Recent advances in the asymmetric catalytic construction of oxa-quaternary carbon centers

Abstract

Compounds bearing oxa-quaternary carbon centers, such as chiral tertiary alcohols, ethers, esters, and acetals, are widely found in a number of bioactive compounds, natural products, agrochemicals and drugs. Besides, they could also serve as privileged building blocks in organic synthesis, especially in a series of bond-forming transformations. Alternatively, among these compounds, enantiomerically pure tertiary alcohols have been extensively used to develop new chiral ligands for a range of organic transformations based on their inherent rigidity and bulky three-dimensional environment. Therefore, developing efficient strategies for the enantioselective catalytic synthesis of these compounds has been of long-standing interest among the chemical and pharmaceutical communities for decades. In contrast to chiral oxa-tertiary stereocenters, the construction of enantioenriched oxa-quaternary carbon centers remains a great challenge in asymmetric synthesis due to the less reactive nature of their precursors and the decreased enantioface differentiation between the two substituents at the prochiral carbon center. Although several tutorial reviews on the asymmetric synthesis of chiral compounds bearing quaternary stereocenters have appeared, there is no specialized review that summarizes the content of enantioselective construction of oxa-quaternary stereocenters. Due to the rapid development in this research field, a timely summarization of the recent achievements is highly valuable. This review exclusively focuses on the recent advances (from 2020 to the beginning of 2023) in asymmetric reactions for the synthesis of enantiomerically pure compounds bearing oxa-quaternary stereocenters.