Categories: C-C Bond Formation > Carbocyclic compounds > Cyclic enones

Synthesis of cyclopentenones

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Cyclization of electron-rich 2-alkyl-1-ethynylbenzene derivatives was catalyzed by TpRuPPh₃(CH₃CN)₂PF₆ in hot toluene to form 1-substituted-1H-indene and 1-indanone products. The cyclization mechanism involves a 1,5-hydrogen shift of an initial metal-vinylidene intermediate.
A. Odedra, S. Datta, R.-S. Liu, J. Org. Chem., 2007, 72, 3289-3292.

The use of allyl-palladium catalysis enables a one-step α,β-dehydrogenation of ketones via their zinc enolates. The optimized protocol utilizes commercially available Zn(TMP)₂ as base and diethyl allyl phosphate as oxidant, operates under salt-free conditions, and tolerates a diverse scope of cycloalkanones.
D. Huang, Y. Zhao, T. R. Newhouse, Org. Lett., 2018, 20, 684-687.

A versatile rhodium-catalyzed intramolecular hydroacylation of 4-alkynals provides cyclopentenones via an unusual trans addition of a rhodium hydride to an alkyne.
K. Tanaka, G. C. Fu, J. Am. Chem. Soc., 2001, 123, 11492-11493.

A highly enantioselective silicon-directed Nazarov reaction is cooperatively catalyzed by a Lewis acid and a chiral Brønsted acid. The silicon group in the dienone substrate stabilized the β-carbocation of the intermediate, thereby determining the position of the double bond in the product.
J. Cao, M.-Y. Hu, S.-Y. Liu, X.-Y. Zhang, S.-F. Zhu, Q.-L. Zhou, J. Am. Chem. Soc., 2021, 143, 6962-6968.

A nickel-catalyzed enal-alkyne cycloaddition directly affords cyclopentenols, whereas an enoate-alkyne cycloaddition affords the analogous cyclopentenones. The mechanism of these processes likely involves formation and protonation of a metallacyclic intermediate. The general strategy provides a straightforward entry to five-membered ring products from simple, stable π-systems.
A. D. Jenkins, A. Herath, M. Song, J. Montgomery, J. Am. Chem. Soc., 2011, 133, 14460-14466.

In a synthesis of substituted 2-cyclopentenones using a commercially available gold(I) catalyst, a proton source as an additive is required to obtain the desired substituted cyclopentenones in good yields.
C. Bürki, A. Whyte, S. Arndt, A. S. K. Hashmi, M. Lautens, Org. Lett., 2016, 18, 5058-5061.

A cationic gold(I)-catalyzed stereospecific [3,3]-sigmatropic rearrangement provides cyclopentenones with a C4-quaternary stereocenter starting from simple chiral vinyl sulfoxides and a propargyl silane.
W. Zhou, A. Voituriez, J. Am. Chem. Soc., 2021, 143, 17348-17353.

A highly efficient catalytic, intermolecular synthesis of the cyclopentane skeleton from simple starting products is reported. Allyl halides, alkynes, and carbon monoxide react under very mild reaction conditions by means of a substoichiometric amount of iron, acetone, and a catalytic amount of Ni(II) iodide.
M. L. Nadal, J. Bosch, J. M. Vila, G. Klein, S. Ricart, J. M. Moretó, J. Am. Chem. Soc., 2005, 127, 10476-10477.

Conjugated addition of primary nitroalkanes to α,β-unsaturated ketones or α,β-unsaturated esters, in the presence of two equivalents of DBU, allows the one-pot prepration of γ-diketones or γ-keto esters, respectively. The reaction of 2-aryl-1-nitroethane derivatives with α,β-unsaturated ketones gives cyclopentenones.
R. Ballini, L . Barboni, G. Bosica, D. Fiorini, Synthesis, 2002, 2725-2728.

A Ni-catalyzed carbonylation of cyclopropanols with benzyl bromides provides multisubstituted cyclopentenones in good yields under 1 atm of CO. The reaction proceeds through cascade carbonylation of benzyl bromides, followed by generation of nickel homoenolate from cyclopropanols via β-C elimination to afford 1,4-diketones, which undergoes intramolecular Aldol condensation.
L. Hou, W. Huang, X. Wu, J. Qu, Y. Chen, Org. Lett., 2022, 24, 2699-2704.

