UC Santa Barbara

ABSTRACT

I. A greener and sustainable technology for Negishi coupling reactions in water is reported. This work demonstrates the efficacy of palladium-containing nanoparticles (NPs) with low palladium loadings, typically ca. 2500 ppm (0.25 mol %), as robust catalysts that operate in water under remarkably mild conditions. The water serves not only as a green reaction medium but is also recyclable, further reinforcing the green aspects of this methodology. A board substrate scope of highly functionalized aromatic and heteroaromatic bromides, including select examples from the Merck Informer Library, readily underwent coupling, thereby underscoring the excellent functional group tolerance associated with this approach. Furthermore, residual palladium levels in the resulting products are found to be particularly low, as confirmed by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Comprehensive characterization of these catalytically active nanoparticles has been carried out using techniques such as Dynamic Light Scattering (DLS), Transmission Electron Microscopy (TEM), cryogenic-TEM (cryo-TEM), and Energy-Dispersive X-ray Spectroscopy (EDX).

II. An optimized methodology had been developed that not only streamlines the preparation of nanoparticles (NPs) featuring ppm levels of palladium loading but also ensures reliable outcomes in cross-coupling reactions due to the utilization of freshly added ligand and palladium catalyst. The scope of this research encompasses four types of coupling reactions: Suzuki–Miyaura, Sonogashira, Mizoroki–Heck, and Negishi, all executed under aqueous micellar conditions. The novelty of this approach lies in the initial generation of storable, shelf-stable nanoparticles that, without either palladium or ligand can be subsequently converted to active NPs. This conversion involves the simple addition of precise quantities of palladium salt and the corresponding ligand, tailored to catalyze the specific type of coupling reaction being targeted, all in an aqueous medium.

III. Ketones plays an important role in the field of organic chemistry. They are present in various molecules like pharmaceuticals, fragrances, and polymers. Moreover, they serve as precursors in synthesizing heterocycles and natural products. Traditional ketone synthesis methods, such as oxidation of alcohols or Friedel-Crafts acylation, have limitations like low regioselectivity and environmental concerns. The Fukuyama reaction, noted for its chemoselectivity and mild conditions, still faces challenges like the need for intermediate thioester synthesis, organozinc reagent synthesis and the use of odorous ethanethiol. Our group developed a new reagent, dipyridyldithiocarbonate (DPDTC), for converting carboxylic acids into thioesters, offering odorless alternatives. We also pioneered a Negishi reaction in water using organozinc reagents, overcoming their typical sensitivity to water. This development paves the way for a more sustainable, efficient Fukuyama reaction approach.