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Synthesis of substituted alkynes

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A simple protocol for iron-catalyzed cross-coupling of nonactivated secondary alkyl bromides and iodides with alkynyl Grignard reagents at room temperature tolerates a wide range of secondary alkyl halides and terminal alkynes to afford substituted alkynes in good yields.
C. W. Cheung, P. Ren, X. Hu, Org. Lett., 2014, 16, 2566-2569.

Pd₂(dba)₃-Ph₃P-catalyzed Kumada-Corriu coupling reactions of unactivated alkyl bromides or iodides with alkynyllithiums or the corresponding Grignard reagents furnish C_sp-C_sp3 bond formation. The superior performance of Ph₃P ligand over the trialkylphosphine ligands indicates that this cross-coupling reaction may be a reductive-elimination-controlled process.
L.-M. Yang, L.-F. Huang, T.-Y. Luh, Org. Lett., 2004, 6, 1461-1463.

An efficient copper-catalyzed homo- and cross-coupling of Grignard reagents with di-tert-butyldiaziridinone as oxidant gives coupling products in good to excellent yields under mild conditions. The reaction has a broad substrate scope and is also effective for the C(sp)-C(sp³) coupling.
Y. Zhu, T. Xiong, W. Han, X. Shi, Org. Lett., 2014, 16, 6144-6147.

Sulfonium ylides can be used as alkyl electrophiles in a palladium-catalyzed methylation protocol for the synthesis of methyl-functionalized internal alkynes via a C(sp)-C(sp³) bond formation process.
Y.-Y. Liu, X.-H. Yang, X.-C. Huang, W.-T. Wei, R.-J. Song, J.-H. Li, J. Org. Chem., 2013, 78, 10421-10426.

A Pd/N-heterocyclic carbene-based catalyst achieves the Sonogashira coupling of an array of functionalized, β-hydrogen-containing alkyl bromides and iodides under mild conditions.
M. Eckhardt, G. C. Fu, J. Am. Chem. Soc., 2003, 125, 13642-13643.

Terminal alkynes can be directly cross-coupled with alkylzinc reagents in the presence of a Pd catalyst at room temperature with air as the oxidant. CO was found to be critical in gaining high chemical yields and selectivities. Good yields were obtained for a wide range of alkynes and alkylzinc reagents.
M. Chen, X. Zheng, W. Li, J. He, A. Lei, J. Am. Chem. Soc., 2010, 132, 4101-4103.

Alkynyltrifluoroborate nucleophiles react smoothly with a wide range of sp³-carbon electrophiles, including propargyl methanesulfonates and unactivated alkyl triflates, to give Sonogashira-type products via a novel ion pair-assisted nucleophilic substitution mechanism.
S. Liu, C. F. Tormena, G. B. Hammond, B. Xu, Org. Lett., 2022, 24, 6298-6303.

A redox-neutral and highly chemoselective visible-light-induced deboronative alkynylation reaction works with primary, secondary and tertiary alkyl trifluoroborates or boronic acids to generate aryl, alkyl and silyl substituted alkynes. This reaction tolerates substrates containing alkenes, alkynes, aldehydes, ketones, esters, nitriles, azides, aryl halides, alkyl halides, alcohols, and indoles.
H. Huang, G. Zhang, L. Gong, S. Zhang, Y. Chen, J. Am. Chem. Soc., 2014, 136, 2280-2283.

Boron "ate" complexes derived from pinacol boronic esters and tert-butyl lithium undergo stereospecific transmetalation to copper cyanide, followed by coupling with alkynyl bromides, allyl halides, propargylic halides, β-haloenones, hydroxylamine esters, and acyl chlorides. This simple transformation converts primary and secondary alkylboronic esters to a wide array of useful compounds.
N. Xu, H. Liang, J. P. Morken, J. Am. Chem. Soc., 2022, 144, 11546-11552.

