Mechanistic Model for Enantioselective Intramolecular Alkene Cyanoamidation via Palladium-Catalyzed C-CN Bond Activation

Grant B. Frost, Nicholas A. Serratore, Jodi M. Ogilvie, Christopher J. Douglas

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8 Scopus citations

Abstract

We studied key aspects of the mechanism of Pd-catalyzed C-CN bond activation and intramolecular enantioselective alkene cyanoamidation. An Abboud-Abraham-Kamlet-Taft (AAKT) linear solvation energy relationship (LSER) model for enantioselectivity was established. We investigated the impact of Lewis acid (BPh3), Lewis base (DMPU), and no additives. BPh3 additive led to diminished enantioselectivity and differing results in 13CN crossover experiments, initial rate kinetics, and natural abundance 12C/13C kinetic isotope effect measurements. We propose two catalytic mechanisms to account for our experimental results. We propose that the DMPU/nonadditive pathway passes through a κ2-phosphoramidite-stabilized Pd+ intermediate, resulting in high enantioselectivity. BPh3 prevents the dissociation of CN-, leading to a less rigid κ2-phosphoramidite-neutral Pd intermediate.

Original languageEnglish (US)
Pages (from-to)3721-3726
Number of pages6
JournalJournal of Organic Chemistry
Volume82
Issue number7
DOIs
StatePublished - Apr 7 2017

Bibliographical note

Funding Information:
We thank National Institutes of Health for funding this work (R01 GM095559). We thank Prof. Steve Kass (UMN) for constructive feedback.

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