Transition Metal (Ni, Cu, Pd)-Catalyzed Alkene Dicarbofunctionalization Reactions

CONSPECTUS: Recently, alkene dicarbofunctionalization, i.e., the powerful organic synthesis method of alkene difunctionalization with two carbon sources, emerged as a formidable reaction with immense promise to synthesize complex molecules expeditiously from simple chemicals. This reaction is generally achieved with transition metals (TMs) through interception by carbon sources of an alkylmetal [beta-H-C(sp(3))-[M]] species, a key intermediate prone to undergo rapid beta-H elimination. Related prior reports, since Paolo Chiusoli and Catellani's work in 1982 [Tetrahedron Lett. 1982, 23, 4517], have used bicyclic and disubstituted terminal alkenes, wherein beta-H elimination is avoided by geometric restriction or complete lack of beta-H's. With reasoning that beta-H-C(sp(3))-[M] intermediates could be rendered amenable to interception with the use of first row late TMs and formation of coordinationassisted transient metallacycles, these two strategies were implemented to address the beta-H elimination problem in alkene dicarbofunctionalization reactions. Because first row late TMs catalyze C(sp(3))-C(sp(3)) coupling, Cu and Ni were anticipated to impart sufficient stability to beta-H-C(sp(3))-[M] intermediates, generated catalytically upon alkene carbometalation, for their subsequent interception by carbon electrophiles/nucleophiles in three-component reactions. Additionally, such an innate property could enable alkene difunctionalization with carbon coupling partners through entropically driven cyclization/coupling reactions. The cyclometalation concept to stabilize intractable beta-H-C(sp(3))-[M] intermediates was hypothesized when three-component reactions were performed. The idea of cyclometalation to curtail beta-H elimination is founded upon Whitesides's [J. Am. Chem. Soc. 1976, 98, 6521] observation that metallacycles undergo beta-H elimination much slower than acyclic alkylmetals. In this Account, examples of alkene dicarbofunctionalization reactions demonstrate that Cu and Ni catalysts could enable cyclization/coupling of alkenylzinc reagents, alkyl halides, and aryl halides to afford complex carbo- and heterocycles. In addition, forming coordination-assisted transient nickellacycles enabled regioselective performance of three-component dicarbofunctionalization of various alkenyl compounds. In situ reaction of [M]-H with alkenes generated after beta-H elimination induced an unprecedented metallacycle contraction process, in which six-membered metal-containing rings shrank to five-membered cycles, allowing creation of new carbon-carbon bonds at allylic (1,3) positions. Applications of these regioselective alkene dicarbofunctionalization reactions are discussed.

Automated summary

Alkene dicarbofunctionalization is a powerful organic synthesis method that utilizes transition metals and carbon sources to synthesize complex molecules. The strategy of cyclometalation and metallacycle contraction is employed to address the issue of beta-H elimination in alkene dicarbofunctionalization reactions.