Rearrangement of 5-trimethylsilylthebaine on treatment with L-selectride: an efficient synthesis of (+)-bractazonine.
Treatment of 5-trimethylsilylthebaine with L-Selectride gave rise to a rearrangement to 10-trimethylsilylbractazonine through migration of the phenyl group, whereas treatment of thebaine with strong Lewis acids is known to lead to a similar rearrangement through migration of the alkyl bridge to give, after reduction, (+)-neodihydrothebaine. It is suggested that the rearrangement of the alkyl group of thebaine is favored due to the formation of a tertiary benzylic cation. However, for 5-trimethylsilylthebaine, the lithium ion of L-Selectride acts as the Lewis acid and the beta-silyl effect dominates in the stabilization of any positive charge. This rearrangement provides a clear example of the greater relative migratory aptitude of phenyl groups over alkyl groups, and provides an efficient synthesis of (+)-bractazonine from thebaine.
Chen
Weibin
W
Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 20 North Pine Street, Baltimore, Maryland 21201, USA.
Wu
Huifang
H
Bernard
Denzil
D
Metcalf
Matthew D
MD
Deschamps
Jeffrey R
JR
Flippen-Anderson
Judith L
JL
MacKerell
Alexander D
AD
Coop
Andrew
A
D000470:Alkaloids / Q000138:chemical synthesis / Q000737:chemistry; D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D013237:Stereoisomerism; D013797:Thebaine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry
D000470:Alkaloids; D007202:Indicators and Reagents; C476081:bractazonine; D013797:Thebaine