6341-60-2Relevant articles and documents
Unveiling p-quinone methide (QM) chemistry to synthesize bedaquiline (TMC 207) like architectures
Ali, Kasim,Panda, Gautam,Roy, Deblina
, (2021)
Bedaquiline (TMC 207) is the first FDA-approved drug to combat multidrug-resistant (MDR) tuberculosis. Herein, we disclosed hydroacylation (tandem C–H activation/C–C bond formation/aromatization) catalyzed by Wilkinson catalyst on quinoline containing new para-quinone methides to simplify the construction of diverse bedaquiline analogs with reduction of steps. Direct installation of three crucial aryl rings in hydroacylation giving rise to α-disubstituted aryl ketone can provide a series of bedaquiline analogs.
Enantioselective Desymmetrization of 2-Aryl-1,3-propanediols by Direct O-Alkylation with a Rationally Designed Chiral Hemiboronic Acid Catalyst That Mitigates Substrate Conformational Poisoning
Estrada, Carl D.,Ang, Hwee Ting,Vetter, Kim-Marie,Ponich, Ashley A.,Hall, Dennis G.
supporting information, (2021/04/07)
Enantioselective desymmetrization by direct monofunctionalization of prochiral diols is a powerful strategy to prepare valuable synthetic intermediates in high optical purity. Boron acids can activate diols toward nucleophilic additions; however, the design of stable chiral catalysts remains a challenge and highlights the need to identify new chemotypes for this purpose. Herein, the discovery and optimization of a bench-stable chiral 9-hydroxy-9,10-boroxarophenanthrene catalyst is described and applied in the highly enantioselective desymmetrization of 2-aryl-1,3-diols using benzylic electrophiles under operationally simple, ambient conditions. Nucleophilic activation and discrimination of the enantiotopic hydroxy groups on the diol substrate occurs via a defined chairlike six-membered anionic complex with the hemiboronic heterocycle. The optimal binaphthyl-based catalyst 1g features a large aryloxytrityl group to effectively shield one of the two prochiral hydroxy groups on the diol complex, whereas a strategically placed "methyl blocker"on the boroxarophenanthrene unit mitigates the deleterious effect of a competing conformation of the complexed diol that compromised the overall efficiency of the desymmetrization process. This methodology affords monoalkylated products in enantiomeric ratios equal or over 95:5 for a wide range of 1,3-propanediols with various 2-aryl/heteroaryl groups.
Catalytic Enantioselective Synthesis of Atropisomeric Biaryls: A Cation-Directed Nucleophilic Aromatic Substitution Reaction
Armstrong, Roly J.,Smith, Martin D.
supporting information, p. 12822 - 12826 (2016/02/18)
A catalytic enantioselective nucleophilic aromatic substitution reaction which yields axially chiral biaryl derivatives in excellent yields with e.r. values of up to 97:3 has been developed. This process uses a chiral counterion to direct the addition of thiophenolate to a prochiral dichloropyrimidine by a tandem desymmetrization/kinetic resolution mechanism. The products can be derivatized to a range of atropisomeric structures without any reduction in enantioenrichment, thus offering access to unexplored chiral biaryl architectures.
