Synthesis of 3-(Diarylmethylenyl)oxindole by a Palladium-Catalyzed Domino Carbopalladation/C−H Activation/C−C Bond-Forming Process

Abstract

[reaction: see text] A highly efficient palladium-catalyzed synthesis of unsymmetrically substituted 3-(diarylmethylenyl)indolinones from readily accessible starting materials is developed. The domino reaction involves a sequence of intermolecular carbopalladation, C-H activation, and C-C bond formation. A plausible mechanistic pathway for the reaction is discussed on the basis of the kinetic isotope effect [K(H)/K(D) (intermolecular) = 1, K(H)/K(D) (intramolecular) = 2.7] as well as the electronic effect.

Synthesis and Structure–Activity Relationships of Constrained Heterocyclic Analogues of Combretastatin A4

“…[18] More recently, compounds with an oxindole moiety were successfully prepared by a sequence of carbopalladation, CÀH activation, and CÀC bond formation, from anilides and aryl iodides as the starting materials (Path B). [19] We therefore decided to investigate the preparation of heterocyclic CA4 analogues containing a stereochemically defined substituted exocyclic alkene, by using these palladium-catalyzed domino processes. [20] We first planned to synthesize CA4 analogues with a heterocycle fused to the B-ring by using the tandem Heck carbocyclization/Suzuki cross-coupling process (Scheme 1).…”

“…Zhu and co-workers reported the synthesis of 3-(diarylmethylene)oxindoles from N-methyl-or N-trimethylsilylethoxymethyl (SEM)-3-arylpropynamides (Figure 2, path B, R = phenyl) and aryl iodides as the other coupling partner. [19] Interestingly, under the reported reaction conditions [Pd(OAc) 2 , NaOAc, DMF], the methylacetylene derivative 12 proved to be a suitable partner (Scheme 2). After heating at 80 8C for 2 h in the presence of 3,4,5-trimethoxyphenyl iodide, the N-methyloxindole 9 f was obtained stereoselectively, albeit in moderate yield (46 %).…”

Pd(OAc)2-catalyzed domino reactions of 1,2-dihaloarenes and 2-haloaryl arenesulfonates with Grignard reagents: efficient synthesis of substituted fluorenes

“…The reaction product would be 2-chloro-2′,4′,6′-trimethylbiphenyl if the reaction occurred via transmetalation followed by reductive elimination (Path Aa). We screened a number of ligands and palladium source and our results are listed in Table 1 [9][10][11][12][13], implying that the reaction proceeded predominately through Path Ab and Pd-associated benzynes were involved.…”

Palladium-catalyzed domino N-arylation/carbopalladation/C–H functionalization: three-component synthesis of 3-(diarylmethylene)oxindoles

“…5 We have developed a palladium-catalyzed domino carbopalladation/C-H functionalization process for the synthesis of 3-(diarylmethylene)oxindoles (1) from arylpropynamide and aryliodide. 6 Li, Wang, and co-workers have elegantly exploited the potential of this approach and have synthesized a variety of heteroatomsubstituted oxindoles by performing the domino transformation under oxidative conditions. 7 We have subsequently devised a three-component variant using arylpropiolamide and two different aryliodides as starting materials (Scheme 1, Eq.…”