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Synthesis of substituted 1,3-enynes


Name Reactions

Sonogashira Coupling

Recent Literature

(2-Bromoethyl)diphenylsulfonium triflate and diphenyl(vinyl)sulfonium triflate are powerful vinylation reagents for Sonogashira cross-coupling reactions with terminal alkynes. The vinylations proceed smoothly at 25 °C under Pd/Cu catalysis to afford various 1- and 2-unsubstituted 1,3-enynes in good yields.
X.-X. Ming, S. Wu, Z.-Y. Tian, J.-W. Song, C.-P. Zhang, Org. Lett., 2021, 23, 6795-6800.

A mild and efficient copper-catalyzed Hiyama-type cross-coupling of vinylsiloxanes with bromoalkynes enables the formation of various sensitive enynes. Cis, trans, and 1,1′-disubstituted vinylsiloxanes can be converted with full retention of stereochemistry. Sensitive groups such as halides, unsaturated ketones, and aldehydes are fully tolerated.
L. Cornelissen, M. Lefrancq, O. Riant, Org. Lett., 2014, 16, 3024-3027.

An efficient cross-coupling of alkynyl bromides and boronates to produce unsymmetric 1,3-diynes is catalyzed by CuFe2O4 nanoparticles in dimethyl carbonate. The protocol also enables a coupling of alkynyl bromides and alkenyl boronic acids to provide conjugated 1,3-enynes. The catalyst was easily separated by an external magnet and recycled 10 times.
S. Ahammed, D. Kundu, B. C. Ranu, J. Org. Chem., 2014, 79, 7391-7398.

The cross-coupling reaction of (E)- and (Z)-alk-1-enyldialkylborane with (trimethylsilyl)ethynyl bromide proceeds in the presence of a catalytic amount of copper(II) acetylacetonate and a base under extremely mild conditions to provide conjugated enynes with a distal carbon-carbon triple bond.
M. Hoshi, N. Kawamura, K. Shirakawa, Synthesis, 2006, 1961-1970.

Cross-coupling of 1-alkynes with vinyl iodides catalyzed by CuI/N,N-dimethylglycine affords conjugated enynes in good to excellent yields. Heating a mixture of 2-bromotrifluoroacetanilide, 1-alkyne in the presence of CuI/L-proline leads to the formation of the corresponding indole.
F. Liu, D. Ma, J. Org. Chem., 2007, 72, 4844-4850.

A palladium(II) complex based on N,N-dimethylethanolamine can be used as a catalyst in copper-free Sonogashira couplings of (E)- or (Z)-bromostyrenes with alkynes to produce conjugated enynes at room temperature in good yields with retention of the configuration.
X. Mi, M. Huang, Y. Feng, Y. Wu, Synlett, 2012, 23, 1257-1261.

An efficient Sonogashira coupling of terminal alkynes and styrenyl bromides is catalyzed by hydroxyapatite-supported copper(I). Trans-styrenyl bromides produce trans-enyne products, whereas cis-styrenyl bromides lead to unsymmetric 1,3-diynes by the cross coupling of terminal alkyne and the alkyne generated from the cis-styrenyl bromide.
D. Saha, T. Chatterjee, M. Mukherjee, B. C. Ranu, J. Org. Chem., 2012, 77, 9379-9383.

A copper(I)-catalyzed coupling of alkynes with vinyl iodides affords various enynes in good to excellent yields, tolerates a variety of functional groups, and does not require the use of expensive additives.
C. G. Bates, P. Saejueng, D. Venkataraman, Org. Lett., 2004, 6, 1441-1444.

A general and efficient palladium catalyzed hydroalkynylation of allenes provides synthetically versatile (E)-1,3-enyne derivatives with high regio- and stereoselectivity under mild conditions. The catalytic system tolerated a broad range of substrates.
Z.-K. Liu, Y. Yang, Z.-P. Zhan, J. Org. Chem., 2022, 87, 1589-1597.

Multifunctional palladium catalysis allows a one-pot stereocontrolled synthesis of tetrasubstituted methyl ketones and enynes. The homogeneous palladium dihalide catalyst is used for the bromo-/chloroallylation of alkynes and in situ for subsequent Wacker-Tsuji oxidation or Sonogashira cross-coupling.
A. N. Thadani, V. H. Rawal, Org. Lett., 2002, 4, 4321-4323.

Alkynyl Grignard reagents, prepared from the corresponding alkynes and methylmagnesium bromide, react with alkenyl bromides or triflates in the presence of FeCl3 as catalyst and lithium bromide as additive to give the corresponding conjugated enynes in high to excellent yields. The reaction shows wide applicability to various terminal alkynes and alkenyl electrophiles.
T. Hatakeyama, Y. Yoshimoto, T. Gabriel, M. Nakamura, Org. Lett., 2008, 10, 5341-5344.

