Asymmetric Cyanation of Activated Olefins with Ethyl Cyanoformate Catalyzed by Ti(IV)-Catalyst: A Theoretical Study

Abstract

The reaction mechanism and origin of asymmetric induction for conjugate addition of cyanide to the C=C bond of olefin were investigated at the B3LYP-D3(BJ)/6-31+G**//B3LYP-D3(BJ)/6-31G**(SMD, toluene) theoretical level. The release of HCN from the reaction of ethyl cyanoformate (CNCOOEt) and isopropanol (HOiPr) was catalyzed by cinchona alkaloid catalyst. The cyanation reaction of olefin proceeded through a two-step mechanism, in which the C-C bond construction was followed by H-transfer to generate a cyanide adduct. For non-catalytic reaction, the activation barrier for the rate-determining C-H bond construction step was 34.2 kcal mol−1, via a four-membered transition state. The self-assembly Ti(IV)-catalyst from tetraisopropyl titanate, (R)-3,3′-disubstituted biphenol, and cinchonidine accelerated the addition of cyanide to the C=C double bond by a dual activation process, in which titanium cation acted as a Lewis acid to activate the olefin and HNC was orientated by hydrogen bonding. The steric repulsion between the 9-phenanthryl at the 3,3′-position in the biphenol ligand and the Ph group in olefin raised the Pauli energy (ΔE≠Pauli) of reacting fragments at the re-face attack transition state, leading to the predominant R-product.

Manganese-Porphyrin-Catalyzed C-H Fluorination: Hydrocarbons, But Not Drugs?

“…Selective C-H functionalization plays an important role 3 in the synthesis of bioactive natural products [4][5][6][7][8][9][10][11][12][13][14] , drug metabolism [15][16] , pharmaceutical industry [17][18][19][20][21][22][23] , DNA repair [24][25][26][27] , and transcription [28][29][30] . C-H bonds can be functionalized in various ways, including but not limited to cyanation [31][32][33][34][35][36][37][38] , oxidation 39 , hydroxylation 40 , epoxidation [41][42] , and halogenation [43][44][45] . Activation of unreactive C-H bonds typically requires harsh conditions 46 due to the high C-H bond dissociation energy 15 and its inert nature 47 .…”

Editorial: Special Issue on “Advanced Strategies for Catalyst Design”

“…Finally, Kim et al and Orian et al have contributed with two theoretical studies [10,11]. In the former, the asymmetric cyanation of olefins with ethyl cyanoformate catalyzed by Ti(IV) has been explored, while in the latter, the acetylene [2+2+2] cycloaddition to benzene catalyzed by Rh/Cr indenyl fragments has been investigated.…”