Continuous flow enantioselective arylation of aldehydes with ArZnEt using triarylboroxins as the ultimate source of aryl groups

Abstract

A continuous flow system for the synthesis of enantioenriched diarylmethanols from aldehydes is described. The system uses an amino alcohol-functionalized polystyrene resin as the catalyst, and the arylating agent is conveniently prepared by transmetallation of triarylboroxins with diethylzinc.

Keywords: asymmetric synthesis; continuous flow; diarylmethanols; solid-supported catalyst; triarylboroxins.

Figure 1

Biologically active diarylmethanol derivatives.

Figure 2

Structures of (R)-1,1,2-triphenyl-2-(piperidin-1-yl)ethanol (1) and its polystyrene-immobilized analogue 2.

Scheme 1

Generation of the mixed ArZnEt species from a boronic acid and Et₂Zn.

Scheme 2

Generation of the mixed ArZnEt species from a triarylboroxin and Et₂Zn.

Scheme 3

Synthesis of the immobilized amino alcohol 2.

Scheme 4

Phenylation of tolualdehyde catalyzed by 2.

Figure 3

Experimental set-up for the continuous flow experiments. (A) Schematic representation and (B) Actual system.

Scheme 5

Continuous flow enantioselective preparation of diarylmethanols.