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Synthesis of pyrrolidines

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A new efficient method for the N-heterocyclization of primary amines with diols catalyzed by a Cp*Ir complex was developed. A variety of five-, six-, and seven-membered cyclic amines were synthesized in good to excellent yields.
K.-I. Fujita, T. Fujii, R. Yamaguchi, Org. Lett., 2004, 6, 3525-3528.

A chiral amine-derived iridacycle complex catalyzes a highly economical borrowing hydrogen annulation to provide chiral N-heterocycles directly from simple racemic diols and primary amines. This catalytic method enabled a rapid access to a wide range of diversely substituted enantioenriched pyrrolidines including key precursors to valuable drugs.
Y. Liu, H. Diao, G. Hong, J. Edward, T. Zhang, G. Yang, B.-M. Yang, Y. Zhao, J. Am. Chem. Soc., 2023, 145, 5007-5016.

The combination of readily available and stable O-benzoylhydroxylamines as alkyl nitrene precursors and a proficient rhodium catalyst provides various pyrrolidines in very good yields.
H. Noda, Y. Asada, M. Shibasaki, Org. Lett., 2020, 22, 8769-8773.

An acid-promoted synthesis of azaheterocycles from N-carbamate-protected amino alcohols involves the activation of the hydroxyl group via the use of orthoesters. Despite the reduced nucleophilicity of carbamate nitrogen, this reaction system provides several types of pyrrolidines and piperidines in very good yields.
H. Park, Y. Kwon, J. E. Shin, W.-J. Kim, S. Hwang, S. Lee, S. Kim, Synthesis, 2017, 49, 2761-2767.

2-substituted pyrrolidines, including nornicotine, can be prepared from very simple materials, such as carbonyl compounds (mainly aromatic aldehydes) and 3-chloropropylamine. In the case of imines derived from aliphatic ketones and aldehydes, this methodology gives significantly lower yields.
M. Yus, T. Soler, F. Foubelo, J. Org. Chem., 2001, 66, 6207-6208.

A synergistic combination of a nickel catalyst and benzaldehyde enables C(sp3)-H alkylation and arylation of amides and thioethers employing simple aryl or alkyl halides. Readily available starting materials, mild reaction conditions, a good functional-group tolerance, and a broad substrate scope make this methodology attractive and practical.
X. Si, L. Zhang, A. S. K. Hashmi, Org. Lett., 2019, 21, 6259-6263.

Enantioselective, Palladium-Catalyzed α-Arylation of N-Boc-pyrrolidine
K. R. Campos, A. Klapars, J. H. Waldman, P. G. Dormer, C.-Y. Chen, J. Am. Chem. Soc., 2006, 128, 3538-3539.

The combination of inexpensive cerium and nickel catalysts enables the use of easily accessible free alcohols as operationally simple and robust carbon pronucleophiles in selective C(sp3)-C(sp2) cross-couplings with the extrusion of formaldehyde. A broad range of free alcohols and aromatic halides can be employed in this transformation.
Y. Chen, X. Wang, X. He, Q. An, Z. Zuo, J. Am. Chem. Soc., 2021, 143, 4896-4902.

Highly efficient catalyst-tuned regio- and enantioselective hydroalkylation reactions of readily available 3-pyrrolines provide chiral C2-alkylated pyrrolidines in the presence of a Co catalyst and C3-alkylated pyrrolidines in the presence of a Ni catalyst. These divergent methods use readily available catalysts, chiral BOX ligands, and reagents.
X. Wang, J. Xue, Z.-Q. Rong, J. Am. Chem. Soc., 2023, 145, 15456-15464.

Highly efficient catalyst-tuned regio- and enantioselective hydroalkylation reactions of readily available 3-pyrrolines provide chiral C2-alkylated pyrrolidines in the presence of a Co catalyst and C3-alkylated pyrrolidines in the presence of a Ni catalyst. These divergent methods use readily available catalysts, chiral BOX ligands, and reagents.
X. Wang, J. Xue, Z.-Q. Rong, J. Am. Chem. Soc., 2023, 145, 15456-15464.

The combination of B2pin2 and KOtBu enables a chemoselective, metal-free reduction of aromatic nitro compounds to the corresponding amines in very good yields in isopropanol. The reaction tolerates various reducible functional groups.
H. Lu, Z. Geng, J. Li, D. Zou, Y. Wu, Y. Wu, Org. Lett., 2016, 18, 2774-2776.

[FeIII(TF4DMAP)Cl] efficiently catalyzes an intermolecular sp3 C-H amination using aryl azides and intramolecular sp3 C-H amination of alkyl azides in good yields. The reaction offers high chemo- and regioselectivity with broad substrate scope and can be used for late-stage functionalization of complex natural/bioactive molecules.
Y.-D. Du, Z.-J. Xu, C.-Y. Zhou, C.-M. Che, Org. Lett., 2019, 21, 895-899.

A Tf2O-promoted intramolecular Schmidt reaction of 2-substituted ω-azido carboxylic acids provides a series of 2-substituted pyrrolidines.
X.-J. Wang, Y. Su, R. Li, P. Gu, J. Org. Chem., 2018, 83, 5816-5824.

A simple, one-pot preparation of cyclic amines via efficient chlorination of amino alcohols with use of SOCl2 obviates the need for the classical N-protection/O-activation/cyclization/deprotection sequence commonly employed for this type of transformation. The reaction pathways and the general scope of this method have also been investigated.
F. Xu, B. Simmons, R. A. Reamer, E. Corley, J. Murry, D. Tschaen, J. Org. Chem., 2008, 73, 312-315.

