Transition States and Origins of 1,4-Asymmetric Induction in Alkylations of 2,2,6-Trialkylpiperidine Enamines
Identifieur interne : 000172 ( Ncbi/Curation ); précédent : 000171; suivant : 000173Transition States and Origins of 1,4-Asymmetric Induction in Alkylations of 2,2,6-Trialkylpiperidine Enamines
Auteurs : Joann M. Um [États-Unis] ; Naeem S. Kaka [Royaume-Uni] ; David M. Hodgson [Royaume-Uni] ; K. N. Houk [États-Unis]Source :
- Chemistry (Weinheim an der Bergstrasse, Germany) [ 0947-6539 ] ; 2010.
Abstract
The asymmetric C-alkylation of chiral enamines derived from terminal epoxides and lithium 2,2,6-trialkylpiperidides has previously been shown to provide α-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 A1,3 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.
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DOI: 10.1002/chem.201000046
PubMed: 20411546
PubMed Central: 3049728
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Houk</name><affiliation wicri:level="2"><nlm:aff id="A1">Department of Chemistry and Biochemistry, UCLA Los Angeles, CA 90095-1569 (USA)</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>Department of Chemistry and Biochemistry, UCLA Los Angeles</wicri:cityArea></affiliation></author></analytic><series><title level="j">Chemistry (Weinheim an der Bergstrasse, Germany)</title><idno type="ISSN">0947-6539</idno><idno type="eISSN">1521-3765</idno><imprint><date when="2010">2010</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">The asymmetric C-alkylation of chiral enamines derived from terminal epoxides and lithium 2,2,6-trialkylpiperidides has previously been shown to provide α-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<sup>1,3</sup> 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.</p></div></front></TEI></record>Pour manipuler ce document sous Unix (Dilib)
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