Solid-phase synthesis of 4-arylazetidin-2-ones via Suzuki and Heck cross-coupling reactions

Application of the Suzuki and the Heck cross-coupling reactions for efficient synthesis of diverse biaryl-and styryl-substituted beta-lactams on solid support using an optimized catalyst system is reported. The coupling of phenylboronic acid with the resin-bound 3-phenoxy-4-iodophenyl beta-lactam la 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 degrees C for 12 h. Efficient cross-coupling of the iodophenyl beta-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 Ic 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 degrees C. The use of this catalyst for the vinylation of aryl iodide la via the Heck reaction was also examined.