A twist on facial selectivity of hydride reductions of cyclic ketones: Twist-boat conformers in cyclohexanone, piperidone, and tropinone reactions
- Neufeldt, S.R. 2
- Jiménez-Osés, G. 2
- Comins, D.L. 1
- Houk, K.N. 2
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1
North Carolina State University
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2
University of California Los Angeles
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ISSN: 0022-3263
Año de publicación: 2014
Volumen: 79
Número: 23
Páginas: 11609-11618
Tipo: Artículo
Otras publicaciones en: Journal of Organic Chemistry
Resumen
The role of twist-boat conformers of cyclohexanones in hydride reductions was explored. The hydride reductions of a cis-2,6-disubstituted N-acylpiperidone, an N-acyltropinone, and tert-butylcyclohexanone by lithium aluminum hydride and by a bulky borohydride reagent were investigated computationally and compared to experiment. Our results indicate that in certain cases, factors such as substrate conformation, nucleophile bulkiness, and remote steric features can affect stereoselectivity in ways that are difficult to predict by the general Felkin-Anh model. In particular, we have calculated that a twist-boat conformation is relevant to the reactivity and facial selectivity of hydride reduction of cis-2,6-disubstituted N-acylpiperidones with a small hydride reagent (LiAlH4) but not with a bulky hydride (lithium triisopropylborohydride). © 2014 American Chemical Society.