Phosphonium coupling

In organic chemistry, phosphonium coupling is a cross-coupling reaction for organic synthesis. It is a mild, efficient, chemoselective and versatile methodology for the formation of C–C, C–N, C–O, and C–S bond of unactivated and unprotected tautomerizable heterocycles. The method was originally reported in 2004.Kang, Fu-An; Kodah, Jason; Guan, Qunying; Li, Xiaobing; Murray, William V., Efficient conversion of Biginelli 3,4-dihydropyrimidin-2(1H)-one to pyrimidines via PyBroP-mediated coupling, Journal of Organic Chemistry (2005), 70(5), 1957-1960. {{doi|10.1021/jo040281j}} The C–OH bond of a tautomerizable heterocycle is activated with a phosphonium salt (PyBroP, PyBOP, BroP, or BOP), and subsequent functionalization with either a nucleophile through SNAr displacement or an organometallic through transition metal catalyzed cross coupling reaction. The in situ activation of the C-OH bond in phosphonium coupling has been applied to cross coupling reactions of tautomerizable heterocycles and arenols using other types of activating reagents.{{cite journal|doi=10.1021/bc990063a|pmid=10563775|title=Rapid Esterification of Nucleosides to Solid-Phase Supports for Oligonucleotide Synthesis Using Uronium and Phosphonium Coupling Reagents|journal=Bioconjugate Chemistry|volume=10|issue=6|pages=1051–1057|year=1999|last1=Pon|first1=Richard T.|last2=Yu|first2=Shuyuan|last3=Sanghvi|first3=Yogesh S.}}{{cite book|doi=10.1016/B978-0-08-100024-3.00002-7|title=Recent Progress of Phosphonium Coupling in Heterocyclic and Medicinal Chemistry|volume=27|pages=29–59|series=Progress in Heterocyclic Chemistry|year=2015|last1=Kang|first1=Fu-An|isbn=9780081000243}}

Phosphonium coupling generates in situ a pseudo aryl or heteroaryl halide (the intermediate phosphonium species), which subsequently reacts with its coupling partner.Chinchilla, Rafael; Najera, Carmen, Recent advances in Sonogashira reactions, Chemical Society Reviews (2011), 40(10), 5084-5121. {{doi|10.1039/c1cs15071e}}Sellars, Jonathan D.; Steel, Patrick G., Transition metal-catalysed cross-coupling reactions of P-activated enols, Chemical Society Reviews (2011), 40(10), 5170-5180. {{doi|10.1039/c1cs15100b}}Li, Bi-Jie; Yu, Da-Gang; Sun, Chang-Liang; Shi, Zhang-Jie, Activation of "Inert" Alkenyl/Aryl C=O Bond and Its Application in Cross-Coupling Reactions, Chemistry--A European Journal (2011), 17(6), 1728-1759. {{doi|10.1002/chem.201002273}}Katritzky, Alan R.; Rachwal, Stanislaw, Synthesis of heterocycles mediated by benzotriazole. 2. Bicyclic systems, Chemical Reviews (Washington, DC, United States) (2011), 111(11), 7063-7120. {{doi|10.1021/cr200031r}}Ackermann, Lutz, Carboxylate-Assisted Transition-Metal-Catalyzed C-H Bond Functionalizations: Mechanism and Scope, Chemical Reviews (Washington, DC, United States) (2011), 111(3), 1315-1345. {{doi|10.1021/cr100412j}}Allen, Anna E.; MacMillan, David W. C., Synergistic catalysis: A powerful synthetic strategy for new reaction development, Chemical Science (2012), 3(3), 633-658. {{doi|10.1039/c2sc00907b}}