Natural product synthesis has been a chief goal for organic chemists and continues to present a formidable challenge due to their complex molecular architecture. Due to the complex nature of these naturally occurring molecules and their relevance in drug targets, there is high demand for reliable synthetic methods to efficiently synthesize natural product scaffolds. A structural motif ubiquitous in natural products is the heterocycle; traditionally synthesized through substitution pathways that are often unpredictable and difficult to control as the molecule becomes increasingly complex. Here we report a removable directing group approach to the intramolecular cyclization of alcohols via directed Pd catalyzed activation of sp3 C-H bonds to provide heterocyclic compounds. Under our conditions, various ring sizes have been achieved in moderate to high yields, where primary secondary and tertiary alcohols are all tolerated. In addition, the intramolecular cyclization to form spirocyclic compounds have also been observed in moderate yields. This discovery provides a novel method for intramolecular cyclization that is both catalytic and site selective, a promising tool for natural product synthesis.

Site selective Pd-catalyzed intramolecular cyclization of oxygen nucleophiles

249th National Meeting (2015)

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