Recent Advances in Catalytic Asymmetric Synthesis of Tertiary Alcohols via Nucleophilic Addition to Ketones

Abstract

Chiral tertiary alcohols are an important class of organic compounds which have found wide applications in both academia and industry. Therefore, various synthetic strategies towards these compounds have already been developed. Among them, the catalytic asymmetric addition of carbon nucleophiles to ketones is the most desirable route owing to its straightforwardness as well as its economic, efficient and versatile advantages. This review summarizes and discusses the recent achievements in this field classified according to the reaction types. Special attention is paid to the mechanisms, advantages and limitations of each reaction. In addition, the applications of these catalytic processes in the synthesis of related natural products, pharmaceuticals or their analogues are briefly discussed as well.

Isothiourea‐Catalyzed Acylative Kinetic Resolution of Tertiary α‐Hydroxy Esters

“…Finally,the KR of propargylic alcohol 25 was achieved with slightly reduced selectivity (s = 6). Consistent with the lower steric hindrance of this substituent, good conversion was obtained when using HyperBTM (1).…”

“…Te rtiary alcohols and their derivatives are present within many natural products and bioactive molecules,h owever, their synthesis in enantiopure form remains as ignificant challenge. [1] Towards this goal, the most commonly investigated method is the enantioselective addition of carboncentred nucleophiles to ketones. [1a-e] Challenging facial differentiation and the potential for unwanted side reactions currently impacts the scope and effectiveness of these methods.T he catalytic kinetic resolution (KR) [2,3] of tertiary alcohols therefore represents ap otentially attractive option.…”

Isothiourea‐Catalyzed Acylative Kinetic Resolution of Tertiary α‐Hydroxy Esters

“…Tertiary alcohols and their derivatives are present within many natural products and bioactive molecules, however, their synthesis in enantiopure form remains a significant challenge . Towards this goal, the most commonly investigated method is the enantioselective addition of carbon‐centred nucleophiles to ketones . Challenging facial differentiation and the potential for unwanted side reactions currently impacts the scope and effectiveness of these methods.…”

Catalyst-free formal [4+1]/[4+2] cyclization cascade sequence of isocyanides with two molecules of acylketene formed in situ from thermal-induced Wolff rearrangement of 2-diazo-1,3-diketones

“…2 and Supplementary materials (online) for details). Considering its intriguing structure, together with our interest in the construction of polycyclic compounds for biological evaluation [52][53][54][55][56], we then decided to explore the possibility of developing an efficient, general and facile methodology for its synthesis.…”