Biomimetic carbene catalyzed oxidative activation of aldehydes

卡宾作为醛类化合物的催化剂被广泛应用。研究得很好的安息香缩合和Strecker反应是突出的例子。在这些方法中，卡宾催化剂用于中间产生所谓的Breslow中间体，其在离子过程中进一步与醛、与活化的贫电子双键或与其它亲电体反应。最近，在Breslow中间体的α-位上的离去基团已经被安装以将烯醇醚转移到活化的酰基碳正离子中。大多数卡宾催化的醛的转化涉及Breslow中间体的离子转化。在该提案中，我们使用单电子转移氧化试剂在仿生过程中形成活化的酰基碳正离子。这种类型的卡宾催化剂也被自然界使用，但迄今为止在合成中没有得到很好的研究。在分子氧中，将测试其他环境友好的单电子转移氧化剂，特别是氮氧化物。在这些有机催化反应中将避免金属基氧化剂。α，β-不饱和醛的活化将产生活化的迈克尔受体，其应经历1，4-加成反应。我们计划研究通过卡宾催化氧化还原活化的醇、保护胺和硫醇的立体选择性分子内1，4-加成反应。此外，酰基碳正离子也将用于分子内无过渡金属的醛C-H-活化反应以形成环酮。

Carbenes have been intensively used as catalysts for the umpolung of aldehydes. The well investigated benzoin condensation and the Strecker reaction are prominent examples. In these processes the carbene catalyst is used to intermediately generate the so called Breslow intermediate which further reacts in an ionic process with an aldehyde, with an activated electron-poor double bond or with other electrophiles. More recently, leaving groups at the -position of the Breslow intermediate have been installed to transfer the enol ether into an activated acylcarbenium ion. Most of the carbene-catalyzed transformations of aldehydes deal with ionic transformations of the Breslow intermediate. In the proposal we use single electron transfer oxidation reagents for the formation of activated acylcarbenium ions in biomimetic processes. This type of carbene catalysis also used by nature is not well investigated so far in synthesis. Among dioxygen other environmentally benign single electron transfer oxidants in particular nitroxides will be tested. Metal based oxidants will be avoided in these organocatalyzed reactions. Activation of ,-unsaturated aldehydes will generate activated Michael acceptors which should undergo 1,4-addition reactions. We plan to study stereoselective intramolecular 1,4-additions of alcohols, protected amines and thiols via carbene catalyzed redox activations. Moreover, acylcarbenium ions will also be used in intramolecular transition metal free aldehyde C-H-activation reactions for the formation of cyclic ketones.