Extending Pummerer Reaction Chemistry. Development of a Strategy for the Regio- and Stereoselective Oxidative Cyclization of 3-(ω-Nucleophile)-Tethered Indoles

• Published in: Journal of organic chemistry 2005-08, Vol.70 (16), p.6429-6440
• Main Authors: Feldman, Ken S, Vidulova, Daniela Boneva, Karatjas, Andrew G
• Format: Article
• Language: English
• Subjects: Chemistry; Cyclization; Electrons; Ethylenes - chemistry; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with n hetero atom and also o and/or s, se, te hetero atoms; Indoles - chemistry; Ketones - chemistry; Molecular Structure; Organic chemistry; Oxidation-Reduction; Preparations and properties; Stereoisomerism; Tryptophan - chemistry
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo050896w

The brominative cyclization of diastereomeric β-silyloxy tryptophan derivatives proceeded with divergent regiochemistry (C(2) or C(3) addition), depending on the relative stereochemistry of the silyloxy substituent. This lack of C(2) vs C(3) regiochemical predictability led to the development of a new approach, which featured Pummerer-type chemistry on an indole C(2) sulfoxide or sulfide substrate, for steering nucleophilic addition to C(3) of the indole. Extension of this transformation from carboxylate nucleophiles to carbon analogues such as allylsilane, silyl enol ether, and silyl ketene iminal bearing substrates led to the formation of spirocyclic oxindole derivatives in good yields with complete regioselectivity for C(3) cyclization and with good diastereoselectivity where relevant.