Enantioselective Synthesis of a PKC Inhibitor via Catalytic C−H Bond Activation

• Published in: Organic letters Vol. 8; no. 8; pp. 1745 - 1747
• Main Authors: Wilson, Rebecca M, Thalji, Reema K, Bergman, Robert G, Ellman, Jonathan A
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 13-04-2006
• Subjects: Catalysis; Indoles - chemical synthesis; Indoles - chemistry; Indoles - pharmacology; Molecular Structure; Protein Kinase C - antagonists & inhibitors; Stereoisomerism; Structure-Activity Relationship
• ISSN: 1523-7060; 1523-7052
• DOI: 10.1021/ol060485h

The syntheses of two biologically active molecules possessing dihydropyrroloindole cores (1 and 2) were completed using rhodium-catalyzed imine-directed C−H bond functionalization, with the second of these molecules containing a stereocenter that can be set with 90% ee during cyclization using chiral nonracemic phosphoramidite ligands. Catalytic decarbonylation and direct indole/maleimide coupling provide efficient access to 2.