Synlett 2004(15): 2815-2817  
DOI: 10.1055/s-2004-835640
LETTER
© Georg Thieme Verlag Stuttgart · New York

Pyrroloisoxazoles as a Building Block for 3-Enoyltetramic Acids

Raymond C. F. Jones*, Terence A. Pillainayagam
Department of Chemistry, Loughborough University, Loughborough, Leics. LE11 3TU, UK
Fax: +44(1908)223926; e-Mail: r.c.f.jones@lboro.ac.uk;
Further Information

Publication History

Received 17 August 2004
Publication Date:
08 November 2004 (online)

Abstract

3-Methylpyrrolo[3,4-c]isoxazoles prepared by nitrile ­oxide cycloaddition, are deprotonated and condensed with aromatic aldehydes; N-O bond cleavage with Mo(CO)6 affords 3-enoyltetramic acids whilst with H2-catalyst further reduction to 3-acyltetramic acids is observed.

7

Similar treatment of 4b afforded the N-methyl derivative.

8

Under these conditions aliphatic ketones MeCO(CH2)2-6Me as electrophiles also gave low yields (12-28%) but of the hydroxy adducts.

9

6-Methyl-3-[2-(4-nitrophenyl)ethenyl]-5,6-dihydro-4 H -pyrrolo[3,4- c ]isoxazol-4-one ( 10b): To 3,6-dimethyl-5,6-dihydro-4H-pyrrolo[3,4-c]isoxazol-4-one (4a, 0.050 g, 0.329 mmol) under nitrogen at 20 °C was added dry MeOH (5 mL) followed by 4-nitrobenzaldehyde (0.109 g, 0.723 mmol, 2.2 mol equiv), and sodium methoxide (0.021 g, 0.395 mmol, 1.2 mol equiv) in dry MeOH (4 mL). The reaction mixture was stirred for 1 min at 20 °C then heated under reflux for 2 h and immediately cooled in an ice bath. The resulting yellow crystals were filtered off and dried in vacuo (0.062 g, 66%); (Anal. Calcd for C14H11N3O4: C, 58.95; H, 3.89; N, 14.73%; [M+] 285.0750. Found: C, 59.09; H, 3.80; N, 14.60%; [M+] 285.0747.). 1H NMR (250 MHz, CDCl3): δ = 1.59 (3 H, d, J = 7 Hz, CH 3CH), 4.88 (1 H, q, J = 7 Hz, CHCH3), 6.03 (1 H, br s, NH), 7.26 (1 H, d, J = 16 Hz, CH=CH), 7.76 (2 H, d, J = 9 Hz, ArH), 8.06 (1 H, d, J = 16 Hz, CH=CH), 8.28 (2 H, d, J = 9 Hz, ArH). 13C NMR (400 MHz, CDCl3): δ = 20.4 (CH3), 48.9 (CHCH3), 112.1 (C), 115.2 (CH=CH), 124.6 and 129.9 (ArCH), 134.8 (ArC), 141.5 (CH=CH), 148.8, 161.8 and 162.8 (C), 173.4 (C=O). MS: m/z = 285 [M+], 270, 176, 164, 147, 102, 90, 55, 43.

10

Crystal data for 10d and 10g are deposited at the Cambridge Crystallographic Centre Database.

11

Condensation products 10 in general displayed no optical rotation. It is assumed loss of optical integrity occurred under the basic conditions used, cf. ref. 3.

12

The acyltetramic acids are drawn as the exo-enol tautomer that forms the major tautomer in CDCl3 solution, and the tautomer observed in the solid state, see ref. 1.