Anionic and Radical Cyclization of Unsaturated Hydrazones: Application to the Synthesis of Chiral Polycyclic Compounds

迄今为止，已经设计了许多在热或光化学激活下进行的自由基反应，但其中很少以不对称方式进行。此外，串联环化（自由基或阴离子）是目前构建复杂天然产物骨架的首选方法。该项目的目的是结合高立体选择性的方法，使用众所周知的SAMP/RAMP腙和串联环化过程，以获得手性多环结构。通过选择性的a-官能化（卤化，苯基硒化）和随后的底物转化为不饱和化合物，进一步的自由基过程可以进行并导致环化产物。立体选择性的C-X键的形成和/或手性腙部分的存在有望控制整个过程的立体选择性。去除腙官能团后，对羰基衍生物进行自由基反应也可以研究记忆效应。以类似的方式，不饱和SAMP腙的去质子化和卤素或苯硒衍生物的处理可以产生由不对称阴离子环化过程产生的化合物。为了提高结构的复杂性，需要注意的是，在键环化步骤之前，不饱和起始原料可以与各种烯烃进行交叉复分解反应。这两种方法可以得到具有相似骨架和复杂性的手性化合物。因此，比较它们在天然化合物的不对称合成中的应用是很有意义的。

To date, numerous radical reactions performed either under thermal or photochemical activation have been deviced, but few of them have been conducted in an asymmetric manner. Moreover, tandem cyclizations (radical or anionic) represent now the methods of choice to built complex natural product skeleton. The aim of the project is to combine highly stereoselective methodologies using the well-known SAMP/RAMP hydrazones and tandem cyclization processes in order to obtain chiral polycyclic structures. By selective a-functionnalization (halogenation, phenylselenation) of hydrazones and subsequent transformation of the substrates into unsaturated compounds, a further radical process could be performed and lead to cyclized products. The stereoselective C-X bond formation and/or the presence of the chiral hydrazone moiety are expected to control the stereoselectivity of the overall process. The memory effect could be also studied by conducting the radical reaction on the carbonyl derivatives after removal of the hydrazone functionality. In a parallel manner, deprotonation of unsaturated SAMP hydrazones and treatment with an halogen or phenylselenium derivatives could deliver compounds resulting from an asymmetric anionic cyclization process. In order to enhance the structural complexity, it should be noted that cross-metathesis reactions could be performed on the unsaturated starting material with various alkenes before the key-cyclization step. These two approaches should afford chiral compounds with similar skeleton and also complexity. Therefore, it will be interesting to compare them before to investigate an application toward the asymmetric synthesis of natural compounds.