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Synthesis of cyclopentanes


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Conia-Ene Reaction

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Reduction of stilbenes with Na metal in dry THF allowed easy access to various 1,2-diaryl-1,2-disodiumethanes. These diorganometallic intermediates gave 1,2-diarylethanes upon aqueous work up, or trans-1,2-diaryl-substituted cyclopentanes by cycloalkylation with 1,3-dichloropropanes.
U. Azzena, G. Dettori, C. Lubinu, A. Mannu, L. Pisano, Tetrahedron, 2005, 61, 8663-8668.

Microscale parallel experimentation was used to discover catalyst systems capable of coupling secondary organotrifluoroborates with aryl chlorides and bromides. A ligand-dependent β-hydride elimination/reinsertion mechanism was implicated in the cross-coupling of more hindered substrates, leading to isomeric mixtures of coupled products in some cases.
S. D. Dreher, P. G. Dormer, D. L. Sandrock, G. A. Molander, J. Am. Chem. Soc., 2008, 130, 9257-9259.

A stannane, which is simple to prepare, was successfully used in standard radical reactions as replacement of Bu3SnH and Ph3SnH. The tin-containing byproducts are removed by mild hydrolysis and extraction with aqueous NaHCO3. The performance of this new reagent was tested for reactions involving halides, selenides, Barton-McCombie deoxygenation and enyne cyclization.
D. L. J. Clive, J. Wang, J. Org. Chem., 2002, 67, 1192-1198.

A ruthenium-catalyzed transfer hydrogenation of olefins utilizing formic acid as a hydrogen donor provides a remarkable and chemoselective synthetic tool for the reduction of functionalized alkenes under mild reaction conditions. An olefin metathesis/transfer hydrogenation sequence under tandem catalysis conditions enables an attractive C(sp3)-C(sp3) bond formation.
G. K. Zieliński, J. Majtczak, M. Gutowski, K. Grela, J. Org. Chem., 2018, 83, 2542-2553.

(terpy)NiBr2 catalyzes a regioselectively difunctionalisation of unactivated olefins with tethered alkyl halides and arylzinc reagents to provide (arylmethyl)carbo- and heterocyclic scaffolds. The reaction shows an excellent functional group tolerance (such as ketones, esters, nitriles, halides, and base-sensitive racemizable stereocenters).
S. KC, P. Basnet, S. Thapa, B. Shrestha, R. Giri, J. Org. Chem., 2018, 83, 2920-2936.

Cs2CO3 promotes a general transition-metal-free cross-coupling between benzylic sulfonylhydrazones and alkyl boronic acids. The reaction is operationally simple and exhibits a broad substrate scope.
R. R. Merchant, J. A. Lopez, Org. Lett., 2020, 22, 2271-2275.

A copper hydride-catalyzed, enantioselective, intramolecular hydroalkylation of halide-tethered styrenes enables the synthesis of enantioenriched cyclobutanes, cyclopentanes, indanes, and six-membered N- and O-heterocycles.
Y.-M. Wang, N. C. Bruno, A. L. Placeres, S. Zhu, S. L. Buchwald, J. Am. Chem. Soc., 2015, 137, 10524-10527.

1,5- and 1,6-Dienes undergo a cyclization/boration reaction in the presence of a catalytic amount of Cp*2Sm·THF. The resulting organoboranes can be oxidized to the corresponding primary cyclic alcohols using standard conditions.
G. A. Molander, D. Pfeiffer, Org. Lett., 2001, 3, 361-363.

A Rh-catalyzed oxygenative carbofunctionalization of terminal alkynes provides cyclic carboxylic acid derivatives. The generation of a disubstituted Rh vinylidene complex upon C-C bond formation at the terminal alkyne is followed by a transfer oxygenation. The newly formed rhodium-complexed ketene intermediate reacts with a variety of heteroatom nucleophiles to give the desired products.
D.-K. Kim, M. Keum, H. Yun, I. Kim, J. M. Joo, C. Lee, Org. Lett., 2023, 25, 1889-1894.

A catalytic reductive cocyclooligomerization of enones and three carbene equivalents provides cyclopentanes via a formal [2 + 1 + 1 + 1]-cycloaddition. The reaction is promoted by a (quinox)Ni catalyst and uses CH2Cl2/Zn as the C1 component.
C. M. Farley, Y.-Y. Zhou, N. Banka, C. Uyeda, J. Am. Chem. Soc., 2018, 140, 12710-12714.

