Synlett 2015; 26(03): 363-366
DOI: 10.1055/s-0034-1379505
letter
© Georg Thieme Verlag Stuttgart · New York

Diastereo- and Facially Selective Imino-Diels–Alder Cycloaddition of 2-Azeditinone-Tethered 1-Azadiene: Synthesis of Functionalized (2-Oxo-4-styrylazetidin-3-yl)–Pyridine Hybrids

Yogesh Kumar
a   Department of Applied Sciences, Punjab Technical University, Kapurthala, Punjab 144603, India   Email: gaurav@ptu.ac.in
,
Prabhpreet Singh
b   Department of Chemistry, Guru Nanak Dev University, Amritsar, Punjab 143005, India
,
Gaurav Bhargava*
a   Department of Applied Sciences, Punjab Technical University, Kapurthala, Punjab 144603, India   Email: gaurav@ptu.ac.in
› Author Affiliations
Further Information

Publication History

Received: 07 October 2014

Accepted after revision: 30 October 2014

Publication Date:
08 January 2015 (online)


Abstract

Highly diastereo- and π-facially selective imino Diels–Alder cycloadditions of 3-allylideneamino-2-azetidinones having stereocentres at its α- and β-positions, with symmetrical dienophiles leading to the formation of biologically potent (2-oxo-4-styrylazetidin-3-yl)–pyridine hybrids have been reported.

 
  • References and Notes

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      We have previously reported the π-facially selective Diels–Alder cycloaddition reactions of 3-butadienyl-2-azetidinones with different dienophiles. For further reference to facially selective DA reaction, see:
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  • 12 For the synthesis of 3-amino-2-azetidinone, see: Vander Steen FH, Koten GV. Tetrahedron 1991; 47: 7503 ; and references cited therein
  • 13 General Procedure for the Preparation of 3-Allylideneamino-2-azetidinones 3To a solution of 3-amino-2-azetidinones 1 (1 equiv) in toluene or xylene was added cinnamaldehyde (2) (1.1 equiv) in the presence of anhydrous Na2SO4 (5 equiv). The progress of the reaction was monitored by TLC. After completion of the reaction, the reaction mixture was filtered, washed with toluene or xylene, and dried to get 3-allylideneamino-2-azetidinones 3.
  • 14 Typical Procedure for the Preparation of 1-[2-Oxo-4-styrylazetidin-3-yl]-1,4,4a,7a-tetrahydropyridines 5 and 7To a stirred solution of 3 was added dienophile 4a, 4b, or 6 in the requisite solvent. The mixture was heated to reflux for 4–6 h, and the progress of the reaction was monitored by TLC. After the completion of reaction, the crude product, so obtained, was purified by flash chromatography on silica gel using a mixture of EtOAc and hexane (2:8) as the eluent system to furnish compounds 5 and 7 as pure products.1-[1-(4-Chlorophenyl)-2-oxo-4-styrylazetidin-3-yl]-4,6-diphenyl-1,4,4a,7a-tetrahydropyrrolo[3,4-b]pyridine-5,7-dione (5a)Pale yellow solid; yield 61%; mp 120–123 °C. 1H NMR (300 MHz, CDCl3): δ = 7.35 (m, 19 ArH), 6.70 (m, 2 H, H4 + H6), 6.18 (m, 2 H, H3 + H5), 5.80 (d, J = 7.2 Hz, 1 H, H1), 4.78 (d, J = 5.4, 7.2 Hz, 1 H, H2), 3.68 (m, 2 H, H8 + H9), 2.34 (d, J = 2.7 Hz, 1 H, H7). 13C NMR (75 MHz, CDCl3): δ = 27.3, 30.7, 47.1, 59.6, 60.1, 117.3, 118.8, 122.3, 123.7, 125.1, 126.5, 126.9, 127,4, 127.8, 128.5, 128.9, 129.0, 129.3, 132.5, 133.2, 133.7, 135.1, 136.7, 137.9, 147.4, 168.9, 174.5, 175.9. MS: m/z = 585 [M+]. Anal. Calcd for C36H28ClN3O3: C, 73.78; H, 4.82; N, 7.17. Found: C, 73.84; H, 4.91; N, 7.11.1-(2-Oxo-1-phenyl-4-styrylazetidin-3-yl)-4-phenyl-1,2,3,4-tetrahydropyridine-2,3-dicarboxylic Acid Dimethyl Ester (7b)Pale yellow solid; yield 48%; mp 116–118 °C. 1H NMR (300 MHz, CDCl3): δ = 7.25 (m, 15 H, ArH), 6.81 (m, 1 H, H6), 6.55 (m, 2 H, H4 + H5), 6.27 (dd, J = 6.0, 15.9 Hz, 1 H, H3), 5.14 (d, J = 6.6 Hz, 1 H, H1), 4.33 (d, J = 6.0, 9.0 Hz, 1 H, H2), 3.79–3.94 (m, 2 H, H8 + H9), 3.53 (s, 3 H, OCH3), 3.48 (s, 3 H, OCH3), 2.85 (dd, J = 1.2, 3.6 Hz, 1 H, H7). 13C NMR (75 MHz, CDCl3): δ = 30.7, 43.7, 50.4, 51.1, 57.8, 59.6, 60.1, 63.2, 117.6, 118.2, 122.6, 123.2, 124.3, 125.1, 126.5, 126.9, 127.1, 128.1, 128.6, 129.4, 129.7, 130.1, 132.1, 133.5, 134.2, 135.7, 136.3, 137.2, 147.6, 169.2, 175.6, 176.2. MS: m/z = 522 [M+]. Anal. Calcd for C32H30N2O5: C, 73.55; H, 5.79; N, 5.36. Found: C, 73.62; H, 5.84; N, 5.31.