Kinetic analysis of copper(I)/Feringa-phosphoramidite catalyzed AlEt3 1,4-addition to cyclohex-2-en-1-one

Darren Willcox, Ryan Nouch, Alexander Kingsbury, David Robinson, Joe V. Carey, Steve Brough, Simon Woodward

Research output: Contribution to journalArticlepeer-review


ReactIR studies of mixtures of AlEt3 (A) and cyclohex-2-en-1-one (CX) in Et2O indicate immediate formation of the Lewis acid.base complex CX·A at -40°C (K = 12.0 M-1, ΔG°react = -1.1 kcal mol-1). Copper(I) catalysts, derived from precatalytic Cu(OAc)2 (up to 5 mol %) and (R,S,S)-P(binaphtholate){N(CHMePh)2} (Feringa's ligand (L), up to 5 mol %) convert CX·A (0.04-0.3 M) into its 1,4-addition product enolate (E) within 2000 s at -40°C. Kinetic studies (ReactIR and chiral GC) of CX·A, CX, and (R)-3-ethylcyclohexanone (P, the H+ quenching product of enolate E) show that the true catalyst is formed in the first 300 s and this subsequently provides P in 82% ee. This true catalyst converts CX·A to E with the rate law [Cu]1.5[L]0.66[CX·A]1 when [L]/[Cu] ≤ 3.5. Above this ligand ratio inhibition by added ligand with order [L]-2.5 is observed. A rate-determining step (rds) of Cu3L2(CX·A)2 stoichiometry is shown to be most consistent with the rate law. The presence of the enolate in the active catalyst best accounts for the reaction's induction period and molecularity as [E] ≡ [CX·A]. Catalysis proceeds through a "shuttling mechanism" between two C2 symmetry related ground state intermediates. Each turnover consumes 1 equiv of CX·A, expels one molecule of E, and forms the new Cu-Et bond needed for the next cycle. The observed ligand (L) inhibition and a nonlinear ligand L ee effect on the ee of P are well simulated by the kinetic model. DFT studies (ωB97X-D/SRSC) support coordination of CX·A to the groundstate Cu trimer and its rapid conversion to E.
Original languageEnglish
Pages (from-to)6901-6908
Number of pages8
JournalACS Catalysis
Issue number10
Publication statusPublished - 6 Oct 2017


  • Aluminum
  • Asymmetric
  • Conjugate addition
  • Copper
  • Density functional theory
  • Mechanism


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