A New Synthetic Methodology for the Pyrrolidine Ring

Abstract

An unprecedented synthesis of pyrrolidine rings has been accomplished by the reaction of azidoacetyl derivatives with maleate and fumarate esters.

Key words

azides - enamines - pyrrolidine - phenothiazine

References and Notes

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• 20a

  Crystal Structure Determination of 2a
  Crystal Data
  Monoclinic, space group P2₁/c, a = 8.9732 (3), b = 21.1876 (7), c = 13.1662 (4) Å, β = 94.560 (4)˚, Z = 4, T = 100 K.
  Data Collection
  A crystal ca. 0.3 × 0.25 × 0.2 mm^³ was used to record 64269 intensities on a Oxford Diffraction Xcalibur E diffractometer using MoKα radiation (λ = 0.71073 Å).
  Structure Refinement
  The structure was refined anisotropically on F ^² (program SHELXL-97)^²0b to wR2 = 0.0854, R1 = 0.0346 for 351 parameters and 7192 unique reflexions. Data have been deposited in Cambridge under the number CCDC-756944.
  

• 20b Sheldrick GM. Acta Crystallogr., Sect. A.: Fundam. Crystallogr.  2008,  64:  112 

19

Analytical Data of Enamine 3a
Yield 0.28 g, 14%; R _f = 0.47; mp 163-164 ˚C. IR (ATR): 2941, 1743, 1676, 1602, 1443, 1335, 1220, 1116, 754 cm^-¹. ^¹H NMR (400 MHz, CDCl₃, TMS): δ = 3.66 (s, 3 H, CH₃), 3.77 (s, 3 H, CH₃), 4.39 (br s, 2 H, CH₂), 5.40 (s, 1 H, CH), 7.23-7.54 (m, 8 H, 8 × CH_ar), 8.47 (s, 1 H, NH). ^¹³C NMR (100 MHz, CDCl₃, TMS): δ = 46.9 (t), 50.9 (q), 52.6 (q), 90.4 (d), 120.9 (s), 126.9 (d), 127.1 (d), 127.3 (d), 128.1 (d), 133.2 (s), 137.6 (s), 164.1 (s), 168.6 (s), 170.0 (s). MS (EI): m/z (%) = 398 (12)[M⁺], 331 (12), 199 (100). Anal. Calcd for C₂₀H₁₈N₂O₅S: C, 60.29; H, 4.55; N, 7.03. Found: C, 60.57; H, 4.61; N, 7.28.

21

Analytical Data of Pyrrolidine 2a
Yield 1.57 g, 58%; R _f = 0.25; mp 192-193 ˚C. IR (ATR): 3342, 1734, 1723, 1675, 1432, 1342, 1297, 1031, 771, 755 cm^-¹. ^¹H NMR (400 MHz, CDCl₃, TMS): δ = 2.75 (s, 2 H, CH₂), 3.23 (s, 1 H, NH), 3.54 (s, 3 H, CH₃), 3.62 (s, 3 H, CH₃), 3.66 (m, 1 H, CH), 3.69 (s, 3 H, CH₃), 3.75 (m, 1 H, CH), 3.79 (s, 3 H, CH₃), 4.70 (m, 1 H, CH), 7.20-7.70 (m, 8 H, 8 × CH_ar). ^¹³C NMR (100 MHz, CDCl₃, TMS): δ = 40.2 (t), 51.4 (q), 51.9 (q), 52.1 (q), 52.2 (q), 53.0 (d), 59.0 (d), 69.3 (s), 126.3 (d), 126.9 (d), 127.0 (d), 127.3 (d), 127.4 (d), 127.8 (d), 128.1 (d), 133.5 (s), 133.4 (d), 138.0 (s), 138.2 (s), 170.3 (s), 170.4 (s), 170.6 (s), 171.1 (s), 173.1 (s). MS (EI): m/z (%) = 542 (5)[M⁺], 483 (3), 451 (3), 316 (16), 284 (12), 224 (18), 199 (100). Anal. Calcd for C₂₆H₂₆N₂O₉S: C, 57.56; H, 4.83; N, 5.16. Found: C, 57.79; H, 4.99; N, 5.47.