Revisiting the bromination of 3β-hydroxycholest-5-ene with CBr4/PPh3 and the subsequent azidolysis of the resulting bromide, disparity in stereochemical behavior

Submitting author affiliation:
Port Said University, Port Said, Egypt

Beilstein Arch. 2022, 202288. https://doi.org/10.3762/bxiv.2022.88.v1

Published 23 Nov 2022

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Abstract

Cholesterol reacts under Appel conditions (CBr4/PPh3) to give 3,5-cholestadiene (elimination) and 3b-bromocholest-5-ene (substitution with retention of configuration). Thus, the bromination of cholesterol deviates from the stereochemistry of the standard Appel mechanism due to participation of the D5 π-electrons. In contrast, the subsequent azidolysis (NaN3/DMF) of 3b-bromocholest-5-ene proceeds predominantly by Walden inversion (SN2) affording 3a-azidocholest-5-ene. The structures of all relevant products were revealed by X-ray single crystal structure analyses, and the NMR data are in agreement to the reported ones. In light of these findings, we herein correct the previous stereochemical assignments reported by one of us in the Beilstein J. Org. Chem. 2015, 11, 1922–1932 and the Monatsh. Chem. 2018, 149, 505–517.

Keywords: Appel reaction; azidolysis; cholesterol; crystal structure; Walden inversion

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Schumacher, C.; Ward, J. S.; Rissanen, K.; Bolm, C.; Aly, M. R. E. S. Beilstein Arch. 2022, 202288. doi:10.3762/bxiv.2022.88.v1

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