The combination of a diboron(4) compound and a pyridine catalyzes a metal-free [3 + 2] cycloaddition of cyclopropyl ketones to alkenes with 1,2-disubstitution and 1,1,2-trisubstitution patterns to provide challenging cyclopentane compounds with various levels of substitution in generally high to excellent yield and diastereoselectivity.
Z. Ding, Z. Liu, Z. Wang, T. Yu, M. Xu, J. Wen, K. Yang, H. Zhang, L. Xu, P. Li, J. Am. Chem. Soc., 2022, 144, 8870-8882.

[IPr·GaCl2][SbF6] catalyzes a tandem process involving a ring-closing carbonyl-olefin metathesis and a transfer hydrogenation in the presence of 1,4-cyclohexadiene as an H2 surrogate to reduce the cyclic alkene intermediates. This stereoselective reaction leads to 1,2-cis-disubstituted cyclopentanes and various cyclohexanes.
A. Djurovic, M. Vayer, Z. Li, R. Guillot, J.-P. Baltaze, V. Gandon, C. Bour, Org. Lett., 2019, 21, 8132-8137.

A stereoselective formal [3 + 2] cycloaddition of cyclopropyl ketones and radical-acceptor alkenes to form polysubstituted cyclopentane derivatives is catalyzed by a chiral Ti(salen) complex via a radical redox-relay mechanism. The cycloaddition constructs two C-C bonds and two contiguous stereogenic centers with generally excellent diastereo- and enantioselectivity.
W. Hao, J. H. Harenberg, X. Wu, S. N. MacMillan, S. Lin, J. Am. Chem. Soc., 2018, 140, 3514-3517.

CuCl2 catalyzes a coupling of unactivated C(sp3)-H bonds of numerous feedstock chemicals with electron-deficient olefins. The active cuprate catalyst undergoes Ligand-to-Metal Charge Transfer (LMCT) to enable the generation of a chlorine radical which acts as a powerful hydrogen atom transfer reagent capable of abstracting strong electron-rich C(sp3)-H bonds.
S. M. Treacy, T. Rovis, J. Am. Chem. Soc., 2021, 143, 2729-2735.

A route to trisubstituted olefins through a palladium-catalyzed alkyne insertion with unactivated alkyl iodides followed by a reduction proceeds under mild conditions and tolerates a range of functional groups and substitution patterns. Mechanistic inquiry suggests that the transformation proceeds through a hybrid radical/organometallic pathway.
E. R. Fruchey, B. M. Monks, A. M. Patterson, S. P. Cook, Org. Lett., 2013, 15, 4362-4365.

Cu(I) catalysis enables an efficient and facile construction of trisubstituted exocyclic alkenes in good yields under mild conditions in the presence of B2pin2. Tetrasubsituted borylated or iodinated alkenes can also be isolated depending on the reaction conditions. A preliminary mechanistic study showed that the reaction undergoes a radical process, where B2pin2 plays an indispensable role.
S. Zhou, F. Yuan, M. Guo, G. Wang, X. Tang, W. Zhao, Org. Lett., 2018, 20, 6710-6714.

Cooperative photoredox- and nickel-catalyzed alkylative cyclization reactions of iodoalkynes with 4-alkyl-1,4-dihydropyridines as alkylation reagents provide alkylated cyclopentylidenes in very good yields under visible light irradiation.
Y. Zhang, Y. Tanabe, S. Kuriyama, Y. Nishibayashi, J. Org. Chem., 2021, 86, 12577-12590.

N-heterocyclic carbenes catalyze intramolecular β-alkylations of α,β-unsaturated esters, amides, and nitriles that bear pendant leaving groups to form a variety of ring sizes. The mechanism is discussed.
C. Fischer, S. W. Smith, D. A. Powell, G. C. Fu, J. Am. Chem. Soc., 2006, 128, 1472-1473.

A simple, chemoselective Ni-catalyzed reductive cyclization/carboxylation of unactivated alkyl halides with CO2 operates under mild conditions.
X. Wang, Y. Liu, R. Martin, J. Am. Chem. Soc., 2015, 137, 6476-6479.

Ruthenium(II) complexes catalyze an efficient conversion of 1,6-dienes into the corresponding exo-methylenecyclopentanes in very good yields with good isomer purity in i-PrOH at 90 °C. In contrast, a Ru(0) complex, (C6Me6)Ru(cod), catalyzed the cycloisomerization only in 1,2-dichloroethane.
Y. Yamamoto, Y.-i. Nakagai, N. Ohkoshi, K. Itoh, J. Am. Chem. Soc., 2001, 123, 6372-6380.

