NMR Spectroscopic Aspects

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

“…This is not in line with behavior analogous to complexes 4 – 6 being involved as, in the simplest analysis, these would imply transition state stoichiometries of Cu LCXA (Grignard), Cu LCXA 2 (organozinc), and Cu 2 L 3 CXA (NMR proposal), respectively. In their solution model studies Gschwind and co-workers also detected an alternative to their dimeric [ L 2 Cu­(μ-Cl) 2 Cu L ] precatalysts, which was the trigonal complex [Cu­(μ-Cl) L ] 3 . This form is (depending on reaction conditions) nearly isoenergetic with the dimer and favored by lower L :Cu ratios and ethereal-based solvent systems.…”

“…This form is (depending on reaction conditions) nearly isoenergetic with the dimer and favored by lower L :Cu ratios and ethereal-based solvent systems. Structures based on (Cu L ) 3 were originally argued against, in favor of Cu 2 L 3 , on the basis that catalyst stereoselectivity in ZnEt 2 1,4-addition was maximized at L :Cu = 1.5 for zinc-based additions. , This is not the case in the aluminum catalysis of Scheme , where the product ee remains high (82%) down to L :Cu = 0.45, rather supporting a Cu 3 : L 1.3 ratio in events leading up to and including the rate-determining step.…”

“…On the basis of kinetic studies transition state 5 was proposed for ACA reactions of ZnEt 2 ; it is essentially a transposition of Noyori’s proposal for 1,4-ZnEt 2 addition (from an earlier kinetic study of achiral sulfonamide catalysts) but with an added chiral ligand. Through intensive NMR studies of CuX/ L model systems (mostly in CD 2 Cl 2 ) Gschwind and co-workers proposed the hypothesis that the dominant transition state in “real” catalytic systems adding ZnEt 2 to cyclohex-2-en-1-one must be 6 .…”

“…Very reactive catalytic systems are realized, allowing even for the formation of chiral quaternary centers by addition to β,β-disubstituted Michael acceptors. , Surprisingly, very little is known about the critical transition state responsible for catalyst turnover in copper-promoted 1,4-additions of AlR 3 to enones, despite their common usage in the synthetic community . Gschwind’s proposal that speciation in ACA reactions is dominated by a single entity suggests that classical reaction kinetics might be an effective way of estimating the composition of the AlR 3 /Cu I /L active species (e.g., Cu x L y etc.) through reaction component order analysis.…”