Density Functional Studies on Conjugate Addition of (Me2CuLi)2 to Cyclohexenone: Stereoselectivity and Rate-Determining Step

Abstract

The reaction pathway of the conjugate addition of a dimeric cuprate (Me 2 CuLi) 2 to 2-cyclohexenone has been studied by means of the B3LYP hybrid density functional method, and intermediates and transition structures (TSs) on the potential surface of the reaction have been determined. A lithium/carbonyl coordination complex (CPli), a copper/olefin complex retaining a closed cuprate structure (CPcl), a copper/olefin complex with an open cuprate structure (CPop), and the TS of CÀC bond formation (TScc) have been located along the gas-phase pathway leading to the conjugate addition product (PD). We studied two diastereoisomeric pathways, and found that the pathway that results in the axial placement of the nucleophilic methyl group in the product was favored throughout the course of the reaction, except in the product complex. Thus, the stereoselectivity of the conjugate addition to cyclohexenone originates from the stereochemical preference of the final, ratelimiting C À C bond formation stage that mainly reflects the steric factors in the formation of 3-methylcyclohexanone enolate in its half-chair form (TSccax).Comparison of the calculated and experimental values for 13 C NMR chemical shift and kinetic isotope effects strongly suggests that the copper/olefin complex of the CPop structural type is the reactive intermediate that directly forms the product. Thus, the open complex CPop, rather than the closed complex CPcl hitherto considered, is a direct precursor of the product and crucial for the stereoselectivity of the conjugate addition. On the basis of theory and experiments, transition-state models for the conjugate addition to substituted cyclohexenones are provided.

Structures and Reactivities of Organocopper Compounds

“…These data are in perfect agreement with the logarithmic reactivity profiles of reactions between CuLiR 2 and enones in diethyl ether and THF as reported by Bertz [143,144]. Moreover, recent theoretical calculations for this type of reactions [145] point to a transition state involving a CIP type of structure for the cuprate moiety (see Fig. 1.37).…”

The Relation between Ion Pair Structures and Reactivities of Lithium Cuprates

“…Finally it should be noted that the reaction of the dimeric lithium cuprate contact ion pair with an enone, as shown here, is in perfect agreement with recent quantum- chemical calculations by Mori and Nakamura. [33] The transition state with the two Li ions of the dimer bonding to the oxygen atom of the enone is shown in Figure 8. [34] Other calculations of Nakamura with a mixed cuprate dimer show a similar transition state.…”

“…Furthermore, the transition state involving the contact ion pair type dimer is in agreement with quantum-chemical calculations. [33] Thus, a uniform picture of structure and reactivity of lithium cuprates is presented.…”

Quantum chemistry of organocuprates as intermediates of catalytic and photochemical reactions

“…copper atom. [47] These results insured Cu(III) formal oxidation state in such complexes. Another class of organocuprates includes complexes formed by addition of organic radicals to copper(II) coordination compounds.…”