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Beta-Lactams pp 105–128Cite as

β-Lactams from Ketene-Imine Cycloadditions: An Update

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Abstract

Recent advances in the preparation of β-lactams by ketene-imine [2+2] cycloadditions are described. Types of ketenes noted include those generated by thermal and photochemical means, with examples of stable and isolable ketenes, as well as reactive intermediates, sometimes observable by spectroscopic methods. Preparations of bis(β-lactams) by such processes are also described.

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References

  1. Staudinger H (1907) Zur Kenntniss der Ketene. Chem Ber 40:51–123. doi:10.1002/jlac.19073560106

  2. Staudinger H (1905) Ketene, eine neue Körperklasse. Chem Ber 38:1735–1739. doi:10.1002/cber.19050380283

    Article  Google Scholar 

  3. Tidwell TT (2005) The first century of ketenes (1905–2005): the birth of a versatile family of reactive intermediates. Angew Chem Int Ed 44:5778–5785. doi:10.1002/anie.200500098

    Article  CAS  Google Scholar 

  4. Seeman JI (2015) Woodward-Hoffmann’s stereochemistry of electrocyclic reactions: from day 1 to the JACS receipt date (May 5, 1964 to November 30, 1964). J Org Chem 80:11632–11671. doi:10.1021/acs.joc.5b01792

    Article  CAS  Google Scholar 

  5. Wikipedia, accessed April 1, 2016

    Google Scholar 

  6. Singh GS, Sudheesh S (2014) Advances in synthesis of monocyclic β-lactams. ARKIVOC 337–385. doi:10.3998/ark.5550190.0015.100

  7. Banik BK (2014) Novel synthesis of β-lactams and their biological evaluation. J Indian Chem Soc 91:1837–1860

    CAS  Google Scholar 

  8. Pracejus H (1960) Organische Katalysatoren, LXI. Asymmetrische Synthesen mit Ketenen, I. Alkaloid-katalysierte asymmetrische Synthesen von α-Phenyl-propionsäureestern. Liebigs Ann Chem 634:9–22. doi:10.1002/jlac.19606340103

    Article  CAS  Google Scholar 

  9. Wynberg H, Staring EG (1982) Asymmetric synthesis of (S)- and (R)-malic acid from ketene and chloral. J Am Chem Soc 104:166–168. doi:10.1021/ja00365a030

    Article  CAS  Google Scholar 

  10. Magriotis PA (2014) Progress in asymmetric organocatalytic synthesis of β-lactams. Eur J Org Chem 2647–2657. doi:10.1002/ejoc.201301720

  11. Tuba R (2013) Synthesis of β-lactams by transition metal promoted Staudinger reactions: alternative synthetic approaches from transition metal enhanced organocatalysis to in situ, highly reactive intermediate synthesis and catalytic tandem reactions. Org Biomol Chem 11:5976–5988. doi:10.1039/c3ob41048j

    Article  CAS  Google Scholar 

  12. Hans M, Wouters J, Demonceau A, Delaude L (2013) Mechanistic insight into the Staudinger reaction catalyzed by N-heterocyclic carbenes. Chem Eur J 19:9668–9676. doi:10.1002/chem.201204428

    Article  CAS  Google Scholar 

  13. Zhang H-M, Gao Z-H, Ye S (2014) Bifunctional N‐heterocyclic carbene-catalyzed highly enantioselective synthesis of spirocyclic oxindolo-β-lactams. Org Lett 16:3079–3081. doi:10.1021/ol501205v

  14. Wang Y, Wei D, Li Z, Zhu Y, Tang M (2014) DFT Study on the mechanisms and diastereoselectivities of lewis acid-promoted ketene–alkene [2+2] cycloadditions: what is the role of lewis acid in the ketene and C=X (X=O, CH2, and NH) [2+2] cycloaddition reactions? J Phys Chem A 118:4288–4300. doi:10.1021/jp500358m

    Article  CAS  Google Scholar 

  15. Zarei M (2013) A convenient synthesis of 2-azetidinones via 2-fluoro-1-methylpyridinium p-toluenesulfonate. Monat Chem 144:1021–1025. doi: 10.1007/s00706-012-0918-y

