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Final Report Summary - CHIBACHA (Chiral Base C−H Activation)

The transition-metal-catalyzed asymmetric C(sp3)−H activation is a powerful tool and an emerging research frontier for the atom-economical and step-economical construction of chiral functionalized molecules from simple hydrocarbon compounds. In this context, the oxidative addition-directed strategy was applied to asymmetric C(sp3)−H bond activation by using different catalytic systems composed of Pd0/base/chiral ligand. Mechanistically, C(sp3)−H bond cleavage in this approach has been shown to occur via a coordinated base-assisted concerted metalation-deprotonation mechanism. In the enantiodetermining step, not only the ligand, but also the base should be able to interact with the substrate via non-covalent bonding, and hence induce enantioselectivity. However, compared with the more studied Pd0/base/chiral ligand catalytic systems, no efficient enantioselective transformation catalyzed by Pd0/chiral base/achiral ligand systems has been reported before this project CHIBACHA.
The EU-funded CHIBACHA (Chiral Base C−H Activation) project is an FP7-PEOPLE-2013 International Incoming Fellowship (IIF) Action. This work was carried out in UMR CNRS5246-ICBMS, University Claude Bernard Lyon 1 and the department of chemistry at University of Basel. The main purpose of this research project was to investigate the feasibility of the concept, i.e. asymmetric C(sp3)−H activation using a chiral base instead of a chiral ligand.
Following the original plan described in the proposal, enantioselective synthesis of chiral indolines was first selected as a benchmark reaction to test the feasibility of our concept. Through an extensive optimization study, it was found that high levels of enantioselectivity (up to 98:2 e.r.) and efficiency (up to 96% yield) can be obtained for a variety of indoline products containing both tri- and tetrasubstituted stereocenters using a chiral catalytic base, which is formed in situ upon deprotonation of a chiral phosphoric acid, as the sole source of chirality.
Given that the chiral base C−H activation concept was successfully realized, we continued to extend this approach to the construction of valuable chiral six-membered nitrogen cycles (up to 95:5 e.r.) and four-membered carbon cycles with a promising e.r. (68:32). As we expected in the proposal, this project thus opened a very important field in asymmetric C(sp3)−H activation and will allow more researchers to work in this area. We are confident that more interesting results related to chiral base C−H activation will be disclosed and reported in the near future.

Related information

Reported by

UNIVERSITAT BASEL
Switzerland

Subjects

Life Sciences
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