Journal of the American Chemical Society (2021)
Update date:2022-08-05
Topics:
Estrada, Carl D.
Ang, Hwee Ting
Vetter, Kim-Marie
Ponich, Ashley A.
Hall, Dennis G.
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.
View MoreShanghai Mio Chemical Co., Ltd
Contact:0086 21- 64401188-622
Address:16 Floor NO.2 Jiefang Building, No. 4855 Dushi Road, 201100 Shanghai, P.R.China
Contact:852-27701081
Address:Room 2509, New Tech Plaza, 34 Tai Yau St., San Po Kong, HK
ShangHai BMG Chemical Co., Ltd
Contact:+86-13524845543
Address:Room 602, no 291 sikai road shanghai
Sichuan Sangao Biochemical Co., Ltd
Contact:+86-28-84874233
Address:19F, Bldg.2, Shudu Center, Tianfu 2nd St., Hi-tech zone, Chengdu 610041, Sichuan Province, China.
Shanghai Micro-mega Industry Co., Ltd.
Contact:0086-21-34628682;57153848
Address:Rm413,No.413,West Meilong Road, Minhang District,Shanghai P R China
Doi:10.1021/ic501831j
(2014)Doi:10.1021/ja01053a033
(1969)Doi:10.1016/S0960-894X(97)10083-X
(1998)Doi:10.1021/om990872d
(2000)Doi:10.1021/bi00839a049
(1969)Doi:10.1021/jo991181u
(2000)