Published papers

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.

Elaborated conditions for lipase-catalyzed preferential monoacetylation enabled the large-scale preparation of hydroquinone monoacetate. This product was then applied to the synthesis of tournefolin B, a highly oxygenated prenylated hydroquinone of plant origin (Tournefortia sarmentosa Lam.). During the course of the synthetic transformations, lipase-catalyzed deacetylation under mild conditions was demonstrated.

The synthesis of 2,2-difluoro-1,4-diazaboroles was achieved through the condensation of aliphatic acyltrifluoroborates and amino-N-heteroarenes under acidic conditions. Various N-heteroarenes, including pyridine, pyrimidine, pyridazine, thiazole, and isoquinoline, were successfully employed in the reaction. Among the synthesized 2,2-difluoro-1,4-diazaboroles, the one with an isoquinoline structure exhibited the most intense light blue emission.

Construction of the hydroquinoline skeleton of symbioimine by Cu-mediated N-alkenylation or O-alkenylation of an allyl aminoalcohol, in which either chemoselectivity could lead to the target compound, was investigated. O-alkenylation followed by Claisen rearrangement was favored with high selectivity under a ligand-free condition. Subsequent intramolecular condensation furnished the hydroquinoline skeleton of symbioimine.

© 2018 The Chemical Society of Japan. The cyclic trimer of dibenzofuran linked at the 4,6-positions, named [3]cyclo-4,6-dibenzofuranylene, was synthesized by Ni(0)-mediated reductive coupling of 4,6-dibromodibenzofuran. DFT calculation indicated that the flake-shaped C2 symmetric structure is the most stable conformer and the propeller-shaped D3 symmetric structure is the minor conformer with a higher energy (+19.1 kcal mol-1). The calculated inversion energy of the C2 conformer through a Cs symmetric transition state was +4.1 kcal mol-1, showing rapid fluctuation, which is consistent with the observation of only one set of 1HNMR signals of dibenzofuran of [3]cyclo-4,6-dibenzofuranylene.

© 2018 Royal Society of Chemistry. All rights reserved. Tris(2-hydroxyphenyl)triazasumanene ((A)-(+)-1), a bowl-shaped molecule, which possesses 2-(20-hydroxyphenyl)pyridine moieties, was successfully synthesised. (A)-(+)-1 showed a single peak emission in CH2Cl2, which overlapped with the emission of the triazasumanene skeleton and diminished at a high concentration, corresponding to the formation of the excited enol form. In contrast, single crystals of (A)-(+)-1 exhibited a dual emission with a large Stokes shift, indicating the presence of the excited keto form by the excited state intramolecular proton transfer (ESIPT) process. In the solution of (A)-(+)-1 containing a mixture of a large amount of a poor solvent (hexane or MeOH) and a small amount of CH2Cl2, colloidal aggregates emerged with the continuous increment of emission intensity by further addition of the poor solvent, demonstrating aggregation-induced enhanced emission (AIEE). The analysis of the morphology and the structure of the aggregates using a scanning electron microscope (SEM) and powder X-ray diffraction (PXRD) revealed the well-ordered structure of the aggregates, which possessed a molecular packing pattern similar to that of an (A)-(+)-1 single crystal.

The metal-free thermal organocatalytic pinacol coupling of arylaldehydes has been developed. The intermolecular coupling of arylaldehydes catalyzed byt-butyl isonicotinate with bis(pinacolato)diboron as the co-reducing agent afforded 1,2-diphenylethane-1,2-diols. This reaction was also applicable to the intramolecular coupling of 1,1′-biphenyl-2,2′-dicarbaldehydes to afford 9,10-dihydrophenanthrene-9,10-diols. Various functional groups were tolerated under this coupling condition.