The Squaramide‐Catalyzed 1,3‐Dipolar Cycloaddition of Nitroalkenes with N‐2,2,2‐Trifluoroethylisatin Ketimines: An Approach for the Synthesis of 5′‐Trifluoromethyl‐spiro[pyrrolidin‐3,2′‐oxindoles]

Abstract

A Cinchona alkaloid-derived squaramidecatalyzed asymmetric cycloaddition of trfluoromethyl-containing azomethine ylides with b-nitroalkenes was realized under mild conditions.Aserieso fb iologically important 5'-trifluoromethyl-spiro[pyrrolidin-3,2'-oxindoles] was synthesizede fficiently by this process in excellent yields,e nantioseletivities and diastereoselectivities.

Enantioselective Synthesis of CF3‐Containing 3,2’‐Pyrrolidinyl Spirooxindoles and Dispirooxindoles via Thiourea‐Catalyzed Domino Michael/Mannich [3+2] Cycloaddition Reactions

“…[5] In particular, the CF 3 group occupying at the a-position to nitrogen can lower the alkalinity of amide and affect the binding affinity of drug receptors. [6,7] In 2015, Wang's group first developed and utilized N-2,2,2-trifluoroethylisatin ketimines as synthon for the enantioselective preparation of CF 3 -containing 3,2'pyrrolidinyl spirooxindoles. Over the past few years, only limited examples of catalytic asymmetric synthesis of various optically active CF 3 -containing 3,2'-pyrrolidinyl spirooxindoles were reported.…”

“…[7] In this context, as part of our continuing investigations of the organocatalytic asymmetric synthesis of 3,2'-pyrrolidinyl spirooxindole compounds, [8] we surmised the two classes of pyrrolidinyl spirooxindoles could be constructed through the domino Michael/Mannich [3 + 2] cycloaddition reaction of N-2,2,2-trifluoroethylisatin ketimines 1 and arylidene azlactones 2 which served as dipolarophiles in catalytic asymmetric [3 + 2] cycloaddition of azomethine ylides is less explored in the literature re-ports. [7] In this context, as part of our continuing investigations of the organocatalytic asymmetric synthesis of 3,2'-pyrrolidinyl spirooxindole compounds, [8] we surmised the two classes of pyrrolidinyl spirooxindoles could be constructed through the domino Michael/Mannich [3 + 2] cycloaddition reaction of N-2,2,2-trifluoroethylisatin ketimines 1 and arylidene azlactones 2 which served as dipolarophiles in catalytic asymmetric [3 + 2] cycloaddition of azomethine ylides is less explored in the literature re-ports.…”

Stereoselective Synthesis of CF3‐Containing Spirooxindoles via 1,3‐Dipolar Cycloaddition by Dipeptide‐Based Phosphonium Salt Catalysis

“…[6] After that, a series of organocatalytic approaches were developed to achieved these asymmetric 1,3-dipolar cycloaddition of N-2,2,2-trifluoroethylisatin ketimines with different electron-deficient olefins. [7] To the best of our knowlege, the catalytic systems of all reported examples are only referring to chiral tertiary amine catalysis. There-fore, on the purpose of extending the utilities of such catalytic 1,3-dipolar cycloaddition process, it is still highly desirable to develop new and efficient catalytic systems for actualizing this transformation.…”

Synthesis of 1-Tetrasubstituted 2,2,2-Trifluoroethylamine Derivatives <i>via</i> Palladium-Catalyzed Allylation of <i>sp</i>³ C–H Bonds

“…The scope of these reactions is mostly limited to unsubstituted 2,2,2-trifluoroethylamines (R 1 =H), however, and reported reactions with 1-substituted-2,2,2-trifluoroethylamines mostly have an electron-withdrawing group as the substituent. [13][14][15] In addition, most of the reported reactions are limited to 1,3-dipolar cycloaddition with electron-deficient olefins, [6][7][8]10,11) and these cyclized products are not readily transformed into N-unprotected 2,2,2-trifluoroethylamines. 16) To overcome these limitations, herein we report our preliminary studies on Pd-catalyzed allylation of sp 3 C-H bonds of 1-mono-substituted 2,2,2-trifluoroethylamines, providing a variety of 1-allylated 2,2,2-trifluoroethylamines with tetrasubstituted carbon stereocenters.…”

“…b). [6][7][8][9][10][11][12] This reaction comprises one of these steps toward functionalization of 2,2,2-trifluoroethylamines when combining condensation with carbonyl compounds and subsequent hydrolysis. Very recently, several groups reported ketimines derived from 2,2,2-trifluoroethylamine as a pronucleophile.…”