Complementary Asymmetric Routes to (R)-2-(7-Hydroxy-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetate

Two distinct and scalable enantioselective approaches to the tricyclic indole (R)-2-(7-hydroxy-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetate, an important synthon for a preclinical S1P(1) receptor agonist, are reported. Route 1 employs a modified version of Smith's modular 2-substituted indole synthesis as the key transformation. Route 2 involves a highly enantioselective CuH-catalyzed 1,4-hydrosilylation as the stereodefining step. Both routes can be performed without chromatography to provide multigram quantities of the tricycle in ≥98% ee.