Versatile Cross Coupling Methods:
Hiyama Coupling (R-X + R'-SiR''3)
Hiyama-Denmark Coupling (R-X + R-SiMe2OH)
Kumada Coupling (R-X + R'-MgX)
Negishi Coupling (R-X + R'-ZnX)
Stille Coupling (R-X + R'-SnR''3)
Suzuki Coupling (R-X + R'-BY3)
Substoichiometric amounts of ZnCl2 promote a room temperature, Pd/P(t-Bu)3-catalyzed cross-coupling of aryl bromides with alkynes. A Pd(I) dimer is a particularly active precatalyst for this reaction. The reaction is general for a broad range of aryl bromides.
A. D. Finke, E. C. Elleby, M. J. Boyd, H. Weissman, J. S. Moore, J. Org. Chem., 2009, 74, 8897-8900.
An efficient ligand-, copper-, and amine-free palladium-catalyzed Sonogashira reaction of aryl iodides and bromides with terminal alkynes at room temperature has been developed. The key reagent is tetrabutylammonium acetate as the base. This method tolerates a broad range of functional groups.
S. Urgaonkar, J. G. Verkade, J. Org. Chem., 2004, 69, 5752-5755.
t-Bu2(p-NMe2C6H4)P is an efficient ligand for palladium catalysts in Heck alkynylation of various aryl halides with a range of aryl- and alkyl-acetylenes in excellent yields, under relatively low Pd loadings. Preliminary mechanistic studies on the negative copper effect and substrate effect of aryl acetylenes help to better understand the cross-coupling pathway of Heck alkynylation.
X. Pu, H. Li, T. J. Colacot, J. Org. Chem., 2013, 78, 568-581.
A highly efficient and practical protocol for the coupling of terminal alkynes with aryl iodides is catalyzed by the inexpensive and environmentally benign combination of Fe/Cu. The versatility, generality, low cost, and environmental friendliness, in combination with exceptionally high reaction rates, render this method particularly attractive for industrial applications.
H. Huang, H. Jiang, K. Chen, H. Liu, J. Org. Chem., 2008, 73, 9061-9064.
An inexpensive catalytic system using a readily available copper/ligand combination for the Sonogashira-type cross-coupling of aryl iodides and phenyl- and hexyl-acetylene affords disubstituted alkynes in good yields.
F. Monnier, F. Turtaut, L. Duroure, M. Taillefer, Org. Lett., 2008, 10, 3203-3206.
A Cu2O-catalyzed cross-coupling reaction of alkynes with aryl iodides tolerates a broad range of functional groups and enables even the conversion of sterically demanding substrates with only 5-10 mol% of the catalyst.
W.-T. Tsai, Y.-Y. Lin, Y.-A. Chen, C.-F. Lee, Synlett, 2014, 25, 443-447.
In the presence of bis(dibenzylideneacetone)palladium(0) and cesium carbonate, a variety of alkynyl halides underwent a ligand-free Suzuki-Miyaura cross-coupling reaction with organoboronic acids at room temperature under aerobic conditions to afford the corresponding unsymmetrical diarylalkynes in good yields.
J.-S. Tang, M. Tian, W.-B. Sheng, C.-C. Guo, Synthesis, 2012, 44, 541-546.
General protocols for the palladium-catalyzed coupling of aryl chlorides and alkynes and aryl tosylates and alkynes were developed. Addition of a copper cocatalyst can inhibit product formation. In the case of highly active catalysts, screening for new catalyst systems need to be carried out both in the presence and absence of copper.
D. Gelman, S. L. Buchwald, Angew. Chem. Int. Ed., 2003, 42, 5993-5996.
The palladium-catalyzed cross-coupling reaction of potassium alkynyltrifluoroborates with aryl halides or triflates proceeds readily with moderate to excellent yields. The potassium alkynyltrifluoroborates are air- and moisture-stable crystalline solids that can be stored indefinitely, which will provide an advantage in applications to combinatorial chemistry.
G. A. Molander, B. W. Katona, F. Machrouhi, J. Org. Chem., 2002, 67, 8416-8423.
A highly active, air- and moisture-stable and easily recoverable magnetic-nanoparticle-supported palladium catalyst enables the Suzuki cross-coupling reaction of alkynyl bromides with organoboron derivatives in very good yields in ethanol. The supported palladium catalyst can be recovered and reused up to 16 times without significant loss of catalytic activity.
X. Zhang, P. Li, Y. Ji, L. Zhang, L. Wang, Synthesis, 2011, 2975-2983.
The use of TMPLi base in a pentane/THF mixture at 25°C or use of a metal alkoxide base in dioxane at elevated temperature enable base-mediated, transition-metal-free alkynylations of aryl chlorides that proceed via benzyne intermediates. Fluoro, trifluoromethyl, silyl, cyano, and alcohol functionalities are compatible with the reaction conditions.