A new methodology for the cycloisomerization of dienes using a Grubbs carbene complex and trimethylsilyl vinyl ether has been established. The utility of this reaction was demonstrated by in the synthesis of exo-methylene heterocyclic compounds, which could act as key intermediates for pharmacologically active compounds.
Y. Terada, M. Arisawa, A. Nishida, Angew. Chem. Int. Ed., 2004, 43, 4063-4067.

A cationic ruthenium catalyst tolerates the use of 1,2-di- and trisubstituted olefins in intramolecular ene-type reactions for the formation of five- and six-membered rings. A wide range of functional groups and of alkene and alkyne substitution has little effect on the course of the reaction. A striking example of the extreme mildness of the ruthenium catalyst system is the formation of silyl enol ethers.
B. M. Trost, F. D. Toste, J. Am. Chem. Soc., 2000, 122, 714-715.

Stereospecific, nickel-catalyzed Heck cyclizations of secondary benzylic ethers proceeds in high yield and enantiospecificity to yield enantioenriched methylenecyclopentanes for benzylic ethers of both π-extended and simple arenes.
M. R. Harris, M. O. Konev, E. R. Jarvo, J. Am. Chem. Soc., 2014, 136, 7825-7828.

Copper-catalyzed [3 + 2] cycloadditions of N-tosylcyclopropylamine with alkynes and alkenes under visible light irradiation provide diversified aminated cyclopentene and cyclopentane derivatives being relevant for drug synthesis. The protocol is operationally simple, economically affordable, and compatible with a range of functionalities.
M. Kumar, S. Verma, V. Mishra, O. Reiser, A. K. Verma J. Org. Chem., 2022, 87, 6263-6272.

Cobalt complex/Zn systems effectively catalyze the reductive coupling of activated alkenes with alkynes in the presence of water to give substituted alkenes with very high regio- and stereoselectivity in excellent yields.
H.-T. Chang, T. T. Jayanth, C.-C. Wang, C.-H. Cheng, J. Am. Chem. Soc., 2007, 129, 12032-12041.

InCl3 and (Cy)(i-Pr)NH efficiently promote the carbocyclization reaction of α-disubstituted aldehydes to give functionalized cyclopentanes in very good yields through a combination of enamine-type catalysis with an indium-catalyzed activation of alkynes.
B. Montaignac, M. R. Vitale, V. Michelet, V. Ratovelomanana-Vidal, Org. Lett., 2010, 12, 2582-2585.

A novel alkenylative cyclization of enyne was developed using Cp*RuCl(cod) under ethylene gas at room temperature.
M. Mori, N. Saito, D. Tanaka, M. Takimoto, Y. Sato, J. Am. Chem. Soc., 2003, 125, 5606-5607.

A chiral iron(III)-salen complex catalyzes an asymmetric Conia-ene-type cyclization of α-functionalized ketones containing an unactivated terminal alkyne and produces an exo-methylenecyclopentane scaffold possessing a stereodefined quaternary center.
S. Shaw, J. D. White, J. Am. Chem. Soc., 2014, 136, 13174-13177.

Palladium-catalyzed inter- and intramolecular enyne coupling reactions were developed. The reaction involves the acetoxypalladation of the alkyne, followed by the insertion of the alkene and the protonolysis of the carbon-palladium bond. The coupling allows the construction of synthetically important carbo- and heterocycles.
L. Zhao, X. Lu, W. Xu, J. Org. Chem., 2005, 70, 4059-4063.

A Ni(II)-catalyzed Conia-ene reaction of various acetylenic 1,3-dicarbonyl compounds has been discovered. The reaction gave mono- and bicyclic olefinic cyclopentantes in good yields in the presence of Ni(acac)2 and Yb(OTf)3.
Q. Gao, B.-F. Zheng, J.-H. Li, D. Yang, Org. Lett., 2005, 7, 2185-2188.

[ReBr(CO)3(thf)]2 catalyzed the reactions of 1,3-dicarbonyl compounds with terminal acetylenes, which gave the corresponding alkenyl derivatives in excellent yields.
Y. Kuninobu, A. Kawata, K. Takai, Org. Lett., 2005, 7, 4823-4825.

A relay strategy, in which ring-closing metathesis and bifunctional chiral amine (thio)urea-catalyzed Michael­ addition reactions proceed in a one-pot fashion, offers an alternative approach to the synthesis substituted cyclopentanes in good yields and good enantioselectivities.
Y. Zhang, X. Song, X. Chen, A. Song, S. Zhang, W. Wang, Synthesis, 2014, 46, 2601-2607.

