Chih‐Wei HsuChun‐Fu WuYung‐Chi LeeWoo‐Jin Yoo2024-11-292024-11-292024-10-10https://scholars.lib.ntu.edu.tw/handle/123456789/723404The replacement of benzene rings with saturated bioisosteric counterparts is a key priority in drug discovery programs, and disubstituted bicyclo[2.1.1]hexanes have been recognized as flexible molecular scaffolds that could act as ortho-substituted benzene bioisosteres. In this study, we outline the synthesis of a wide range of 2-substituted bicyclo[2.1.1]hexan-1-ols, which have the potential to emulate ortho-phenolic derivatives, via SmI2-mediated reductive cyclization reactions. The synthetic utility of this methodology was exemplified by the preparation of several saturated analogs of pharmaceutically relevant compounds.enCyclizationC−C Bond FormationIsostereSamarium(II) IodideSynthetic Methods[SDGs]SDG3journal article10.1002/adsc.202400891