Mechanistic Insight into Fast and Highly Efficient Organocatalytic Activity of a Tripodal Dimeric Hexaurea Capsular Assembly in Michael Addition Reactions

Abstract

A tris(2-aminoethyl)-amine-based dimeric capsular assembly of pentafluorophenyl urea ( C1 ) has been employed as a catalyst in a wide range of Michael addition reactions. This capsular catalyst assembly dramatically accelerates the Michael addition reaction of β-nitrostyrenes ( 2a–2d ) with various Michael donors such as ketoesters ( 3a, 3e ), 1,3-diketones ( 3b ), diesters ( 3C ), and cyanoesters ( 3d ) at room temperature to yield the corresponding nitroalkanes in significantly high yields within a very short reaction time. Significant improvement in solubility and use of conventional organic solvents in reaction along with a drastic decrease in reaction time (high value of the rate constant of the reaction) has been achieved through C1 as compared to the previously reported homologous tripodal monomeric urea catalyst ( L1 ). The addition of enolate to β-nitrostyrenes to generate an anionic intermediate seemed to be highly stabilized by the six urea units of capsular assembly. Control experiments and in situ kinetic studies are performed for this addition reaction and based on the results, a plausible mechanism has been proposed for the formation of Michael adduct inside the capsular cavity.

Michael addition reaction of malonates with nitro-olefins catalyzed by 1,1-diaminoazine, a bifunctional hydrogen bonding organocatalyst

“…11 Many other organocatalysts like urea and thiourea derivatives have been employed in the MAR (Scheme 1a). [12][13][14][15][16][17][18] In 2003, Takemoto and co-workers reported an efficient enantioselective Michael addition of malonates to nitroolefins catalysed by a thiourea-derived bifunctional organocatalyst. 19 In 2004, L. Deng and co-workers utilized natural cinchona alkaloids such as quinidine and quinine for a synthetically important C-C bond forming conjugate addition reaction.…”