An intramolecular Friedel-Crafts-type cyclization of vinyl chlorides and subsequent Pd-catalyzed cross-coupling reactions allow the synthesis of 3,5-diarylcyclopentenones. The requisite vinyl chloride-bearing arylacetic acid precursors are readily available by straightforward alkylation of arylacetic acid esters.
Y. Xu, M. McLaughlin, C.-y. Chen, R. A. Reamer, P. G. Dormer, I. W. Davies, J. Org. Chem., 2009, 74, 5100-5103.

A N-heterocyclic carbene-catalyzed reaction of enals with α-diketones enables an asymmetric construction of cyclopentenones in a highly diastereo- and enantioselective manner. The protocol tolerates substrates with both aromatic and aliphatic groups.
Z. Chen, X. Kong, S. Niu, S. Yang, J. Liu, B. Chen, B. Luo, B. Luo, C. Zhou, C. Ding, X. Fang, Org. Lett., 2021, 23, 3403-3408.

A novel AgOTf-catalyzed ring-contractive rearrangement of 5-substituted 6-diazo-2-cyclohexenones provides a new and efficient access to 5-alkylidene-2-cyclopentenones. The reaction proceeds through metal-carbenoid formation followed by endocyclic allyl [1,2] migration with excellent stereoselectivity and broad substrate scope.
L. Zhao, J. Wang, H. Zheng, Y. Li, K. Yang, B. Cheng, X. Jin, X. Yao, H. Zhai, Org. Lett., 2014, 16, 6378-6381.

The reaction of (Z)-1,4-diketones with various functionalized nitroalkanes in the presence of DBU provides 4-alkylidenecyclopent-2-en-1-ones with E selectivity. An intramolecular aldol condensation probably forms a cyclopentadienone intermediate, which reacts with the nitroalkane in a Michael addition-elimination.
R. Ballini, G. Bosica, D. Fiorini, M. V. Gil, M. Petrini, Org. Lett., 2001, 3, 1265-1267.

A solvent-free ytterbium(III) triflate promoted, zinc(II) chloride catalyzed Conia-ene reaction allows the construction of cyclic enones. In the presence of zinc(II) chloride and ytterbium(III) triflate, a variety of linear β-alkynic β-keto esters and β-diketones were cyclized under neat conditions in good yields. The selectivity toward five- or six-membered-ring carbocycles depends on substituents at the terminal alkynes.
Y. Liu, R.-J. Song, J.-H. Li, Synthesis, 2010, 3663-3669.

The Au-catalyzed hydrative rearrangement of 1,1-diethynylcarbinol acetates in wet CH₂Cl₂ produces either 5-acetoxy-2-alkyl-2-cyclopentenones or acetoxymethyl α-alkylallenones as a major product depending on the temperature, reaction time, and catalyst loading.
C. H. Oh, S. Karmakar, J. Org. Chem., 2009, 74, 370-374.

A Au-catalyzed C-H insertion affords 2-bromocyclopent-2-en-1-ones from alkynone substrates with broad scope and synthetically desirable diastereoselectivities. The proposed key intermediate capable of the observed insertion into unactivated C–H bonds is a fully functionalized gold vinylidene.
Y. Wang, M. Zarca, L.-Z. Gong, L. Zhang, J. Am. Chem. Soc., 2016, 138, 7516-7519.

Synthesis of 5-Hydroxycyclopent-2-enones from Allenyl Vinyl Ketones via an Interrupted Nazarov Cyclization
V. M. Marx, D. J. Burnell, Org. Lett., 2009, 11, 1229-1231.

A gold-catalyzed oxidative reaction of propargylic carbonates or acetates using 3,5-dichloropyridine as the oxidant provides efficient access to α-functionalized-α,β-unsaturated ketones with excellent regio- and diastereocontrol. In addition, these alkene products could be further transformed into valuable 5-hydroxycyclopent-2-enones via cyclocondensation with acetone or cyclodimerization under basic conditions.
N. Sun, M. Chen, Y. Liu, J. Org. Chem., 2014, 79, 4055-4067.

