The origin for highly enantioselective induction of 1-naphthol to isatin-derived N-Boc ketimines catalyzed by quinine thiourea catalyst: an experimental and computational study

Abstract

An enantioselective aza-Friedel-Crafts reaction of 1-naphthol with isatin derived N-Boc ketimines by cinchona based bifunctional thiourea as organo-catalyst is reported. In general the derivatives of Betti base are formed in excellent enantioselectivities (95-99%) with high yields (<99%). The combination of experimental and computational studies have revealed the origin of the stereoselectivity of the aza-Friedel-Crafts reaction of 1-naphthol with isatin derived N-Boc ketimines by cinchona based bifunctional thiourea as organo-catalyst. The attractive electrostatic interactions in the Re face transition state and the deleterious lone-pair/p interactions in the Si face transition state governed the formation of Re-face as a major product in this aza Friedel-Crafts reaction. The NMR studies performed to examine the formation of the complex with 1-naphthol, isatin derived N-Boc ketimines and cinchona based bifunctional thiourea catalyst has corroborated the calculated complex geometry employed in the study.

Asymmetric Synthesis of 3‐Amino Oxindoles Using Isatin‐Derived N‐Boc Ketimines with Activated Nitroolefin Catalyzed by Organocatalysts

“…Otherhand, we found that the nitroolefin activated by tertiary amine of organocatalyst OC‐7 via abstracting of proton from methyl group of nitroolefin (Figure ). Based on these experimental data we have proposed the catalytic cycle of this reaction as shown in the Scheme –…”

Direct Asymmetric Arylation of Imines

“…The most efficient bifunctional cinchona thiourea system was reported for the reaction of 1-naphthol with isatin derived N-Boc ketimine derivatives to provide products in excellent yields (99%) and enantioselectivity (up to 99%) (Scheme 55). [69] However, the compound with R 1 =H was observed to give reduced ee of 63%. Based on the kinetics, NMR experiments and DFT studies, the origin of stereoselectivity using bi-functional cinchona thiourea catalyst for the reaction of 1-naphthol with isatin derived N-Boc ketimine derivatives was unravelled.…”

Organocatalyzed Asymmetric Friedel‐Crafts Reactions: An Update

“…The thiourea catalyst is responsible for the preorientation and activation of the substrates performing as a bifunctional organocatalyst. Phenylglyoxal is activated after construction of hydrogen bonds between the carbonyl groups of 162 and thiourea scaffold, whereas the 1‐naphthol endures nucleophilic activation through hydrogen bonding with the quinuclidine scaffold of the catalyst . The C‐2 carbon atom of 155 attacks the Re face of 162 , therefore explaining the detected stereo and regioselectivity …”