Asymmetric transfer hydrogenation of unsaturated ketones; factors influencing 1,4- vs 1,2- regio- and enantioselectivity, and alkene vs alkyne directing effects

Thomas H Hall,Martin Wills,Vijyesh K Vyas,K.L Michael Chu,Hannah Adams

doi:10.1016/j.tet.2020.131771

Thomas H Hall, Martin Wills + Show 3 more

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https://doi.org/10.1016/j.tet.2020.131771

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Journal: Tetrahedron	Publication Date: Nov 19, 2020
Citations: 4	License type: cc-by

Affiliation: University of Warwick

Abstract

A detailed study has been completed on the asymmetric transfer hydrogenation (ATH) of a series of enones using Ru(II) catalysts. Electron-rich rings adjacent to the CO group reduce the level of CO reduction compared to CC. The ATH reaction can readily discriminate between double and triple bonds adjacent to ketones, reducing the double bond but leaving a triple bond intact in the major product.

Highlights

Asymmetric transfer hydrogenation (ATH) of ketones using Ru(II)/arene/TsDPEN complexes such as 1e7 (Fig. 1) is a wellestablished process that generates alcohols in high enantioselectivities [1,2,3,4,5,6]
The catalysts are well-suited to the reductions of acetophenone derivatives and alkynyl(acetylenic) ketones, which are reduced in high ee through relatively well-understood transition states (Fig. 2) [2]
Deng et al [7] described the reductions of ketones with catalyst 1 to the corresponding allylic alcohols, using a combination of formic acid and trimethylamine (FA/TEA) as solvent and reducing agent, in high yield; enantioselectivities depended on the substitution pattern on the alkene (Fig. 3a)

Summary

Introduction

Asymmetric transfer hydrogenation (ATH) of ketones using Ru(II)/arene/TsDPEN complexes such as 1e7 (Fig. 1) is a wellestablished process that generates alcohols in high enantioselectivities [1,2,3,4,5,6]. The catalysts are well-suited to the reductions of acetophenone derivatives and alkynyl(acetylenic) ketones, which are reduced in high ee through relatively well-understood transition states (Fig. 2) [2]. ATH, using the Ru(II) catalysts 1e5, of a,b-unsaturated ketones reveals a rather more complex pattern of selectivities. Deng et al [7] described the reductions of ketones with catalyst 1 to the corresponding allylic alcohols, using a combination of formic acid and trimethylamine (FA/TEA) as solvent and reducing agent, in high yield; enantioselectivities depended on the substitution pattern on the alkene (Fig. 3a). Using chalcone as the substrate for TH with the achiral ligand N-tosylethyenediamine (TsEN), the reduction product was a ca. 3:1 mixture of saturated ketone and saturated alcohol [7]

Methods

Results

Conclusion