Siteselective and Enantiocomplementary C(sp<sup>3</sup>)–H Oxyfunctionalization for Synthesis of α-Hydroxy Acids
Xin Lian, Yingle Mao, Zunyun Fu, Weijie Zhang, Jia-Yan Chen, Dan Zhuo, Mingyue Zheng, Jiewei Wu, Cangsong Liao
Abstract
Oxyfunctionalization of abundant carboxylic acids represents a direct approach to synthesizing α-hydroxy acids, which are valuable intermediates of various active pharmaceutical ingredients. Although ideal, the transformation is yet to be accomplished. Herein, enantiocomplementary C( sp 3 )–H oxyfunctionalization for the synthesis of α-hydroxy acids was realized by a cooperative strategy of substrate engineering, homologue screening and protein engineering of α-ketoglutarate-dependent nonheme iron aryloxyalkanoate dioxygenases. The reaction provided concise synthetic routes toward three types of 67 α-hydroxy acids with high efficiency and selectivity (yield up to 90% and ee up to >99%). The distinctive complementary reactions add to a growing repertoire of biocatalytic oxyfunctionalization reactions.