Using 0.5 mol % [Ru(p-cymene)Cl2]2 with the bidentate phosphines dppf or DPEphos as the catalyst, primary amines have been converted into secondary amines, and secondary amines into tertiary amines. N-Heterocyclization reactions of primary amines have been achieved, as well as alkylation reactions of primary sulfonamides.
M. H. S. A. Hamid, C. L. Allen, G. W. Lamb, A. C. Maxwell, H. C. Maytum, A. J. A. Watson, J. M. J. Williams, J. Am. Chem. Soc., 2009, 131, 1766-1774.

A one-pot synthesis of nitrogen-containing heterocycles from alkyl dihalides and primary amines and hydrazines occurs under microwave irradiation via a simple and efficient cyclocondensation in an alkaline aqueous medium.
Y. Ju, R. S. Varma, J. Org. Chem., 2006, 71, 135-141.

An intramolecular amination of organoboronates provides azetidines, pyrrolidines, and piperidines via a 1,2-metalate shift of an aminoboron "ate" complex.
P. Xu, M. Zhang, B. Ingoglia, C. Allais, A.-M. R. Dechert-Schmitt, R. A. Singer, J. P. Morken, Org. Lett., 2021, 23, 3379-3383.

A facile method provides N-aryl-substituted azacycles from arylamines and cyclic ethers in the presence of POCl3 and DBU. Using this method, various azacycloalkanes, isoindolines, and tetrahydroisoquinolines were prepared in high yields. This synthetic method offers an efficient approach to the production of five- and six-membered azacycles.
M. T. La, S. Kang, H.-K. Kim, J. Org. Chem., 2019, 84, 6689-6696.

Dirhodium-catalyzed intramolecular nitrene insertion into sp3 C-H bonds enables a regio- and diastereoselective synthesis of N-unprotected pyrrolidines at rt without external oxidants, nitrene stabilizing groups, or directing functionality.
S. Munnuri, A. M. Adebesin, M. P. Paudyal, M. Yousufuddin, A. Dalipe, J. R. Falck, J. Am. Chem. Soc., 2017, 139, 18288-18294.

A copper-catalyzed intermolecular carboamination of potassium N-carbamoyl-β-aminoethyltrifluoroborates with terminal, 1,2-disubstituted, and 1,1-disubstituted vinylarenes bearing a number of functional groups provides 2-arylpyrrolidines. 1,3-Dienes are also good substrates, and their reactions give 2-vinylpyrrolidines.
C. Um, S. R. Chemler, Org. Lett., 2016, 18, 2515-2518.

A novel gold-catalyzed tandem cycloisomerization/hydrogenation of chiral homopropargyl sulfonamides provides various enantioenriched pyrrolidines in excellent yields and excellent enantioselectivities.
Y.-F. Yu, C. Shu, T.-D. Tan, L. Li, S. Rafique, L.-W. Ye, Org. Lett., 2016, 18, 5178-5181.

Stereoselective syntheses of pyrrolidines and piperidines bearing hydrophobic chains have been achieved through a metal free, Lewis acid-mediated 5/6-endo-dig reductive hydroamination cascade of enynyl amines. The brevity of the developed strategy allowed for the collective stereoselective total synthesis of various alkaloids.
S. J. Gharpure, R. K. Patel, K. S. Gupta, Org. Lett., 2023, 25, 5850-5855.

Pd-catalyzed alkene carboamination and carboalkoxylation reactions of a wide range of (hetero)arylthianthrenium triflates afforded the corresponding biologically important pyrrolidine and tetrahydrofuran derivatives. Mechanistic studies indicated that this reaction proceeds through a syn-heteropalladation mechanistic pathway.
B. Peng, L. Dai, R. Liu, Org. Lett., 2023, 25, 2606-2610.

The use of Et3SiH and a catalytic amount of I2 enables transition-metal-free, intramolecular hydroalkoxylation/reduction and hydroamination/reduction of unactivated alkynes at room temperature to provide 2,4- and 2,5-disubstituted pyrrolidines as well as a 2,3-disubstituted tetrahydrofurans with high diastereoselectivity.
S. Fujita, M. Shibuya, Y. Yamamoto, Synthesis, 2017, 49, 4199-4204.

A metal-free method for a direct anti-Markovnikov hydroamination of unsaturated amines is enabled by irradiation of the amine substrates with visible light in the presence of catalytic quantities of easily synthesized 9-mesityl-10-methylacridinium tetrafluoroborate and thiophenol as a hydrogen-atom donor. The reaction furnished nitrogen-containing heterocycles with complete regiocontrol.
T. M. Nguyen, D. A. Nicewicz, J. Am. Chem. Soc., 2013, 135, 9588-9591.

A Mn-catalyzed N-F bond activation enables a visible-light-promoted generation of amidyl radicals from N-fluorosulfonamides. In the presence of a cheap silane, (MeO)3SiH as hydrogen-atom donor and F-atom acceptor, intra- and intermolecular hydroaminations of alkenes, two-component carboamination of alkenes, and even three-component carboamination of alkenes can be realized.
Y.-X. Ji, J. Li, C.-M. Li, S. Qu, B. Zhang, Org. Lett., 2021, 23, 207-212.

A highly enantioselective iridium-catalyzed hydrogenation of cyclic enamines is efficient method for the synthesis of optically active cyclic tertiary amines including natural product crispine A.
G.-H. Hou, J.-H. Xie, P.-C. Yan, Q.-L. Zhou, J. Am. Chem. Soc., 2009, 131, 1366-1367.

