Versatile Relay and Cooperative Palladium(0) N‐Heterocyclic Carbene/Copper(I) N‐Heterocyclic Carbene Catalysis for the Synthesis of Tri‐ and Tetrasubstituted Alkenes

Abstract

Abstract:Two new and efficient dual catalytic procedures for the synthesis of tri-and tetra-substituted alkenes using aryl bromides and chlorides are reported. The formation of these vinyl arenes occurs independently in a one-pot relay and a one-pot cooperative procedure using well-defined Pd-NHC and Cu-NHC complexes. Mechanistic studies were performed to elucidate the key role of the solvent in each procedure as well as the formation of the key intermediate, [Cu(alkenylboron) (NHC)], allowing the transmetallation with the Pd-NHC co-catalyst in the cooperative catalysis.

Synergistic Pd/Cu Catalysis in Organic Synthesis

“…In 2015, Cazin and co‐workers reported the efficient synthesis of tri‐ and tetrasubstituted alkenes from disubstituted alkynes with aryl halides by using copper and palladium catalysis . It was found that the selection of solvents had an important effect on the formation of products.…”

Stereoselective Synthesis of Borylated 1,3‐Dienes by Synergistic Cu/Pd Catalysis

“…Indeed, the use of this type of electrophiles entails an additional challenge because there is potential for competitive migratory insertion of the LCu‐Bpin intermediate across the alkenyl bromide . Based on previous work by our group and that of Semba/Nakao, and Cazin on the use of synergistic Cu/Pd catalysis for the carboboration of alkynes, we envisioned that a β‐boryl alkenylcopper intermediate could be catalytically generated and exploited in a stereoretentive Pd‐catalyzed cross‐coupling with an alkenyl halide under cooperative catalysis regime (Scheme e). This approach features several advantages since 1) syn ‐selectivity would result from a syn ‐selective alkyne borylcupration; 2) alkynes are used as pro‐nucleophiles thus avoiding the stoichiometric use of an alkenyl metal reagent; 3) activation of the alkenyl halide by the Pd co‐catalyst would facilitate the coupling under mild conditions thus preventing competitive migratory insertion; 4) three different components would be assembled in a single operation thus providing high modularity to this transformation.…”

Selective Synthesis of Tetrasubstituted Olefins by Copper‐Mediated Acetoxythiolation of Internal Alkynes: Scope and Mechanistic Studies

“…[1][2][3][4][5][6][7] New synthetic methods are continuouslyb eing screened, and intense research devotedt oa chieving more performant pathways while keeping simple methodologies is ongoing. [8][9][10][11][12][13][14][15][16][17][18] The interest in these particular substrates resides in their versatility as startingm aterials and in their pharmacological, photochemical, and electrochemical properties. [19][20][21][22][23][24] To mention some wellknown examples, (Z)-tamoxifen ( Figure 1) is used in the treatment and prevention of breast cancer, [21] isocombretastatine A-4s hows antitubulin activity, [22] rofecoxib (a selectivei nhibitor of cyclooxygenase-2) displays activity in the prevention of colorectal adenoma, [23] and nileprost was is considered ap romising antiulcer agent.…”

“…[24] Some of the most general methods for the synthesis of tetrasubstituted olefins involvea ddition reactions to internal alkynes, usually carbometalations, which are followed by oxidative couplings, cross-couplings,o rt he addition of electrophiles. [8][9][10][11][12][13][14] Very recently,p hotoredox-based methods have also been described. [17,18] These methods, however,s uffer from the followingd isadvantages:1 )the main one is the highly reactive nature of organometallic reagents, which are difficult to handle and unable to be transferred to an industrial scale owing to high costs;2 )poor tolerance to the presence of reactive functional groups owing to the nucleophilic character of the organometallic reagent;3 )the olefins are usually obtained as mixtures of Z/E isomers, ap roblem that increases as the number of different substituents increases.…”

“…The synthesis of tetrasubstituted olefins with complete control of the regio‐ and stereoselectivities is still a challenge for synthetic chemists, as highlighted in recent reviews . New synthetic methods are continuously being screened, and intense research devoted to achieving more performant pathways while keeping simple methodologies is ongoing . The interest in these particular substrates resides in their versatility as starting materials and in their pharmacological, photochemical, and electrochemical properties .…”