Recent Advances in Catalytic Nonenzymatic Kinetic Resolution of Tertiary Alcohols

Abstract

The kinetic resolution (KR) of racemates is one of the most widely used approaches to access enantiomerically pure compounds. Over the past two decades, catalytic nonenzymatic KR has gained popularity in the field of asymmetric synthesis due to the rapid development of chiral catalysts and ligands in asymmetric catalysis. Chiral tertiary alcohols are prevalent in a variety of natural products, pharmaceuticals, and biologically active chiral compounds. The catalytic nonenzymatic KR of racemic tertiary alcohols is a straightforward strategy to access enantioenriched tertiary alcohols. This short review describes recent advances in catalytic nonenzymatic KR of tertiary alcohols, including organocatalysis and metal catalysis.

Catalytic Enantioselective Azide–Alkyne Cycloaddition Chemistry Opens Up New Prospects for Chiral Triazole Syntheses

“…Nonetheless, an obvious advantage of this methodology is the simultaneous construction of two chiral tertiary alcohols. This is different from previous KR methodologies as they are all based on the conversion of the OH group, 17 and thus inevitably produce only one alcohol product.…”

Kinetic resolution of racemic tertiary allylic alcohols through SN2′ reaction using a chiral bisphosphoric acid/silver(i) salt co-catalyst system

“…In contrast to the catalytic KR of racemic secondary alcohols, 4 reliable methods for the non-enzymatic KR of tertiary alcohols remain few. 5–9 Several groups have reported the use of chiral Lewis base (nucleophilic) catalysts 6 and chiral transition metal catalysts. 7 In the methodologies reported for the KR of racemic tertiary alcohols in recent years, chiral phosphoric acids (CPAs), which are one of the most powerful and privileged organocatalysts employed in a broad range of enantioselective transformations, 10 have proven to be excellent catalysts.…”

ArPNO-catalyzed acylative kinetic resolution of tertiary alcohols: access to 3-hydroxy-3-substituted oxindoles

“…1 For their construction, one of the most efficient routes is the kinetic resolution (KR) of 3-hydroxy-3-substituted oxindoles (Scheme 1). 2 In 2003, Zhao and co-workers pioneered the first highly efficient KR of 3-hydroxy-3-substituted oxindoles catalyzed by a chiral triazolium-based N-heterocyclic carbene (NHC) C1 with high s -factors, in which the cinnamaldehyde was employed as the acylating reagent under oxidative NHC catalysis (Scheme 1a). 3 In 2018, Smith and co-workers developed isothiourea HyperBTM C2 -catalyzed asymmetric esterification with excellent enantioselectivities and broad substrate scope, in which an isobutyric anhydride was used as the acylating reagent under 1 mol% catalyst loading (Scheme 1b).…”