Direct Trifluoromethylation of Alcohols Using a Hypervalent Iodosulfoximine Reagent.

Jorna Kalim,Emmanuel Magnier,Antonio Togni,Ewa Pietrasiak,Thibaut Duhail,Elsa Anselmi

doi:10.1002/chem.202005104

Abstract

The direct trifluoromethylation of a variety of aliphatic alcohols using a hypervalent iodosulfoximine reagent afforded the corresponding ethers in moderate to good yields (14-72 %). Primary, secondary, and even tertiary alcohols, including examples derived from natural products, underwent this transformation in the presence of catalytic amounts of zinc bis(triflimide). Typical reaction conditions involved a neat mixture of 6.0 equivalents of the alcohol with 1.0 equivalent of the reagent, with the majority of reactions complete within 2 h with 2.5 mol % of the Lewis acid catalyst. Furthermore, experimental evidence was provided that the C-O bond-forming process occurred via the coordination of the alcohol to the iodine atom and subsequent reductive elimination.

Highlights

The direct trifluoromethylation of a variety of aliphatic alcohols using a hypervalent iodosulfoximine reagent affords the corresponding ethers in moderate to good yields (14-72%)
In 2009, one of our groups reported the use of hypervalent iodine compound 1 (Scheme 1b) for the trifluoromethylation of primary and secondary alcohols using zinc triflimide in either catalytic or stoichiometric amounts.[17,18]
Through a series of control experiments, we provide strong evidence that the mechanism for this reaction involves the coordination of the alcohol substrate to the hypervalent iodine species, affording the trifluoromethyl ether through a reductive elimination process

Summary

Introduction

The direct trifluoromethylation of a variety of aliphatic alcohols using a hypervalent iodosulfoximine reagent affords the corresponding ethers in moderate to good yields (14-72%). In 2009, one of our groups reported the use of hypervalent iodine compound 1 (Scheme 1b) for the trifluoromethylation of primary and secondary alcohols using zinc triflimide in either catalytic (usually requiring more than 30 mol-%) or stoichiometric amounts.[17,18]

Results

Conclusion