Kinetic Analysis of Copper(I)/Feringa-Phosphoramidite Catalyzed AlEt3 1,4-Addition to Cyclohex-2-en-1-one

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 center dot A at-40 degrees C (K = 12.0 M-1, Delta G(react) degrees=-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 center dot 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 center dot A to E with the rate law [Cu](1.5)[L](0.66)[CX center dot 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 center dot 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] E [CX center dot A]. Catalysis proceeds through a "shuttling mechanism" between two C-2 symmetry related ground state intermediates. Each turnover consumes 1 equiv of CX center dot 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 (wB97X-D/SRSC) support coordination of CX center dot A to the groundstate Cu trimer and its rapid conversion to E.