Highly Efficient Kinetic Resolution of Aryl-Alkenyl Alcohols by Ru-Catalyzed Hydrogen Transfer.

Yipeng You,Ming Yu Jin,Guanyu Tao,Xiangyou Xing

doi:10.3390/molecules26247475

Abstract

No matter through asymmetric reduction of ketones or kinetic resolution of secondary alcohols, enantioselective synthesis of the corresponding secondary alcohols is challenging when the two groups attached to the prochiral or chiral centers are spatially or electronically similar. For examples, dialkyl (sp3 vs. sp3), diaryl (sp2 vs. sp2), and aryl-alkenyl (sp2 vs. sp2) alcohols are difficult to produce with high enantioselectivities. By exploiting our recently developed Ru-catalysts of minimal stereogenicity, we reported herein a highly efficient kinetic resolution of aryl-alkenyl alcohols through hydrogen transfer. This method enabled such versatile chiral building blocks for organic synthesis as allylic alcohols, to be readily accessed with excellent enantiomeric excesses at practically useful conversions.

Highlights

Introduction by RuCatalyzed Hydrogen Transfer.The Noyori asymmetric hydrogenation (AH) and asymmetric transfer hydrogenation (ATH) of carbonyl compounds are the most practical and atom-economical approaches for producing optically enriched secondary alcohol products, and have found widespread applications in both academic and industrial settings [1,2,3]
By exploiting our recently developed Ru-catalysts, an example of kinetic resolution of various aryl-alkenyl secondary alcohols through transfer hydrogenation was reported with high efficiencies
Amine-based nucleophiles were found to serve as a strong driving force for the kinetic resolution process, so that the corresponding α,β-unsaturated ketones that derive from the dehydrogenation of one reactive enantiomer would readily undergo a conjugate addition

Summary

Introduction

Introduction by RuCatalyzed Hydrogen Transfer.The Noyori asymmetric hydrogenation (AH) and asymmetric transfer hydrogenation (ATH) of carbonyl compounds are the most practical and atom-economical approaches for producing optically enriched secondary alcohol products, and have found widespread applications in both academic and industrial settings [1,2,3]. Asymmetric transfer hydrogenation, from the viewpoint of its mechanism, has two ways to generate enantiomerically enriched secondary alcohols, either by asymmetric reduction of the corresponding ketones [4,5,6,7,8,9] or by kinetic resolution of racemic secondary alcohols (Figure 1A) [10,11,12,13]. Due to the reversibility of the dehydrogenation-hydrogenation process, kinetic resolution of secondary alcohols via transfer hydrogenation is highly dependent on the redox properties of the alcohols formed as well as the chiral recognition capabilities of the catalyst, and still remains a challenging task [10,11,12,13,14]. Adding an external nucleophile, such as an amine or an alcohol, would drive the reversible dehydrogenation

Methods

Results

Conclusion