Synthesis of Diversely Functionalized Oxindoles Enabled by Migratory Insertion of Isocyanide to a Transient σ‐Alkylpalladium(II) Complex

Abstract

Palladium-catalyzed intramolecular carbopalladation of N-aryl acrylamides followed by migratory insertion of an isocyanide-coordinated C(sp(3) )-Pd intermediate afforded an alkylimidoyl-Pd(II) complex, which can be intercepted by a nucleophile, including heteroarenes. In addition to amides, the alkylimidoyl-Pd(II) complex was successfully converted into esters, ketones, and bis-heterocyclic compounds. An unprecedented palladium-catalyzed enantioselective domino process involving isocyanide was also documented.

Catalytic Enantioselective and Diastereoselective Allylic Alkylation with Fluoroenolates: Efficient Access to C3‐Fluorinated and All‐Carbon Quaternary Oxindoles

“…The importance of the 3,3-disubstituted oxindole ring, a common motif in many natural compounds and drugs, has fueled the development of intriguing synthetic strategies. [3] Following reports on the medicinal potential of 3-substituted 3-fluorooxindoles, [4] several groups have developed effective enantioselective fluorination methods for 3-alkyl and 3-aryloxindoles. [5] By contrast, catalytic asymmetric C-C bond formation with 3-fluorooxindoles has remained difficult and only three reports on conjugate additions have appeared in the literature.…”

Water as a Hydride Source in Palladium‐Catalyzed Enantioselective Reductive Heck Reactions

“…This experiment further illustrated the difficulties associated with the development of this type of domino process.Infact, although the reduction is not involved in the stereocentergenerating step,t he presence of an ucleophile (HCOONa) might modify the coordination sphere of the metal center, hence the enantioselectivity of the carbopalladation step. [15] An important advantage of the present method is the easy access to D-labeled compounds.Thus,using D 2 OasaDatom donor in combination with Cat 2 B 2 under otherwise standard catalytic conditions,a crylamides 1 were converted to oxindoles 2 bearing aC H 2 Ds ubstituents in good yields and enantioselectivities with ah igh level of D-incorporation (Scheme 5). These compounds would be difficult to access by applying other reductive Heck conditions.…”

“…[11] Song and coworkers have subsequently reported reduction of N-heteroaromatics with as imilar catalytic system, [12] while Prabhu et al proposed that hydrogen (H 2 gas) generated under these catalytic conditions was responsible for the reduction of olefins. [13] Prompted by the difficulties,w hich we encountered in using intramolecular reductive Heck reaction for the construction of complex natural products, [14] and our long-standing interests in the development of domino enantioselective carbopalladation/ intermolecular nucleophilic trapping of the resulting C(sp 3 )-Pd complex for the synthesis of biologically relevant heterocycles, [15] we became interested in developing an enantioselective reductive cyclization of acetanilides 1 for the synthesis of 3,3-disubstituted oxindoles 2.H erein, we report that in the presence of acatalytic amount of Pd(OAc) 2 , tBuPhOX( L1,F igure 1), and as toichiometric amount of tetrahydroxydiboron [B 2 (OH) 4 ]a nd water, intramolecular hydroarylation of acetanilides 1 occurred smoothly to afford 2 in excellent yields and high enantioselectivities (Scheme 1b). We also document that the deuterated compounds are easily accessible using the couple Cat 2 B 2 /D 2 Oa saDa tom donor.…”

Catalytic Enantioselective Double Carbopalladation/C−H Functionalization with Statistical Amplification of Product Enantiopurity: A Convertible Linker Approach

“…[14] However,t he development of an enantioselective version is highly challenging. [15][16][17][18] N-(2-Iodophenyl)-Nmethyl methacrylamide (4a)a nd 5 were chosen as our test substrates (Scheme 2). After initial survey of reaction conditions,wewere pleased to find that the racemic products 6a and 10 a can be produced in 84 %o verall yield by heating aT HF solution of 4a and 5 in the presence of Pd(OAc) 2 (10 mol %), dppp (L1,2 0mol %), and Cs 2 CO 3 (3.0 equiv) at 80 8 8C.…”