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

Laura M. Wickham, Ramesh Giri

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Abstract

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 [β-H-C(sp3)-[M]] species, a key intermediate prone to undergo rapid β-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 β-H elimination is avoided by geometric restriction or complete lack of β-H’s. With reasoning that β-H-C(sp3)-[M] intermediates could be rendered amenable to interception with the use of first row late TMs and formation of coordination-assisted transient metallacycles, these two strategies were implemented to address the β-H elimination problem in alkene dicarbofunctionalization reactions.

Because first row late TMs catalyze C(sp3)-C(sp3) coupling, Cu and Ni were anticipated to impart sufficient stability to β-H-C(sp3)-[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 β-H-C(sp3)-[M] intermediates was hypothesized when three-component reactions were performed. The idea of cyclometalation to curtail β-H elimination is founded upon Whitesides’s [J. Am. Chem. Soc.1976, 98, 6521] observation that metallacycles undergo β-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 β-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.

Original languageEnglish (US)
Pages (from-to)3415-3437
Number of pages23
JournalAccounts of Chemical Research
Volume54
Issue number17
DOIs
StatePublished - Sep 7 2021

All Science Journal Classification (ASJC) codes

  • Chemistry(all)

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