View source for Castro–Stephens coupling

{{Use dmy dates|date=January 2024}}
{{Reactionbox
|Name = Castro–Stephens coupling
|Type = Coupling reaction
|NamedAfter = Charles E. Castro <br> Robert D. Stephens
|Section3 = {{Reactionbox Identifiers
|RSC_ontology_id = 0000525
}}
}}
The '''Castro–Stephens coupling''' is a [[cross coupling reaction]] between a [[copper(I) acetylide]] and an [[aryl halide]] in [[pyridine]], forming a disubstituted [[alkyne]] and a copper(I) halide.<ref name = CastroStephens1963/><ref name = OrgSynth/>

:[[File:General scheme for Castro-Stephens coupling.png|700px|General scheme for Castro-Stephens coupling]]

The reaction was described in 1963 by chemists Castro and Stephens.<ref name = CastroStephens1963>{{cite journal|title = The Substitution of Aryl Iodides with Cuprous Acetylides. A Synthesis of Tolanes and Heterocyclics|first1 = R. D.|last1 = Stephens|first2 = C. E.|last2 = Castro|journal = [[J. Org. Chem.]]|year = 1963|volume = 28|issue = 12|pages = 3313–3315|doi = 10.1021/jo01047a008}}</ref><ref name = OrgSynth>{{OrgSynth|first1 = D. C.|last1 = Owsley|first2 = C. E.|last2 = Castro|collvol = 6|collvolpages = 916|volume = 52|pages = 128|year = 1972|prep = CV6P0916|doi = 10.15227/orgsyn.052.0128|title = Substitution of Aryl Halides with Copper(I) Acetylides: 2-Phenylfuro[3,2-''b'']pyridine}}</ref> The reaction is similar to the much older [[Rosenmund–von Braun synthesis]] (1914)<ref>{{cite journal|last1 = Rosenmund|first1 = Karl W.|authorlink1 = Karl Wilhelm Rosenmund|last2 = Struck|first2 = Erich|title = Das am Ringkohlenstoff gebundene Halogen und sein Ersatz durch andere Substituenten. I. Mitteilung: Ersatz des Halogens durch die Carboxylgruppe|language = German|trans-title=The halogen bound to the ring carbon and its replacement by other substituents. I. Notice: Replacement of the halogen by the carboxyl group|journal = [[Ber. Dtsch. Chem. Ges. A/B]]|year = 1919|volume = 52|issue = 8|pages = 1749–1756|doi = 10.1002/cber.19190520840|url = https://zenodo.org/record/1426663}}</ref><ref>{{cite journal|last1 = von Braun|first1 = Julius|last2 = Manz|first2 = Gottfried|title = Fluoranthen und seine Derivate. III. Mitteilung|language = German|trans-title=Fluoranthene and its derivatives. III. Notification|journal = [[Justus Liebigs Ann. Chem.]]|year = 1931|volume = 488|issue = 1|pages = 111–126|doi = 10.1002/jlac.19314880107}}</ref> between aryl halides and [[copper(I) cyanide]] and was itself modified in 1975 as the [[Sonogashira coupling]] by adding a palladium catalyst and preparing the [[organocopper compound]] ''[[in situ]]'', allowing copper to also be used catalytically.<ref>{{cite journal|last1 = Sonogashira|first1 = Kenkichi|authorlink1 = Kenkichi Sonogashira|last2 = Tohda|first2 = Yasuo|first3 = Nobue|last3 = Hagihara|journal = [[Tetrahedron Lett.]]|title = A convenient synthesis of acetylenes: Catalytic substitutions of acetylenic hydrogen with bromoalkenes, iodoarenes and bromopyridines|year = 1975|volume = 16|issue = 50|pages = 4467–4470|doi = 10.1016/s0040-4039(00)91094-3}}</ref><ref>{{cite journal|last = Sonogashira|first = Kenkichi|authorlink = Kenkichi Sonogashira|journal = [[J. Organomet. Chem.]]|title = Development of Pd-Cu catalyzed cross-coupling of terminal acetylenes with sp<sup>2</sup>-carbon halides|year = 2002|volume = 653|issue = 1–2|pages = 46–49|doi = 10.1016/s0022-328x(02)01158-0}}</ref>

A typical reaction [[diphenylacetylene]] is obtained by the coupling of [[iodobenzene]] with Cu[[phenylacetylene|C<sub>2</sub>C<sub>6</sub>H<sub>5</sub>]] in hot [[pyridine]]:<ref name = CastroStephens1963/>

:[[Image:Castro-Stephens application.png|650px|Application of Castro–Stephens coupling with phenyliodide.]]

Unlike the Sonogashira coupling, the Castro–Stephens coupling can produce heterocyclic compounds when a nucleophilic group is ''[[arene substitution pattern|ortho]]'' to the aryl halide, although this typically requires use of [[dimethylformamide]] (DMF) as solvent.<ref>{{cite journal|title = Synthesis of natural isocoumarins, artemidin and 3-propylisocoumarin|first1 = Gunes|last1 = Batu|first2 = Robert|last2 = Stevenson|journal = [[J. Org. Chem.]]|year = 1980|volume = 45|issue = 8|pages = 1532–1534|doi = 10.1021/jo01296a044}}</ref><ref>{{cite journal|title = Copper(I) Substitutions. Scope and Mechanism of Cuprous Acetylide Substitutions|first1 = Charles E.|last1 = Castro|first2 = R.|last2 = Havlin|first3 = V. K.|last3 = Honwad|first4 = A. M.|last4 = Malte|first5 = Steve W.|last5 = Moje|journal = [[J. Am. Chem. Soc.]]|year = 1969|volume = 91|issue = 23|pages = 6464–6470|doi = 10.1021/ja01051a049| bibcode=1969JAChS..91.6464C }}</ref>

:[[File:Castro-Stephens 3-n-Propylisocoumarin synthesis.png|700px|Application of Castro-Stephens coupling with ''o''-iodobenzoic acid to produce an isocoumarin.]]

==References==
{{reflist}}
{{Organic reactions}}
{{DEFAULTSORT:Castro-Stephens coupling}}
[[Category:Carbon-carbon bond forming reactions]]
[[Category:Name reactions]]