Cationic Au complexes containing strongly basic NHC ligands and noncoordinating anions such as BArF4 catalyze a cis haloalkynylation between terminal alkynes and aromatic haloalkynes, whereas introduction of a weakly basic triflate counteranion results in the stereoselective hydroalkynylation of the haloalkyne, yielding haloenyne products in good yields and complete trans selectivity.
P. D. García-Fernández, J. Iglesias-Sigüenza, P. S. Rivero-Jerez, E. Díez, E. Gómez-Bengoa, R. Fernández, J. M. Lassaletta, J. Am. Chem. Soc., 2020, 142, 16082-16089.

A rhodium catalyst enables a chemo- and regioselective cross-dimerization of terminal arylacetylenes and terminal propargylic alcohols and amides. This method features a convenient and atom economical access to functionalized enynes.
H.-D. Xu, R.-W. Zhang, X. Li, S. Huang, W. Tang, W.-H. Hu, Org. Lett., 2013, 15, 840-843.

A simple procedure for the synthesis of substituted (E)-2-alkene-4-ynecarboxylic esters has been achieved using hydroxyapatite-supported palladium as efficient catalyst surface. The highly efficient catalyst can be recycled.
B. C. Ranu, L. Adak, K. Chattopadhyay, J. Org. Chem., 2008, 73, 5609-5612.

An efficient, palladium-catalyzed synthesis of 2-alkene-4-ynoates and -nitriles by a simple reaction of vic-diiodo-(E)-alkenes with acrylic esters and nitriles in water leads to (E)-isomers from acrylic esters exclusively, whereas (Z)-isomers are obtained in high stereoselectivity from reactions of acrylonitrile. The in situ prepared Pd(0) nanoparticles can be recycled.
B. C. Ranu, K. Chattopadhyay, Org. Lett., 2007, 9, 2409-2412.

B. C. Ranu, K. Chattopadhyay, Org. Lett., 2007, 9, 2409-2412.

A straightforward one-pot approach to highly diverse conjugated enynes, starting from carbonyl precursors has been developed. The low nucleophilic phosphazene bases, which are used for the generation of the alkenyl nonaflates and the terminal alkynes, are compatible with NfF and do not impede the subsequent Sonogashira reaction.
I. M. Lyapkalo, M. A. K. Vogel, Angew. Chem. Int. Ed., 2006, 45, 4019-4023.

An efficient synthesis of structurally diverse fused furans in good yields from 2-alkynyl­cycloalk-2-enols via gold(III) bromide catalyzed cycloisomerization was achieved under moderate reaction conditions.
C. Praveen, P. Kiruthiga, P. T. Perumal, Synlett, 2009, 1990-1996.

2-Alkynyl esters are stereo- and regioselectively converted to E-β-chloro-α-iodo-α,β-unsaturated esters by exposure to Bu4NI in refluxing dichloroethane. Single-isomer tetrasubstituted olefins bearing four different carbon substituents are then synthesized by sequential palladium-catalyzed coupling reactions.
A. B. Lemay, K. S. Vulic, W. W. Ogilvie, J. Org. Chem., 2006, 71, 3615-3618.

Dinuclear and mononuclear palladium complexes with N,N'-bis[2-(diphenylphosphino)phenyl]amidinate (DPFAM) as a ligand catalyzed the cross-addition of triisopropylsilylacetylene (TIPSA) to unactivated internal alkynes, giving enynes selectively. The reactions of TIPSA with several terminal alkynes also gave cross-adducts selectively, although the yields were moderate.
N. Tsukada, S. Ninomiya, Y. Aoyama, Y. Inoue, Org. Lett., 2007, 9, 2919-2921.

Alkynylboration of alkynes with alkynyl(pinacol)boranes in the presence of nickel catalysts gave cis-1-borylbut-1-en-3-yne derivatives. Some boryl-substituted enynes were reacted with sp2 halides under Suzuki-Miyaura coupling conditions.
M. Suginome, M. Shirakura, A. Yamamoto, J. Am. Chem. Soc., 2006, 128, 14438-14439.

Conjugated allenynes can be accessed via a decarboxylative coupling of propargyl esters of propiolates. In this process, allenyl-palladium intermediates are coupled with acetylides that are generated in situ to form the conjugated allenynes. Finally, the coupling is demonstrated to occur stereospecifically in an anti-SN2' fashion to provide a route to enantioenriched allenes.
M. K. Smith, J. A Tunge, Org. Lett., 2017, 19, 5497-5500.