Solid-Phase Synthesis of 4-Arylazetidin-2-ones via Suzuki and Heck Cross-Coupling Reactions

• Published in: Journal of organic chemistry 1997-10, Vol.62 (22), p.7820-7826
• Main Authors: Ruhland, Beatrice, Bombrun, Agnes, Gallop, Mark A
• Format: Article
• Language: English
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo9711854

Application of the Suzuki and the Heck cross-coupling reactions for efficient synthesis of diverse biaryl- and styryl-substituted β-lactams on solid support using an optimized catalyst system is reported. The coupling of phenylboronic acid with the resin-bound 3-phenoxy-4-iodophenyl β-lactam 1a proceeded in 89% isolated yield by employing 20 mol % of the bidentate phosphine−palladium complex, [1,1‘-bis(diphenylphosphino)ferrocene]palladium(II) dichloride {PdCl2(dppf)} as catalyst in the presence of triethylamine (TEA, 10 equiv) in DMF at 65 °C for 12 h. Efficient cross-coupling of the iodophenyl β-lactam to heterocyclic boronates and aryl boronates substituted with various electron-donating and -withdrawing groups is also demonstrated. The reverse coupling reactions of immobilized arylboronic acid 1c with a variety of substituted aryl iodides were found to proceed in excellent yields using the same catalyst system in a 3/7 mixture (v/v) of H2O:DMF at 40 °C. The use of this catalyst for the vinylation of aryl iodide 1a via the Heck reaction was also examined.