Mechanistic-Insight-Driven Rate Enhancement of Asymmetric Copper-Catalyzed 1,4-Addition of Dialkylzinc Reagents to Enones

Nouch, Ryan; Woodward, Simon; Willcox, Darren; Robinson, David; Lewis, William

Abstract

Combination of [Cu(MeCN)4]TFA•TFAH (TFA = O2CCF3) with Feringa's phosphoramidite ligand (LA) provides an exceptionally active (0.75 mol%) catalyst for asymmetric conjugate additions of ZnR2 (R = Et, Me at-40 to-80 o C) to enones. Kinetic and other studies of the addition of ZnEt2 to cyclohex-2-en-1-one indicate a transition state stoichiometry composition: (ZnEt2)3(enone)4Cu2(LA)3 that is generated by transmetalation from Et2Zn(enone)2. Catalyst genesis is significantly slower than turnover (which has limited previous attempts to attain useful kinetic data); in the initial stages varying populations of catalytically inactive, off-cycle, species are present. These issues are overcome by a double-dosing kinetic analysis protocol. A rest state of [LACu(Et)(µ-TFA)(µ-{(enone)(ZnEt)2(enolate)})CuLA2] + (through the equivalence of enolate = enone + ZnEt2) is supported by DFT studies (B3LYP/6-31G*). Rate determining ZnEt2(enone)2 transmetalation
drives the exceptionally high catalytic activity of this system.

Citation

Nouch, R., Woodward, S., Willcox, D., Robinson, D., & Lewis, W. (2020). Mechanistic-Insight-Driven Rate Enhancement of Asymmetric Copper-Catalyzed 1,4-Addition of Dialkylzinc Reagents to Enones. Organometallics, 39(6), 834-840. https://doi.org/10.1021/acs.organomet.0c00005

• Journal Article Type: Article
• Acceptance Date: Feb 20, 2020
• Online Publication Date: Mar 3, 2020
• Publication Date: Mar 23, 2020
• Deposit Date: Mar 3, 2020
• Publicly Available Date: Mar 3, 2020
• Journal: Organometallics
• Print ISSN: 0276-7333
• Electronic ISSN: 1520-6041
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 39
• Issue: 6
• Pages: 834-840
• DOI: https://doi.org/10.1021/acs.organomet.0c00005
• Keywords: Inorganic Chemistry; Organic Chemistry; Physical and Theoretical Chemistry
• Public URL: https://nottingham-repository.worktribe.com/output/4082308
• Publisher URL: https://pubs.acs.org/doi/abs/10.1021/acs.organomet.0c00005