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Synlett 2002(4): 0619-0621
DOI: 10.1055/s-2002-22707
LETTER
© Georg Thieme Verlag Stuttgart · New York

Extending the Scope of a Known Furan Synthesis - A Novel Route to 1,2,4-Trisubstituted Pyrroles

Marko Friedricha, Andreas Wächtlerb, Armin de Meijere*a
a Institut für Organische Chemie, Universität Göttingen, Tammannstrasse 2, 37077 Göttingen, Germany
b Merck KgaA, Central Process Development, 64271 Darmstadt, Germany
Fax: +49(551)399475; e-Mail: Armin.deMeijere@chemie.uni-goettingen.de;
Further Information

Publication History

Received 16 January 2002
Publication Date:
05 February 2007 (online)

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Abstract

2-(Acylmethylene)propanediol diacetates, which cyclize readily under acidic conditions to give furans (76-84%) react with primary amines under palladium catalysis to give 1,2,4-trisubstituted pyrroles in moderate to good yields (39-53%). When glycine methyl ester is used as the amine, substituted methyl pyrrol-1-ylacetates (31-82%) are obtained.

Key words

heterocycles - Wittig olefination - palladium catalysis - allylic substitution

    References

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5

All new compounds were fully characterized by spectroscopic methods (IR, 1H and 13C NMR, MS); bulk purity was established in most cases by satisfactory elemental analysis data. Spectroscopic data of representative examples are: 4-Hydroxymethyl-2-methylfuran (6a): IR (KBr): 3357 (OH), 2923, 2878, 1740, 1557, 1449, 1385, 1272, 1234, 1123, 1021, 977, 918, 809, 737 cm-1. 1H NMR (250 MHz, CDCl3): δ = 1.90 (s, 1 H, OH), 2.28 (s, 3 H, 2-CH3), 4.51 (s, 2 H, CH 2OH), 6.03 (br s, 1 H, 3-H), 7.26 (br s, 1 H, 5-H). 13C NMR (62.9 MHz, CDCl3, DEPT): δ = 13.36 (+, 2-CH3), 56.36 (-, CH2OH), 105.70 (+, C-3), 125.84 (Cquat, C-4), 137.87 (+, C-5), 152.87 (Cquat, C-2). MS (EI, 70 eV): m/z (%) = 112(9) [M+], 88(10), 61(16), 45(15), 43(100). Calcd for C6H8O2: 112.0524; (correct HRMS). N -Benzyl-4-acetoxymethyl-2-methylpyrrole (7a): IR (film): 3088, 3063, 3030, 2934, 1734 (CO), 1662, 1605, 1521, 1496, 1454, 1416, 1366, 1238, 1149, 1021, 943, 796, 734, 696 cm-1. 1H NMR (250 MHz, CDCl3): δ = 2.06 (s, 3 H), 2.12 (s, 3 H), 4.93 (s, 2 H), 4.98 (s, 2 H), 5.99 (s, 1 H, 3-H), 6.67 (br s, 1 H, 5-H), 7.01-7.04 (m, 2 H), 7.26-7.32 (m, 3 H). 13C NMR (62.9 MHz, CDCl3, DEPT): δ = 11.94 (+, 2-CH3), 21.27 (+, COCH3), 50.36 (-), 60.42 (-), 108.04 (+, C-3), 117.13 (Cquat, C-4), 121.06 (+, C-5), 126.47 (+), 127.42 (+), 128.71 (+), 129.57 (Cquat, C-2), 137.77 (Cquat), 171.25 (Cquat, COMe). MS (EI, 70 eV): m/z (%) = 243(70) [M+], 201(25), 184(43) [M+ - OCOMe], 172(12), 91(100) [C7H7 +]. Methyl (4-Acetoxymethyl-2-methylpyrrol-1-yl)acetate (10a): IR(film): 3443, 2952, 1732 (CO), 1666, 1525, 1436, 1419, 1368, 1347, 1232, 1158, 1141, 1023, 943, 798, 731, 694, 658 cm-1. 1H NMR (250 MHz, CDCl3): δ = 2.05 (s, 3 H, COCH3), 2.15 (s, 3 H, 2-CH3), 3.77 (s, 3 H, CO2CH3), 4.52 (s, 2 H, N-CH2), 4.94 (s, 2 H, CH2OAc), 5.97 (br s, 1 H, 3-H), 6.63 (br s, 1 H, 5-H). 13C NMR (62.9 MHz, CDCl3, DEPT): δ = 11.63 (+, 2-CH3), 21.20 (+, COCH3), 48.03 (-, N-CH2), 52.51 (+, CO2 CH3), 60.21 (-, CH2OAc), 108.32 (+, C-3), 117.80 (Cquat, C-4), 121.30 (+, C-5), 129.72 (Cquat, C-2), 168.99 (Cquat), 171.25 (Cquat).