College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577, Japan.
J Am Chem Soc. 2013 Mar 20;135(11):4558-66. doi: 10.1021/ja401074u. Epub 2013 Mar 7.
This report details the development of a spirobiindane-based chiral hypervalent iodine reagent, especially focusing on its structural elucidation for effective asymmetric induction of the chiral spiro center during the oxidative dearomatizing spirolactonization of naphthols. In this study we synthesized a new series of ortho-functionalized spirobiindane catalysts and demonstrated that the enantioselectivity can be dramatically improved by the presence of the substituents ortho to the iodine atom. The structural elucidation of a spirobiindane-based hypervalent iodine catalyst has led to further improvement in the stereoselective construction of the spiro center during the oxidative dearomatizing spirolactonization of naphthols. Thus, catalytic oxidation with the highest reported level of enantioselectivity in hypervalent iodine chemistry has been achieved with also an excellent level of asymmetric induction (92% ee for substrate 3a). As a result, this study, dealing with a series of modified iodine catalysts, can provide important clues about the transition state and reaction intermediate to help scientists understand the origin of the stereoselectivity. A plausible transition-state model and intermediate in the reaction for the stereoselective formation of spirolactone products are postulated by considering the ortho-substituent effect and the results of X-ray analysis. In this reaction model, the high enantiomeric excess obtained by using the spirobiindane catalysts could be well explained by the occupation of the equatorial site and extension of the surroundings around the hypervalent iodine bonds by the introduced ortho-substituent. Thus, this study would contribute to estimation of the chiral hypervalent iodine compounds in asymmetric reactions.
本报告详细介绍了一种基于螺双茚的手性高碘试剂的开发，特别侧重于其结构阐明，以在萘酚的氧化去芳构化螺内酯化反应中有效诱导手性螺中心的不对称诱导。在这项研究中，我们合成了一系列新的邻位官能化螺双茚催化剂，并证明碘原子邻位取代基的存在可以显著提高对映选择性。螺双茚基高价碘催化剂的结构阐明导致在萘酚的氧化去芳构化螺内酯化反应中，螺中心的立体选择性构建得到进一步改善。因此，在高价碘化学中实现了催化氧化，具有最高报道水平的对映选择性（底物 3a 的 92%ee），同时也具有出色的不对称诱导（92%ee）。因此，这项涉及一系列改性碘催化剂的研究，可以为过渡态和反应中间体提供重要线索，以帮助科学家理解立体选择性的起源。通过考虑邻位取代基效应和 X 射线分析的结果，提出了螺内酯产物立体选择性形成的可能过渡态模型和中间体。在该反应模型中，通过使用螺双茚催化剂获得的高对映过量可以通过占据赤道位和通过引入的邻位取代基扩展高碘键周围的环境得到很好的解释。因此，这项研究将有助于对手性高价碘化合物在不对称反应中的评估。