  16. Zarei M (2014) An efficient and green method for the synthesis of 2-azetidinones mediated by propylphosphonic anhydride (T3). Monat Chem 145:1495–1499. doi:10.1007/s00706-014-1217-6

    Article  CAS  Google Scholar 

  17. Mandler MD, Truong PM, Zavalij PY, Doyle MP (2014) Catalytic conversion of diazocarbonyl compounds to imines: applications to the synthesis of tetrahydropyrimidines and β-lactams. Org Lett 16:740–743. doi:10.1021/ol403427s

    Article  CAS  Google Scholar 

  18. Feroci M (2011) Investigation of the role of electrogenerated N-heterocyclic carbene in the Staudinger synthesis in ionic liquid. Int J Org Chem 1:191–201. doi:10.4236/ijoc.2011.14028

    Article  CAS  Google Scholar 

  19. Toyoda Y, Ninomiya M, Ebihara M, Koketsu M (2013) The staudinger reaction with 2-imino-1,3-thiaselenanes toward the synthesis of C4 spiro-β-lactams. Org Biomol Chem 11:2652–2659. doi:10.1039/c3ob00073g

    Article  CAS  Google Scholar 

  20. Feroci M, Chiarotto I, Orsini M, Inesi A (2010) Electrogenerated NHC as an organocatalyst in the Staudinger reaction. Chem Commun 46:4121–4123. doi:10.1039/c002325f

  21. Okano T (2013) Heterocyclic synthesis via catalysis of N-heterocyclic carbenes: very classical and very modern chemical species. Heterocyclic Commun 19:311–326. doi:10.1515/hc-2013-0075

    Article  CAS  Google Scholar 

  22. Hafner A, Ley SV (2015) Generation of reactive ketenes under flow conditions through zinc-mediated dehalogenation. Synlett 1470–1474. doi:10.1055/s-0034-1380679

  23. Hosseinkhani B, Islami MR, Hosseinkhani S (2015) Highly stereoselective synthesis of isoindole derivatives containing an azetidinone ring. Synlett 2277–2279. doi:10.1055/s-0035-15660066

  24. Stoll T, Alker A, Kolczewski S, Menzi A, Revil-Baudard V (2015) New short access to pyrrolo[2,3-c]pyridazin-6-ones via b-spirolactams. Tetrahedron Lett 56:772–774. doi:10.1016/j.tetlet.2014.12.017

    Article  CAS  Google Scholar 

  25. Karlsson S, Bergman R, Löfberg C, Moore P, Ponten F, Tholander J, Sörensen H (2015) Development of a large-scale route to an MCH1 receptor antagonist: investigation of a Staudinger ketene-imine cycloaddition in batch and flow mode. Org Proc Res Dev 19:2067–2074. doi:10.1021/acs.oprd.5b00319

    Article  CAS  Google Scholar 

  26. de Bruin B, Tang Z, Mandal S, Paul ND, Lutz M, Li P, van der Vlugt JI (2015) Rhodium catalysed conversion of carbenes into ketenes and ketene imines using PNN pincer complexes. Org Chem Front 2:1561–1577. doi:0.1039/c5qo00287g

    Article  Google Scholar 

  27. Zhang H-M, Gao Z-H, Ye S (2014) Bifunctional N-heterocyclic carbene-catalyzed highly enantioselective synthesis of spirocyclic oxindolo-β-lactams. Org Lett 16:3079–3081. doi:10.1021/ol501205v

    Article  CAS  Google Scholar 

  28. Hans M, Wouters J, Demonceau A, Delaude L (2015) Probing the diastereoselectivity of Staudinger reactions catalyzed by N-heterocyclic carbenes. Chem Eur J 21:10870–10877. doi:10.1002/chem.201501060

    Article  CAS  Google Scholar 

  29. Santoro S, Liao R-Z, Marcelli T, Hammar P, Himo F (2015) Theoretical study of mechanism and stereoselectivity of catalytic kinugasa reaction. J Org Chem 80:2649–2660. doi:10.1021/jo502838p

