title: Non-Directed Allylic C-H Acetoxylation in the Presence of Lewis Basic Heterocycles.
abstract: We outline a strategy to enable non-directed Pd(II)-catalyzed C-H functionalization in the presence of Lewis basic heterocycles. In a high-throughput screen of two Pd-catalyzed C-H acetoxylation reactions, addition of a variety ofN-containing heterocycles is found to cause low product conversion. A pyridine-containing test substrate is selected as representative of heterocyclic scaffolds that are hypothesized to cause catalyst arrest. We pursue two approaches in parallel that allow product conversion in this representative system: Lewis acids are found to be effectivein situblocking groups for the Lewis basic site, and a pre-formed pyridineN-oxide is shown to enable high yield of allylic C-H acetoxylation. Computational studies with density functional theory (M06) of binding affinities of selected heterocycles to Pd(OAc)2provide an inverse correlation of the computed heterocycle-Pd(OAc)2binding affinities with the experimental conversions to products. Additionally,1H NMR binding studies provide experimental support for theoretical calculations.
authors: Global Discovery Chemistry, Novartis Institutes for BioMedical Research, Inc., Cambridge, Massachusetts 02139.
authors: Hasnain A
authors: HA
authors: Malik
authors: Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095.
authors: Buck L H
authors: BL
authors: Taylor
authors: Global Discovery Chemistry, Novartis Institutes for BioMedical Research, Inc., Cambridge, Massachusetts 02139.
authors: John R
authors: JR
authors: Kerrigan
authors: Global Discovery Chemistry, Novartis Institutes for BioMedical Research, Inc., Cambridge, Massachusetts 02139.
authors: Jonathan E
authors: JE
authors: Grob
authors: Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095.
authors: K N
authors: KN
authors: Houk
authors: Department of Chemistry, Stanford University, Stanford, California 94305.
authors: J
authors: J
authors: Du Bois
authors: Global Discovery Chemistry, Novartis Institutes for BioMedical Research, Inc., Cambridge, Massachusetts 02139.
authors: Lawrence G
authors: LG
authors: Hamann
authors: Global Discovery Chemistry, Novartis Institutes for BioMedical Research, Inc., Cambridge, Massachusetts 02139.
authors: Andrew W
authors: AW
authors: Patterson