N-Methyl-(R)-3-(tert-Butyl)-Sulfinyl-1,4-Dihydropyridine: A Novel NADH Model Compound

Kun Xie,You-Cheng Liu,Thomas Mak,Yao Fu,Yi Cui,Jian-Ge Wang

doi:10.3390/12030415

Abstract

We have synthesized a novel chiral NADH model compound, N-methyl-(R)-3-(tert-butyl)-sulphinyl-1,4-dihydropyridine with high enantioselectivity and used it in the reduction of methyl benzoylformate, producing (S)-methyl mandelate in 95% ee. The absolute structure of its precursor, 3-(tert-butyl)sulfinyl pyridine, was determined by X-ray analysis.

Highlights

Since Ohno and coworkers reported the first example of asymmetric reduction of ketones with a coenzyme NADH model compound in 1975 [1], numerous efforts have been made to construct other models mimicking such asymmetric reduction [2]
To the best of our knowledge, far only three such chiral sulfoxides have been reported as coenzyme NADH models (Figure 1)
It is well known that the tert-butyl group has a large steric hindrance and the C(4) prochiral hydrogen atoms in the dihydropyridine nucleus are expected to be diastereomerically distinguished by the neighboring chiral tert-butylsulfinyl group and the formal hydride transfer from the model compound to the carbonyl substrate should be highly enantioselective

Summary

Introduction

Since Ohno and coworkers reported the first example of asymmetric reduction of ketones with a coenzyme NADH model compound in 1975 [1], numerous efforts have been made to construct other models mimicking such asymmetric reduction [2]. Most of the model compounds reported consist of 3carbonylated (e.g. amide or ester) 1,4-dihydropyridines with a chiral group attached far from the C(4) reaction center, which often result in products of relatively low optical purity [3]. It is well known that the tert-butyl group has a large steric hindrance and the C(4) prochiral hydrogen atoms in the dihydropyridine nucleus are expected to be diastereomerically distinguished by the neighboring chiral tert-butylsulfinyl group and the formal hydride transfer from the model compound to the carbonyl substrate should be highly enantioselective.

Results

Conclusion