title: Transition states and origins of 1,4-asymmetric induction in alkylations of 2,2,6-trialkylpiperidine enamines.
abstract: The asymmetric C-alkylation of chiral enamines derived from terminal epoxides and lithium 2,2,6-trialkylpiperidides has previously been shown to provide alpha-alkylated aldehydes by intermolecular nucleophilic substitution in good levels of asymmetric induction. We now report a computational study of the origins of asymmetric induction in these reactions. Computational modeling with density functional theory (B3LYP/6-31G(d)) agrees closely with the experimental observations. This stereoselectivity is attributed to a preferential conformation of the enamine and the piperidine ring that places the C-6 alkyl substituent in an axial position due to A(1, 3) strain. Preferential attack occurs away from the axial group, for steric reasons. The effects of changing the C-6 substituent from methyl to isopropyl were studied, and twist transition states were found to contribute significantly in the latter alkylations.
authors.affiliation: Department of Chemistry and Biochemistry, UCLA, Los Angeles, CA 90095-1569, USA.
authors.forename: Joann M
authors.initials: JM
authors.lastname: Um
authors.forename: Naeem S
authors.initials: NS
authors.lastname: Kaka
authors.forename: David M
authors.initials: DM
authors.lastname: Hodgson
authors.forename: K N
authors.initials: KN
authors.lastname: Houk
mesh_terms: D000447:Aldehydes / Q000737:chemistry; D000478:Alkylation; D008968:Molecular Conformation; D010880:Piperidines / Q000737:chemistry*
chemical_list: D000447:Aldehydes; D010880:Piperidines; C032727:piperidine
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