A palladium-catalyzed enantioselective redox-relay Heck reaction of 2-indole triflates and disubstituted alkenes is reported. This process combines readily available indole triflates with a variety of alkenes to afford a range of indole derivatives bearing a stereocenter adjacent to C2. Enantioselectivity is achieved through use of a simple pyridine-oxazoline ligand. Tuning the electronics of the indole, through judicious choice of N-protecting group, is required to ensure selective β-hydride elimination away from the indole core. Utility of this method is highlighted in a modular formal synthesis of an S1P1 agonist precursor developed by Merck.
Bibliographical noteFunding Information:
The work was supported by National Institute of Health (NIGMS R01GM063540). Q.Y. acknowledges Shanghai Jiao Tong University for a postdoctoral fellowship.
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- Heck reaction
- asymmetric catalysis
- enantioselective catalysis