Development of Catalytic Reactions Using Bis(pinacolato)diboron and Their Applications to Syntheses of Pharmaceuticals and Luminescent Dyes

Abstract

We have developed three catalytic reactions involving borylation and C-C bond formation using bis(pinacolato)diboron (B₂pin₂), and have extended their use to the synthesis of pharmaceuticals and luminescent dyes. In addition, we have also elucidated the photophysical properties of those dyes. The first reaction is a Cu-catalyzed stereoselective borylation of glycosyl bromide to β-glycosyl trifluoroborates, which has been further expanded to synthesize aryl β-C-glycosides via Pd-catalyzed stereospecific cross-coupling with aryl bromides. These methods were applied to the stereospecific synthesis of the SGLT2 inhibitor, canagliflozin. The second reaction involves the copper-catalyzed borylation of acyl chlorides to form acyl trifluoroborates, which have further been applied to the synthesis of fluorescent C,N-chelated 2,2-difluoro-1,4-diazaboroles via condensation with various amino-heterocycles. The third reaction is an organocatalytic pinacol coupling of aryl aldehydes using B₂pin₂ as a reductant and a substituted pyridine catalyst. The resulting diols were converted to various substituted benzils, revealing the luminescent properties such as phosphorescence, fluorescence, and self-recovering phosphorescence-to-phosphorescence mechanochromism. These studies demonstrated the usefulness of the developed methods for producing pharmaceuticals, pharmaceutical candidates and novel materials, as well as making possible the investigation of the products physical properties.

Graphical Abstract