Enantioselective Aza‐Henry Reaction of Imines Bearing a Benzothiazole Moiety Catalyzed by a Cinchona‐Based Squaramide

Abstract

An efficient enantioselective aza-Henry reaction of nitroalkanes to imines bearing a benzothiazole moiety catalyzed by a Cinchona-based squar-A C H T U N G T R E N N U N G amide has been developed. In the reaction of imines, the corresponding products were obtained in good to excellent yields (up to 99%) with excellent enantioselectivities (up to > 99% ee) for most of the aromatic substituted imines. The imines with electron-withdrawing groups gave better yields than those bearing electron-donating groups in the aza-Henry reaction.Moreover, a one-pot three-component enantioselective aza-Henry reaction using 2-aminobenzothiazoles, aldehydes, and nitromethane was also developed. Moderate to good yields and high enantioselectivities were obtained in the one-pot cases (up to 98% ee).

Chiral phosphoric acid-catalyzed enantioselective construction of structurally diverse benzothiazolopyrimidines

“…With this proposal in mind, we examined the aza-Diels–Alder reaction of 2-benzothiazolimine18 2a with ( E )- N -benzyl propenylcarbamate ( 3a ) in the presence of chiral phosphoric acids 1 . Gratifyingly, in dichloromethane at room temperature, the reaction promoted by 1a afforded benzothiazolopyrimidine 4a as a single diastereomer, with an enantiomeric excess of 95% albeit with a low yield (Table 1, entry 1).…”

Squaramide‐Catalyzed Asymmetric Reactions

“…The aza‐Henry reaction is an important and efficient method for carbon‐carbon bond formation in organic chemistry . An efficient Cinchona ‐based squaramide‐catalyzed enantioselective aza‐Henry of imines bearing a benzothiazole moiety 49 with nitromethane 2 was developed by our group in 2013 . The corresponding products 50 were obtained in good to excellent yields (70‐99 % yield) with excellent enantioselectivities (51‐>99 % ee ) in most cases (Scheme ).…”

A General Asymmetric Formal Synthesis of Aza‐Baylis–Hillman Type Products under Bifunctional Catalysis

“…All these imines ( 2 a – 2 e ) have a moderate capability of forming a hydrogen bond with Takemoto's catalyst 4 c because the sulfonyl group weakens the availability of the lone pair on the nitrogen (C=N:). Therefore, we hypothesized that a more hydrogen coordinated imine such as 2 g would increase the enantiomeric excess. Pleasantly, the reaction of imine 2 g led to the final product 3 g with the highest enantiomeric excess (>99 % ee , entry 7) with a moderate conversion of 67 % due to the lower reactivity of this imine compared with the sulfonyl‐imines.…”