Rapid and Modular Access to Quaternary Carbons from Tertiary Alcohols via Bimolecular Homolytic Substitution

Quaternarycarbons are ubiquitous in bioactive molecules; however,synthetic methods for the construction of this motif remain underdeveloped.Here, we report the synthesis of quaternary carbons from tertiaryalcohols, a class of structurally diverse, bench-stable feedstocks,via the merger of photoredox catalysis and iron-mediated S(H)2 bond formation. This alcohol-bromide cross-coupling is enabledby a novel halogen-atom transfer (XAT) reagent, which is the firstreductively activated XAT reagent to be reported. A wide variety ofsterically congested quaternary products can be accessed through thismild and practical protocol including products derived from both alkylationand benzylation of tertiary fragments. We further demonstrate thesynthetic utility of this method through the expedited synthesis ofa liver receptor agonist and through a two-step conversion of ketonesand esters to quaternary products, which enables the modular controlof up to three of the four substituents on a quaternary center.