A twist on facial selectivity of hydride reductions of cyclic ketones: Twist-boat conformers in cyclohexanone, piperidone, and tropinone reactions

  1. Neufeldt, S.R. 2
  2. Jiménez-Osés, G. 2
  3. Comins, D.L. 1
  4. Houk, K.N. 2
  1. 1 North Carolina State University
    info

    North Carolina State University

    Raleigh, Estados Unidos

    ROR https://ror.org/04tj63d06

  2. 2 University of California Los Angeles
    info

    University of California Los Angeles

    Los Ángeles, Estados Unidos

    ROR https://ror.org/046rm7j60

Revista:
Journal of Organic Chemistry

ISSN: 0022-3263

Año de publicación: 2014

Volumen: 79

Número: 23

Páginas: 11609-11618

Tipo: Artículo

DOI: 10.1021/JO5022635 SCOPUS: 2-s2.0-84916221592 WoS: WOS:000346038300031 GOOGLE SCHOLAR

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.