Cross electrophile coupling is a type of cross-coupling reaction that occurs between two electrophiles. It is often catalyzed by transition metal catalyst(s). Unlike conventional cross-coupling reactions of an electrophile with an organometallic reagent,[1] the coupling partners in cross electrophile coupling reactions are both electrophiles.[2] Generally, additional reductant to regenerate active catalyst is needed in this reaction.
Cross selectivity
editReductive dimerization of electrophiles has long been known (Wurtz reaction, Ullman reaction, etc.),[3][4] Few methods exist for achieving cross selectivity.
Using excess of one reagent
editUsing excess amount of one reagent can provide synthetically useful yields of cross-coupled product when the starting reagents have similar reactivity. (e.g. coupling between two alkyl halides). This strategy has been used with a Ni catalyst and zinc as reductant.[5] Dimerization of the more reactive alkyl halide was the major byproduct.
Alkyl-alkyl (Csp3-Csp3) cross electrophile coupling using metallaphotoredox catalysis has also been achieved.[6] In this case, small alkyl electrophiles were used excess amount. Tris(trimethylsilyl)silanol can be employed as a halogen abstractor in combination with photoredox and Ni catalysis.
Sequential oxidative addition
editIn cases where two electrophiles have disparate reactivity, this difference can be used to achieve high selectivity for cross product.
For example, aryl halide and alkyl halide can be differentiated by the reactivity trends of two electrophiles whether it prefers heterolytic or homolytic pathway.[7] [8] Through detailed mechanistic studies, the origin of high selectivity was revealed : Aryl halides do faster oxidative addition to Ni(0) center than alkyl halides, however, alkyl halides form radicals when it react with nickel center. The catalysis begins with oxidative addition of an aryl halide to Ni(0). The resulting Ni(II) species reacts with an alkyl radical generated from alkyl halides to form diorganonickel(III) intermediate which can undergo reductive elimination of the cross coupled product. Reduction of Ni(II) to Ni(0) by Mn closes the catalytic cycle.
Reductive cross coupling of two different aryl (pseudo)halide was achieved. Use of two different metals (Ni and Pd) was essential for the observed cross-selectivity of chemically similar two reactants. Aryl triflates generally prefer oxidative addition to the electron-rich Pd(0) catalyst whereas Ni(0) selectively reacts with aryl bromides.[9]
Transmetallation of the aryl-nickel(II) onto the Aryl-palladium(II) forms a Pd(II)Ar1Ar2 species followed by reductive elimination to give product. Finally, reduction of Ni(II) by additive zinc regenerates Ni(0).
References
edit- ^ Hartwig JF (2010). Organotransition metal chemistry : from bonding to catalysis. University Science Books. ISBN 9781891389535. OCLC 781082054.
- ^ Everson DA, Weix DJ (June 2014). "Cross-electrophile coupling: principles of reactivity and selectivity". The Journal of Organic Chemistry. 79 (11): 4793–8. doi:10.1021/jo500507s. PMC 4049235. PMID 24820397.
- ^ Hassan J, Sevignon M, Gozzi C, Schulz E, Lemaire M (2002). "Aryl−Aryl Bond Formation One Century after the Discovery of the Ullmann Reaction". Chemical Reviews. 102 (5): 1369–1469. doi:10.1021/cr000664r. PMID 11996540.
- ^ Wurtz A (1855). "Ueber eine neue Klasse organischer Radicale". Justus Liebigs Annalen der Chemie. 96 (3): 364–375. doi:10.1002/jlac.18550960310. ISSN 1099-0690.
- ^ Yu X, Yang T, Wang S, Xu H, Gong H (April 2011). "Nickel-catalyzed reductive cross-coupling of unactivated alkyl halides". Organic Letters. 13 (8): 2138–41. doi:10.1021/ol200617f. PMID 21434609.
- ^ Smith RT, Zhang X, Rincón JA, Agejas J, Mateos C, Barberis M, García-Cerrada S, de Frutos O, MacMillan DW (December 2018). "3 Coupling of Aliphatic Bromides". Journal of the American Chemical Society. 140 (50): 17433–17438. doi:10.1021/jacs.8b12025. PMC 6697083. PMID 30516995.
- ^ Everson DA, Jones BA, Weix DJ (April 2012). "Replacing conventional carbon nucleophiles with electrophiles: nickel-catalyzed reductive alkylation of aryl bromides and chlorides". Journal of the American Chemical Society. 134 (14): 6146–59. doi:10.1021/ja301769r. PMC 3324882. PMID 22463689.
- ^ Biswas S, Weix DJ (October 2013). "Mechanism and selectivity in nickel-catalyzed cross-electrophile coupling of aryl halides with alkyl halides". Journal of the American Chemical Society. 135 (43): 16192–7. doi:10.1021/ja407589e. PMC 3946589. PMID 23952217.
- ^ Ackerman LK, Lovell MM, Weix DJ (August 2015). "Multimetallic catalysed cross-coupling of aryl bromides with aryl triflates". Nature. 524 (7566): 454–7. Bibcode:2015Natur.524..454A. doi:10.1038/nature14676. PMC 4552586. PMID 26280337.