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Synlett 2008(3): 355-358  
DOI: 10.1055/s-2008-1032046
LETTER
© Georg Thieme Verlag Stuttgart · New York

Resin-Bound (Succinimid-1-yloxycarbonylmethyl)triphenylphosphonium Ylide - A Synthon for Rapid Access to Diverse Heterocycles under Microwave Heating

Bernd Henkel*
Morphochem AG, Gmunder Straße 37-37a, 81379 München, Germany
Fax: +49(89)78005555; e-Mail: bernd.henkel@morphochem.de;
Further Information

Publication History

Received 22 October 2007
Publication Date:
16 January 2008 (online)

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Abstract

The synthesis of a novel and versatile resin-bound (succinimid-1-yloxycarbonylmethyl)triphenylphosphonium ylide is described. The use of this resin to the synthesis of several diverse heterocycles, whilst allowing for ease of workup, is reported.

Key words

Wittig reactions - solid-phase synthesis - heterocycles - olefination - microwave heating

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1

New address: Sanofi-Aventis Deutschland GmbH, Industriepark Höchst, D729, 65926 Frankfurt am Main, Germany; fax: +49 (69)30549497; email: Bernd.Henkel@sanofi-aventis.com.

7

Procedure for the Synthesis of Resin-Bound 4Triphenylphosphino resin (10 g, 15.5 mmol; Polymer Laboratories) was swollen in 70 mL of abs. toluene and bromoacetic acid N-hydroxysuccinimidyl ester (7.317 g, 31 mmol) was added. This mixture was agitated for 16 h. The resin was filtered off and washed three times with toluene, CH2Cl2, and Et2O each. Finally, the resin was dried under high vacuum yielding 13.52 g resin-bound (succinimid-1-yloxycarbonylmethyl)triphenylphosphonium bromide (95.5%), loading approx. 1.2 mmol/g after weight gain.The ylide was formed by treatement of the resin with a mixture of CH2Cl2-Et3N (80 mL, 1:1) for 16 h. The resin was filtered off and washed twice with CH2Cl2-Et3N (1:1) and three times with CH2Cl2 and Et2O. The resin was dried under high vacuum yielding 12.2 g (100%) of 4, loading approx. 1.1 mmol/g after weight loss.

8

Synthesis of 4-Methoxy-1 H -quinolin-2-one; General ProcedureResin-bound 4 (182 mg, 0.2 mmol) was loaded into a Smith Process glass reaction vial and swollen in abs. dioxane (1 mL). Anthranilic acid methyl ester (0.039 mL, 0.3 mmol) and a little stirring bar were added. The vial was sealed and heated for 15 min to 180 °C in the microwave system Smith Creator. After cooling down the vial was opened and the resin filtered off. The resin was washed twice with dioxane and discarded. The solvent was evaporated and the remainder subjected to preparative HPLC [C18-RP-Phase; MeOH and AcOH (0.5%), H2O and AcOH (0.5%)]; yield 24 mg (69%). 1H NMR (400 MHz, DMSO-d 6): δ = 3.92 (s, 3 H), 5.88 (s, 1 H), 7.13-7.17 (t, 1 H, J = 7.4 Hz), 7.28-7.30 (d, 1 H, J = 8.1 Hz), 7.48-7.52 (t, 1 H, J = 7.5 Hz), 7.75-7.77 (d, 1 H, J = 8.0 Hz), 11.36 (s, 1 H). 13C NMR (100 MHz, DMSO-d 6): δ = 56.0, 96.6, 114.4, 115.2, 121.3, 122.1, 130.9, 138.2, 163.1, 163.2.