Multiple Functional Organocatalyst-Promoted Inert C–C Activation: Mechanism and Origin of Selectivities

Abstract

Although breakthroughs in the N-heterocyclic carbene (NHC)-catalyzed inert C–C bond activation strategy have been achieved, understanding the role of the catalyst as well as the origin of its chemo- and stereoselectivities is still one of the most challenging questions in the field of organocatalysis. Herein, we propose an NHC and NHC·H+ cooperative catalytic model for these kinds of reactions and perform density functional theory calculations in the case of an NHC-catalyzed [4 + 2] annulation reaction of conjugated dienal and α-aryl ketone. The calculated results indicate that the organocatalyst either works as a Lewis base to prevent the bad frontier molecular orbital overlap mode, promoting [2 + 2] cycloaddition, or as a noncovalent organocatalyst to provide a hydrogen bonding network to facilitate the release of CO2. The latter is remarkably different from its well-known role as a Lewis base. In addition, we devised an atomic electrophilicity index to correctly predict the site of the stereoselective C–C bond formation involved in [4 + 2] cycloaddition. Further analysis results show that hydrogen bonds significantly contribute to the favorable stereoselective pathway, which was associated with axial chirality of the main final product in an experiment. The obtained insights should be valuable for the prediction and rational design of organocatalytic inert C–C activations with special chemoselectivity and high stereoselectivity.

Carbene-Catalyzed Enantioselective Sulfonylation of Enone Aryl Aldehydes: A New Mode of Breslow Intermediate Oxidation

“…This barrier difference kinetically favors the ( Re )-face addition by ∼1500 times at the reaction temperature using simple transition state theory (TST) (Supporting Information Section S4.1). We note that this ( Re )-face selectivity for the addition of NHC to aldehyde is different from the ( Si )-face selectivity for a similar reaction previously reported, potentially due to the different interactions between the side groups of the substrate and the different NHC molecules used. The NHC-adduct S-INT2 can be converted to the Breslow intermediate I under a protonated base assistance, in accordance with previous reports .…”

“…We note that this ( Re )-face selectivity for the addition of NHC to aldehyde is different from the ( Si )-face selectivity for a similar reaction previously reported, potentially due to the different interactions between the side groups of the substrate and the different NHC molecules used. The NHC-adduct S-INT2 can be converted to the Breslow intermediate I under a protonated base assistance, in accordance with previous reports . Concerted 1,2-proton transfer via a seven-membered cyclic transition structure S-TS2 has the lowest barrier (22.4 kcal mol –1 ) compared to other modes of Breslow intermediate formation (Supporting Information Section S4.2).…”

A DFT study of NHC-catalyzed reactions between 2-bromo-2-enals and acylhydrazones: mechanisms, and chemo- and stereoselectivities

“…S1, ESI†), in agreement with previous studies. 30 When using water as the mediator, the proton H4 transfer to O3 requires much lower barriers (19.3/22.4 kcal mol −1 via re -TS2 w / si -TS2 w , Fig. S2, ESI†) as compared to the direct pathways.…”

Mechanism of a cobalt-catalyzed hydroarylation reaction and origin of stereoselectivity

“…Moreover, we also explored theoretically the origin of the observed stereoselectivity of this novel hydroarylation/cyclization reaction. As part of our continuing interest in the mechanistic investigation of transition metal catalysis 7 and organocatalysis, 8 we have now performed a theoretical study of the title reaction using the DFT computational method, a powerful tool for elucidating the mechanisms of organocatalytic 9 and organometallic reactions. 10…”