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

• Christian Schumacher,
• Jas S. Ward,
• Kari Rissanen,
• Carsten Bolm and
• Mohamed Ramadan El Sayed Aly

Beilstein J. Org. Chem. 2023, 19, 91–99, doi:10.3762/bjoc.19.9

• from the stereochemistry of the standard Appel mechanism due to participation of the Δ5 π-electrons. In contrast, the subsequent azidolysis (NaN3/DMF) of 3β-bromocholest-5-ene proceeds predominantly by Walden inversion (SN2) affording 3α-azidocholest-5-ene. The structures of all relevant products were

• –517. Keywords: Appel reaction; azidolysis; cholesterol; crystal structure; Walden inversion; Introduction 3β-Hydroxycholest-5-ene (cholesterol) is a structural and physiologic amphipathic steroid in human and animals as well. Cholesterol is an essential component of the plasma membrane, where it

• configuration at C3 (Walden inversion). Consequently, the newly introduced substituent is located on the α-face of the steroid. Interestingly, this result contrasts the one observed when 3β-mesylcholest-5-ene is treated with TMSN3/BF3·OEt2 [12]. There, the process proceeds by retention of configuration locating

Proton transfers in the Strecker reaction revealed by DFT calculations

• Shinichi Yamabe,
• Guixiang Zeng,
• Wei Guan and
• Shigeyoshi Sakaki

Beilstein J. Org. Chem. 2014, 10, 1765–1774, doi:10.3762/bjoc.10.184

• approach of CN− to 4 concomitantly take place with a Walden inversion. The transition state TS4/8 was successfully located; see Figure 1. However, this pathway needs a large energy barrier of 58.8 = [+51.3 − (−7.5)] kcal/mol, indicating that it is difficult to occur. Starting from the ion-pair intermediate