In a copper-catalyzed cross-coupling of N-tosylhydrazones with trialkylsilylethynes, that leads to the formation of C(sp)-C(sp³) bonds, Cu carbene migratory insertion is proposed to play the key role.
F. Ye, X. Ma, Q. Xiao, H. Li, Y. Zhang, J. Wang, J. Am. Chem. Soc., 2012, 134, 5742-5745.

A highly efficient cross-coupling of trialkylsilylethynes with N-tosylhydrazones has been achieved in dioxane at 90-110 °C using an SBA-15-immobilized l-proline-Cu(I) complex as the heterogeneous catalyst and LiOtBu as the base. The reaction generates a wide variety of alkyltrialkylsilylalkynes in good yields. The recyclable catalyst can be easily recovered through a simple centrifugation.
Q. Ye, W. Huang, L. Wei, M. Cai, J. Org. Chem., 2023, 88, 2973-2984.

A coupling of substituted Hantzsch esters or Meyer nitriles with benziodoxole-activated alkynes provides products containing C_sp3-Csp bonds involving primary, secondary, and tertiary carbon centers in good yields. K₂S₂O₈ was the optimum radical initiator in this reaction.
X. Liu, R. Liu, J. Dai, X. Cheng, G. Li, Org. Lett., 2018, 20, 6906-6909.

An organic photocatalyst mediates a deconstructive alkynylation of an unstrained ketone under blue light irradiation. This alkynylation method offers a broad substrate scope and excellent functional group tolerance. A trifluoromethylation reagent for the trifluoromethylation reaction of various alkynyl bromides is also described.
H. Wu, S. Chen, D. Xiao, F. Li, K. Zhou, X. Yin, C. Liu, X. He, Y. Shang, Org. Lett., 2023, 25, 1166-1171.

Hydroboration with catecholborane, followed by treatment with easily available reagents such as alkenyl sulfones or alkynyl phenyl sulfones in the presence of a radical initiator, represents an effective and simple one-pot procedure for direct vinylation, formylation, and cyanation.
A.-P. Schaffner, V. Darmency, P. Renaud, Angew. Chem. Int. Ed., 2006, 45, 5847-5849.

An efficient protocol for the palladium-catalyzed Heck alkynylation using XPhos as ligand and Cs₂CO₃ as the base, couples a wide range of functionalized terminal alkynes and substituted benzyl chlorides. An excess amount of base and higher reaction temperatures allows the synthesis of allenes in a one-pot procedure.
C. H. Larsen, K. W. Anderson, R. E. Tundel, S. L. Buchwald, Synlett, 2006, 2941-2946.

A highly efficient palladium-catalyzed Sonogashira coupling of benzylic ammonium salts with terminal alkynes provides a series of internal alkyne derivatives in good yields. The reaction offers a broad substrate scope and high functional group tolerance.
S. Xu, Z. Zhang, C. Han, W. Hu, T. Xiao, Y. Yuan, J. Zhao, J. Org. Chem., 2019, 84, 12157-12164.

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.

1,1-diarylpropadienes and 1,3-diarylpropynes can be prepared by the sequential lithiation of 1-aryl-1-propynes, transmetalation, and the corresponding Pd(0)-catalyzed cross-coupling with aryl halides.
S. Ma, Q. He, X. Zhang, J. Org. Chem., 2005, 70, 3336-3338.

The reaction of alkynylboron dihalides with benzylic, allylic, and propargylic alcohols provides an efficient route to internal acetylenes without isomerization of the product alkynes under the reaction conditions.
G. W. Kabalka, M.-L. Yao, S. Borella, Org. Lett., 2006, 8, 879-881.

A photoinduced, copper-catalyzed, three-component reaction of haloalkane, alkenes, and alkyne under mild reaction conditions helps to introduce privileged functionalities into propargylic systems.
Y. Zhang, D. Zhang, J. Org. Chem., 2020, 85, 3213-3223.

