Development of the Regiodivergent Asymmetric Prenylation of 3‐Substituted Oxindoles. Issue 18 (6th March 2017)

• Record Type: Journal Article
• Authors: Trost, Barry M.; Chan, Walter H.; Malhotra, Sushant
• Is Part Of: Chemistry. Volume 23:Issue 18(2017)
• Page Start: 4405
• Page End: 4414
• Publication Date: 2017-03-06
• Subjects: allylic alkylation -- flustramines -- oxindoles -- palladium -- prenylation; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201605810
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: This paper describes our efforts to design a Pd‐catalyzed asymmetric prenylation of 3‐substituted oxindoles that affords access to both the linear and reverse‐prenylated products. Both 3‐alkyl‐ and 3‐aryloxindoles performed well under our optimized reaction conditions. The regiodivergent alkylation of monoterpene‐derived electrophiles using this methodology was also investigated. The utility of this methodology in natural product synthesis was demonstrated through the efficient total syntheses of four Flustra alkaloids, which also allowed the absolute stereochemistry of the prenylated oxindole products to be assigned. Surprisingly, the same enantiomer of ligand produced linear and branched regioisomers of opposite chirality. Abstract : An orthogonal set of reaction conditions has been developed for the asymmetric Pd‐catalyzed prenylation of 3‐alkyl‐ and 3‐aryloxindoles, allowing for selective formation of both the prenyl and reverse‐prenyl oxindoles. The subtle factors that guide regioselectivity are applied to reactions using hemi‐ and monoterpenoid electrophiles. The absolute stereochemistry of the products was determined through the asymmetric synthesis of flustramines A and B.