The combination of chiral bicyclo[3.3.0]octadiene ligands, an active rhodium hydroxide complex, and neutral reaction conditions enabled a highly enantioselective rhodium-catalyzed arylation of aliphatic N-tosylaldimines in high yield. The application of this method is demonstrated by the enantioselective synthesis of chiral 2-aryl pyrrolidines and piperidines in a one-pot procedure.
Z. Cui, H.-J. Yu, F.-F. Yang, W.-Y. Gao, C.-G. Feng, G.-Q. Lin, J. Am. Chem. Soc., 2011, 133, 12394-12397.

(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.

A combination of a photoredox and a palladium catalyst catalyzes a dehydrative coupling reaction of alkyl amines with allylic alcohols to provide a range of homoallylic amines.
Y. Masuda, M. Ito, M. Murakami, Org. Lett., 2020, 22, 4467-4470.

Regioselective protonolytic C-C bond cleavage of acylated aminomethyl cyclopropanes can be achieved using trifluoroacetic acid to provide 2,2-substituted pyrrolidines via an intermediate tertiary carbenium ion. The strength of the acid and the amine substituent are important factors to achieve high regioselectivity, suggesting intramolecular proton transfer from the protonated amide function.
M. Skvorcova, A. Jirgensons, Org. Lett., 2017, 19, 2478-2481.

N-Iodosuccinimide promotes an attractive and productive protocol for the position-selective intramolecular C-H amination of aliphatic groups (Hofmann-Löffler reaction) employing sulfonimides as nitrogen sources initiated by visible light. The overall transformation provides pyrrolidines under mild and selective conditions as demonstrated for 17 different substrates.
C. Q. O'Broin, P. Fernández, C. Martínez, Kilian Muñiz, Org. Lett., 2016, 18, 436-439.

The combination of phthaloyl peroxide with commercially available halide salts provides an unique halogenating system for Hofmann-Löffler-Freytag-type reactions to produce N-chloroamides, δ-brominated products, and even biologically relevant pyrrolidines under mild conditions in good yields.
D. Chang, R. Zhao, C. Wei, Y. Yao, Y. Liu, L. Shi, J. Org. Chem., 2018, 83, 3305-3315.

Efficient Ti-catalyzed radical formal [3+2] cycloadditions of N-acylaziridines and alkenes provide pyrrolidines from readily available starting materials. The overall redox-neutral reaction was achieved via a redox-relay mechanism, which harnesses radical intermediates for selective C-N bond cleavage and formation.
W. Hao, X. Wu, J. Z. Sun, J. C. Siu, S. N. MacMillan, S. Lin, J. Am. Chem. Soc., 2017, 139, 12141-12144.

With the aid of visible light irradiation, the reaction of photocatalytically generated alkyl radicals possessing pendant leaving groups with imines provides substituted pyrrolidines, piperidines, and azepanes under mild, redox-neutral conditions.
L. R. E. Pantaine, J. A. Milligan, J. K. Matsui, C. B. Kelly, G. A. Molander, Org. Lett., 2019, 21, 2317-2321.

The union of vinyl sulfones with photoredox-generated α-amino radicals enables direct C-H vinylations of N-aryl tertiary amines, as well as decarboxylative vinylations of N-Boc α-amino acids, to provide allylic amines of broad diversity in high yield and with excellent olefin geometry control. The utility of this reaction has been demonstrated via the syntheses of several natural products and a number of established pharmacophores.
A. Noble, D. W. C. MacMillan, J. Am. Chem. Soc., 2014, 136, 11602-11605.

The air- and moisture-stable CoBr2·6H2O catalyzes a convenient reductive cyclization of enynes and diynes in the presence of H2 as a reductant to provide the corresponding cyclized products in good yields without olefin isomerization and over-reduction.
K. Isoda, Y. Sato, Org. Lett., 2023, 25, 2103-2107.

An enantioselective cross-electrophile divinylation reaction of 2-bromo-1,6-dienes offers a mild route to chiral cyclic architectures, which are key structural motifs found in various biologically active compounds. The use of chiral t-Bu-pmrox and 3,5-difluoro-pyrox ligands resulted in the formation of divinylated products with high chemo-, regio-, and enantioselectivity.
J.-B. Qiao, Y.-Q. Zhang, Q.-W. Yao, Z.-Z. Zhao, X. Peng, X.-Z. Shu, J. Am. Chem. Soc., 2021, 143, 12961-12967.

A metal-free C(sp3)-H aroylation of amines via visible-light photoredox catalysis provides useful α-amino aryl ketones. A series of experiments indicate that this transformation undergoes a photoredox catalytic radical-radical cross-coupling pathway.
G.-Q. Xu, T.-F. Xiao, G.-X. Feng, C.-Liu, B. Zhang, P.-F. Xu, Org. Lett., 2021, 23, 2846-2852.

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 ruthenium catalyzed, atom-economical domino redox isomerization/cyclization of easily available, linear aminopropargyl alcohols provides added-value nitrogen heterocycles in a single catalytic step and displays a broad scope and functional group tolerance.
B. M. Trost, N. Maulide, R. C. Livingston, J. Am. Chem. Soc., 2008, 130, 16502-16503.

Optically pure C2-symmetrical cyclic amines were efficiently synthesized from the corresponding diols obtained from an enantioselective borohydride reduction of diketones in the presence of a chiral β-ketoiminato cobalt(II) catalyst.
M. Sato, Y. Gunji, T. Ikeno, T. Yamada, Synthesis, 2004, 1434-1438.

A cationic manganese porphyrin catalyst enables a formal [3+2] cycloaddition between aziridines and styrenes to give the corresponding pyrrolidines.
T. Ozawa, T. Kurahashi, S. Matsubara, Synlett, 2013, 24, 2763-2767.

