A step-economic and one-pot access to chiral C^α-tetrasubstituted α-amino acid derivatives via a bicyclic imidazole-catalyzed direct enantioselective C-acylation

Abstract

The first four-step sequential reaction for the synthesis of Cα-tetrasubstituted chiral α-amino acid derivatives via auto-tandem catalysis has been developed.

Design, Synthesis, and Application of Chiral Bicyclic Imidazole Catalysts

“…After simple alkylation, HO-DPI could be smoothly derivatized to a series of alkoxy substituted catalysts Alkoxy-DPI (Figure ). Among these catalysts, BnO-DPI showed superior performance in asymmetric Steglich rearrangement, asymmetric phosphorylation of lactams, and sequential four-step acylation reaction …”

“…Almost all substrates afforded the corresponding products in good yields with excellent enantioselectivities (97–99% ee). Based on experimental results, the effect of the chiral bicyclic imidazole BnO-DPI in each step of the acylation sequential process was elucidated and a mechanism for the acylation sequence was proposed (Scheme ). Use of BnO-DPI as the nucleophilic catalyst promotes all four steps of the sequential acylation reaction and the key intermediate product 36 was formed by direct enantioselective C -acylation.…”

Recent advances in catalytic asymmetric [1,3]-rearrangement reactions

“…[37][38][39][40][41] Since 2010, Zhang and coworkers rationally designed a rigid bicyclic structure, i.e., DPI with a stereocontrol group at the 7-position. 42,43 The novel type of chiral bicyclic imidazole nucleophilic compound not only avoids the ortho group's influence on activity but also provides an efficiently adjustable stereocenter site, and is successfully applied in an asymmetric Steglich rearrangement with good to excellent yields and enantioselectivity. 44 Thereafter in 2014, the same group further developed a new chiral imidazole nucleophilic catalyst, acyloxy-DPI C9, in order to achieve a higher enantioselectivity for the Black rearrangement (Scheme 11, top).…”

Chemical Synthesis of the Anti‐COVID‐19 Drug Remdesivir

“…In 2010, a novel chiral bicyclic imidazole organocatalyst was developed by our group (Zhang et al., 2010 ). Over the past decade, this kind of organocatalyst was successfully applied in a number of asymmetric reactions (Liu et al., 2012 ; Wang et al., 2017 ; Wang et al., 2020 ; Wang, Zhang, Liu, Xie, & Zhang, 2014 ; Wang, Zhang, Xie, & Zhang, 2014 ; Wang, Zhou, Zhang, Zhang, & Zhang, 2020 ; Zhang et al., 2019 ; Zhang, Wang, Xie, Sun, & Zhang, 2014 ; Zhou et al., 2019 ; Zhou et al., 2021 ). In 2012, the first catalytic asymmetric synthesis of P ‐stereogenic phosphoric acid derivatives was developed by our group using the chiral bicyclic imidazole catalyst (Liu et al., 2012 ).…”