Synlett 2015; 26(01): 55-58
DOI: 10.1055/s-0034-1379637
cluster
© Georg Thieme Verlag Stuttgart · New York

Stereoselective Suzuki Coupling Reaction of an α-Bromo-α-fluoro-β-lactam

Atsushi Tarui
Faculty of Pharmaceutical Sciences, Setsunan University, 45-1, Nagaotoge-cho, Hirakata, Osaka 573-0101, Japan   Email: aando@pharm.setsunan.ac.jp   Email: tarui-a@pharm.setsunan.ac.jp
,
Erina Miyata
Faculty of Pharmaceutical Sciences, Setsunan University, 45-1, Nagaotoge-cho, Hirakata, Osaka 573-0101, Japan   Email: aando@pharm.setsunan.ac.jp   Email: tarui-a@pharm.setsunan.ac.jp
,
Ayumi Tanaka
Faculty of Pharmaceutical Sciences, Setsunan University, 45-1, Nagaotoge-cho, Hirakata, Osaka 573-0101, Japan   Email: aando@pharm.setsunan.ac.jp   Email: tarui-a@pharm.setsunan.ac.jp
,
Kazuyuki Sato
Faculty of Pharmaceutical Sciences, Setsunan University, 45-1, Nagaotoge-cho, Hirakata, Osaka 573-0101, Japan   Email: aando@pharm.setsunan.ac.jp   Email: tarui-a@pharm.setsunan.ac.jp
,
Masaaki Omote
Faculty of Pharmaceutical Sciences, Setsunan University, 45-1, Nagaotoge-cho, Hirakata, Osaka 573-0101, Japan   Email: aando@pharm.setsunan.ac.jp   Email: tarui-a@pharm.setsunan.ac.jp
,
Akira Ando*
Faculty of Pharmaceutical Sciences, Setsunan University, 45-1, Nagaotoge-cho, Hirakata, Osaka 573-0101, Japan   Email: aando@pharm.setsunan.ac.jp   Email: tarui-a@pharm.setsunan.ac.jp
› Author Affiliations
Further Information

Publication History

Received: 22 September 2014

Accepted after revision: 09 November 2014

Publication Date:
28 November 2014 (online)

Abstract

A new strategy has been developed for the synthesis of α-aryl-α-fluoro-β-lactams via the Suzuki cross-coupling of α-bromo-α-fluoro-β-lactam with a range of different aryl-(9-BBN) reagents. This method provides facile access to multisubstituted α-fluoro-β-lactams in a diastereoselective manner. The synthetic utility of α-bromo-α-fluoro-β-lactam has been demonstrated by the arylation of α-bromo-α-fluoro-β-lactam.

