Categories: Synthesis of N-Heterocycles > Lactams >
Synthesis of β-lactams
A convenient Kinugasa reaction protocol enables a one-pot synthesis of 4-substituted β-lactams from inexpensive calcium carbide and nitrone derivatives. Calcium carbide is thereby activated by TBAFˇ3H2O in the presence of CuCl/NMI. The reaction provides rapid access to practical quantities of β-lactams substituted at position 4.
A. Hosseini, P. R. Schreiner, Org. Lett., 2019, 21, 3746-3749.
Catalytic generation of a ketene species directly from a terminal alkyne in the presence of a Rh(I) catalyst and 4-picoline N-oxide provides a novel and efficient entry to the Staudinger synthesis of β-lactams with high trans diastereoselectivity under mild conditions. Mechanistic studies suggest that the reaction proceeds through a metalloketene rather than free ketene intermediate.
I. Kim, S. W. Roh, D. G. Lee, C. Lee, Org. Lett., 2014, 16, 2482-2485.
Thermally promoted reactions of α-acyl-α-diazoacetates with imines deliver α-alkoxycarbonyl-substituted β-lactams with outstanding diastereoselectivity. DFT calculations revealed the occurrence of 1,3-oxazin-4-one intermediates.
J. Synofzik, D. Dar'in, M. S. Novikov, G. Kantin, O. Bakulina, M. Krasavin, J. Org. Chem., 2019, 84, 12101-12110.
A rhodium-hydride complex (Rh-H), generated from Et2Zn and RhCl(PPh3)3, catalyzes a 1,4-reduction of α,β-unsaturated esters. The resulting rhodium enolate reacted as a Reformatsky-type reagent with various imines to give syn-β-lactams in good to excellent yields with high diastereoselectivity.
M. Isoda, K. Sato, M. Funakoshi, K. Omura, A. Tarui, M. Omote, A. Ando, J. Org. Chem., 2015, 80, 8398-8405.
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.
N-Tosyl-3-halo-3-butenylamines underwent efficient Ullmann-type coupling to afford 2-alkylideneazetidines, which could be readily converted to the corresponding β-lactams by oxidation with O3.
H. Lu, C. Li, Org. Lett., 2006, 8, 5365-5367.
A catalytic, highly diastereoselective synthesis of trans-β-lactams is based on a phosphonium fluoride precatalyst that both activates the nucleophile and directs the reaction process for high yield and diastereoselectivity.
C. J. Abraham, D. H. Paull, C. Dogo-Isonagie, T. Lectka, Synlett, 2009, 1651-1654.
A chiral N-heterocyclic carbene catalyzed the Staudinger reaction of arylalkylketenes with a variety of N-tert-butoxycarbonyl arylimines to give the corresponding cis-β-lactams in good yields with good diastereoselectivities and excellent enantioselectivities.
A.-R. Zhang, L. He, X. Wu, P.-L. Shao, S. Ye, Org. Lett., 2008, 10, 277-280.
A catalytic enantioselective Staudinger reaction is described that preferentially furnishes trans β-lactams. The use of an N-triflyl protecting group for the imine is crucial for the success of the reaction.
E. C. Lee, B. L. Hodous, E. Bergin, C. Shih, G. C. Fu, J. Am. Chem. Soc., 2005, 127, 11586-11587.
The Staudinger synthesis, an overall [2 + 2] cycloaddition of a ketene with an imine, provides a nicely convergent route to biologically and synthetically interesting β-lactams. A planar-chiral derivative of 4-(pyrrolidino)pyridine serves as a very effective enantioselective catalyst coupling a range of symmetrical and unsymmetrical ketenes with various imines with very good stereoselection and yield.
B. L. Hodous, G. C. Fu, J. Am. Chem. Soc., 2002, 124, 1578-1579.
Pd-Catalyzed Carbonylation of Diazo Compounds at Atmospheric Pressure: A Catalytic Approach to Ketenes
Z. Zhang, Y. Liu, L. Ling, Y. Li, Y. Dong, M. Gong, X. Zhao, Y. Zhang, J. Wang, J. Am. Chem. Soc., 2011, 133, 4330-4341.
The transformation of diazoketones to ketenes can be realized not only by utilizing photochemical reaction conditions but also under the action of microwave irradiation. In the presence of imines, the generated ketenes react further to afford β-lactams. Various trans-substituted β-lactams derived from amino acids have been prepared.
M. R. Linder, J. Podlech, Org. Lett., 2001, 3, 1849-1851.
A practical methodology for the catalytic, asymmetric synthesis of β-lactams results from the development of a catalyzed reaction of ketenes (or their derived zwitterionic enolates) and imines using benzoylquinine as chiral catalyst and proton sponge as the stoichiometric base.
A. E. Taggi, A. M. Hafez, H. Wack, B. Young, D. Ferraris, T. Lectka, J. Am. Chem. Soc., 2002, 124, 6626-6635.
Efficient conversion of Schiff bases and carboxylic acids to β-lactams can be carried out at room temperature in CH2Cl2, using a cyanuric chloride-N,N-dimethyl formamide complex. The complex is easily prepared by reaction of cyanuric chloride and DMF at room temperature.
M. Zarei, A. Jarrahpour, Synlett, 2011, 2572-2576.
A general and highly efficient synthesis of 4-alkylidene-2-azetidinones was achieved by the Cu(I)-catalyzed intramolecular C-N coupling of amides with vinyl bromides. This 4-exo ring closure was found to be fundamentally preferred over other modes (5-exo, 6-exo, and 6-endo) of cyclization under copper catalysis.
Q. Zhao, C. Li, Org. Lett., 2008, 10, 4037-4040.
Umpolung enables a facile synthesis of α-methylene-β-lactams. Under the catalysis of triphenylphosphine, a number of 2-propiolamidoacetates or α-propiolamido ketones underwent cyclization to afford the corresponding 4-substituted 3-methyleneazetidin-2-ones in high yields.
L. Zhu, Y. Xiong, C. Li, J. Org. Chem., 2015, 80, 628-633.
exo-Methylene-β-lactams were synthesized in two steps from commercially available 3-bromo-2-(bromomethyl)propionic acid and reacted with arene diazonium salts in a Heck-type arylation with high exo- and E-selectivity in the presence of catalytic amounts of Pd(OAc)2 under ligand-free conditions. The reaction provides arylidene-β-lactams in high yields as single isomers.
N. Riemer, M. Riemer, M. Krüger, G. J. Clarkson, M. Shipman, B. Schmidt, J. Org. Chem., 2021, 86, 8786-8796.