The oxidation of selected anions (N 3 − , SCN − , I − and Br − ) by ceric ammonium nitrate (CAN) in the presence of substituted cyclopropyl alcohols provides a novel approach to β-functionalized ketones.The protocol has a number of advantages including short reaction times, ease of reagent handling and mild, neutral reaction conditions. Overall, this method provides an alternative pathway to important starting materials and intermediates in organic synthesis.Ketones substituted in the β position are important starting materials in organic chemistry. Among this group, β-haloketones are extremely useful intermediates in organic synthesis and act as precursors to enones, annulated compounds, heterocyclic derivatives, and dicarbonyl products. 1 In spite of their importance as precursors to a large range of important intermediates, 2 only a few of methods have been developed to synthesize β-substituted ketones. 3 The synthesis of β-substituted ketones by 1,4-addition of HX (X = Cl, Br, I) or trimethylsilyl iodide to the corresponding enone are sometimes experimentally inconvenient since the use of reactive or moisture sensitive reagents are required. 3b, 3d More recent approaches to β-substituted ketones, while useful, provide access to a limited range of compounds. 4,5 As a consequence, the development of new synthetic methods offering a general approach for the introduction of diverse functionality to the beta position of a carbonyl group still constitutes a challenge in organic chemistry.Cerium(IV) ammonium nitrate (CAN) has found wide applications in carbon-heteroatom bond forming reactions in organic synthesis. 6 The reported carbon-heteroatom bond formations mediated with CAN include C-Br, C-I, C-S, C-N, and C-Se bonds. These reactions usually involve the generation of heteroatom-centered radicals from the oxidation of anions and addition of the heteroatom radicals to alkenes or alkynes.Based on this precedent, we reasoned that Ce(IV) oxidation of an anion in the presence of a cyclopropyl alcohol would provide a route to β-substituted ketones as shown in Scheme 1. Since cyclopropyl units are readily accessible via the Kulinkovich reaction, 7 the ring opening of cyclopropanols and the carbon-heteroatom bond formation mediated with CAN could provide a novel, efficient, and general approach to a variety of β-substituted ketones.The synthesis of substituted cyclopropyl alcohols 1-4 shown in Table 1 were carried out using the Kulinkovich reaction and provided good isolated yields in the range of 63-82%. In an initial experiment, sodium azide was chosen as the first anion to react with a cyclopropyl alcohol since oxidation of this anion with CAN has been previously reported. 8 Reaction of 1 with NaN 3 in the presence of 2 equivalents of CAN in methanol produced a moderate yield (50%) of the 3-azido-1-phenyl propanone along with dimer and nitrated products as side products.rof2@lehigh.edu.
NIH Public Access
NIH-PA Author ManuscriptNIH-PA Author Manuscript
NIH-PA Author ManuscriptSince solvent is known to play...