Under different conditions, the reaction of propargyl alcohols and terminal alkynes leads to the selective formation of 1,4-diynes and polysubstituted furans/pyrroles. Water is the only byproduct in the atom economic, selective synthesis of 1,4-diynes and pyrroles, whereas the synthesis of furans is fully atom economic.
T. Wang, X.-l. Chen, L. Chen, Z.-p. Zhan, Org. Lett., 2011, 13, 3324-3327.

A rhodium-catalyzed chemo-, regio-, and enantioselective intermolecular decarboxylative alkynylation of terminal allenes with arylpropiolic acids provides branched allylic 1,4-enynes under mild conditions. This reaction offers a broad functional group compatibility.
C. P. Grugel, B. Breit, Org. Lett., 2018, 20, 1066-1069.

A highly enantioselective Sonogashira type synergistic Rh and Cu catalysis of readily available terminal alkynes and racemic allylic carbonates provides branched 1,4-enynes under neutral conditions. Aliphatic and aromatic terminal alkynes with various functional groups could be used directly.
W.-Y. Huang, C.-H. Lu, S. Ghorai, B. Li, C. Li, J. Am. Chem. Soc., 2020, 142, 15276-15281.

A direct dehydrative coupling of terminal alkynes with allylic alcohols is catalyzed by Pd(PPh₃)₄ in the presence of an N,P-ligand and Ti(OiPr)₄. The coupling reaction tolerates various functional groups and provides a valuable synthetic tool to access 1,4-enynes.
Y.-X. Li, Q.-Q. Xuan, L. Liu, D. Wang, Y.-J. Chen, C.-J. Li, J. Am. Chem. Soc., 2013, 135, 12536-12539.

A mild Suzuki-Miyaura cross-coupling reaction achieves the synthesis of a broad range of β,γ-alkynyl esters and amides using air-stable potassium alkynyltrifluoroborates as nucleophilic partners. Propargyl esters and amides were obtained in high yields using a low catalyst loading.
G. A. Molander, K. M. Traister, Org. Lett., 2013, 15, 5052-5055.

A general, inexpensive, copper-catalyzed coupling of terminal alkynes with diazo compounds provides ready access to 3-alkynoates. This reaction proceeds efficiently under nonbasic conditions at room temperature and tolerates various functional groups.
A. Suárez, G. C. Fu, Angew. Chem. Int. Ed., 2004, 43, 3580-3582.

Highly substituted α,α-disubstituted β-alkynyl esters are readily prepared from allenyl esters and either alkyl halide, acid chloride, or alkyl chloroformate, mediated by an amide base. This highly efficient and mild process tolerates various functional groups and provides α,α-disubstituted β-alkynyl esters in good to excellent yields.
W. Wang, B. Xu, G. B. Hammond, Org. Lett., 2008, 10, 3713-3716.

A three-component reaction of a terminal alkyne, a diazo ester, and an allylic carbonate provides 1,5-enynes with an all-carbon quaternary center via cooperative Cu/Rh catalysis with Xantphos as the ligand. In reactions using propargylic alcohols, a Meyer-Schuster rearrangement results in an unprecedented acylation-allylation of carbenes.
H. Chen, W. Yang, J. Zhang, B. Lu, X. Wang, J. Am. Chem. Soc., 2024, 146, 4727-4740.

A highly diastereoselective addition of terminal alkynes to unsymmetrical gem-disubstituted cyclopropenes to give alkynylcyclopropanes in good to excellent yields is catalyzed by the Herrmann-Beller phosphapalladacycle. The stereofacial discrimination at the approach of the bulky alkynylpalladium species is believed to be responsible for the diastereoselectivity control of the addition reaction.
A. Tenaglia, K. Le Jeune, L. Giordano, G. Buono, Org. Lett., 2011, 13, 636-639.

An iron(III)-promoted hydroalkynylation of unactivated mono-, di-, and trisubstituted alkenes provides structural diversified alkynes via Csp-Csp³ bond formation.
Y. Shen, B. Huang, J. Zheng, C. Lin, Y. Liu, S. Cui, Org. Lett., 2017, 19, 1744-1747.