Treatment of an allenyl vinyl ketone with trifluoroacetic acid leads to Nazarov cyclization, in which the intermediate carbocation is trapped efficiently by trifluoroacetate. Hydrolysis of the ester with methanol and basic alumina provides a trans-disubstituted 5-hydroxycyclopent-2-enone in very good yields.
E. A. Uhrich, W. A. Batson, M. A. Tius, Synthesis, 2006, 2139-2142.

A planar chiral DMAP catalyst efficiently promotes asymmetric Morita-Baylis-Hillman reactions of cyclopentenone with various aldehydes in the presence of MgI₂ as cocatalyst.
A. Bugarin, B. T. Connell, Chem. Commun., 2010, 46, 2644-2646.

Iminium catalysis of the challenging Morita-Baylis-Hillman reaction of cyclopenten-2-one provides allylic alcohols in excellent yields. Experimental evidence shows that secondary amines act as co-catalysts activating the enone moiety towards the nucleophilic attack at the β-position by DABCO as the Lewis base catalyst.
R. Innocenti, G. Menchi, A. Trabocchi, Synlett, 2018, 29, 820-824.

The acid-catalyzed Nazarov reaction of easily accessible β-alkoxy divinyl ketones provides 5-oxycyclopent-2-enones. The effects of the β-alkoxy group on the catalyst efficiency and the regioselectivity are based on the stabilization of the intermediates and the spontaneous elimination of the group followed by trapping.
M. Shindo, K. Yaji, T. Kita, K. Shishido, Synlett, 2007, 1096-1100.

Indanones and 2-cyclopentenones have been successfully prepared in good to excellent yields by the palladium-catalyzed carbonylative cyclization of unsaturated aryl iodides and dienyl triflates, iodides, and bromides, respectively. The mechanism is discussed.
S. V. Gagnier, R. C. Larock, J. Am. Chem. Soc., 2003, 125, 4804-4807.

An electrochemically intermolecular α-amination of cyclopentanone with a broad range of anilines provides various α-enaminones under metal-free conditions in very good yields in one step.
K. Hu, P. Qian, J.-H. Su, Z. Li, J. Wang, Z. Zha, Z. Wang, J. Org. Chem., 2019, 84, 1647-1653.

A Au(III)-catalyzed isomerization-A3-coupling/cyclization cascade enables an efficient and convenient synthesis of 2,4-disubstituted cyclopentenones.
J. Li, Y. Xu, X. Hu, S. Zhu, L. Liu, Org. Lett., 2020, 22, 9478-9483.

Commercially available Co₂(CO)₈ and Co₄(CO)₁₂, and enyne-Co₂(CO)₆ complexes are sufficiently effective in catalyzing the Pauson-Khand reaction under one atmosphere of CO pressure. The efficiencies of these cyclization protocols could be enhanced by the presence of cyclohexylamine.
M. E. Krafft, L. V. R. Boñaga, C. Hirosawa, J. Org. Chem., 2001, 66, 3004-3020.

A chiral iridium diphosphine complex catalyzes an enantioselective intramolecular Pauson-Khand-type reaction to give various chiral bicyclic cyclopentenones. A low partial pressure of carbon monoxide is important to achieve excellent enantioselectivity.
T. Shibata, N. Toshida, M. Yamasaki, S. Maekawa, K. Takagi, Tetrahedron, 2005, 61, 9974-9979.

An entrapped Rh catalyst derived by a sol-gel process (see article for method), has been used in a Pauson-Khand reaction under mild conditions. The catalyst can be reused at least 10 times without losing activity. This catalytic system is not effective for intermolecular reactions.
K. H. Park, S. U. Song, Y. K. Chung, Tetrahedron Lett., 2003, 44, 2827-2830.

The Nazarov reaction can be performed under mild, metal-free reaction conditions using molecular iodine as the catalyst. Various divinyl ketones including aromatic systems undergo the I₂-catalyzed reaction with good yields. Addition of iodine to the double bond or a putative iodine-catalyzed cis-trans isomerization seem not to be important side reactions here.
J. J. Koenig, T. Arndt, N. Gildemeister, J.-M. Neudörfl, M. Breugst, J. Org. Chem., 2019, 84, 7587-7605.