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

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.

heterocycles - Wittig olefination - palladium catalysis - allylic substitution

References

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<A NAME="RG00802ST-5">5</A>

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 (C_quat, C-4), 137.87 (+, C-5), 152.87 (C_quat, 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 (C_quat, C-4), 121.06 (+, C-5), 126.47 (+), 127.42 (+), 128.71 (+), 129.57 (C_quat, C-2), 137.77 (C_quat), 171.25 (C_quat, 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 (C_quat, C-4), 121.30 (+, C-5), 129.72 (C_quat, C-2), 168.99 (C_quat), 171.25 (C_quat).

For reviews see:

<A NAME="RG00802ST-6A">6a</A> Tsuji J. Minami I. Acc. Chem. Res.  1987,  20:  140 

<A NAME="RG00802ST-6B">6b</A> Trost BM. Chemtracts: Org. Chem.  1988,  1:  415 

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