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

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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.