(NH₄)₂S₂O₈ mediates a metal-free three-component alkene oxyalkynylation using H₂O or alcohol as oxygenation agent. The reversed regioselectivity should be dictated by an alkene radical cation intermediate.
Y. Li, R. Lu, S. Sun, L. Liu, Org. Lett., 2018, 20, 6836-6839.

Alkynyl halides serve as a source of Br⁺ and acetylide ions in an efficient one-step preparation of alkynyl epoxides, important organic building blocks, from readily available starting materials.
A. Trofimov, N. Chernyak, V. Gevorgyan, J. Am. Chem. Soc., 2008, 130, 13538-13539.

An alkynylation of cyclopropanols with 1-bromo-1-alkynes provides synthetically useful alk-4-yn-1-ones. In this C-C bond formation, functionalized cyclopropanols act as a new class of homoenolate equivalent.
R. V. N. S. Murali, N. N. Rao, J. K. Cha, Org. Lett., 2015, 17, 3854-3856.

Copper(II)-mediated ring opening/alkynylation of cyclopropanols with inexpensive and commercially available terminal alkynes proceeded efficiently to afford synthetically useful alk-4-yn-1-ones in good yields with good functional group tolerance.
B.-Q. Cheng, S.-X. Zhang, Y.-Y. Cui, X.-Q. Chu, W. Rao, H. Xu, G.-Z. Han, Z.-L. Shen, Org. Lett., 2020, 22, 5456-5461.

A silver-promoted oxidative ring opening/alkynylation of cyclopropanols with ethynylbenziodoxolones (EBX) enables the formation of alkylated alkynes. Control experiments support a radical mechanism.
C.-Y. Wang, R.-J. Song, Y.-X. Xie, J.-H. Li, Synthesis, 2016, 48, 223-230.

A practical Pd-catalyzed protocol for the hydroalkynylation of enones proceeds efficiently with various alkynes as well as with several cyclic and acyclic enones, providing synthetically relevant β-alkynyl ketones in good to excellent yields.
L. Villarino, R. García, F. López, J. L. Mascareñas, Org. Lett., 2012, 14, 2996-2999.

A rapid and simple conjugate alkynylation of acyclic enones using sp-hybridised potassium organotrifluoroborates in the presence of BF₃•OEt₂ is suitable for the preparation of small compound libraries.
F. Bertolini, S. Woodward, Synlett, 2009, 51-54.

A visible-light-induced oxidation of alcohols generates alkoxyl radicals mediated by iodine(III) reagents under mild reaction conditions. The β-fragmentation of alkoxyl radicals enables selective C(sp³)-C(sp³) bond cleavage and alkynylation/alkenylation reactions with various strained cycloalkanols and linear alcohols.
K. Jia, F. Zhang, H. Huang, Y. Chen, J. Am. Chem. Soc., 2016, 138, 1514-1517.

An efficient Na₂S₂O₈-promoted radical coupling of tertiary cycloalkanols with alkynyl hypervalent iodide reagents provides β-, γ- and δ-alkynylated ketones via C-C bond cleavage. This tandem ring-opening/alkynylation procedure offers mild conditions and wide substrate scope.
S. Wang, L.-N. Guo, H. Wang, X.-H. Duan, Org. Lett., 2015, 17, 4798-4801.

An asymmetric 1,3-rearrangement of an alkynyl group of alkynyl alkenyl carbinols took place in the presence of a hydroxyrhodium/(R)-binap catalyst to yield β-alkynylketones in high yields with high enantioselectivity. The present method includes a key β-alkynyl elimination step in the catalytic cycle.
T. Nishimura, T. Katoh, K. Takatshu, R. Shintani, T. Hayashi, J. Am. Chem. Soc., 2007, 129, 14158-14159.

The use of Me-StackPhos as ligand enables a Cu-catalyzed enantioselective conjugate alkynylation of Meldrum’s acid acceptors. The reaction tolerates a wide range of alkynes furnishing highly useful β-alkynyl Meldrum's acid building blocks in high yields and excellent enantioselectivity.
S. Mishra, J. Liu, A. Aponick, J. Am. Chem. Soc., 2017, 139, 3352-3355.

