Stereoconvergent, Redox‐Neutral Access to Tetrahydroquinoxalines through Relay Epoxide Opening/Amination of Alcohols

Abstract

We present an economical catalytic procedure to convert readily available 1,2‐diaminobenzenes and terminal epoxides into valuable 1,2,3,4‐tetrahydroquinoxalines in a highly enantioselective fashion. This procedure operates through relay zinc and iridium catalysis, and achieves redox‐neutral and stereoconvergent production of valuable chiral heterocycles from racemic starting materials with water as the only side product. The use of commercially available reagents and catalysts and a convenient procedure also make this catalytic method attractive for practical application.

Catalytic Enantioselective Access to Dihydroquinoxalinones via Formal α‐Halo Acyl Halide Synthon in One Pot

“…Thef easibility of DROC process with more sterically hindered N-methyl ortho-phenylendiamine was next examined, with av iew to directly install typical N-methyl substitution found in some pharmaceutically active derivatives,thus avoiding afollowing sensitive N-alkylation step. [27] Gratifyingly,t he corresponding N-methyl derived dihydroquinoxalinones 3t and 3u were isolated in 68 %, 77 %y ield and with 88 % ee,8 9% ee,r espectively.W hent he one-pot process was carried out from the corresponding alkenes, heterocycles 3t and 3u were isolated with 92 % ee and 96 % ee,s howing that as light erosion of the enantioselectivity occurred when starting from aldehydes.P reliminary investigations were then carried out using ortho-amino phenol and ortho-amino thiophenol with benzaldehyde as the reagent. Pleasingly,d ihydrobenzoxazinone (R)-3v was obtained in 60 %o verall yield and 89 % ee.…”

“…Then, commercially available substituted ortho ‐phenylendiamines [26] were coupled with either mono‐, di‐substituted, 2‐naphthyl and heteroaromatic aldehydes providing diversely substituted dihydroquinoxalinones ( 3 l – s ) with high yields (60–77 %) and high to excellent enantioselectivity (85–99 % ee ). The feasibility of DROC process with more sterically hindered N ‐methyl ortho ‐phenylendiamine was next examined, with a view to directly install typical N ‐methyl substitution found in some pharmaceutically active derivatives, thus avoiding a following sensitive N ‐alkylation step [27] . Gratifyingly, the corresponding N ‐methyl derived dihydroquinoxalinones 3 t and 3 u were isolated in 68 %, 77 % yield and with 88 % ee , 89 % ee , respectively.…”

Catalytic Enantioselective Access to Dihydroquinoxalinones via Formal α‐Halo Acyl Halide Synthon in One Pot

“…The feasibility of DROC process with more sterically hindered N ‐methyl ortho ‐phenylendiamine was next examined, with a view to directly install typical N ‐methyl substitution found in some pharmaceutically active derivatives, thus avoiding a following sensitive N ‐alkylation step. [27] Gratifyingly, the corresponding N ‐methyl derived dihydroquinoxalinones 3 t and 3 u were isolated in 68 %, 77 % yield and with 88 % ee , 89 % ee , respectively. When the one‐pot process was carried out from the corresponding alkenes, heterocycles 3 t and 3 u were isolated with 92 % ee and 96 % ee , showing that a slight erosion of the enantioselectivity occurred when starting from aldehydes.…”

Ni-Catalyzed Enantioconvergent Coupling of Epoxides with Alkenylboronic Acids: Construction of Oxindoles Bearing Quaternary Carbons

“…(2) Despite the considerable progress made in this field, the enantioconvergent transformation of racemic epoxides, which could be used to prepare chiral alcohol products with high conversion and high enantioselectivity in an atom economical manner, has not been widely studied. [57][58][59][60][61][62][63] (3) With respect to the construction of quaternary stereocenters, Pd-and Cu-catalyzed enantioconvergent couplings of 1,1-disubstituted epoxides with nucleophiles were reported by Trost and Nishibayashi, respectively. 57,58 A elegant example of redox-triggered C-C coupling of alcohols and 1,1-disubstituted epoxides via iridium catalysis, has been developed by Krische and co-workers.…”