Revisiting the bromination of 3 β -hydroxycholest-5-ene with CBr 4 /PPh 3 and the subsequent azidolysis of the resulting bromide, disparity in stereochemical behavior

Cholesterol reacts under Appel conditions (CBr 4 /PPh 3 ) to give 3,5-cholestadiene (elimination) and 3  -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  5 π  electrons. In contrast, the subsequent azidolysis (NaN 3 /DMF) of 3  -bromocholest-5-ene proceeds predominantly by Walden inversion (S N 2) affording 3  -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.