An asymmetric palladium and copper co-catalyzed Heck/Sonogashira reaction between o-iodoacrylanilides and terminal alkynes to synthesizechiral oxindoles was developed. In particular,awide range of CF 3 -substituted o-iodoacrylanilides reacted with terminal alkynes,a ffording the corresponding chiral oxindoles containing trifluoromethylated quaternary stereogenic centers in high yields with excellent enantioselectivities (94-98 %e e). This asymmetric Heck/Sonogashira reaction provides ag eneral approach to access oxindole derivatives containing quaternary stereogenic centers including CF 3 -substituted ones.Organofluorine compounds have found broad applications in medicinal chemistry and agrochemistry because of their stabilities,r eactivities,a nd unique biological activities. [1] In contrast, chiral 3,3-disubstituted oxindole cores are important structural motifs that can be frequently found in many bioactive natural products and synthetic analogues. [2] Therefore,i ti sh ighly desirable to develop enantioselective protocols to access fluorine-containing 3,3-disubstituted oxindoles because incorporation of fluorine into these oxindole molecules may endow them new biological properties.I ndeed, it has been recently shown that the introduction of af luorine atom or at rifluoromethyl group to C3 of an oxindole molecule enhances its biological activities. [3] While enantioselective approaches to prepare chiral 3-fluorinated oxindoles have been well established, [4] methods to prepare enantioenriched oxindoles containing CF 3 -substituted quaternary stereogenic carbon centers [5] at C3 are rather limited. To the best of our knowledge,asymmetric radical trifluoromethylation of 3-substituted oxindoles is the only known reaction that affords enantioenriched 3-trifluoromethyloxindoles,a nd has been recently disclosed by Katayev and co-workers (Figure 1A). [6] In recent years,e nantioselective intramolecular Heck reactions of anilide-tethered haloarene alkenes have been emerging as effective approaches to prepare chiral oxindole cores. [7] However,only aryl-or alkyl-substituted alkenes have been studied for these asymmetric reactions,a nd the substrates that contain CF 3 -substituted alkenes have not been employed for this Heck-type enantioselective cyclization. In general, Heck reactions of CF 3 -substituted alkenes have been much less studied than those of common alkenes,a nd this is largely due to potential b-fluorine elimination. [8] There was only one example of Pd-catalyzed Heck-type cyclization employing CF 3 -substittued alkenes,and CF 3 groups in starting alkenes were converted into CF 2 groups through b-fluorine elimination. [8d] Therefore,itremains elusive to develop Hecktype asymmetric cyclization with CF 3 -substituted alkenes to build CF 3 -substituted quaternary stereogenic centers.During our continuous effort in developing enantioselective protocols to make chiral oxindoles, [9] we became interested in the synthesis of chiral oxindoles containing trifluoromethylated quaternary stereocenters at C3. We en...

The synthesis of a series of aromatic amide-derived non-biaryl atropisomers with a phosphine group and multiple stereogenic centers is reported. The novel phosphine ligands exhibit high diastereo- and enantioselectivities (up to >99:1 d.r., 95-99 % ee) as well as yields in the silver-catalyzed asymmetric [3+2] cycloaddition of aldiminoesters with nitroalkenes, which provides a highly enantioselective strategy for the synthesis of optically pure nitro-substituted pyrrolidines. In addition, the experimental results with regard to the carbon stereogenic center as well as the amide stereochemistry confirmed the potential of hemilabile atropisomers as chiral ligand in catalytic asymmetric [3+2] cycloaddition reaction.

New Schiff bases derived from chiral d‐camphor were determined to be effective phosphine ligands for the asymmetric palladium‐catalyzed allylic alkylation of activated methylene compounds, the allylic etherification of alcohols, and the allylic amination of primary amines or secondary amines, in which the corresponding products with various functional groups were achieved in good yields with excellent enantioselectivities (up to >99 % ee). Remarkably, the palladium catalyst derived from Schiff base L2 afforded the highest level of enantioselectivity reported to date for allylic substitution reactions, including allylic etherification and allylic amination, which revealed the privileged role of d‐camphor‐derived Schiff bases in palladium‐catalyzed allylic substitution reactions.