RESUMO
Under open-flask conditions, ammonia borane hydroborates olefins in refluxing tetrahydrofuran. Unlike conventional hydroboration, the Lewis base (ammonia) is not dissociated from the boron center. Terminal alkenes selectively provide ammonia-trialkylborane complexes. On the other hand, internal alkenes afford aminodialkylboranes via a metal-free hydroboration-dehydrogenation sequence. Alkaline hydrogen peroxide oxidation of the products provides the corresponding alcohols in high yields.
RESUMO
BACKGROUND: The Michael acceptor scaffolding is a source of rich biological activity for α-methylene-γ-butyrolactones and their derivatives. A wide variety of these structures are present in many natural products that are well-known for their useful medicinal properties. RESULTS: The first example of a borylated α-methylene-γ-butyrolactone is presented herein, along with its antipancreatic cancer activities against Panc-1, MIA PaCa-2 and BXPC-3. The synthetic route chosen allows for a wide range of lactones to be synthesized through different cross-coupling reactions starting from arylic bromide precursors. The precursors were synthesized by way of a highly efficient, chemoselective and indium-promoted Barbier reaction. Specifically, the indium metal reacted with only one of two present bromide functionalities: an allylic bromide in the presence of an arylic one. The bromide precursors were also tested for activity in the same bioassay as the borylated lactone and parthenolide. CONCLUSION: Notably, these brominated compounds demonstrate a significantly higher level of activity than parthenolide.
