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Synthesis of γ-lactams

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A selective electrochemical aminoxyl-mediated Shono-type oxidation of pyrrolidines provides pyrrolidinones with high selectivity and functional group compatibility.
N. R. Deprez, D. J. Clausen, J.-X. Yan, F. Peng, S. Zhang, J. Kong, Y. Bai, Org. Lett., 2021, 23, 8834-8837.

An oxidative copper-catalyzed arylation of various ring-size lactams with arylboronic acids gives N-arylated products in good yield without any additional bases, ligands, or additives.
T. Bathini, V. S. Rawat, B. Sreedhar, Synlett, 2015, 26, 1348-1351.

A quick, efficient, one-pot, BF3·OEt2-mediated reaction of various substituted arenes with azido alkanoic acid chlorides affords substituted N-aryl lactams in good to excellent yields at room temperature.
D. Caturvedi, A. K. Chaturvedi, N. Mishra, V. Mishra, Synlett, 2012, 23, 2627-2630.

An Al(OTf)3-catalyzed cascade cyclization and ionic hydrogenation reaction of nitrogen substituted ketoamides enables an efficient and versatile synthesis of N-substituted lactams, pyrrolindinones, piperidones, and structurally related heterocycles in good yields.
J. Qi, C. Sun, Y. Tian, X. Wang, G. Li, Q. Xiao, D. Yin, Org. Lett., 2014, 16, 190-192.

A gold-catalyzed tandem cycloisomerization/oxidation of homopropargyl amides provides ready access to synthetically useful chiral γ-lactams with excellent ee by combining the chiral tert-butylsulfinimine chemistry and gold catalysis. The use of readily available starting materials, a simple procedure, and mild reaction conditions are other significant features of this method.
C. Shu, M.-Q. Liu, S.-S. Wang, L. Li, L.-W. Ye, J. Org. Chem., 2013, 78, 3292-3299.

A highly enantioselective Ir(III)-catalyzed intramolecular C(sp3)-H amidation reaction of dioxazolone substrates provides optically enriched γ-lactams using an α-amino-acid-based chiral ligand. This reaction proceeds with excellent efficiency and with outstanding enantioselectivity for both activated and unactivated alkyl C(sp3)-H bonds under very mild conditions.
H. Wang, Y. Park, Z. Bai, S. Chang, G. He, G. Chen, J. Am. Chem. Soc., 2019, 141, 7194-7201.

Amino diphenylphosphinates undergo ring expansion of cyclobutanones toward γ-lactams under mild conditions. Due to the ambivalent character of the aminating agent, rearrangement occurs from a Criegee-like intermediate prior to the formation of an oxime species. The migrating aptitude of adjacent groups is in line with the parent Baeyer-Villiger reaction.
M. Ong, M. Arnold, A. W. Walz, J. M. Wahl, Org. Lett., 2022, 24, 6171-6175.

A nickel-catalyzed reductive cross-coupling reaction of easily accessible 3-butenyl carbamoyl chloride with primary alkyl iodide provides chiral α-alkylated pyrrolidinones with broad substrate scope and high enantiomeric excess using a newly designed chiral 8-quinoline imidazoline ligand (Quinim).
X. Wu, J. Qu, Y. Chen, J. Am. Chem. Soc., 2020, 142, 15654-15660.

A phosphazene base-catalyzed intramolecular hydroamidation of amide alkenes provides cyclic amides. The reaction using a catalytic amount of P4-base had a good functional group tolerance and a broad substrate scope and could also be used to synthesize lactams, cyclic ureas, and oxazolidinones.
J. Matsuoka, Y. Fujimoto, A. Miyawaki, Y. Yamamoto, Org. Lett., 2022, 24, 9447-9451.

The use of Ph2GeCl2 as a cocatalyst greatly improves the yield of α-C(sp3)-H alkylation of primary amines catalyzed by a PC-HAT hybrid system. The α-position of the amino group selectively reacted even when weaker C-H bonds existed in the substrates.
K. Sakai, K. Oisaki, M. Kanai, Org. Lett., 2022, 24, 3325-3330.

A chiral isothiourea and an Ir complex cooperatively catalyze [3 + 2] asymmetric annulation reactions of vinyl aziridines with pentafluorophenyl esters to provide a broad range of optically active γ-lactams in good yields with high asymmetric induction.
Q. Wang, T. Fan, J. Song, Org. Lett., 2023, 25, 1246-1251.

A K2S2O8-mediated transition metal-free oxidative cross-coupling reaction of activated olefins with N-alkyl amides provides N-allylic amides in good yield.
M. Li, L. Zhang, L. Ma, Y. Chen, J. Org. Chem., 2021, 86, 3989-3998.

