Asymmetric 1,2-Perfluoroalkyl Migration: Easy Access to Enantioenriched α-Hydroxy-α-perfluoroalkyl Esters

Abstract

This study has led to the development of a novel, highly efficient, 1,2-perfluoro-alkyl/-aryl migration process in reactions of hydrate of 1-perfluoro-alkyl/-aryl-1,2-diketones with alcohols, which are promoted by a Zn(II)/bisoxazoline and form α-perfluoro-alkyl/-aryl-substituted α-hydroxy esters. With (-)-8-phenylmenthol as the alcohol, the corresponding menthol esters are generated in high yields with excellent levels of diastereoselectivity. The mechanistic studies show that the benzilic ester-type rearrangement reaction takes place via an unusual 1,2-migration of electron-deficient trifluoromethyl group rather than the phenyl group. The overall process serves as a novel, efficient, and simple approach for the synthesis of highly enantioenriched, biologically relevant α-hydroxy-α-perfluoroalkyl carboxylic acid derivatives.

The Wonderful Chemistry of Trifluoromethyl α‐Haloalkenyl Ketones

“…In fact, the reaction that we serendipitously discovered is not trivial: to the best of our knowledge this is the first example of easy migration of a trifluoromethyl group to a neighboring electrophilic carbon atom. An example of highly stereoselective intramolecular Lewis‐acid‐catalyzed 1,2‐perfluorinated group migration in 1,2‐diketones was reported recently …”

Experimental and Theoretical Study of an Intramolecular CF3‐Group Shift in the Reactions of α‐Bromoenones with 1,2‐Diamines

“…In our case, the intramolecular transfer of the CF 3 group proceeds in much milder conditions due to the presence of an internal basic center. Very recently, the first example of an asymmetric migration of a perfluorinated moiety to a carbonyl group was published by Tang and co‐workers 17…”

“…Very recently,t he first example of an asymmetric migration of ap erfluorinatedm oiety to ac arbonyl group was published by Ta ng and co-workers. [17] Rather unpredictable resultsw ere obtainedw hen a-bromoenones 1 weret reated with N,N'-dicyclopropylethylenediamine in THF.I nt his case the reactionp roceedsh ighly chemo-and stereoselectively to give the corresponding acylated piperazines 4b-i in good yields as the only product (Table 1).…”

Recent Advances in Catalytic Enantioselective Rearrangement

“…More recently, the same group reported a highly stereoselective Zn(II)/bisoxazoline L13 catalyzed 1,2‐perfluoroalkyl and perfluoroaryl migration reaction of 1,2‐diketones 102 with (–)‐8‐phenylmenthol 103 (Scheme ) . A wide range of enantioenriched α‐hydroxy‐α‐perfluoroalkyl esters 104 were obtained in high yields with excellent diastereoselectivities.…”