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

Synthesis of cyclopentenones


Name Reactions

Nazarov Cyclization

Pauson-Khand Reaction

Recent Literature

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 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.

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 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.

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.

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.

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.

Y. Xu, M. McLaughlin, C.-y. Chen, R. A. Reamer, P. G. Dormer, I. W. Davies, J. Org. Chem., 2009, 74, 5100-5103.

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.

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.

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 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.

The Rh(I)-catalyzed [3 + 2] cycloaddition of cyclopropenones and alkynes provides a highly efficient and regioselective route to cyclopentadienones (CPDs) that would be otherwise difficult to obtain. The versatility of the method is explored with a wide range of alkynes and diaryl- as well as arylalkylcyclopropenones.
P. A. Wender, T. J. Paxton, T. J. Williams, J. Am. Chem. Soc., 2006, 128, 14814-14815.

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.