Mild, rhodium-catalyzed hydroaminations of unactivated olefins with primary and secondary alkylamines form the corresponding five- and six-membered products in excellent yields. A variety of functional groups such as hydroxyl, halo, cyano, and carboalkoxyl groups were tolerated.
Z. Liu, J. F. Hartwig, J. Am. Chem. Soc., 2008, 130, 1570-1571.

[Ir(COD)Cl]2 is an effective precatalyst for the intramolecular hydroamination of a range of unactivated alkenes with pendant secondary amines. The catalyst can be used at relatively low loadings and without the need for added ligands or other cocatalysts.
K. D. Hesp, M. Stradiotto, Org. Lett., 2009, 11, 1449-1452.

A mild, effective gold(I)-catalyzed hydroamination of unactivated olefins to form protected nitrogen heterocycles has been developed. The substrate scope is broader than in reactions realized with late-transition-metal catalyst systems.
X. Han, R. A. Widenhoefer, Angew. Chem. Int. Ed., 2006, 45, 1747-1749.

Treatment of an N-4-pentenyl or N-5-hexenyl urea with a catalytic 1:1 mixture of a gold(I) N,N-diaryl imidazol-2-ylidine complex and AgOTf gave the corresponding nitrogen heterocycle in excellent yield via an intramolecular exo-hydroamination.
C. F. Bender, R. A. Widenhoefer, Org. Lett., 2006, 8, 5303-5305.

Homogeneous carboamination, carboalkoxylation and carbolactonization of terminal alkenes are realized via oxidative gold catalysis, providing expedient access to various substituted N- or O-heterocycles. Deuterium-labeling studies established the nature of the alkene functionalization and the indispensible role of Au(I)/Au(III) catalysis.
G. Zhang, L. Cui, Y. Wang, L. Zhang, J. Am. Chem. Soc., 2010, 132, 1474-1475.

The combination of carbaboranylmercuric chloride as a bulky Lewis acid and silver triflate efficiently catalyzes a cycloisomerization of 1,3-dienes at room temperature to give allyl-substituted azacycles and cycloalkanes in excellent yields with very high regioselectivity.
H. Yamamoto, I. Sasaki, S. Shiomi, N. Yamasaki, H. Imagawa, Org. Lett., 2012, 14, 2250-2253.

AgHMDS/DTBM-Segphos or Ag2O/CA-AA-Amidphos catalytic systems achieve stereodivergent [3 + 2] cycloadditions of iminoesters with various α-substituted acrylates to provide chiral C4-ester-quaternary exo- or endo-pyrrolidines with high yields and excellent diastereo- and enantioselectivities.
Z. Chen, W. Zhong, S. Liu, T. Zou, K. Zhang, C. Gong, W. Guo, F. Kong, L. Nie, S. Hu, H. Wang, Org. Lett., 2023, 25, 3391-3396.

AgHMDS/DTBM-Segphos or Ag2O/CA-AA-Amidphos catalytic systems achieve stereodivergent [3 + 2] cycloadditions of iminoesters with various α-substituted acrylates to provide chiral C4-ester-quaternary exo- or endo-pyrrolidines with high yields and excellent diastereo- and enantioselectivities.
Z. Chen, W. Zhong, S. Liu, T. Zou, K. Zhang, C. Gong, W. Guo, F. Kong, L. Nie, S. Hu, H. Wang, Org. Lett., 2023, 25, 3391-3396.

Dual Rh(II)/Pd(0) relay catalysis of N-sulfonyl triazoles and 2-hydroxymethylallyl carbonates provides N-sulfonyl pyrrolidines in good yields with high diastereoselectivities. The reaction proceeds via a relay mechanism involving O-H insertion onto the α-imino Rh(II)-carbene, [3,3]-sigmatropic rearrangement, dipole formation through Pd(0)-catalyzed decarboxylation, and intramolecular N-allylation.
L.-Z. Huang, Z. Xuan, J.-U. Park, J. H. Kim, Org. Lett., 2022, 24, 6951-6956.

A CO2 extrusion, nickel capture, migratory insertion sequence with terminal and internal alkynes provides stereodefined functionalized olefins from carboxylic acids. A hydrogen atom transfer enables even a direct vinylation of unactivated C-H bonds.
N. A. Till, R. T. Smith, D. W. C. MacMillan, J. Am. Chem. Soc., 2018, 140, 5701-5705.

A catalyst composed of Pd(OAc)2 and S-Phos allows the conversion of aryl chlorides as electrophiles in Pd-catalyzed alkene carboamination and carboetherification, minimizes N-arylation, and prevents formation of regiosisomieric mixtures. Various heterocycles, including pyrrolidines, isoxazolidines, tetrahydrofurans, and pyrazolidines, are efficiently generated with this method.
B. R. Rosen, J. E. Ney, J. P. Wolfe, J. Org. Chem., 2010, 75, 2756-2759.

The stereoselective synthesis of N-acyl- and N-Boc-protected pyrrolidines via Pd-catalyzed reactions of γ-(N-acylamino) alkenes and γ-(N-Boc-amino) alkenes with aryl bromides proceeds with generally high levels of diastereoselectivity by formation of two bonds in a single operation.
M. B. Bertrand, J. P. Wolfe, Tetrahedron, 2005, 61, 6447-6459.

A mild and facile Pd-catalyzed intramolecular hydroamination of unactivated alkenes takes place at room temperature and tolerates acid-sensitive functional groups. The tridentate ligand on Pd effectively inhibits β-hydride elimination, thus the formation of hydroamination products is preferred over oxidative amination products.
F. E. Michael, B. M. Cochran, J. Am. Chem. Soc., 2006, 128, 4246-4247.

