咪唑並[1,5-a]吡啶及其衍生物不論在生物活性、藥物或是發光材料方面都是具有潛力的分子結構,合成方法除了傳統的有機合成之外,以過渡金屬Pd催化C3碳氫鍵活化並做耦合反應,在前幾年被發表出來,但是以Ni金屬對此結構做碳氫鍵官能基化反應則尚未被報導。在本篇論文中,我們發現利用Ni金屬催化劑在溫和的反應條件下,咪唑並[1,5-a]吡啶可以與炔類反應生成烯基化產物 (分別是C3與C5取代),反應中沒有路易士酸存在時,主要產物為C3烯基化,如果在反應中額外加入路易士酸時,則會改變催化產物的位向選擇性,主要產物會變成C5烯基化。而咪唑並[1,5-a]吡啶的C5碳氫鍵活化反應條件也可以應用在烷基化反應之中,惟需要較高的反應溫度。整體來說,我們是第一個演示了Ni金屬催化劑對咪唑並[1,5-a]吡啶碳氫鍵活化並官能基化的反應,也是首個利用過渡金屬催化劑搭配路易士酸在咪唑並[1,5-a]吡啶C5位置做官能基化的反應,其中烯基化與烷基化反應都有不錯的總產率與位向選擇性。
Imidazo[1,5-a]pyridines are core motifs in bioactive compounds, drugs and photofunctional materials. In addition to the well-known organic synthetic methods, Pd-catalyzed C3 functionlization via C−H activation has recently been reported. To the best of our knowledge, there are no reports on Ni-catalyzed C−H functionalization of imidazo[1,5-a]pyridines. Herein, we discover the Ni-catalyzed C3 alkenylation of imidazo[1,5-a]pyridines with internal alkynes under mild conditions at ambient temperature. Regioselectivity can be switched to C5 alkenylation in the presence of Lewis acid. In addition, the present methodology is also applied to C5 alkylation of imidazo[1,5-a]pyridines with various alkenes upon heating. In summary, we have first demonstrated Ni-catalyzed C−H activation of imidazo[1,5-a]pyridines to perform alkenylation or alkylation with high regioselectivity. It is worth mentioning that this is the first example for C5 functionalization of imidazo[1,5-a]pyridines by using nickel and a Lewis acid.
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