SOLID-PHASE SYNTHESIS OF BIARYLS VIA THE STILLE REACTION

The solid-phase synthesis of biphenyls by heterogenous cross-coupling of trialkylphenylstannanes with aryl electrophiles is described. Tributylphenyltin attached by an amide bond to the Rink amide resin undergoes palladium-catalyzed coupling with aryl triflates and aryl iodides to produce after acid cleavage 4-biphenylacetamide in 3-15% yield. 4-Iodophenylacetic acid attached to the Rink amide resin by an amide bond also undergoes heterogeneous palladium-catalyzed coupling with trialkylphenyltins to give after acid cleavage of the support 4-biphenylacetamide in 21-33% yield. 4-Iodobenzylbromide was then attached to the photocleavable (+/-)-2-methoxy-5-[2-[(2-nitrophenyl)dithio]-1-oxopropyl]phenylacetamide (NpSSMpact) resin through the formation of a thioether bond. Both substituted and unsubstituted trimethylphenyltins were shown to undergo palladium-catalyzed Stille coupling with the resin bound aryl iodide to give after photolytic cleavage biphenyls containing no residual ual amide, carboxylic acid, or alcohol appendages.