Exploitation of Nitroxyl Radidal-type Organocatalysts for Alcohol Oxidation and their Use in Fine Synthetic Chemistry

本课题旨在开发氮杂金刚烷n -氧基（AZADO）型硝基自由基作为醇氧化催化剂的合成潜力及其在精细合成化学中的应用。在本次研究期间，我们确定了以下事项。(1) AZADO型硝基自由基的构效关系：我们合成了一组AZADO型催化剂，并对其氧化催化功能进行了研究，以阐明AZADO与TEMPO相比具有极强攻击性的分子基础。我们的实验得出的结论是，在催化活性位点附近的空间因子的减轻是催化活性的关键因素。(2)我们已经开发了几种对映体修饰的AZADOs的合成路线，并研究了它们作为仲醇氧化的对映选择性催化剂的用途。这些结果使我们能够建立一个初步的机制假设模型，这对进一步的发展是有用的。(3)建立了一种实用、高效的叔烯丙醇氧化重排成β-取代α，β-不饱和酮的方法。所开发的方法既适用于无环底物，也适用于中元环底物和大环底物。我们已经阐明了氧化铵盐的反阴离子在这种氧化重排中起着至关重要的作用。(4)我们发现了一种新的AZADO衍生物，使我们能够在室温下将醇类进行无金属、无卤素的有氧氧化，生成羰基化合物。

This research project aimed exploitation of synthetic potential of azaadamantane N-oxyl (AZADO)-type nitroxyl radicals as oxidation catalyst for alcohol oxidation and their use in fine synthetic chemistry. We have established the following matters in this research period.(1) The structure-activity correlation of AZADO-type nitroxyl radicals: We synthesized a panel of AZADO-type catalysts and examined their function as oxidation catalyst to clarify the molecular basis of the extremely aggressive nature of AZADO compare to TEMPO. Our experiments have led the conclusion that alleviation of the steric factor near the catalytically active site critically determine the catalytic activity.(2) We have developed several synthetic route to enantiomerically modified AZADOs and have examined their use as enantioselective catalyst for oxidation of secondary alcohols. The results allowed us to develop a tentative mechanistic hypothetic model, which is useful for further development.(3) We have developed a ractical and highly efficient methods for oxidative rearrangement of tertiary allylic alcohols to β-substituted α,β-unsaturated ketones employing oxoxammonium salts. The methods developed are applicable to acyclic substrates as well as medium membered ring substrates and macrocyclic substrates. We have elucidated that counter anion of the oxoxmmonium salt plays crucial roles on this oxidative rearrangement.(4) We have discovered a novel AZADO derivative that made us possible to conduct metal-free, halogen-free aerobic oxidation of aloohols to carbonyl compounds under an ambient temperature.