联烯基自由基中间体—多取代联烯合成的新思路

Allenes are important structural motifs found in natural products and are key intermediates in the synthesis of complex molecules. Classical methods for the synthesis of allenes include prototropic rearrangements, sigmatropic rearrangements, nucleophilic substitutions, 1,4-additions to enynes and other methods. Among these methods, 1,4-addition to 1,3-enynes by simultaneous introduction of two functional groups, has played a special role in allene synthesis and attracts increasing attention. All these methods proceed via an ionic pathway. Compared to the allenyl anion, the allenyl radical and cation are oxidized species and are less utilized in organic synthesis. .1,4-Difunctionalization of 1,3-enynes via a radical pathway is rare, as is intermolecular 1,4-difunctionalization. This is probably due to the inconvenient generation of short-lived allenyl radicals. Reactions that proceed via an allenyl radical pathway however, could be very useful. The allenyl radical is very reactive and is susceptible to oxidation to an allenyl cation, a good electrophile, or reduction to the allenyl anion, a nucleophile. Consequently, reactions which could not proceed by an allenyl anion pathway may encounter an acceptable allenyl radical pathway. We will study 8 unprecedented 1,4-difunctionalization reactions of 1,3-enyens to deliver new allene motifs via allenyl radical intermediates. These target reactions are unkonwn and would be difficult to be realized via allenyl anion pathways.

联烯是一类重要的化合物，常常出现在天然产物结构中也是重要的反应中间体。尽管合成联烯有一些经典方法，多取代联烯、联烯氰、联烯氟等联烯骨架的合成仍旧是难点。联烯基自由基因其不易合成、寿命短、活性高、选择性差等因素，到目前为止在联烯的合成中不是一个非常有效的中间体，相关研究也比较少见。申请人将引入多功能的氧化性烷基化试剂、胺化试剂等关键试剂，通过烯炔的1，4-双官能团化，探索温和条件下生成联烯基自由基的有效方法。本申请将进一步研究联烯基自由基的性质和可能转化，寻找该中间体直接发生自由基反应的条件，研究该中间体被氧化成联烯基正离子或者还原成联烯基负离子后进一步发生反应的可能性，拓展出有别于经典方法的反应模式，合成经典方法难以获得的联烯类型，建立起通过联烯基自由基为中间体的联烯合成新方法，与现有经典方法形成互补，进而拓展联烯合成化学。

烯炔的1,4-加成能够在底物分子的基础上同时引入两个官能团，在多取代联烯的合成中具有巨大优势。申请人通过对联烯基自由基生成、联烯基自由基的性质和可能的化学转化的研究，寻找到了该中间体直接发生自由基反应的条件，并探讨了该中间体被氧化成联烯基正离子或者还原成联烯基负离子后进一步发生反应的可能性。基于此研究，我们拓展出了有别于经典方法的反应模式，合成了经典方法难以获得的联烯类型，建立起了通过联烯基自由基为中间体的联烯合成新方法，该方法实现了对现有经典方法的补足，进而拓展联烯合成化学。发表包括JACS、Nature Commun.、ACS Catal. 、Chem. Sci.等在内的多篇高影响因子论文。