Enantioselective Thiolysis and Aminolysis of Cyclic Anhydrides Using a Chiral Diamine-Derived Thiourea Catalyst.

Jae Ho Shim,Sung Joo Park,Deok-Chan Ha,Hyeon Soo Kim,Ji Yeon Lee,Byung Kook Ahn

doi:10.1021/acsomega.1c04741

Abstract

Catalytic desymmetrization of cyclic anhydrides has been widely investigated in the field of organocatalysis. Using this approach, many stereocenters can be established in a single, symmetry-breaking transformation. Herein, a thiourea organocatalyst was prepared in a single step from a chiral diamine, (R,R)-1,2-diphenylethylenediamine, and used for the desymmetrization of various cyclic anhydrides through double hydrogen-bonding activation. The asymmetric ring-opening reaction of the cyclic anhydride proceeded via the enantioselective addition reaction catalyzed by diamine thiourea. Thiolysis afforded the desired products in the yields of 86–98% and enantioselectivities of 60–94%, while aminolysis afforded the yields of 90–94% and enantioselectivities of 90–95%.

Highlights

An organocatalyst is composed of carbon, hydrogen, sulfur, and other nonmetallic elements commonly found in organic molecules
Various bicyclic and tricyclic anhydrides were subjected to methanolysis under the same conditions, and very good yields of 65−90% as well as enantioselectivities were achieved; the reaction time was too long despite the use of excess amount of catalyst
The ability of thiourea to form hydrogen bonds was enhanced by increasing the acidity of hydrogen on thiourea (Ar substituent); this was achieved by introducing an electron-withdrawing group (EWG)

Summary

■ INTRODUCTION

An organocatalyst is composed of carbon, hydrogen, sulfur, and other nonmetallic elements commonly found in organic molecules. Since 1998, many studies have been conducted on stereoselective syntheses using organic catalysts that are devoid of metals.[1] Among them, the asymmetric ring-opening reaction of cyclic mesoanhydrides is useful for the synthesis of biologically active substances. In this context, mesochiral, prochiral, and racemic cyclic anhydrides have been used as synthetic building blocks of natural products containing α-amino acid, α-hydroxy acid, and hemiester moieties. Nagao used (R,R)-1,2-diphenylethylenediamine (DPEN) as the basic skeleton of the chiral catalyst within which thiourea is introduced for application in the asymmetric ring-opening reaction by hydrogen-bonding catalysis.[10,11] We envisaged that we could use this catalyst for investigating the thiolysis of a range of cyclic anhydrides

■ RESULTS AND DISCUSSION

■ CONCLUSIONS

■ ACKNOWLEDGMENTS

■ REFERENCES