An enantioselective Conia-ene reaction of acetylenic β-dicarbonyl compounds employs a DTBMSegphos-Pd(II)/Yb(III) dual catalyst system that allows for the asymmetric synthesis of all-carbon quaternary centers and generates a methylene cyclopentane containing an alkene that can be further manipulated.
B. K. Corkey, F. D. Toste, J. Am. Chem. Soc., 2005, 127, 17168-17169.

Nitroalkenes readily undergo palladium-catalyzed [3 + 2] cycloaddition with trimethylenemethane to generate nitrocyclopentanes in excellent yield and enantioselectivity. Nitrocyclopentanes are highly versatile synthetic intermediates and provide convenient access to both cyclopentylamines and cyclopentenones.
B. M. Trost, D. A. Bringley, P. S. Seng, Org. Lett., 2012, 14, 234-237.

An intramolecular iodo-aldol cyclization of prochiral α-substituted enoate aldehydes and ketones produces hetero- and carbocycles containing quaternary centers adjacent to secondary or tertiary centers. The reactions occur in good yields and are highly trans-selective with hydroxyl and iodomethyl groups on opposite faces of the ring system.
F. Douelle, A. S. Capes, M. F. Greaney, Org. Lett., 2007, 9, 1931-1934.

A novel approach to 3(2H)-furanones combines a transition-metal-catalyzed activation of alkynes with a heterocyclization and subsequent 1,2-alkyl shift. Starting 2-hydroxy-2-alkynylcarbonyl compounds can be prepared by simple oxygenation of alkynyl carbonyl compounds using 2-iodoxybenzoic acid (IBX).
S. F. Kirsch, J. T. Binder, C. Liébert, H. Menz, Angew. Chem. Int. Ed., 2006, 45, 5878-5880.

V. Mamane, T. Gress, H. Krause, A. Fürstner, J. Am. Chem. Soc., 2004, 126, 8654-8655.

Cobalt-catalyzed transformations of cyclic alkenes such as cyclopentene and cycloheptene with internal alkynes led to a chemoselective Alder-ene or a [2 + 2] cycloaddition reaction depending on the electronic nature of the alkyne and the bite angle of a bidentate phosphine ligand used.
G. Hilt, A. Paul, J. Treutwein, Org. Lett., 2010, 12, 1536-1539.

Ru(bipy)3Cl2 is a visible light photocatalyst for [2+2] enone cycloadditions. Various aryl enones participate readily in the formation of the cyclobutane products, and the diastereoselectivity is excellent. A mechanism is proposed in which a photogenerated Ru(bipy)3+ complex promotes one-electron reduction of the enone substrate, which undergoes subsequent radical anion cycloaddition.
M. A. Ischay, M. E. Anzovino, J. Du, T. P. Yoon, J. Am. Chem. Soc., 2008, 130, 12886-12887.

The reaction of various 1,6-enynes with N2CHSiMe3 in the presence of RuCl(COD)Cp* as catalyst precursor leads to the general formation of alkenylbicyclo[3.1.0]hexanes at room temperature in good yield with high stereoselectivity. The catalytic formation of alkenylbicyclo[3.1.0]hexanes also takes place in the presence of N2CHCO2Et or N2CHPh.
F. Monnier, C. Vovard-Le Bray, D. Castillo, V. Aubert, S. Dérien, P. H. Dixneuf, L. Toupet, A. Ienco, C. Mealli, J. Am. Chem. Soc., 2007, 129, 6037-6049.

F. Monnier, C. Vovard-Le Bray, D. Castillo, V. Aubert, S. Dérien, P. H. Dixneuf, L. Toupet, A. Ienco, C. Mealli, J. Am. Chem. Soc., 2007, 129, 6037-6049.

Bicyclo[2.1.1]hexanes have become increasingly popular building blocks in medicinal chemistry as bridged scaffolds that provide unexplored chemical space. An intramolecular crossed [2 + 2] photocycloaddition of styrene derivatives provides bicyclo[2.1.1]hexanes in excellent yields enabled by triplet energy transfer.
T. Rigotti, T. Bach, Org. Lett., 2022, 24, 8821-8825.

Pd(OAc)2/PCy3HBF4 catalyzes an addition of aryl halides and alkynes to norbornenes to construct saturated bridged C-C bonds. This efficient difunctionalization of norbornenes includes C-X/C-H bond cleavage and highly selective C(sp3)-C(sp2)/C(sp3)-C(sp) bond formation. The reaction offers broad substrate scope and excellent functional group tolerance.
Y. Shi, C.-L. Ji, C. Liu, J. Org. Chem., 2023, 88, 261-271.