Supporting Information

 
  • References and Notes

    • 1a Jeschke P. ChemBioChem 2004; 5: 570
    • 1b Müller K, Faeh C, Diederich F. Science 2007; 317: 1881
    • 1c Zhang W, Cai C. Chem. Commun. 2008; 5686
    • 1d O’Hagan D. J. Fluorine Chem. 2010; 131: 1071
  • 2 Purser S, Moore PR, Swallow S, Gouverneur V. Chem. Soc. Rev. 2008; 37: 320
    • 3a Rosenblum SB, Huynh T, Afonso A, Davis HR, Yumibe N, Clader JW, Burnett DA. J. Med. Chem. 1998; 41: 973
    • 3b Kværnø L, Werder M, Hauser H, Carreira EM. J. Med. Chem. 2005; 48: 6035
  • 4 Hagmann WK. J. Med. Chem. 2008; 51: 4359
    • 5a Uoto K, Ohsuki S, Takenoshita H, Ishiyama T, Iimura S, Hirota Y, Mitsui I, Terasawa H, Soga T. Chem. Pharm. Bull. 1997; 45: 1793
    • 5b Li X.-G, Lähitie M, Kanerva LT. Tetrahedron: Asymmetry 2008; 19: 1857
    • 5c Liu N, Cao S, Shen L, Wu J, Yu J, Zhang J, Li H, Qian X. Tetrahedron Lett. 2009; 50: 1982
    • 6a Sato K, Tarui A, Matsuda S, Omote M, Ando A, Kumadaki I. Tetrahedron Lett. 2005; 46: 7679
    • 6b Tarui A, Kawashima N, Sato K, Omote M, Miwa Y, Minami H, Ando A. Tetrahedron Lett. 2010; 51: 2000
    • 7a Tarui A, Nishimura H, Ikebata T, Tahira A, Sato K, Omote M, Minami H, Miwa Y, Ando A. Org. Lett. 2014; 16: 2080
    • 7b Tarui A, Ikebata T, Sato K, Omote M, Ando A. Org. Biomol. Chem. 2014; 12: 6484
    • 8a Tarui A, Kondo S, Sato K, Omote M, Minami H, Miwa Y, Ando A. Tetrahedron 2013; 69: 1559
    • 8b Tarui A, Kawashima N, Kawakita T, Sato K, Omote M, Ando A. J. Org. Chem. 2013; 78: 7903
  • 9 Liang Y, Fu GC. J. Am. Chem. Soc. 2014; 136: 5520
  • 10 Jiang X, Sakthivel S, Kulbitski K, Nisnevich G, Gandelman M. J. Am. Chem. Soc. 2014; 136: 9548
    • 11a Lundin PM, Fu GC. J. Am. Chem. Soc. 2010; 132: 11027
    • 11b Wilsily A, Tramutola F, Owston NA, Fu GC. J. Am. Chem. Soc. 2012; 134: 5794
    • 11c Zultanski SL, Fu GC. J. Am. Chem. Soc. 2013; 135: 624
    • 12a Welch JT, Araki K, Kawecki R, Wichtowski JA. J. Org. Chem. 1993; 58: 2454
    • 12b Kawecki R, Welch JT. Tetrahedron Lett. 1993; 34: 3087
  • 13 Typical Experimental Procedure for the Ni-Catalyzed Suzuki Coupling Reaction of α-Bromo-α-fluoro-β-lactam: 4,4′-Di-tert-butylbipyridine (29.5 mg, 0.11 mmol) and NiBr2·diglyme (35 mg, 0.10 mmol) were added to a flask equipped with a magnetic stirrer bar. To the flask was added anhyd benzene (7.5 mL) and the resulting mixture was stirred vigorously for 2 h (a light-green slurry formed). The solution of the activated Ph-(9-BBN) solution (1.25 mmol) was added to the slurry, and the whole mixture was stirred for 20 min at same temperature. Then, 1 (0.5 mmol) was added to the slurry and the resulting mixture was stirred for 1 h under reflux. The reaction was quenched by brine and the mixture was extracted with EtOAc, and then the extract was dried over MgSO4. The solvent was removed in vacuo and the residue was purified by silica gel column chromatography (hexane–EtOAc) to give the desired product 3.(3S,4R/3R,4S)-1-Benzyl-3-fluoro-3,4-diphenylazetidin-2-one (3a): colorless solid (145 mg, 87%); mp 78.0–79.0 °C (uncorrected). 1H NMR (400 MHz, CDCl3): δ = 3.98 (dd, J = 14.8, 2.4 Hz, 1 H), 4.66 (d, J = 3.5 Hz, 1 H), 5.03 (d, J = 14.8 Hz, 1 H), 7.16–7.18 (m, 2 H), 7.29–7.33 (m, 5 H), 7.38 (m, 5 H), 7.42–7.44 (m, 3 H). 13C NMR (100 MHz, CDCl3): δ = 44.4 (d, J = 2 Hz), 68.6 (d, J = 25 Hz), 102.2 (d, J = 225 Hz), 125.2 (d, J = 7 Hz), 128.0, 128.2 (d, J = 2 Hz), 128.5, 128.6, 128.7, 128.8, 129.0, 129.2 (d, J = 2 Hz), 132.1, 134.2 (d, J = 24 Hz), 134.4, 164.8 (d, J = 25 Hz). 19F NMR (84 MHz, CDCl3): δ = –102.5 (s, 1 F). MS: m/z = 331 [M+]. HRMS (EI): m/z [M+] calcd for C22H18FNO: 331.1372; found: 331.1378.
  • 14 See supporting information for the determination of the relative configuration and the diastereoselective formation of coupling products.
  • 15 The ee value was determined to be 92% by HPLC analysis [Daicel CHIRALPAK AD-H, hexane–EtOH = 98:2, flow rate = 2.0 mL/min, λ = 254 nm, t R (major) = 10.0 min and t R (minor) = 8.9 min]. [α]D 25 +63.4 (c = 1.05, CHCl3). See the Supporting Information for enantiopurity of 3a.