Catalytic enantioselective construction of vicinal quaternary carbon stereocenters

Abstract

This review summarizes the advances in the catalytic enantioselective construction of vicinal quaternary carbon stereocenters, introduces major synthetic strategies and discusses their advantages and limitations, highlights the application of known...

Construction of all-carbon quaternary stereocenters by catalytic asymmetric conjugate addition to cyclic enones in natural product synthesis

“…However, the construction of all-carbon quaternary stereocenters still poses a distinct challenge in organic synthesis and the development of methods for constructing such centers is imperative. [1][2][3][4][5][6][7][8][9][10][11] Innovative chiral catalysts have enabled the efficient construction of all-carbon quaternary centers by various asymmetric reactions such as dearomative cyclization, 12,13 polyene cyclization, 14,15 arylation, 16 allylation, [17][18][19] and Michael addition. 20 Catalytic asymmetric conjugate addition can be used to synthesize ketones containing all-carbon quaternary centers from enones and is an indispensable method for accessing enantiopure and/or enantioenriched materials for various synthetic purposes.…”

Recent Advances in the Construction of Quaternary Stereocenters via Palladium-Catalyzed Decarboxylative Asymmetric Allylic Alkylation

“…Moreover, this strategy provides an opportunity to simultaneously generate two adjacent stereogenic centers, which could be considered a worthy future goal. 70 Thus, the value of some catalytic enantioselective methods for facilitating asymmetric total synthesis of bioactive molecules bearing multiple quaternary stereocenters has been demonstrated. In light of this, continued innovation in ligand and catalyst improvements based on a better mechanistic understanding of the DAAA process could continue to advance this field.…”

Highly Enantioselective CuAAC of Functional Tertiary Alcohols Featuring an Ethynyl Group and Their Kinetic Resolution

“…The KR of α‐monofluorinated α‐ethynyl alcohol 6 with vicinal tetrasubstituted‐tertiary carbon stereocenters was also achieved. Catalytic enantioselective construction of such structures is still challenging [29] . Racemic α‐monofluoroalkyl alcohol 6 a ( anti / syn ratio 7.5:1) reacted with 2 a , giving (1 S ,2 S )‐ 6 a with 48 % recovery and 90 % ee with 6.7:1 dr, along with monofluorinated α‐triazole‐substituted alcohol 7 a in 50 % yield, 89 % ee , and 10:1 dr. Analogous alcohols 6 b – d readily afforded the respective chiral alcohols 6 b – d and 7 b – d in up to 99 % and 93 % ee , with good dr values.…”

“…Catalytic enantioselective construction of such structures is still challenging. [29] Racemic a-monofluoroalkyl alcohol 6 a (anti/syn ratio 7.5:1) reacted with 2 a, giving (1S,2S)-6 a with 48 % recovery and 90 % ee with 6.7:1 dr, along with monofluorinated a-triazole-substituted alcohol 7 a in 50 % yield, 89 % ee, and 10:1 dr. Analogous alcohols 6 b-d readily afforded the respective chiral alcohols 6 b-d and 7 b-d in up to 99 % and 93 % ee, with good dr values. Notably, monofluorinated alcohol 6 was more reactive than the corresponding a-difluoroalkyl alcohol 4, so the reaction reached completion in one day.…”