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

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

References and Notes

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1

New address: Sanofi-Aventis Deutschland GmbH, Industriepark Höchst, D729, 65926 Frankfurt am Main, Germany; fax: [phone]; email: [e-mail].

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.