Chemistry: A European Journal 2007-01-01

Biaryls made easy: PEPPSI and the Kumada-Tamao-Corriu reaction.

Michael G Organ, Mirvat Abdel-Hadi, Stephanie Avola, Niloufar Hadei, Joanna Nasielski, Christopher J O'brien, Cory Valente

Index: Chemistry 13 , 150, (2007)

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Abstract

An easily employed, highly versatile Kumada-Tamao-Corriu (KTC) protocol utilizing the PEPPSI (Pyridine, Enhanced, Precatalyst, Preparation, Stabilization and Initiation) precatalysts 1 and 2 is detailed. The ease-of-use of these catalysts and the synthesis of a wide range of hindered biaryls, large coupling partners and drug-like heterocycles, in high yield, makes the PEPPSI-KTC protocol very attractive. The high reactivity of the PEPPSI system allowed a tetra-ortho-substituted heterocycle, 11 to be synthesized at room temperature for the first time using any protocol. The PEPPSI protocols also tolerated the Boc protecting group and phenols required no protection in modified conditions. A relatively large scale (10 g) reaction was also performed with no loss in performance. Furthermore, PEPPSI-IPr, 1, was compared to previously reported highly active phosphine ligands 42, 43, and 44 and was shown to result in significantly better yields under identical conditions. Finally, we demonstrated that the PEPPSI catalyst system is very adept at performing sequential KTC coupling reactions, analogous to multicomponent reactions, which allow complex polyaryl and polyheteroaryl architectures to be produced in one single operation.