Catalytic in-situ generation of functionalized alkali metal reagents and their application in C-C and C-Si bond-forming reactions

合成化学没有碳亲核基锂，镁（Grignard），锌是很难想象的。其制备的常用方法包括还原金属化和相应卤化物的卤素-金属交换，并且所得的极性有机金属试剂可以通过金属转移相互转化。这些程序往往缺乏化学选择性，亲核试剂的高反应性往往不利于它们的官能团耐受性。近几十年来，Paul Knochel提出了解决这些问题的可行方案，从而将多官能化锌和格氏试剂转化为日常化学品。基于早期的实例，我们的实验室引入了N-芳基-N '-甲硅烷基二氮烯作为芳基亲核试剂，当与路易斯碱性活化剂如醇盐或硅烷醇盐碱金属盐反应时，其释放芳基碱金属沿着二氮。这些亲核试剂可以用通常与这些亲核试剂不相容的官能团修饰。活化剂的催化量足以促进亲电试剂的自催化芳基化。该项目旨在推广这种方法，包括广泛的碳（双）亲核试剂和各种（双）亲电试剂应用于羰基化合物的1，2-加成，缺电子芳烃的SNAr反应以及硅亲电试剂的加成反应。努力把羰基化学不对称催化也包括在内。总的来说，新工具将能够使用活性碱金属试剂合成高度官能化的分子。

Synthetic chemistry without carbon nucleophiles based on lithium, magnesium (Grignard), and zinc is difficult to imagine. The usual methods for their preparation include reductive metalation and halogen-metal exchange of the corresponding halides, and the resulting polar organometallic reagents can be interconverted by transmetalation. These procedures often lack chemoselectivity, and the high reactivity of the nucleophiles is frequently detrimental to their functional-group tolerance. Paul Knochel presented in recent decades viable solutions to these problems, thereby turning polyfunctionalized zinc and Grignard reagents into everyday chemicals. Based on an early example, our laboratory introduced N-aryl-N’-silyldiazenes as aryl pronucleophiles that release aryl alkali metals along with dinitrogen when reacted with a Lewis-basic activator such as alkoxide or silanolate alkali salts. Those pronucleophiles can be decorated with functional groups that are usually not compatible with these nucleophiles. Catalytic amounts of the activator are sufficient to promote the autocatalytic arylation of electrophiles. This project aims at the generalization of this approach, including a broad range of carbon (bis)nucleophiles and various (bis)electrophiles applied to 1,2-addition to carbonyl compounds, SNAr reactions of electron-deficient arenes, and addition reactions to silicon electrophiles. Efforts to turn the carbonyl chemistry into an asymmetric catalysis are also covered. Overall, the new tool will enable the synthesis of highly functionalized molecules employing reactive alkali metal reagents.