Categories: Synthesis of N-Heterocycles > Lactams >
Synthesis of β-lactams
Name Reactions
Recent Literature
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.