T. Truong, O. Daugulis, Org. Lett., 2011, 13, 4172-4175.
Cross coupling of ortho-substituted aryl Grignard reagents with alkynyl Grignard reagents can be performed without adding any transition metal in the presence of 2,2,6,6-tetramethylpiperidine-N-oxyl radical (TEMPO) as an environmentally benign organic oxidant. Importantly, functional groups such as esters, amides, and cyanides are tolerated.
M. S. Maji, S. Murarka, A. Studer, Org. Lett., 2010, 12, 3878-3881.
A palladium-catalyzed domino coupling reaction of 1,1-dibromo-1-alkenes with triarylbismuth nucleophiles furnishes disubstituted alkynes directly. The couplings are very fast, affording high yields of alkynes in a short reaction time.
M. L. N. Rao, D. N. Jadhav, P. Dasgupta, Org. Lett., 2010, 12, 2048-2051.
A triethylamine-catalyzed metalation of terminal alkynes with trimethylaluminum (a readily available, inexpensive, and nontoxic metalating agent) gives alkynyldimethylaluminum reagents. These compounds react efficiently with various aromatic and heterocyclic halides in the presence of a palladium catalyst offering a simple entry to numerous internal alkynes.
B. Wang, M. Bonin, L. Micouin, Org. Lett., 2004, 6, 3481-3484.
Unsymmetrical diarylalkynes are accessible by a one-pot procedure from two different aryl halides and (trimethylsilyl)acetylene. A Pd/Cu-catalyzed Sonogashira coupling of an aryl halide with (trimethylsilyl)acetylene is followed by desilylation of the formed aryl(trimethylsilyl)acetylene with aqueous potassium hydroxide and a second Sonogashira coupling with an aryl iodide.
R. Severin, J. Reimer, S. Doye, J. Org. Chem., 2010, 75, 3518-3521.
In the presence of Pd(OAc)2 and Xphos, alkynyl carboxylic acids smoothly underwent a decarboxylative coupling reaction with various benzyl halides or aryl halides, providing internal alkynes in good yields. It is noteworthy that the optimal conditions are compatible with a wide range of aryl halides.
W.-W. Zhang, X.-G. Zhang, J.-H. Li, J. Org. Chem., 2010, 75, 5259-5264.
Employing propiolic acid as a difunctional alkyne, and using the consecutive reactions of a Sonogashira coupling and a decarboxylative coupling, unsymmetrically substituted diaryl alkynes were obtained in good yield.
J. Moon, M. Jeong, H. Nam, J. Ju, J. H. Moon, H. M. Jung, S. Lee, Org. Lett., 2008, 10, 945-948.
A convenient approach to selectively prepare a wide range of functionalized propiolic acids was developed by AgI-catalyzed carboxylation of terminal alkynes using carbon dioxide as carboxylative agent under ligand-free conditions.
X. Zhang, W.-Z. Zhang, X. Ren, L.-L. Zhang, X.-B. Lu, Org. Lett., 2011, 13, 2402-2405.
A palladium-catalyzed cross-coupling reaction between a wide range of aryl iodides and lithium tetrakis(ethoxycarbonylethynyl)indates (0.35 equiv) enables an efficient synthesis of ethyl arylpropiolates. Lithium tetrakis(ethoxycarbonylethynyl)indates can be generated in situ from ethyl propiolate and n-butyllithium and a subsequent transmetallation with indium trichloride.
Y. Park, D. Kang, W. H. Jeon, T. Ryu, P. H. Lee, Synthesis, 2014, 46, 2305-2311.
Various substituted phenols are ethynylated at the ortho position with silylated chloroethyne in the presence of a catalytic amount of GaCl3 and lithium phenoxide. The lithium salt is essential for the catalysis, and addition of 2,6-di(tert-butyl)-4-methylpyridine inhibits desilylation and hydration of the products. The mechanism is discussed.
K. Kobayahi, M. Arisawa, M. Yamaguchi, J. Am. Chem. Soc., 2002, 124, 8528-8529.
A carbenoid Fritsch-Buttenberg-Wiechell (FBW) rearrangement of a substituted dibromoolefinic precursor is used to generate a lithium acetylide, and subsequent trapping with carbon-based electrophiles provides a wide range of di- and triynes. The lithium acetylide formed from the FBW reaction can also undergo transmetalation to provide zinc, copper, tin, or platinum acetylides.
T. Luu, Y. Morisaki, N. Cunningham, R. R. Tykwinski, J. Org. Chem., 2007, 72, 9622-9629.
A copper-catalyzed reaction of terminal alkynes with cyanogen iodide (ICN) produces alkynyl cyanides in the presence of of tetramethylpiperidine as a sterically congested base. Some control experiments revealed that the reaction involves the noncatalyzed formation of alkynyl iodides followed by copper-catalyzed cyanation of the iodides without the formation of copper(I) acetylide.
K. Okamoto, M. Watanabe, N. Sakata, M. Murai, K. Ohe, Org. Lett., 2013, 15, 5810-5813.