    Article  CAS  Google Scholar 

  30. Zarei M (2014) A straightforward approach to 2-azetidinones from imines and carboxylic acids using dimethyl sulfoxide and acetic anhydride. Tetrahedron Lett 55:5354–5357. doi:10.1016/j.tetlet.2014.07.089

    Article  CAS  Google Scholar 

  31. Jarrahpour A, Heiran R (2014) Synthesis of new nanocopolymer containing β-lactams. J Iran Chem Soc 11:75–83. doi:10.1007/s13738-013-0277-6

    Article  CAS  Google Scholar 

  32. Jarrahpour A, Ebrahimi E, Sinou V, Latour C, Brunel JM (2014) Diastereoselective synthesis of potent antimalarial cis-β-lactam agents through a [2+2] cycloaddition of chiral imines with a chiral ketene. Eur J Med Chem 87:364–371. doi:10.1016/j.ejmech.2014.09.077

    Article  CAS  Google Scholar 

  33. Jarrahpour A, Nazari M (2015) Synthesis of some new polycyclic aromatic monocyclic β-lactams. Iran J Sci Tech, Trans A: Science 39:259–265. url:http://ijsts.shirazu.ac.ir

  34. Domingo LR, Sáez JA (2014) Understanding the selectivity in the formation of β-lactams vs. β-lactams in the Staudinger reactions of chloro-cyan-ketene with unsaturated imines. A DFT study. RSC Adv. 4:58559–58566. doi:10.1039/C4RA10291F

    Article  CAS  Google Scholar 

  35. Zheng R, Wang Y, Zhang L (2015) Ruthenium-catalyzed rearrangement of propargyl sulfoxides: formation of a,β-unsaturated thioesters. Tetrahedron Lett 56:3144–3146. doi:10.1016/j.tetlet.2014.11.138

  36. Huang Z, Wang C, Tokunaga E, Shibata N (2015) Stereoselective synthesis of β‐lactam-triflones under catalyst-free conditions. Org Lett 17:5610–5613. doi:10.1021/acs.orglett.5b02827

    Article  CAS  Google Scholar 

  37. Jarrahpour A, Shirvani P, Sinou V, Latour C, Brunel (2016) Synthesis and biological evaluation of some new β-lactam-triazole hybrids. J M Med Chem Res 25:149–162. doi:10.1007/s00044-015-1474-x

  38. Behzadi M, Saidi K, Islami MR, Khabazzadeh H (2016) Experimental and theoretical investigation of benzyl-N-pyrrolylketene, one- step procedure for preparing of new β-lactams by [2+2] cycloaddition reaction. J Chem Sci 128:111–117. doi:10.1007/s12039-015-1007-7

    Article  CAS  Google Scholar 

  39. Mortazavi ZFA, Islami MR, Khaleghi M (2015) Highly stereoselective synthesis of saccharin-substituted β-lactams via in situ generation of a heterosubstituted ketene and a zwitterionic intermediate as potential antibacterial agents. Org Lett 17:3034–3037. doi:10.1021/acs.orglett.5b01309

    Article  CAS  Google Scholar 

  40. Hosseinkhani B, Islami MR, Hosseinkhani S (2015) Highly stereoselective synthesis of isoindole derivatives containing an azetidinone ring. Synlett 2277–2279. doi:10.1055/s-0035-1560066

  41. Sharma P, Ahuja M, Kumar A, Sahu V (2015) Contribution of reactivity indexes in the formation of β-lactams through [2+2] cycloaddition between substituted ketenes and imines. Chem Phys Lett 628:85–90. doi:10.1016/j.cplett.2015.04.005

    Article  CAS  Google Scholar 

  42. Tang Z, Mandal S, Paul ND, Lutz M, Li P, van der Vlugt JI, de Bruin B (2015) Rhodium catalysed conversion of carbenes into ketenes and ketene imines using PNN pincer complexes. Org Chem Front 1561–1577. doi:10.1039/c5qo00287g

  43. Berber N, Arslan M, Bilen C, Sackes Z, Gencer N, Arslan O (2015) Synthesis and evaluation of new phthalazine substituted β-lactam derivatives as carbonic anhydrase inhibitors. Russ J Bioorg Chem 41:414–420. doi:10.1134/S1068162015040111

