oklahoma Statewide Shared NMR Facility by the National Science Foundation (BIR-9512269), the Oklahoma State Regents for Higher Education, the W. M. Keck Foundation, and Conoco, Inc. Tables of all X-ray data have been deposited with the Cambridge Crystallographic Data Centre (CCDC), United Kingdom. The CCDC numbers for 5a and 8b are CCDC-282834 and CCDC-282833, respectively.