The asymmetric synthesis of CF₃-containing spiro[pyrrolidin-3,2′-oxindole] through the organocatalytic 1,3-dipolar cycloaddition reaction

Abstract

A new strategy for the construction of optically active 5'-CF3 spiro[pyrrolidin-3,2'-oxindole] was described. A series of unprecedented 1,3-dipoles were obtained by condensation of CF3CH2NH2 with isatins. The 1,3-dipolar cycloaddition reactions of these ketimines with enals gave the products bearing four contiguous stereogenic centers in excellent yields, diastereoselectivities and enantioselectivities.

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

“…[6] The arylidene azlactones 2 a-2 p were prepared according to the reported literature procedures. [6] The arylidene azlactones 2 a-2 p were prepared according to the reported literature procedures.…”

“…[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.…”

“…[5a] Synthetically, it is very meaningful to install the CF 3 group into the 5'-position of 3,2'-pyrrolidinyl spirooxindole core. [6] Since then, the enantioselective [3 + 2] cycloaddition of N-2,2,2-trifluoroethylisatin ketimines with activated olefins have emerged as one of the most efficient and accessible methodologies towards the construction of CF 3 -containing 3,2'-pyrrolidinyl spirooxindoles and 3,2'-pyrrolidinyl FULL PAPER DOI: 10.1002/adsc.201801608 [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.…”

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.…”