The gold(I)-catalyzed reaction of methylenecyclopropanes with sulfonamides produces the corresponding pyrrolidine derivatives in moderate to good yields via a domino ring-opening ring-closing hydroamination process.
M. Shi, L.-P. Liu, J. Tang, Org. Lett., 2006, 8, 4043-4046.

A simple iron-catalyzed intramolecular hydroamination of unactivated olefins proceeds under mild conditions and tolerates aminoolefins containing halide moieties.
K. Komeyama, T. Morimoto, K. Takaki, Angew. Chem. Int. Ed., 2006, 45, 2938-2941.

An unstabilized azomethine ylide generated from commercial trimethylamine N-oxide undergoes a remarkable 1,3-dipolar cycloaddition with electron-rich and unpolarized olefins to give challenging 3,4-di­substituted pyrrolidines in good yield. A broad range of substituents on the alkenes are tolerated provided they are compatible with excess LDA.
J. E. Davoren, D. L. Gray, A. R. Harris, D. M. Nason, W. Xu, Synlett, 2010, 2490-2492.

Organoselenium catalysis enables an efficient synthesis of oxygen and nitrogen heterocycles via exo-cyclization under mild conditions in the presence of 1-fluoropyridinium triflate. The reaction offers good functional group tolerance and excellent regioselectivity.
R. Guo, J. Huang, H. Huang, X. Zhao, Org. Lett., 2016, 18, 504-507.

A Pd-catalyzed reaction of vinyl iodides and N-tosylhydrazones assembles η3-allyl ligands through carbene insertion. Intramolecular trapping with nitrogen nucleophiles generates good yields of cinnamyl and pentadienyl amines like those found in alkaloid natural products.
A. Khanna, C. Maung, K. R. Johnson, T. T. Luong, D. L. Van Vranken, Org. Lett., 2012, 14, 3233-3235.

Enantioselective intramolecular oxidative amidation of alkenes has been achieved using a (pyrox)Pd(II)(TFA)2 as catalyst and O2 as the stoichiometric oxidant. The reactions proceed at room temperature in very good yields and with high enantioselectivity. Catalyst-controlled stereoselective cyclization reactions are demonstrated for a number of chiral substrates.
R. I. McDonald, P. W. White, A. B. Weinstein, C. P. Tam, S. S. Stahl, Org. Lett., 2011, 13, 2830-2833.

An asymmetric intramolecular hydroamination of allenes catalyzed by phosphinegold(I)-bis-p-nitrobenzoate complexes is applicable to the enantioselective formation of vinyl pyrrolidines and piperidines in high ee.
R. L. LaLonde, B. D. Sherry, E. J. Kang, F. D. Toste, J. Am. Chem. Soc., 2007, 129, 2452-2453.

Palladium-catalyzed intramolecular amination of unactivated C-H bonds at the γ and δ positions of picolinamide (PA) protected amine substrates enables the synthesis of azetidine, pyrrolidine, and indoline compounds. The method features relatively low catalyst loading, use of inexpensive reagents, convenient operating conditions and predictable selectivities.
G. He, Y. Zhao, S. Zhang, C. Lu, G. Chen, J. Am. Chem. Soc., 2012, 134, 3-6.

4-CN-pyridine is an effective cyanation reagent under catalyst-free, paired electrochemical reaction conditions. Mechanistic studies support a nucleophilic reaction pathway, and the cyanation protocol can be applied to diverse substrates including N,N-dialkyl anilines, indole derivatives and amino acids (via decarboxylative cyanation).
G. S. Kumar, P. S. Shinde, H. Chen, K. Muralirajan, R. Kancherla, M. Rueping, Org. Lett., 2022, 24, 6357-6363.

A wide variety of mixed anhydrides formed in situ from carboxylic acids and acyl chlorides can subsequently undergo metal insertion-decarboxylation-recombination to provide ketones in very good yield when subjected to metallaphotoredox catalysis. A three-step synthesis of the medicinal agent edivoxetine is also described.
C. Le, D. W. C. MacMillan, J. Am. Chem. Soc., 2015, 137, 11938-11941.

Lithium iodide promotes a convenient [3 + 2]-cycloaddition reaction between N-tosylaziridines and α,β-unsaturated ketones under mild conditions to provide N-tosylpyrrolidines in high yields. Quaternary carbon-possessing 3,3-disubstituted pyrrolidines including spiro compounds can also be obtained. An intramolecular version can be used for the synthesis of tropane derivatives.
Y. Nakagawa, K. Yamaguchi, S. Hosokawa, J. Org. Chem., 2021, 86, 7787-7796.

Depending on the use of copper(I) and silver(I) complexes with (S)-DM- or (S)-DTBM-Segphos as ligands, a catalytic enantioselective 1,3-dipolar cycloaddition between imino esters and electrophilic alkenes provides diastereodivergently exo- or endo-cycloadducts. Functional groups of the dipolarophile and the choice of the catalyst play an important role in promoting reverse diastereoselectivities.
G. S. Caleffi, O. Larrañaga, M. Ferrándiz-Saperas, P. R. R. Costa, C. Nájera, A. de Cózar, F. P. Cossío, J. M. Sansano, J. Org. Chem., 2019, 84, 10593-10605.

In the presence of MgI2 as Lewis acid, donor-acceptor cyclopropanes or corresponding cyclobutanes react with 1,3,5-triazinanes, leading to the 2-unsubstituted pyrrolidines and piperidines under mild conditions in good yields. This protocol tolerates various functional groups and provides an efficient entry to pyrrolidines and piperidines.
L. K. B. Garve, A. Kreft, P. G. Jones, D. B. Werz, J. Org. Chem., 2017, 82, 9235-9242.

