TY - JOUR
T1 - Mechanistic Model for Enantioselective Intramolecular Alkene Cyanoamidation via Palladium-Catalyzed C-CN Bond Activation
AU - Frost, Grant B.
AU - Serratore, Nicholas A.
AU - Ogilvie, Jodi M.
AU - Douglas, Christopher J.
N1 - Funding Information:
We thank National Institutes of Health for funding this work (R01 GM095559). We thank Prof. Steve Kass (UMN) for constructive feedback.
Publisher Copyright:
© 2017 American Chemical Society.
PY - 2017/4/7
Y1 - 2017/4/7
N2 - 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.
AB - 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.
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U2 - 10.1021/acs.joc.7b00196
DO - 10.1021/acs.joc.7b00196
M3 - Article
C2 - 28294618
AN - SCOPUS:85017179402
SN - 0022-3263
VL - 82
SP - 3721
EP - 3726
JO - Journal of Organic Chemistry
JF - Journal of Organic Chemistry
IS - 7
ER -