We describe an asymmetric organocatalytic method to synthesize 1,7-dicarbonyl compounds containing a β-stereocenter. The chemistry relies on the formation of γ-keto radicals, generated upon oxidative ring opening of cyclobutanols mastered by an organic photoredox catalyst. These nonstabilized primary radicals are stereoselectively intercepted by an iminium ion intermediate, formed upon activation of aliphatic and aromatic enals by a chiral secondary amine catalyst. This organocatalytic photoredox method served to prepare scaffolds found in natural products and drug molecules.
Hin-Fung Wong, T.; Ma, D.; Di Sanza, R.; Melchiorre, P.
Org. Lett. 2022, 24 (8), 1695–1699
DOI:
10.1021/acs.orglett.2c00326
Observations
We are in a changing era for drug discovery: the growing perception is that basic chemical research will play a greater role in pharmaceutical development. One current challenge is to develop a new kind of chemistry that yields a screening collection of optimal chiral molecules that increase the probability of success in identifying drug-candidate structures. PHOTO-CYCLE seeks to provide some solutions by developing effective technology to rapidly generate, in one single step, architecturally complex chiral natural-like compounds. Specifically, we will use photochemical organocatalytic cascade processes to synthesise polycyclic lactones and polyfunctionalized cyclohexanols, which are common motifs in biologically active molecules. We will combine asymmetric organocatalysis and photochemistry, two powerful strategies of modern chemical research. They have extraordinary potential for the sustainable preparation of novel organic molecules, which are needed to drive innovation in the pharmaceutical industry.
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