Categories: Synthesis of N-Heterocycles > Lactams

Synthesis of 3-pyrrolin-2-ones

Recent Literature

A 3 + 2 cycloaddition of α-imino rhodium carbenoids generated from 1-sulfonyl 1,2,3-triazoles with ketene silyl acetals offers a novel and straightforward synthesis of biologically interesting 3-pyrrolin-2-ones with broad substrate scope.
R.-Q. Ran, J. He, S.-D. Xiu, K.-B. Wang, C.-Y. Li, Org. Lett., 2014, 16, 3704-3705.

Regioselective ring closing ene-yne metathesis provided an efficient access to different substituted 1-benzazepine scaffolds. Five- and six-membered lactams were efficiently prepared by ring-closing metathesis affording highly functionalizable compounds.
E. Benedetti, M. Lomazzi, F. Tibiletti, J.-P. Goddard, L. Fensterbank, M. Malacria, G. Palmisano, A. Penoni, Synthesis, 2012, 44, 3523-3533.

A visible-light-induced excited-state copper-catalyzed [4 + 1] annulation reaction of acrylamides and aroyl chlorides provides a wide range of γ-H, -OH, and -OR-substituted α,β-unsaturated-γ-lactams . The procedures offer mild reaction conditions, broad substrate scope, and high functional group tolerance.
S. Sarkar, A. Banerjee, J. A. Shah, U. Mukherjee, N. C. Frederiks, C. J. Johnson, M.-Y. Ngai, J. Am. Chem. Soc., 2022, 144, 20884-20894.

A palladium-catalyzed cyclocarbonylation of propargyl amines in the presence of benzene-1,3,5-triyl triformate (TFBen) as the CO source and also as the key promotor provides various substituted 2-oxo-dihydropyrroles in good yields.
J. Ying, Z. Le, X.-F. Wu, Org. Lett., 2020, 22, 194-198.

Dimethyl sulfoxide (DMSO) and N-iodosuccinimide mediate a metal-free regioselective 5-exo-dig oxidative cyclization of propargyl-substituted ynamides via in situ generated enol equivalents. The reaction allows easy access to functionalized pyrrolidone skeletons. The role of DMSO as oxidant in the transformation is clarified, and a tentative reaction pathway is proposed.
B. Prabagar, S. Nayak, R. Prasad, A. K. Sahoo, Org. Lett., 2016, 18, 3066-3069.

An efficient copper-catalyzed oxidative cyclization of diynes as readily available substrates provides a range of functionalized γ-lactams. This copper-catalyzed oxidative process proceeds through an alkyne oxidation, carbene/alkyne metathesis, and donor-donor carbene oxidation sequence. This simple method offers high flexibility and mild reaction conditions.
T.-T. Zhang, K.-F. Wei, G.-X. Ru, X.-H. Zhu, L-X. Xie, W.-B. Shen, Synlett, 2023, 34, 149-152.

A heterocycle-heterocycle interconversion strategy provides 4,5-disubstituted 3-hydroxy-2-pyrrolidinones in good yields. The reported reductive rearrangement approach especially allows access to unsubstituted 3-hydroxy-2-pyrrolidinone at the nitrogen position for further functionalization.
P. Kamath, V. Jadhav, M. Lal, Synlett, 2021, 32, 1146-1150.

Conventional approaches for the synthesis of tetramic acid derivatives often require highly functionalized starting materials and harsh heating conditions in basic media. A silver-catalyzed strategy enables a mild synthesis of tetramic acid derivatives from easily available propargylic amines and carbon dioxide in the presence of DBU.
T. Ishida, R. Kobayashi, T. Yamada, Org. Lett., 2014, 16, 2430-2433.

An unprecedented C(CO)-C(Ar) bond cleavage of β-enaminones under mild and transition-metal-free conditions followed by 1,3-O/C migration and aerobic hydroxylation provides various 5-hydroxy-1H-pyrrol-2(5H)-ones with broad functional group tolerance.
T. Chen, X. Zhang, W. Wang, Y. Feng, Y. Wang, J. Shen, J. Org. Chem., 2021, 86, 2917-2928.

An efficient sequential halolactamization-hydroxylation reaction of 4-monosubstituted 2,3-allenamides with CuX₂ (X = Br, Cl) provides 4-halo-5-hydroxypyrrol-2(5H)-ones in high yields. Halolactamizations of a fully substituted 2,3-dienamide afforded 4-halo-pyrrol-2(5H)-ones.
S. Ma, H. Xie, Org. Lett., 2000, 2, 3801-3803.