Reactivity and Selectivity Controlling Factors in the Pd/Dialkylbiarylphosphine-Catalyzed C-C Cleavage/Cross-Coupling of an N-Fused Bicyclo α-Hydroxy-β-Lactam

Li Ping Xu, Jose B. Roque, Richmond Sarpong, Djamaladdin G. Musaev

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20 Scopus citations

Abstract

Density functional theory was employed in order to elucidate the mechanism and factors that lead to the observed regioselectivity in the dialkylbiarylphosphine (Phos)/Pd-catalyzed C-C cleavage/cross-coupling of an N-fused bicyclo α-hydroxy-β-lactam, 1. We have identified that (a) a complex [(1)(Cs2CO3)]-PdL(PhBr) forms prior to a "base-mediated oxidative addition"(b) Cs-carbonate (rather than a halide) deprotonates the alcohol substrate in the lowest energy pathway en route to Pd-alcoholate formation; (c) reactions using Phos ligands bearing OCF3 and OCF2H substituents on the "B"-ring are predicted to be selective toward proximal ring opening of 1; (d) steric repulsion between the bottom "B"-ring of the Phos ligand and the piperidine moiety of 1 controls the regioselectivity of the C-C cleavage followed by cross-coupling; and (e) the α- vs β-selective functionalization of the piperidine moiety in 1 is influenced by the bulkiness of the R2-substituent of the coupling partner. These studies will aid in the design of selective functionalizations of the piperidine moiety in 1.

Original languageEnglish (US)
Pages (from-to)21140-21152
Number of pages13
JournalJournal of the American Chemical Society
Volume142
Issue number50
DOIs
StatePublished - Dec 16 2020
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General Chemistry
  • Biochemistry
  • Catalysis
  • Colloid and Surface Chemistry

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