Synlett 2007(8): 1284-1288  
DOI: 10.1055/s-2007-977449
LETTER
© Georg Thieme Verlag Stuttgart · New York

Stereoselective 1,3-Dipolar Cycloaddition of a Maleate Derivative with Azomethine Ylides Derived from α-Amino Esters: Synthesis of 3-Pyrrolines

Adrien Soreta, Régis Guillotb, Gérard Rousseaua, Luis Blancoa, Sandrine Deloisy*a
a Laboratoire de Synthèse Organique et Méthodologie, Institut de Chimie Moléculaire et des Matériaux d’Orsay (CNRS), Bât. 420, Université Paris-Sud, 91405 Orsay Cedex, France
Fax: +33(1)69156278; e-Mail: sdeloisy@icmo.u-psud.fr;
b Service de Cristallographie, ICMMO (CNRS), Bât. 420, Université Paris-Sud, 91405 Orsay Cedex, France
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Publikationsverlauf

Received 13 December 2006
Publikationsdatum:
08. Mai 2007 (online)

Abstract

A new preparation of 3-pyrrolines is described by [3+2] cycloadditions of N-metalated azomethine ylides derived from α-amino esters with a dimethyl 7-oxabicyclo[2.2.1]hepta-2,5-diene-2,3-dicarboxylate derivative, followed by retro-Diels-Alder reactions. This two-step sequence appears superior to the direct reaction of ylides with dimethyl acetylenedicarboxylate and should be applicable to solid-phase synthesis.

7

Trimethyl (1 S *,3 S *,3a R *,4 R *,7 S *,7a S *)-7-[4-(Benzyl-oxy)phenylmethyl]-3-phenyl-2,3,3a,4,7,7a-hexahydro-1 H -4,7-epoxyisoindole-1,3a,7a-tricarboxylate (4a)
White solid; mp 106 °C. 1H NMR (400 MHz, CDCl3): δ = 2.93 (s, 3 H), 3.25 (d, J = 15.2 Hz, 1 H), 3.48 (d, J = 15.2 Hz, 1 H), 3.81 (s, 3 H), 3.86 (s, 3 H), 4.41 (s, 1 H), 4.45 (s, 1 H), 4.95 (s, 1 H), 5.07 (s, 2 H), 6.15 (d, J = 6.0 Hz, 1 H), 6.66 (d, J = 6.0 Hz, 1 H), 6.96 (d, J = 8.4 Hz, 2 H), 7.27 (d, J = 8.4 Hz, 2 H), 7.29-7.92 (m, 10 H). 13C NMR (100 MHz, CDCl3): δ = 35.0, 51.5, 52.0, 52.4, 66.6, 70.0, 70.1, 73.5, 82.6, 83.9, 94.5, 114.5, 127.2, 127.6, 128.1, 128.4, 128.5, 128.6, 129.3, 131.4, 133.4, 137.2, 137.8, 141.3, 157.6, 169.8, 170.9, 171.2. IR (KBr): 3307, 1744, 1731, 1609, 1581, 1511, 1452, 1431, 1245, 1222, 1106 cm-1. MS (ES+): m/z (%) = 320 (100) [pyrroline 10 + H]+, 342 (16) [pyrroline 10 + Na]+. Anal. Calcd for C34H33NO8: C, 69.97; H, 5.70; N, 2.40. Found: C, 69.81; H, 5.67; N, 2.27.

8

Trimethyl (1 S *,3 S *,3a R *,4 S *,7 R *,7a S *)-1-[4-(Benzoyl-oxy)phenylmethyl]-4-[4-(benzyloxy)phenylmethyl]-3-phenyl-2,3,3a,4,7,7a-hexahydro-1 H -4,7-epoxyisoindole-1,3a,7a-tricarboxylate (7f) Oil. 1H NMR (250 MHz, CDCl3): δ = 1.95 (d, J = 15.0 Hz, 1 H), 2.40 (d, J = 15.0 Hz, 1 H), 3.09 (d, J = 14.0 Hz, 1 H), 3.49 (d, J = 14.0 Hz, 1 H), 3.73 (s, 3 H), 3.84 (s, 3 H), 3.99 (s, 3 H), 4.77 (d, J = 1.8 Hz, 1 H), 4.94 (s, 2 H), 5.97 (br s, 1 H), 6.00 (dd, J = 5.5, 1.8 Hz, 1 H), 6.49 (d, J = 5.5 Hz, 1 H), 6.75 (d, J = 8.8 Hz, 2 H), 6.90 (d, J = 8.8 Hz, 2 H), 7.04 (d, J = 8.5 Hz, 2 H), 7.31-7.60 (m, 15 H), 8.15 (d, J = 7.0 Hz, 2 H). 13C NMR (62.9 MHz, CDCl3): δ = 35.1, 37.1, 52.1, 52.5, 52.8, 65.2, 69.8, 70.8, 74.4, 81.7, 83.6, 96.9, 114.1, 120.9, 127.4, 127.7, 127.8, 127.9, 128.1, 128.5, 130.1, 130.4, 131.0, 131.6, 131.8, 132.5, 133.2, 133.3, 133.4, 137.1, 137.4, 145.6, 149.6, 157.1, 165.0, 169.5, 170.6, 172.9. IR (neat): 3327, 3060, 3028, 3005, 2951, 2851, 1738, 1729, 1713, 1604, 1584, 1506, 1469, 1451, 1433, 1245, 1198, 1169, 1080, 1060 cm-1. MS (ES+): m/z (%) = 522 (100) [pyrroline 9f + Na]+.

