Theoretical Calculations on the Mechanism of Enantioselective Copper(I)-Catalyzed Addition of Enynes to Ketones

Abstract

Computational investigations on the bisphospholanoethane (BPE)-ligated Cu-catalyzed enantioselective addition of enynes to ketones were performed with the density functional theory (DFT) method. Two BPE-mesitylcopper (CuMes) catalysts, BPE-CuMes and (S,S)-Ph-BPE–CuMes, were employed to probe the reaction mechanism with the emphasis on stereoselectivity. The calculations on the BPE-CuMes system indicate that the active metallized enyne intermediate acts as the catalyst for the catalytic cycle. The catalytic cycle involves two steps: (1) ketone addition to the alkene moiety of the metallized enyne; and (2) metallization of the enyne followed by the release of product with the recovery of the active metallized enyne intermediate. The first step accounts for the distribution of the products, and therefore is the stereo-controlling step in chiral systems. In the chiral (S,S)-Ph-BPE–CuMes system, the steric hindrance is vital for the distribution of products and responsible for the stereoselectivity of this reaction. The steric hindrance between the phenyl ring of the two substrates and groups at the chiral centers in the ligand skeleton is identified as the original of the stereoselectivity for the titled reaction.

Chiral bisphosphine Ph-BPE ligand: a rising star in asymmetric synthesis

“…124 In addition to the two major types of aldol reactions mentioned above, the combination of Ph-BPE and copper catalyst has also been applied to various other types of aldol reactions. 125 Specifically, it has been found to be effective in enabling the reaction between alkyl aldehydes and esters. In 2018, Yin et al developed a simple methodology for the rapid synthesis of chiral a,b-unsaturated d-lactones with a broad substrate scope.…”

Green transformation of CO2 into γ-amino alcohols with continuous stereocenters

“…Based on these results and the mechanistic studies on Cu-catalyzed addition of other types of nucleophiles to ketones, we proposed a catalytic cycle for the CO 2 trapping reaction (Scheme 4). 16…”

Estudo computacional das reações de borilação de substratos insaturados catalisadas por Ag e Cu

“…Os resultados computacionais obtidos por métodos baseados na DFT foram comparados aos resultados obtidos por métodos mais precisos, como CCSD(T) (Coupled Cluster Singles-and-Doubles with Approximate Triples Correction) e sua variante, o DLPNO-CCSD(T), 148,149 do inglês Domain Based Local Pair Natural Orbital Coupled Cluster, usando o conjunto de bases Def2-TZVP, 119,150,151 implementados no programa ORCA. 152 Entre os funcionais citados, o que apresentou melhor resultado, quando comparado com o CCDS(T), foi o funcional B3LYP-D3, o qual também já demonstrou ser um método eficiente nos estudos de reações catalisadas por complexos de metais de transição, [153][154][155][156][157] por esse motivo foi o funcional empregado nos cálculos da reação de boraformilação. Para o catalisador DTB-dppbz foram realizadas correções térmicas na temperatura do experimento, a 323K, através do programa GoodVibes.…”