1,5-Disubstituted pyrrolidin-2-ones were synthesized in good yields via the nucleophilic substitution of 5-(benzotriazol-1-yl)-1-substituted-pyrrolidin-2-ones with allylsilanes, organozinc reagents, and phosphorus compounds.
A. R. Katritzky, S. Mehta, H.-Y. He, X. Cui, J. Org. Chem., 2000, 65, 4364-4369.

Upon Ir catalysis, N-benzoyloxyamides serve as efficient acylnitrenoid precursors to afford γ-lactams. The generation of a putative Ir-carbonylnitrenoid via N-O bond cleavage is facilitated by the chelation of countercations. This convenient reaction offers a step-economic route to γ-lactams.
S. Huh, S. Y. Hong, S. Chang, Org. Lett., 2019, 21, 2808-2812.

Kolbe Anodic Decarboxylation as a Green Way To Access 2-Pyrrolidinones
M. Quertenmont, I. Goodall, K. Lam, I. Markó, O. Riant, Q. Wan, Org. Lett., 2020, 22, 1771-1775.

A Ru-catalyzed enantioselective annulation of 1,4,2-dioxazol-5-ones provides γ-lactams in good yield and high ee via intramolecular carbonylnitrene C-H insertion. Enantioselective nitrene insertion to allylic/propargylic C-H bonds was also achieved with remarkable tolerance to carbon-carbon multiple bonds.
Q. Xing, C.-M. Chan, Y.-W. Yeung, W.-Y. Yu, J. Am. Chem. Soc., 2019, 141, 3849-3853.

Ir catalysis achieves a lactam synthesis directly from lactones and amines via aminolysis of lactone, N-alkylation of amine with hydroxyamide, and intramolecular transamidation of aminoamide.
K. Kim, S. H. Hong, J. Org. Chem., 2015, 80, 4152-4156.

Use of porous TiO2 nanosheets-supported Pt nanoparticles (Pt/P-TiO2) as heterogeneous catalyst enables a challenging reductive amination of biomass-derived levulinic acid at ambient temperature and H2 pressure. Pt/P-TiO2 also showed good applicability for reductive amination of levulinic esters, 4-acetylbutyric acid, 2-acetylbenzoic acid, and 2-carboxybenzaldehyde.
C. Xie, J. Song, H. Wu, Y. Hu, H. Liu, Z. Zhang, P. Zhang, B. Chen, B. Han, J. Am. Chem. Soc., 2019, 141, 4002-4009.

A carbamoyl fluoride-enabled enantioselective Ni-catalyzed carbocarbamoylation of unactivated alkenes provides a broad range of chiral γ-lactams bearing an all-carbon quaternary center in good yield and high enantioselectivity.
Y. Li, F.-P. Zhang, R.-H. Wang, S.-L. Qi, Y.-X. Luan, M. Ye, J. Am. Chem. Soc., 2020, 142, 19844-19849.

Concerted proton-coupled electron transfer (PCET) mediated by an excited state iridium complex enables amide activation in the presence of a weak phosphate base to furnish a reactive amidyl radical that readily adds to pendant alkenes. The thiophenol cocatalyst furnishes the product and regenerate the active forms of the photocatalyst.
D. C. Miller, G. J. Choi, H. S. Orbe, R. R. Knowles, J. Am. Chem. Soc., 2015, 137, 13492-13495.

Depending on the Lewis base catalyst, a Michael addition of α-aminonitriles to simple activated alkenes provides functionalized γ-amino acid esters or γ-lactams. The scope, versatility, and efficiency of the methods were demonstrated.
Z.-Y. He, H.-C. Jang, L.-S. Teng, Z.-L. Wei, W.-W. Liao, Synthesis, 2021, 53, 1833-1841.

A photoinitiated deaminative [3 + 2] annulation reaction of N-aminopyridinium salts with alkenes provides functionalized γ-lactams. This transformation shows good functional group tolerance as well as excellent diastereoselectivity.
C. Shi, L. Guo, H. Gao, M. Luo, C. Yang, W. Xia, Org. Lett., 2022, 24, 4365-4370.

A N-heterocyclic carbene catalyzed formal [3 + 2] annulation of enals with 2-aminoacrylates provides various γ-lactam derivatives in good yields with excellent diastereo- and enantioselectivities. In this process, two consecutive stereocenters and a quaternary carbon center are constructed.
X.-S. Li, L.-L. Zhao, X.-K. Wang, L.-L. Cao, X.-Q. Shi, R. Zhang, J. Qi, Org. Lett., 2017, 19, 3943-3946.

An asymmetric palladium-catalyzed vinylogous addition/allylic amination process between 1,3-dienes and α-ketoamides provides multifunctionalized γ-lactams, including those bearing two tetrasubstituted stereogenic centers. This protocol features advantages of ready substrate availability, broad applicability, high efficiency, and excellent stereoselectivity.
G.-L. Shen, Y.-Y. Tan, Y. Hu, Z.-H. Chen, W. Du, Y.-C. Chen, Org. Lett., 2023, 25, 6649-6653.