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 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.

A copper-catalyzed coupling of Grignard or organozinc nucleophiles with chloroynamides, formed in situ from 1,2-dichloroenamides, provides a broad range of ynamides. The reaction is readily scaled and overcomes typical limitations in ynamide synthesis such as the use of ureas, carbamates, and bulky or aromatic amide derivatives.
S. J. Mansfield, R. C. Smith, J. R. J. Yong, O. L. Garry, E. A. Anderson, Org. Lett., 2019, 21, 2918-2922.

In a copper-catalyzed intermolecular aminoalkynylation of alkenes, N-fluoro-N-alkylsulfonamides (NFASs) are used as nitrogen-centered radical precursors and alkynyltrimethoxysilanes as alkynylating reagents. This radical relay process presents an efficient and straightforward approach to various highly enantioenriched 2-alkynyl-2-arylethylamines in good yields.
Z. Hu, L. Fu, P. Chen, W. Cao, G. Liu, Org. Lett., 2021, 23, 107-112.

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 photoinduced copper-catalyzed monofluoroalkylation of alkynes with readily available monofluoroalkyl triflates provides valuable propargyl fluorides in good yields under mild conditions. This C-C bond formation avoids the use of highly toxic fluorination reagents. Preliminary mechanistic studies reveal that a ligand-matched alkynyl copper complex might be the key photoactive substance.
D.-D. Hu, C. Li, Q. Gao, T.-M. Nie, K.-F. Zhang, B.-B. Wu, Y. Li, X.-S. Wang, Org. Lett., 2023, 25, 4514-4519.

A palladium-catalyzed decarboxylative coupling reaction of aryl alkynyl carboxylic acids and ICH₂CF₃ enables a trifluoroethylation of alkynes in good yields. The catalytic system showed high functional group tolerance.
J. Hwang, K. Park, J. Choe, H. Min, K. H. Song, S. Lee, J. Org. Chem., 2014, 79, 3267-3271.

An enantioselective copper-catalyzed trifluoromethylalkynylation of styrenes affords structurally diverse CF₃-containing propargylic compounds in good yield with excellent enantioselectivities under very mild conditions via a radical relay process. The reaction offers wide substrate scope and good functional group tolerance. The trifluoromethylalkynylated products can be converted into synthetically useful chiral terminal alkynes, allenes, and Z-alkenes.
L. Fu, S. Zhou, X. Wan, P. Chen, G. Liu, J. Am. Chem. Soc., 2018, 140, 10965-10969.

2,4,6-Trimethylpyridine catalyzes a trifluoromethylalkynylation of unactivated alkenes with alkynyl sulfones and Togni's reagent to provide various β-trifluoromethylated alkynes under metal-free conditions with a broad substrate scope and wide functional group compatibility. A mechanism involving catalytic nonchain radical processes is proposed.
S. Zhou, T. Song, H. Chen, Z. Liu, H. Shen, C. Li, Org. Lett., 2017, 19, 698-701.

The use of mesoporous graphitic carbon nitride (mpg-CN) as a recyclable, nontoxic, and heavy-metal-free photocatalyst enables an efficient, eco-friendly, and divergent perfluoroalkylation of terminal alkynes. Switching the reaction solvents provides libraries of perfluoroalkylated alkynes, alkenes, and alkenyl iodides to be synthesized in good yields.
X. Shi, T. Song, Q. Li, X. Guo, Y. Yang, Org. Lett., 2022, 24, 8724-8728.

Related

The reaction of alkoxides with boron trichloride results in the generation of cations that can be allylated in subsequent transformations. The absence of Brønsted acids can make a significant difference in such syntheses.
G. W. Kabalka, M.-L. Yao, S. Borella, J. Am. Chem. Soc., 2006, 128, 11320-11321.