Highly Efficient and Diastereoselective Construction of Trifluoromethyl‐Containing Spiro[pyrrolidin‐3,2′‐oxindole] by a Catalyst‐free Mutually Activated [3+2] Cycloaddition Reaction

Abstract

A catalyst-free self-catalyzed [3+2] cycloaddition reaction of isatin-derived α-(trifluoromethyl)imines with vinylpyridines is reported. The reaction offers a straightforward and atom-economical procedure for the preparation of a series of 5'-trifluoromethyl-spiro[pyrrolidin-3,2'-oxindoles] in excellent yields and diastereoselectivities. The reaction mechanism has been investigated by control experiments, DFT calculation of pK values and the kinetic profiles, revealing that this reaction featured the mutual activation between isatin-derived α-(trifluoromethyl)imines and vinylpyridine to generate the reactive species.

Recent Advances in the Construction of Trifluoromethyl‐Containing Spirooxindoles through Cycloaddition Reactions

“…Two simultaneous generated intermediates underwent a cycloaddition to gain the required product (Scheme 7). [17]…”

“…In the meantime, the prontonated pyridine moiety also played an important role in the activation of the vinyl group through the conjugate of positive charge. Two simultaneous generated intermediates underwent a cycloaddition to gain the required product (Scheme ) …”

A Catalyst‐Free Self‐Catalyzed [3+2] Cycloaddition Reaction of 3‐Isothiocyanato Oxindoles and Vinylpyridines

“…Due to the unique mutual activation that vinylpyridine performs in the reaction, this catalyst‐free cycloaddition can be achieved under mild reaction conditions in one‐pot which closely match the perspective of green and sustainable chemistry. Very recently, we achieved a catalyst‐free self‐catalyzed [3+2] cycloaddition reaction of α‐(trifluoromethyl)imines with vinylpyridines to afford spiro[pyrrolidin‐3,2′‐oxindole] derivatives . Herein, we wish to report another catalyst‐free self‐catalyzed [3+2] cycloaddition reaction of 3‐isothiocyanato oxindoles with vinylpyridines.…”

Catalytic Asymmetric Synthesis of α-Trifluoromethyl Homoallylic Amines via Umpolung Allylation/2-Aza-Cope Rearrangement: Stereoselectivity and Mechanistic Insight

“…Recently, N -2,2,2-trifluoroethylisatin ketimine derived from 2,2,2-trifluoroethylamine hydrochloride (CF 3 CH 2 NH 3 Cl) emerged as a cost-efficient CF 3 -containing reagent for the asymmetric construction of α-trifluoromethyl amines, in which the carbon adjacent to electron-withdrawing CF 3 served as the nucleophilic site (Scheme a). Previously, we disclosed that the metalated azomethine ylide was a viable nucleophile in asymmetric Michael addition reaction .…”