Addition of amide enolates to acylsilanes generates β-silyloxy homoenolates by undergoing a 1,2-Brook rearrangement. These unique nucleophiles formed in situ can then undergo addition to alkyl halides, aldehydes, ketones, and imines. γ-Amino-β-hydroxy amide products derived from a diastereoselective addition to N-diphenylphosphinyl imines can be efficiently converted to γ-lactams.
R. B. Lettan, II, C. V. Galliford, C. C. Woodward, K. A. Scheidt, J. Am. Chem. Soc., 2009, 131, 8805-8814.

A highly diastereoselective reaction of 2,5-bis(trimethysilyloxy)furan with imines gives β-carboxy-γ-lactams and their ethyl ester derivatives in high yields via a Mukaiyama-aldol type reaction with high diastereomeric ratio employing Sc(OTf)3 as catalyst.
M. Pohmakotr, N. Yotapan, P. Tuchinda, C. Kuhakarn, V. Reutrakul, J. Org. Chem., 2007, 72, 5016-5019.

The hypervalent iodine reagent PIFA promotes the efficient intramolecular electrophilic cyclization of easily accessible alkynylamides and alkynyl carboxylic acids, leading to pyrrolidinone and lactone skeletons, respectively. A synthetic study and a mechanistic proposal for these transformations are presented.
I. Tellitu, S. Serna, M. T. Herrero, I. Moreno, E. Domínguez, R. SanMartin, J. Org. Chem., 2007, 72, 1526-1529.

The utility of a Design of Experiments (DoE) approach for the rapid and efficient optimisation of a microwave assisted Ugi 3cc reaction of levulinic acid with a range of amine and isonitrile substrates has enabled the preparation of lactam derivatives in moderate to excellent yields in a reaction time of only 30 min compared to the conventional methodology which required up to 48 h.
H. Tye, M. Whittaker, Org. Biomol. Chem., 2004, 2, 813-815.

The reaction of amide and thioamide dianions with epibromohydrin resulted in regioselective formation of 5-(hydroxy­methyl)pyrrolidin-2-ones (pyroglutaminols) and -thiones.
I. Freifeld, H. Armbrust, P. Langer, Synthesis, 2006, 1807-1808.

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.

A versatile and highly stereoselective borylative cyclization provides polyfunctionalized γ-lactams. The reaction system enables the construction of di- and trisubstituted γ-lactam cores, with examples containing enantioenriched quaternary carbons.
A. Torelli, A. Whyte, I. Polishchuk, J. Bajohr, M. Lautens, Org. Lett., 2020, 22, 7915-7919.

A versatile and highly stereoselective borylative cyclization provides polyfunctionalized γ-lactams. The reaction system enables the construction of di- and trisubstituted γ-lactam cores, with examples containing enantioenriched quaternary carbons.
A. Torelli, A. Whyte, I. Polishchuk, J. Bajohr, M. Lautens, Org. Lett., 2020, 22, 7915-7919.

Several Pd-catalyzed oxidative cyclizations proceed in excellent yield under simple aerobic conditions. Importantly, this system provided entry into enatioselective catalysis with a readily available Pd-sparteine complex.
R. M. Trend, Y. K. Ramtohul, E. M. Ferreira, B. Stoltz, Angew. Chem. Int. Ed., 2003, 42, 2892-2895.

A convenient and highly regioselective method allows the synthesis of 5-methylenepyrrolidinone derivatives from various nitriles and acrylamides via a cobalt-catalyzed reductive coupling reaction. A possible mechanism involves the formation of a cobaltaazacyclopentene intermediate from nitrile and acrylamide, protonation, keto-amide cyclization, and dehydration.
Y.-C. Wong, K. Parthsarathy, C.-H. Cheng, J. Am. Chem. Soc., 2009, 131, 18252-18253.

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.

N-Alkenyl β-ketoamides undergo a mild cyclization in the presence of Au[P(t-Bu)2(o-biphenyl)]Cl and AgOTf with excellent regioselectivities and yields. The reaction provides an efficient method to prepare highly substituted lactams.
C.-Y. Zhou, C.-M. Che, J. Am. Chem. Soc., 2007, 129, 5828-5829.

Preferential Rh(II) carbenoid intramolecular C-H versus O-H insertion derived from α-diazo-acetamides can be achieved in water by creating a large hydrophobic environment around the reactive carbenoid center using an appropriate combination of the catalyst and amide groups.
N. R. Candeias, P. M. P. Gois, C. A. M. Afonso, J. Org. Chem., 2006, 71, 5489-5497.

An intramolecular vinylation of various iodoenamides using CuI as the catalyst and N,N'-dimethylethylenediamine as the ligand led to five- to seven-membered lactams in moderate to excellent yields.
T. Hu, C. Li, Org. Lett., 2005, 7, 2035-2038.

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.