Institute of Inorganic and Analytical Chemistry, Friedrich Schiller University Jena, Humboldtstraße 8, 07743, Jena, Germany.
Chemistry. 2023 Apr 21;29(23):e202300035. doi: 10.1002/chem.202300035. Epub 2023 Mar 15.
Magnesium and calcium are too inert to deprotonate amines directly. For the synthesis of bulky amides alternative strategies are required and in the past, N-bound trialkylsilyl groups have been used to ease metalation reactions. The in situ Grignard reagent formation in stirred suspensions of magnesium or calcium with hydryl halide and imine in THF allows the synthesis of a plethora of amides with bulky silyl-free substituents. Ball milling protocols partially favor competitive side reactions such as aza-pinacol coupling reactions. Calcium is the advantageous choice for the in situ Grignard reagent formation and subsequent addition onto the imines yielding bulky calcium bis(amides) whereas the stronger reducing heavier alkaline-earth metals strontium and barium are less selective and hence, the aza-pinacol coupling reaction becomes competitive. Exemplary, the solid-state molecular structures of [(Et O)Mg(N(Ph)(CHPh ) ] and [(Et O) Ca(N(Ph)(CHPh ) ] have been determined.
镁和钙太惰性，不能直接使胺去质子化。对于大体积酰胺的合成，需要采用替代策略，过去曾使用 N 键合的三烷基硅基基团来促进金属化反应。在镁或钙的搅拌悬浮液中，与卤代烃和亚胺在 THF 中原位形成格氏试剂，允许用大体积无硅取代基合成大量的酰胺。球磨方案部分有利于竞争性副反应，例如氮杂频哪醇偶联反应。钙是原位格氏试剂形成和随后加成到亚胺上的有利选择，生成大体积的钙双（酰胺），而较强的还原重堿土金属锶和钡的选择性较低，因此氮杂频哪醇偶联反应变得具有竞争力。例如，已确定了 [(EtO)Mg(N(Ph)(CHPh ) ] 和 [(EtO)Ca(N(Ph)(CHPh ) ] 的固态分子结构。