    Article  CAS  Google Scholar 

  44. Jarrahpour A, Shirvani P, Sinou V, Latour C, Brunel JM (2016) Synthesis and biological evaluation of some new β-lactam-triazole hybrids. Med Chem Res 25:149–162. doi:10.1007/s00044-015-1474-x

    Article  CAS  Google Scholar 

  45. Jarrahpour A, Nazari M (2015) Synthesis of some new polycyclic aromatic monocyclic β-lactams. Iran J Sci Tech, Trans A Sci 39:259–265

    Google Scholar 

  46. Jarrahpour A, Aye M, Sinou V, Latour C, Brunel JM (2015) Synthesis of some new monocyclic β-lactams as antimalarial agents. J Iran Chem Soc 12:2083–2092. doi:10.1007/s13738-015-0685-x

    Article  CAS  Google Scholar 

  47. Li X, Jin X, Xu J (2015) Annuloselectivity in Reactions Of Diacyl Dichlorides And Imines: Combined Experimental And Theoretical Studies. J Org Chem 80:6976–6985. doi:10.1021/acs.joc.5b00573

    Article  CAS  Google Scholar 

  48. Arumugam N, Almansour AI, Kumar RS, Rajesh R, Periyasami G, Raghunathan R (2014) Synthesis and antimicrobial evaluation of novel bis-β-lactam grafted macrocycles. Med Chem 10:730–737. doi:10.2174/1573406410666140226115258

  49. Bains D, Kumar Y, Singh P, Bhargava G (2016) [2+2] Cycloaddition reactions of butadienyl ketene with 1,4-diazabuta-1,3-dienes: synthesis of functionalized butadienyl-4-iminomethyl-azetidin-2-ones and Butenylidene-butadienyl-[2,2′-biazetidine]-4,4′-diones. J Het Chem in press. still not final as of May 1, 2016, 53:1665–1669. doi:10.1002/jhet.2465

  50. Jetti V, Chidurala P, Pagadala R, Meshram JS, Ramakrishna C (2014) Ultrasound-assisted one-pot synthesis of bis-azetidinones in the presence of zeolite. J Het Chem E183–E188 doi:10.1002/jhet.1922pdfJHC2014E183

  51. Tidwell TT (2013) Preparation of bis-β-Lactams by ketene-imine cycloaddition. Top Heterocycl Chem 30:111–146. doi:10.1007/7081_2012_89

    CAS  Google Scholar 

  52. Arumugam N, Almansour AI, Kumar RS, Rajesh R, Periyasami G, Raghunathan R (2014) Synthesis and antimicrobial evaluation of novel bis-β-lactam grafted macrocycles. Med Chem 10:730–737. doi:10.2174/1573406410666140226115258

    Article  CAS  Google Scholar 

  53. Ibrahim YA, Al-Awadi NA, Al-Azemi TF, Abraham SJE (2013) Sequential staudinger ketene–imine cycloaddition, RCM approach to polycyclic macrocyclic bisazetidinones. RSC Adv 3:6408–6416. doi:10.1039/c3ra40649k

  54. Qi H, Li X, Xu J (2011) Stereoselective control in the Staudinger reactions involving monosubstituted ketenes with electron acceptor substituents: experimental investigation and theoretical rationalization. Org Biomol Chem 9:2702–2714. doi:10.1039/c0ob00783h

    Article  CAS  Google Scholar 

  55. Zheng R, Wang Y, Zhang L (2015) Ruthenium-catalyzed rearrangement of propargyl sulfoxides: formation of a, b-unsaturated thioesters. Tetrahedron Lett 56:3144–3146. doi:10.1016/j.tetlet.2014.11.138

    Article  CAS  Google Scholar 

  56. Liang Y, Jiao L, Zhang S, Yu Z-X, Xu J (2009) New insights into the torquoselectivity of the Staudinger REACTION. J Am Chem Soc 131:1542–1549. doi:10.1021/ja808046e

    Article  CAS  Google Scholar 

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Tidwell, T.T. (2017). β-Lactams from Ketene-Imine Cycloadditions: An Update. In: Banik, B. (eds) Beta-Lactams. Springer, Cham. https://doi.org/10.1007/978-3-319-55621-5_4

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