Nickel-catalysed asymmetric Michael Additions of 2-acetylazaarenes to nitroalkenes.
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Azaarenes are of widespread chemical significance, being present in numerous chiral, biologically active natural products, and serving as building blocks for the discovery of new medicines, agrochemicals, and functional molecules. Consequently, the development of new methods to prepare chiral azaarene-containing compounds is an important goal. The Lam group and others have previously demonstrated the synthetic utility of azaarenes as activating groups in a variety of catalytic asymmetric processes, which are summarised in Chapter 1. Chapter 2 presents a recent achievement in this area: the development of a mild and highly enantioselective conjugate addition of acetylazaarenes to nitroalkenes, under nickel catalysis, to afford densely functionalised products. The reaction scope includes a broad range of acetylazaarenes as well as (hetero)aromatic and aliphatic nitroalkenes. When α-nitroacrylate esters are employed as conjugate acceptors, products bearing a quaternary stereogenic centre are formed in high yield and with excellent enantioselectivity. The methodology is easily scalable, allowing multigram preparations to be carried out with catalyst loadings of 1 mol% without loss of yield or enantioselectivity. Further transformations of the products, including diastereoselective transfer hydrogenation, are briefly described. Finally, Chapter 3 gives an overview of unsuccessful efforts to develop routes to α-sulfonyl organoboron compounds, for subsequent use in ate complex homologation chemistry, via catalytic asymmetric conjugate addition processes.