研究室工作進展 May. 17th, 2013.

Mechanistic Study on the Cleavage and Reorganization of C(sp3)-H and C=N Bonds in Carbodiimides: Synthesis of 1,2-Dihydrothiopyrimidines and 2,3-Dihydropyrimidinthiones via Four-Component Coupling

 Yang Wang, Fei Zhao, Yi Zhou, Yue Chi, Zitao Wang, Wen-Xiong Zhang,* and Zhenfeng Xi

 Chem. Eur. J. 2013, DOI: 10.1002/chem.201301633.

This study reveals the light of dawn on the cleavage and reorganization of C(sp3)-H and C=N bonds of carbodiimides in this three-component reaction of terminal alkynes, sulfur, and carbodiimides by the combined methods including (i) isolation and X-ray structure of six-membered-ring lithium species 2-S, (ii) trapping of the Oxygen-analogues (B-O and D-O) of both four-membered-ring intermediate B-S and ring-opening intermediate D-S, (iii) deuterium labeling studies, (iv) theoretical study. These results show that (i) this reaction rate-determining step is [2+2] cycloaddition, (ii) the C=N bond cleavage takes place before the C(sp3)-H bond cleavage, (iii) the hydrogen attached to the C6 in 2-S is from carbodiimide, (iv) three types of new aza-heterocycles, such as 1,2-dihydrothiopyrimidines, N-acyl 2,3-dihydropyrimidinthiones and 1,2-dihydropyrimidinamino acids are constructed efficiently based on 2-S. All results strongly support that the reaction undergoes through [2+2] cycloaddition/4π electrocyclic ring-opening/1,5-H shift/6π electrocyclic ring-closing as key steps. The research strategy on the synthesis, isolation and reactivity investigation of important intermediates in metal-mediated reactions not only gives the in-depth understanding of reaction mechanisms but also leads to the discovery of new synthetically useful reactions based on the important intermediates.

背景介紹

碳二亞胺(R1-N=C=N-R2),作為一類具有累積C=N雙鍵的雜聯烯類化合物，在有機合成化學與金屬有機化學領域中發揮着非常重要的作用。所有報道的反應僅涉及碳二亞胺的兩個反應位點：中心碳和C=N雙鍵。自2007年以來我們一直開展金屬促進或催化的碳二亞胺新反應化學及機理研究。2009年，我們發現了端炔、單質硫和碳二亞胺，在有機锂試劑的促進下，多組分偶聯可制備2,3-二氫嘧啶硫酮的新反應。在這個反應中，碳二亞胺分子的一個C=N雙鍵和一個Csp3-H鍵被切斷。該成果為活化碳二亞胺分子中化學鍵和有效地利用碳二亞胺提供了一種新思路和新方法(Wen-Xiong Zhang,* Zhenfeng Xi,* et. al. J. Am. Chem. Soc. 2009, 131, 15108.)。經過近三年的努力，通過對該反應中六元環金屬有機活性中間體2-S的分離和結構鑒定，氧類似物前體B-O和D-O的合成、捕獲，同位素标記實驗并結合計算化學等，我們揭開了該反應的機理經曆: [2+2]環加成、4π-電環化開環、[1,5]-氫遷移和6π-電環化關環等關鍵步驟。并進一步建立了六元環中間體2-S在合成化學中的應用(Yang Wang, Fei Zhao, Yi Zhou, Yue Chi, Zitao Wang, Wen-Xiong Zhang,* and Zhenfeng Xi Chem. Eur. J. 2013, DOI: 10.1002/chem.201301633)。