Hoveyda-Grubbs catalyst in combination with BF3·OEt2 efficiently promotes tandem cross metathesis intramolecular aza-Michael reaction between enones and unsaturated carbamates resulting in the creation of β-amino carbonyl units. The use of microwave irradiation dramatically accelerates the process, but also inverts the stereoselectivity in the addition process.
S. Fustero, D. Jiménez, M. Sánchez-Roselló, C. del Pozo, J. Am. Chem. Soc., 2007, 129, 6700-6701.

1,3-Dipolar cycloaddition of in situ generated azomethine ylides to electron deficient olefins catalyzed by tris(pentafluorophenyl)borane is described.
P. Srihari, S. R. Yaragorla, D. Basu, S. Chandrasekhar, Synthesis, 2006, 2646-2648.

The Au(I)-catalyzed intramolecular hydroamination of N-allenyl carbamates was effective for the formation of various cyclic amines. γ-Hydroxy and δ-hydroxy allenes underwent Au-catalyzed intramolecular hydroalkoxylation to form the corresponding oxygen heterocycles in good yield. 2-Allenyl indoles underwent Au-catalyzed intramolecular hydroarylation to form 4-vinyl tetrahydrocarbazoles in good yield.
Z. Zhang, C. Liu, R. E. Kinder, X. Han, H. Qian, R. A. Widenhoefer, J. Am. Chem. Soc., 2006, 128, 9066-9073.

Under selected conditions, the Zr-catalyzed reaction of EtMgCl with imines produces C,N-dimagnesiated compounds, which can be further trapped with electrophiles. The overall transformation provides a new route to bifunctional or cyclic nitrogen-containing compounds such as 1-azaspirocyclic γ-lactams, pyrrolidines and azetidines.
V. Gandon, P. Bertus, J. Szymoniak, Synthesis, 2002, 1115-1120.

Ph3PAuOTf catalyzes efficient intra- and intermolecular hydroamination of unactivated olefins with sulfonamides.
J. Zhang, C.-G. Yang, C. He, J. Am. Chem. Soc., 2006, 128, 1798-1799.

An efficient alkene aza-Cope-Mannich cyclization between 2-hydroxy homoallyl tosylamine and aldehydes in the presence of iron(III) salts gives 3-alkyl-1-tosyl pyrrolidines in good yields via a γ-unsaturated iminium ion, 2-azonia-[3,3]-sigmatropic rearrangement, and intramolecular Mannich reaction. The cyclization of 2-hydroxy homopropargyl tosylamines gives dihydro-1H-pyrroles.
R. M. Carballo, M. Purino, M. A. Ramírez, V. S. Martín, J. I. Padrón, Org. Lett., 2010, 12, 5334-5337.

Oxetane desymmetrization enables an asymmetric synthesis of chiral pyrrolidines bearing an all-carbon quaternary stereocenter in the 3-position either using a readily available tert-butylsulfinamide chiral auxiliary or a catalytic system with a chiral phosphoric acid as the source of chirality.
R. Zhang, M. Sun, Q. Yan, X. Lin, X. Li, X. Fang, H. H. Y. Sung, J. D. Williams, J. Sun, Org. Lett., 2022, 24, 2359-2364.

A P(NMe2)3-mediated tandem (1 + 4) annulation between aroylformates and δ-tosylamino enones provides functionalized pyrrolidines in good yields with exclusive chemoselectivity and high diastereoselectivity. The reaction proceeds through an unprecedented P(NMe2)3-mediated reductive amination/base-catalyzed Michael addition cascade.
R. Liu, J. Liu, J. Cao, R. Li, R. Zhou, Y. Qiao, W.-C. Gao, Org. Lett., 2020, 22, 6922-6926.

Bisphosphine-catalyzed mixed double-Michael reactions between amino-acid-derived pronucleophiles as Michael donors and electron-deficient acetylenes as acceptors afford β-amino carbonyl derivatives of oxazolidines, thiozolidines, and pyrrolidines in excellent yields and with high diastereoselectivities under operationally simple and mild conditions.
V. Sriramurthy, G. A. Barcan, O. Kwon, J. Am. Chem. Soc., 2007, 129, 12928-12929.

In the presence of 1.1 equiv of (Diacetoxyiodo)benzene (PIDA) and suitable halogen sources, a variety of olefins underwent haloamidation, haloetherification, and halolactonization to the corresponding 1,2-bifunctional cyclic skeletons in very good isolated yields. Subsequent mild nucleophilic substitution gives key intermediates for biologically interesting compounds in high yields.
G.-Q. Liu, Y.-M. Li, J. Org. Chem., 2014, 79, 10094-10109.

Iodocyclization of unsaturated tosylamides promoted by Oxone oxidation of KI afforded, in good yields, N-tosyl iodopyrrolidines and piperidines. A new, simple method for the conversion of alcohols to tosylamides is presented.
M. C. Marcotullio, V. Campagna, S. Sternativo, F. Costantino, M. Curini, Synthesis, 2006, 2760-2766.

The aza-Payne rearrangement of 2,3-aziridin-1-ols under basic conditions gives epoxy amines. Subsequent nucleophilic attack of the epoxide by dimethylsulfoxonium methylide yields a bis-anion, which upon a 5-exo-tet ring-closure yields the desired pyrrolidine. This process takes place with complete transfer of stereochemical fidelity and can be applied to sterically hindered aziridinols.
J. M. Schomaker, S. Bhattacharjee, J. Yan, B. Borhan, J. Am. Chem. Soc., 2007, 129, 1996-2003.