9

Trimethyl (1 S *,3 S *,3a R *,4 S *,7 R *,7a S *)-4-[4-(Benzyl-oxy)phenylmethyl]-1-methyl-3-phenyl-2,3,3a,4,7,7a-hexahydro-1 H -4,7-epoxyisoindole-1,3a,7a-tri-carboxy-late (7b)
Oil. 1H NMR (400 MHz, CDCl3): δ = 1.62 (s, 3 H), 1.96 (d, J = 14.8 Hz, 1 H), 2.37 (d, J = 14.8 Hz, 1 H), 3.63 (s, 3 H), 3.91 (s, 3 H), 3.94 (s, 3 H), 4.21 (br s, 1 H), 4.84 (br s, 1 H), 4.94 (s, 2 H), 5.71 (s, 1 H), 5.94 (d, J = 5.2 Hz, 1 H), 6.45 (d, J = 5.2 Hz, 1 H), 6.74 (d, J = 8.8 Hz, 2 H), 6.89 (d, J = 8.8 Hz, 2 H), 7.24-7.60 (m, 10 H). 13C NMR (100 MHz, CDCl3): δ = 21.3, 34.9, 51.7, 52.4, 52.6, 65.7, 69.2, 69.7, 69.9, 80.9, 83.0, 96.7, 113.9, 127.2, 127.6, 127.7, 128.2, 128.3, 130.3, 130.4, 130.8, 132.0, 136.9, 137.3, 145.4, 156.9, 169.3, 171.7, 171.9. IR (neat): 3450, 3062, 3032, 3003, 2951, 1744, 1726, 1654, 1611, 1511, 1454, 1434, 1249, 1225, 1079 cm-1. MS (ES+): m/z (%) = 274 (33), 334 (100), 598 (15) [M + H]+. HRMS (ES+): m/z calcd for C35H36O8N: 598.2435; found: 598.2453.

10

Trimethyl (2 S *,5 S *)-2-Methyl-5-phenyl-2,5-dihydro-1 H -pyrrole-2,3,4-tricarboxylate (9b) White solid; mp 62-63 °C. 1H NMR (400 MHz, CDCl3): δ = 1.66 (s, 3 H), 2.74 (br s, 1 H), 3.60 (s, 3 H), 3.80 (s, 3 H), 3.83 (s, 3 H), 5.35 (s, 1 H), 7.20-7.35 (m, 5 H). 13C NMR (100 MHz, CDCl3): δ = 24.8, 52.2, 52.4, 52.9, 69.0, 73.0, 127.4, 128.3, 128.4, 140.1, 140.9, 141.2, 163.5, 163.7, 172.9. IR (KBr): 3359, 2992, 2950, 2832, 1733, 1715, 1656, 1449, 1433, 1334, 1244, 1204 cm-1. MS (ES+): m/z (%) = 274 (74), 334 (77) [M + H]+, 356 (100) [M + Na]+. HRMS (ES+): m/z calcd for C17H19O6NNa: 356.1105; found: 356.1119.

