Kinetic Resolution of 2‐N‐Acylamido Tertiary Allylic Alcohols: Asymmetric Synthesis of Oxazolines

Abstract

A series of cyclohexyl‐fused SPINOL‐derived phosphoric acids (Cy‐SPA) have been developed to catalyze the kinetic resolution of 2‐N‐acylamido tertiary allylic alcohols, providing access to chiral oxazolines bearing C‐2 alkyl substituents with high enantioselectivities (with s‐factors up to 153). Gram‐scale reaction with 1 mol% catalyst loading and transformations of the chiral products demonstrates the value of these methods.

Kinetic Resolution of Tertiary Allylic Alcohols: Highly Enantioselective Access to Cyclic Ethers Bearing an α-Tetrasubstituted Stereocenter

“…There are few approaches for the KR of tertiary alcohols by virtue of the nucleophilicity of the alcohols. , Moreover, dehydrative functionalization is a long-standing problem for the KR of tertiary alcohols, mainly because of the poor leaving ability of the hydroxy group and the difficulty of stereocontrol . The only example of intramolecular dehydrative cyclization for the KR of tertiary alcohols, albeit with a relatively limited scope, was made by Yang and co-workers, who employed chiral phosphoric acid catalysis on tertiary 2- N -acylamido allylic alcohols (Scheme b). , We report herein an intramolecular asymmetric allylic substitution for the highly enantioselective KR of various acyclic diols bearing tertiary allylic alcohol moieties under chiral phosphoric acid catalysis (Scheme c). This approach enables asymmetric access to structurally and stereochemically diverse saturated oxygenated heterocycles.…”

Recent advances in intramolecular kinetic resolution reactions

“…With their continuous studies on the kinetic resolution of alcohols, in 2021, the Yang group disclosed the kinetic resolution of 2- N -acylamido tertiary allylic alcohols via an intramolecular dehydration reaction catalyzed by a spirocyclic phosphoric acid (Scheme 39). 49 These efficient kinetic resolution processes generated both the recovered chiral alcohols and 2-alkyl-substituted oxazoline derivatives with high enantioselectivities and moderate to high selectivity factors. Recently, the same group also disclosed another example of the kinetic resolution of 2-amido α-tertiary benzylamines using a similar catalytic strategy (Scheme 40).…”

Recent Advances in (Dynamic) Kinetic Resolution and Desymmetrization Catalyzed by Chiral Phosphoric Acids

“…Recently, our group disclosed that the CPA‐catalyzed asymmetric intramolecular dehydrative condensation was also applicable for the efficient KR of 2‐N‐acyl‐substituted tertiary allyl alcohols 17 , which generated both the recovered allyl alcohols and 2‐alkyl‐substituted oxazoline derivatives 18 with high enantioselectivities (Scheme 7). [14] It is worth mentioning that a type of novel spirocyclic phosphoric acids (Cy‐SPA, CPA‐6 ) was developed in these reactions, which could be readily prepared from Ding's Cy‐SPINOL scaffolds [15] . These types of spirocyclic PA catalysts provided significant improvement of the KR performances in these reactions, comparing to the normal SPINOL‐derived CPA catalysts.…”