Pd(PhCN)2Cl2/P(t-Bu)3: A Versatile Catalyst for Sonogashira Reactions of Aryl Bromides at Room Temperature

Reaction Scheme

Abstract

The Suzuki-Miyaura cross-coupling of unprotected, nitrogen-rich heterocycles using precatalysts P1 or P2 is reported. The procedure allows for the reaction of variously substituted indazole, benzimidazole, pyrazole, indole, oxindole, and azaindole halides under mild conditions in good to excellent yields. Additionally, the mechanism behind the inhibitory effect of unprotected azoles on Pd-catalyzed cross-coupling reactions is described based on evidence gained through experimental, crystallographic, and theoretical investigations.

Substrates

Procedure

An oven-dried test tube was charged with the aryl halide (1.00 mmol, 1.00 eq.), boronic acid (2.00 mmol, 2.00 eq.), SPhos-Pd-G3 (0.02-0.035 mmol, 0.02-0.035 eq.), and K3PO4 (2.00 mmol, 2.00 eq.). The reaction vessel was evacuated and backfilled with argon (this process was repeated a total of three times). Dioxane (4 mL) and H2O (0.8 mL) were then added via syringe, and the test tube was placed in a preheated oil bath and stirred at 100 �C for 15-20 h. The reaction mixture was then cooled to room temperature and was subsequently filtered through a short plug of Celite, the filter cake washed with EtOAc (25 mL), and the solvent removed in vacuo. The crude product was purified by column chromatography.

Products

Materials

     
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