Highly Chemo- and Enantioselective Synthesis of 3-Allyl-3-aryl Oxindoles via the Direct Palladium-Catalyzed α-Arylation of Amides

Abstract

A new NHC x Pd-catalyzed asymmetric alpha-arylation of amides is reported that gives direct access to synthetically valuable, allylated oxindoles with quaternary carbon centers. The reaction is made possible by the introduction of a new chiral NHC ligand. The palladium complexes derived therefrom combine excellent reactivity with high chemo- and enantioselectivity for the title transformation.

Recent Developments in Inter- and Intramolecular Enolate Arylation

“…45 In 2010, Dorta and coworkers 46 reported a new N-heterocyclic carbene (NHC) Á Pd-catalyzed asymmetrical a-arylation of amides that allows direct access to important allylated oxindoles with quaternary carbon centers, previously accessible only via a two-step procedure (Scheme 22). Broad diversity in the amide and electron-rich and electron-poor ortho-or para-substituted aromatic groups was tolerated, affording the desired products in high yields and selectivities using the (R a ,R a )-palladium complex.…”

Transition‐Metal‐Mediated Routes to 3,3‐Disubstituted Oxindoles through Anilide Cyclisation

“…[85] The NHC ligand 103j, [86] as well as the well defined Pd complex 103k (R 1 = R 2 = iPr), [87] were also extremely efficient in terms both of yield and of enantioselectivity (Table 4, Entries xi and xii). The Pd complex 103k was also useful for preparing 3-allyl-3-aryloxindoles (Table 4, Entry xiii), [88] and although the development of asymmetric routes to 3,3-disubstituted oxindoles focuses heavily on the use of 3-aryl-substituted compounds, it should be noted that use of the Pd complex 103k resulted in a 70 % ee of a 3-allyl-3-methyl-substituted oxindole (Table 4, Entry xiv). [88] Cross-coupling reactions usually require reactive aryl coupling partners such as aryl iodides, bromides, triflates etc., which are usually more expensive and less readily available than the corresponding aryl chlorides.…”

“…The Pd complex 103k was also useful for preparing 3-allyl-3-aryloxindoles (Table 4, Entry xiii), [88] and although the development of asymmetric routes to 3,3-disubstituted oxindoles focuses heavily on the use of 3-aryl-substituted compounds, it should be noted that use of the Pd complex 103k resulted in a 70 % ee of a 3-allyl-3-methyl-substituted oxindole (Table 4, Entry xiv). [88] Cross-coupling reactions usually require reactive aryl coupling partners such as aryl iodides, bromides, triflates etc., which are usually more expensive and less readily available than the corresponding aryl chlorides. Intramolecular enolate arylations of aryl chlorides were originally achieved by Hartwig with use of PCy 3 as a ligand, [76] but Ackermann and co-workers more recently found that secondary phosphane oxides such as 103l, an air-and moisture-stable preligand, promote the cyclisation of aryl chlorides, albeit in racemic form.…”

Novel achiral indole-substituted titanocenes: Synthesis and preliminary cytotoxicity studies

“…The methylation of indoles was achieved by N-alkylation with NaH and methyliodide [23]. Introduction of an aldehyde group into indoles 3c and 3d was achieved using a halogen-lithium exchange with n-BuLi followed by a DMF quench and subsequent work up in aq HCl [24].…”