Enantioselective Reaction of 2H‐Azirines with Phosphite Using Chiral Bis(imidazoline)/Zinc(II) Catalysts

Abstract

The first highly enantioselective nucleophilic addition reaction of phosphites with 2H-azirines has been developed. The reaction was applied to various 3-substituted 2H-azirines using novel chiral bis(imidazoline)/Zn catalysts to afford products in good yield with high enantioselectivity. The transformation of the obtained optically active aziridines showed that 2H-azirines act as either α,β- or β,β-dicarbocationic amine synthons.

Copper(I)-catalyzed asymmetric decarboxylative Mannich reaction enabled by acidic activation of 2H-azirines

“…The same diastereo- and enantioselectivities were observed both in the decarboxylative version and in the proton-transfer version, indicating that the same copper(I) intermediate was generated. It is reasonable that the proton-transfer version led to very low yield as 2 H -azirine 2a is a poor electrophile as described in literature 25,28 . As 2 H -azirine 2a is an imine base, it is also reasonable that the protonation of 2a by 1a might occur smoothly to give an iminium cation, which is a highly electrophilic species.…”

“…4. After protection of 3a with an acid chloride, the rearrangement of the aziridine moiety in 3a to an oxazoline group produced 6 in 63% yield with maintained enantioselectivity 25 .The reduction of cyano group by DIBAL-H afforded carbamate 7 in 60% yield after protection of the free amine with Boc 2 O. Moreover, the acidic opening of the aziridine group in 3a with HCl proceeded smoothly to furnish amine 8 in 80% yield.…”

Enantioselective Reaction of 2H‐Azirines

“…The first highly enantioselective nucleophilic addition of phosphites to 2 H ‐azirines was reported by Nakamura and Hayama in 2017, although the enantioselective reaction of phosphorous nucleophiles with ketimines remains rare (Scheme ) . This reaction was applied to a variety of 3‐substituted 2 H ‐azirines ( 25 ) by using a chiral zinc(II)/bis(imidazoline)‐phenol ( 28 ) catalyst to afford the corresponding products ( 27 ) in good yields with high enantioselectivities.…”

Catalytic Enantioselective Aza‐Benzoin Reactions of Aldehydes with 2H‐Azirines

“…reported a highly enantioselective imine amidation to assemble chiral aziridines by utilizing a novel chiral N , N′ ‐dioxide/Sc III catalyst . Shortly after, Nakamura and co‐workers reported a chiral bis(imidazoline)/Zn II ‐catalyzed nucleophilic addition of phosphites to 2 H ‐azirines, thereby generating aziridines in good yields with high to excellent enantioselectivities . While pioneering works are influential, practical applications of these protocols are always affected by their scope, to a certain extent .…”