Experimental and Computational Investigation of Facial Selectivity Switching in Nickel–Diamine–Acetate-Catalyzed Michael Reactions

Abstract

Chiral Ni complexes have revolutionized both asymmetric acid−base and redox catalysis. However, the coordination isomerism of Ni complexes and their open-shell property still often hinder the elucidation of the origin of their observed stereoselectivity. Here, we report our experimental and computational investigations to clarify the mechanism of β-nitrostyrene facial selectivity switching in Ni(II)−diamine−(OAc) 2 -catalyzed asymmetric Michael reactions. In the reaction with a dimethyl malonate, the Evans transition state (TS), in which the enolate binds in the same plane with the diamine ligand, is identified as the lowest-energy TS to promote C−C bond formation from the Si face in βnitrostyrene. In contrast, a detailed survey of the multiple potential pathways in the reaction with α-keto esters points to a clear preference for our proposed C−C bond-forming TS, in which the enolate coordinates to the Ni(II) center in apical−equatorial positions relative to the diamine ligand, thereby promoting Re face addition in β-nitrostyrene. The N−H group plays a key orientational role in minimizing steric repulsion.

Crystallization-Enabled Stereoconvergent Michael Additions of β-Keto Esters to Nitroolefins

“…We began by examining the enantioselective Michael addition of a crystalline β-keto ester 1a to nitrostyrene, including an aromatic 4,4′-biphenyl ester group to promote crystallinity in product 3a (biphenyl ester 3a mp: 105–107 °C vs ethyl ester mp: 71–74 °C, Figure b). We were excited to see nickel diamine catalyst I ,, facilitated both the enantioselective C–C bond formation and a CIDT at the resulting α-carbon stereogenic center. After slight modifications to previously successful CIDT conditions, , which included ethereal solvent and a concentrated reaction mixture ([nitrostyrene] 0 = 1.0 M), we obtained crystalline product 3a in good yield with excellent enantio- and diastereoselectivity upon filtration (see Supporting Information for full optimization).…”