J. M. Schomaker, S. Bhattacharjee, J. Yan, B. Borhan, J. Am. Chem. Soc., 2007, 129, 1996-2003.

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 mild and convenient free-radical cyclization of organohalides in the presence of a NiCl2 • DME/Pybox complex as the catalyst and zinc powder in methanol efficiently gives carbo-, oxa-, and azacycles as products in high yields from unsaturated alkyl halides.
H. Kim, C. Lee, Org. Lett., 2011, 13, 2050-2053.

An efficient method to activate hydroxyl groups of amino alcohols has been developed, which avoids the use of toxic reagents and tolerates various functional groups. This strategy has been applied to the synthesis of functionalized p-methoxyphenyl-protected azetidines, pyrrolidines, and piperidines.
R. M. de Figueiredo, R. Fröhlich, M. Christmann, J. Org. Chem., 2006, 71, 4147-4154.

A copper(I)/ClickFerrophos complex catalyzed the asymmetric 1,3-dipolar cycloaddition of methyl N-benzylideneglycinates with electron deficient alkenes to give exo-2,4,5-trisubstituted and 2,3,4,5-substituted pyrrolidines in good yields with high diastereo- and enantioselectivities.
S.-i. Fukuzawa, H. Oki, Org. Lett., 2008, 10, 1747-1750.

An l-tert-leucine-derived AmidPhos/silver(I) catalytic system enables an asymmetric [3+2] cycloaddition of azomethine ylides with electronic-deficient alkenes. Under optimal conditions, highly functionalized endo-4-pyrrolidines were obtained in very good yields and enantioselectivities.
Z. Zhou, X. Zheng, J. Liu, J. Li, P. Wen, H. Wang, Synlett, 2017, 28, 999-1003.

Highly Endo-Selective and Enantioselective 1,3-Dipolar Cycloaddition of Azomethine Ylide with α-Enones Catalyzed by a Silver(I)/ThioClickFerrophos Complex
I. Oura, K. Shimizu, K. Ogata, S.-i. Fukuzawa, Org. Lett., 2010, 12, 1752-1755.

A successful stereochemical reversal in AgOAc catalyzed [3+2] cycloaddition is based on the formation of hydrogen bonding between ligand and reactant. Simple ligand design provides an efficient and convenient route to prepare both enantiomers of a chiral compound.
W. Zeng, G.-Y. Chen, Y.-G. Zhou, Y.-X. Li, J. Am. Chem. Soc., 2007, 129, 750-751.

Chiral complexes of calcium promote asymmetric 1,4-addition reactions and [3+2] cycloaddition reactions of α-amino acid derivatives with α,β-unsaturated carbonyl compounds. The reactions proceeded smoothly in the presence of 5-10 mol % of the chiral calcium catalyst to afford the desired adducts in high yields with high diastereo- and enantioselectivities.
S. Saito, T. Tsubogo, S. Kobayashi, J. Am. Chem. Soc., 2007, 129, 5364-5365.

A nucleophilic addition/ring-contractive rearrangement of α-bromo N-alkoxylactams with organometallic reagents provides an efficient access to α-acylpyrrolidines with good yields and a broad substrate scope. Moreover, a diastereoselective reaction of a chiral N-alkoxylactam is also described.
N. Takeda, Y. Kobori, K. Okamura, M. Yasui, M. Ueda, Org. Lett., 2020, 22, 9740-9744.

Using a confined imidodiphosphate catalyst, a highly enantioselective intramolecular carbonyl-ene reaction of olefinic aldehydes delivers diverse trans-3,4-disubstituted carbo- and heterocyclic five-membered rings in high yields and with good to excellent diastereo- and enantioselectivities.
L. Liu, M. Leutzsch, Y. Zheng, M. W. Alachraf, W. Thiel, B. List, J. Am. Chem. Soc., 2015, 137, 13268-13271.

A [3 + 2]-annulation of N-Ts-α-amino aldehydes and 1,3-bis(silyl)propenes allows an efficient, stereoselective synthesis of densely functionalized pyrrolidines.
P. Restorp, A. Fischer, P. Somfai, J. Am. Chem. Soc., 2006, 128, 12646-12647.

A remarkable Pd-catalyzed diamination of unactivated alkenes using N-fluorobenzenesulfonimide (NFBS) as an aminating reagent is described. The reaction incorporates one nitrogen donor from the substrate and the other from the NFBS, thereby generating cyclic diamine derivatives in a single step. The products are differentially protected at both nitrogens, allowing for maximal synthetic flexibility.
P. A. Sibbald, F. E. Michael, Org. Lett., 2009, 11, 1147-1149.

The reaction of 1,1-cyclopropandiesters with aldimines, generated in situ by the condensation of primary amines or anilines with aldehydes, in the presence of Yb(OTf)3 as catalyst leads to pyrrolidines in good yields.
C. A. Carson, M. A. Kerr, J. Org. Chem., 2005, 70, 8242-8244.

A tandem ring-opening-cyclization reaction of cyclopropanes with imines in the presence of 5 mol% of scandium triflate was developed for the highly diastereoselective synthesis of multisubstituted pyrrolidines.
Y.-B. Kang, Y. Tang, X.-L. Sun, Org. Biomol. Chem., 2006, 4, 299-301.

Successive nucleophilic and electrophilic allylation of a bis-Boc-carbonate derived from 2-methylene-1,3-propane diol provides enantiomerically enriched 2,4-disubstituted pyrrolidines. An initial enantioselective iridium-catalyzed transfer hydrogenative carbonyl C-allylation is followed by Tsuji-Trost N-allylation using 2-nitrobenzenesulfonamide and a Mitsunobu cyclization.
G. Luo, M. Xiang, M. J. Krische, Org. Lett., 2019, 21, 2493-2497.

