Palladium‐Catalyzed Synthesis of Tetrasubstituted Olefins by Triple Domino Process

Abstract

An efficient, highly regio-and stereoselective protocol for the synthesis of tetrasubstituted olefins was developed to take place by a palladium(0)-catalyzed triple domino process. It involves the formation of three new CÀC bonds through double carbopalladation and CÀH activation across 2-bromoaryl alkynyl biaryls/heteroaryls with norbornene. This method is practically simple with broad substrate scope and tolerates a wide range of substituents. The products bearing 9Hpyrrolo[1,2-a]indole motifs reveal intriguing solid state fluorescence properties and thus form a new class of aggregation induced emission (AIE) fluorophores.

Versatile Catalytic Reactions of Norbornadiene Derivatives with Alkynes

“…Perumal and co‐workers developed a Pd(0)‐catalyzed regio‐ and stereoselective method for the synthesis of helical tetrasubstituted olefins by the triple domino process between 2‐bromoaryl alkynylbiaryls/heteroaryls ( 128 ) with norbornene [Eq. (91) …”

Recent Development in Palladium-Catalyzed Domino Reactions: Access to Materials and Biologically Important Carbo- and Heterocycles

“…The products bearing 9Hpyrrolo[1,2-a]indole motifs constituted a new class of aggregation induced emission (AIE) fluorophores. 28 Scheme 18. Synthesis of quasi-dimeric polycyclic carbon skeletons.…”

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 .…”