DEVELOPMENT OF NEW BORYLATING OLEFINATION METHODOLOGIES: MODIFIED JULIA REACTION

Details

Supervisors

Robiette, Raphaël

Faculty

Faculté des sciences

Degree label

Master [120] en sciences chimiques, à finalité approfondie

Abstract

enOrganoboron compounds have become central reagents in organic synthesis, a development that gained considerable momentum following the introduction of the Suzuki cross-coupling reaction in 1979. Their synthetic utility arises from their ready accessibility and from the versatility of the C–B bond, which can be converted into a broad range of functional groups under mild reaction. Vinylboronates (also termed alkenylboronates) are of particular relevance in this respect, as they constitute highly reactive partners in Suzuki–Miyaura cross-couplings. It is within this framework that the laboratory of Professor R. Robiette seeks to establish general routes to borylated exo-glycals. Two olefination strategies, the boron Wittig and Peterson reactions, had already been examined to that end; however, neither gave access to the desired borylated exo-glycals, both remaining confined to aldehyde and ketone substrates. The present work set out to circumvent this limitation by turning to a third approach, the modified Julia (Julia–Kocienski) olefination, a reaction already known to deliver other classes of substituted exo-glycals.The first stage of the project focused on the preparation of the key reagent of this transformation, a borylated heteroaryl sulfone, a family of compounds with no precedent in the literature, which was investigated along two lines. Direct α-borylation of a methyl Het-sulfone failed to furnish any borylated material: the carbanion generated from sulfone 2 did not react with the boron electrophile, undergoing autocondensation instead. The complementary route, in which a thioether is borylated and then oxidised to the sulfone, behaved more favourably at the borylation step, providing the Bpin- and BF₃K-bearing thioethers of the BT series. Both, however, lost their boron substituent through C–B cleavage upon oxidation. Only when the sturdier BMIDA group was adopted could the targeted borylated sulfones be secured across the three heterocycles examined (BT 20, PT 27 and PYR 39).In the second stage, these BMIDA-sulfones were reacted with a model carbonyl substrate (benzaldehyde) to access the corresponding vinyl boronate 46. Despite an extensive variation of base, solvent, temperature, stoichiometry and heterocycle, the product was detected only in less than 5 % yield from the PT-sulfone, the reaction being predominantly governed by deborylation of the reagent. Control experiments with PT sulfone-Me 23 and with the PT-CH₂CH₂-Bpin sulfone 48 attributed this limitation to the borylated reagent itself, the boron moiety interfering with the reaction even when separated from the sulfonyl carbanion by a two-carbon spacer. Although the borylated exo-glycals could not be obtained, the formation of vinyl boronate 46, albeit in limited amount, provides a first proof of concept that a borylating modified Julia olefination is feasible.