A palladium-catalyzed cascade cyclization-coupling reaction with suppressed β-hydride elimination provides an efficient synthetic route to 4-methylene-3-arylmethylpyrrolidines. One of the N-sulfonyl oxygens is suggested to coordinatively stabilize an alkylpalladium intermediate, thus preventing the intermediate from the usual β-elimination.
C.-W. Lee, K. S. Oh, K. S. Kim, K. H. Ahn, Org. Lett., 2000, 2, 1213-1216.

An iron catalyst enables a reductive cyclization of 1,6- and 1,7-enynes. Alcohol, ketone, ester, ether, halide, amine, amide, imine, nitrile, silyl, and alkyne groups are tolerated under the mild reaction conditions. An enantioselective transformation was also conducted.
T. Xi, X. Chen, H. Zhang, Z. Lu, Synthesis, 2016, 48, 2837-2844.

Indium hydride generated from readily available Et3SiH and InCl3 offers mild conditions and low toxicity, and is therefore a promising alternative to Bu3SnH.
N. Hayashi, I. Shibata, A. Baba, Org. Lett., 2004, 6, 4981-4983.

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.

An enantioselective, palladium-catalyzed [3 + 2] cycloaddition of trimethylenemethane (TMM) with imines in the presence of novel phosphoramidite ligands gives the corresponding pyrrolidine cycloadducts with excellent yields and selectivities.
B. M. Trost, S. M. Silverman, J. Am. Chem. Soc., 2012, 134, 4941-4954.

FeCl2 and an iminopyridine ligand form in the presence of diethylzinc and magnesium bromide etherate an active catalyst for the reductive cyclization of N- and O-tethered 1,6-enynes to give pyrrolidine and tetrahydrofuran derivatives.
A. Lin, Z.-W. Zhang, J. Yang, Org. Lett., 2014, 16, 386-389.

A Rh-catalyzed [4 + 1] cycloaddition of 3-methyleneazetidines to diazo compounds provides 4-methyleneproline derivatives under very mild conditions with a high degree of chemoselectivity. This method can incorporate the proline ester scaffold in pharmaceuticals and natural products. An intramolecular version of the reaction effectively provides proline-fused tricyclic heterocycles.
W. Cai, J. Wu, H. Zhang, H. B. Jalani, G. Li, H. Lu, J. Org. Chem., 2019, 84, 10877-10891.

A rhodium-catalyzed asymmetric arylative cyclization of nitrogen-tethered alkyne-enoate with arylboronic acids, in which two new carbon-carbon bonds and one stereocenter are formed, provides access to pyrrolidines and piperidines with good enantioselectivities by to the use of a C1-symmetric chiral monosubstituted diene ligands.
F. Serpier, B. Flamme, J.-L. Brayer, B. Folléas, S. Darses, Org. Lett., 2015, 17, 1720-1723.

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 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 convenient two-step preparation of alkylidenepyrrolidines is reported.
M. C. Elliot, S. V. Wordingham, Synthesis, 2006, 1162-1170.

Catalytic hydrogenation of acetylenic aldehydes using a chirally modified cationic rhodium catalysts enables highly enantioselective reductive cyclization to afford cyclic allylic alcohols. Using an achiral hydrogenation catalyst, some chiral racemic acetylenic aldehydes engage in highly syn-diastereoselective reductive cyclizations.
J. U. Rhee, M. J. Krische, J. Am. Chem. Soc., 2006, 128, 10674-10675.

Reductive radical cyclization of N-allyl-N-dimethylphosphinoyl-2-aminopropyl phenyl selenide using tris(trimethylsilyl)silane (TTMSS) / AIBN under UV irradiation gave the corresponding pyrrolidine in 74% yield and a cis/trans ratio of 10/1 which was superior to thermal cyclization
D. Shanks, S. Berlin, M. Besev, H. Ottosson, L. Engman, J. Org. Chem., 2004, 69, 1487-1491.

Depending on the steric hindrance of the ligand, a regioselective palladium-catalyzed diamination of unactivated alkenes, provides either amino-functionalized piperidines or pyrrolidines. 6-Endo diamination occurred with a less sterically hindered quinox ligand to afford 3-aminopiperidines, while 5-exo diamination occurred with a bulky pyox ligand to give amino-substituted pyrrolidines.
X. Liu, C. Hou, Y. Peng, P. Chen, G. Liu, Org. Lett., 2020, 22, 9371-9375.

An enantioselective catalytic Suzuki-Miyaura reaction of meso 1,2-diborylcycloalkanes provides enantiomerically enriched substituted carbocycles and heterocycles that retain a synthetically versatile boronic ester. With appropriately constructed substrates, compounds bearing additional stereogenic centers and fully substituted carbon atoms can be generated in a straightforward fashion.
M. Zhang, P. S. Lee, C. Allais, R. A. Singer, J. P. Morken, J. Am. Chem. Soc., 2023, 145, 8308-8313.

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 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.

A new Pd-catalyzed oxidation reaction for the stereospecific conversion of enynes into cyclopropyl ketones proceeds with net inversion of geometry with respect to the starting olefin. This result is consistent with a mechanism in which the key cyclopropane-forming step involves nucleophilic attack of a tethered olefin onto the PdIV-C bond.
L. L. Welbes, T. W. Lyons, K. A. Cychosz, M. S. Sanford, J. Am. Chem. Soc., 2007, 129, 5836-5837.