11

Trimethyl (2 S *,5 S *)-2-[4-(Benzoyloxy)phenylmethyl]-5-phenyl-2,5-dihydro-1 H -pyrrole-2,3,4-tricarboxylate (9f) Oil. 1H NMR (250 MHz, CDCl3): δ = 2.83 (br s, 1 H), 3.32 (s, 2 H), 3.54 (s, 3 H), 3.80 (s, 3 H), 3.90 (s, 3 H), 4.68 (br s, 1 H), 7.14 (d, J = 8.5 Hz, 2 H), 7.26-7.30 (m, 5 H), 7.42 (d, J = 8.5 Hz, 2 H), 7.46-7.52 (m, 2 H), 7.57-7.67 (m, 1 H), 8.20 (d, J = 7.0 Hz, 2 H). 13C NMR (62.9 MHz, CDCl3): δ = 42.5, 52.0, 52.5, 52.8, 69.1, 77.5, 121.1, 127.7, 128.1, 128.5, 128.6, 129.5, 130.0, 131.8, 133.1, 133.5, 140.4, 140.7, 141.1, 150.0, 162.7, 164.5, 165.0, 171.9. IR (neat): 3367, 3063, 3032, 3005, 2953, 2847, 1739, 1731, 1713, 1659, 1601, 1507, 1452, 1434, 1250, 1200, 1168, 1082, 1063, 1024 cm-1. MS (ES+): m/z (%) = 552 (100) [M + Na]+. HRMS (ES+): m/z calcd for C30H27O8NNa: 552.1629; found: 552.1628.

12

Trimethyl (3 S *,4 S *,5 R *)-5-Phenyl-4,5-dihydro-3 H -pyrrole-2,3,4-tricarboxylate (10) Oil. 1H NMR (400 MHz, CDCl3): δ = 3.15 (s, 3 H), 3.76 (s, 3 H), 3.87 (dd, J = 9.2, 6.0 Hz, 1 H), 3.93 (s, 3 H), 4.72 (dd, J = 6.0, 2.4 Hz, 1 H), 5.86 (dd, J = 9.2, 2.4 Hz, 1 H), 7.05-7.08 (m, 2 H), 7.22-7.32 (m, 3 H). 13C NMR (100 MHz, CDCl3): δ = 51.8, 52.7, 52.9, 56.5, 56.6, 78.9, 127.4, 128.2, 128.3, 135.6, 161.9, 164.0, 170.0, 170.1. IR (neat): 3059, 3033, 3007, 2956, 2919, 2847, 1726, 1648, 1452, 1437, 1369, 1312, 1258, 1217, 1101 cm-1. MS (ES+): m/z (%) = 260 (100), 342 (82) [M + Na]+. HRMS (ES+): m/z calcd for C16H17O6NNa: 342.0948; found: 342.0955.

14

Trimethyl (2 S *,5 S *)-1-(Phenylcarbamoyl)-5-phenyl-2,5-dihydro-1 H -pyrrole-2,3,4-tricarboxylate (11) White solid; mp 156-157 °C. 1H NMR (250 MHz, CDCl3): δ = 3.69 (s, 3 H), 3.86 (s, 3 H), 3.93 (s, 3 H), 5.60 (d, J = 3.0 Hz, 1 H), 5.96 (d, J = 3.0 Hz, 1 H), 6.76 (br s, 1 H), 6.99 (t, J = 8.6 Hz, 1 H), 7.14 (d, J = 7.6 Hz, 2 H), 7.19-7.22 (m, 2 H), 7.41-7.48 (m, 3 H), 7.72 (d, J = 7.2 Hz, 2 H). 13C NMR (62.9 MHz, CDCl3): δ = 52.3, 52.6, 52.9, 67.0, 69.3, 119.2, 123.2, 127.9, 128.6, 129.1, 129.2, 131.2, 136.5, 137.8, 140.6, 152.9, 161.8, 161.9, 169.5. IR (neat): 3365, 3033, 3007, 2956, 2919, 2847, 1749, 1726, 1646, 1541, 1447, 1434, 1363, 1333, 1279, 1247 cm-1. MS (ES+): m/z (%) = 461 (100) [M + Na]+. HRMS (ES+): m/z calcd for C23H22O7N2Na: 461.1319; found: 461.1328.

15

X-ray Crystal Data of 9b C17H19NO6, M = 333.33, triclinic, space group P-1, Z = 2, a = 6.0095 (8) Å, b = 8.1268 (13) Å, c = 18.151 (3) Å, α = 78.363 (3)°, β = 89.035 (2)°, γ = 77.285 (3)°, V = 846.6 (2) Å3, d = 1.308 g/cm3, 3217 independent reflections were collected with MoKα radiation on Kappa X8 APEX II system. Data analysis was carried out with Bruker program SMART and SAINT,17 the structure was solved and refined by direct methods using SHELXTL program18 to R1 = 0.0572, wR2 = 0.1505. The supplementary crystallographic data can be obtained free of charge from the Cambridge Crystallographic Data Centre via www.ccdc.cam.uk/data_request/cif. Please quote reference number CDDC 630085.

17

Bruker SMART and SAINT, Bruker AXS Inc., Madison, Wisconsin, USA, 1997.

18

Bruker SHELXTL, Version 6.3.1, Bruker AXS Inc., Madison, Wisconsin, USA, 2004.