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New Transformations of Secondary Alkylboronic Esters

Final Report Summary - TASTE (New transformations of secondary alkylboronic esters)

Our proposal for the fellowship concerned the expansion of the synthetic utility of chiral boronic esters, for which our research group has recently developed efficient synthetic methods. In specific, the main tasks described in the proposal were: a) the stereoselective replacement of boron to halides and other heteroatoms, b) the reaction of boronic esters with carbon electrophiles and c) their oxidative arylation as a conceptually novel approach to (metal-free) cross coupling of secondary organometallics. We have progressed significantly with regard to (a) and (b) during the course of the fellowship.

Concerning objectives (a) and (b), we have published last year our results on the stereo-defined reaction of boronate complexes with a variety of electrophiles including carbon, nitrogen, oxygen and halide-based ones. We discovered that boron-ate complexes of chiral boronic esters can react in this context always with inversion of configuration. In an effort to expand the range of carbon electrophiles, we turned our attention to N-containing heterocycles, such as quinoline and pyridine. Transformations of this type would be certainly of high importance, leading to the formation of chiral dihydroquinolines and dihydropyridines, building blocks that are of high importance for the pharmaceutical industry, and so the socio-economic impact of such research could be clearly visible. We reasoned that this would greatly expand the potential of our chemistry and it was the focus of the fellow's work during the fellowship period. After extensive experimentation we identified optimum conditions and a chiral auxiliary that would render the reaction of boron-ate complexes with quinoline diastereoselective, namely (-)-8-phenyl menthol. Moreover, we found that addition of the same ate complex to chiral pyridinium ions affords excellent diastereoselectivities as well.

In addition, we looked at the development of an improved protocol that would avoid the use of chiral auxiliaries and we found that properly substituted pyridines and quinolines can react with our boron reagents to afford highly selective transformations with the inherent chirality of the boronic esters as the stereo-defining element.

In conclusion, we have extended that the utility of the carbon-boron bond so that to address stereoselective reactions with carbon electrophiles, of unprecedented efficiency. This greatly expands the synthetic chemist's toolbox with useful transformations that enable the synthesis of valuable compounds.