銠金屬催化之碳－氫鍵活化反應 以合成含氮雜環衍生物及相關天然物之研究

Rhodium(III)-Catalyzed C–H Activation as a Key Step for the Synthesis of N-Heterocycles and Related Natural Products

賈亞庫馬(Jayakumar)

指導教授 ： 鄭建鴻

國立清華大學/理學院/化學系/博士(2014年)

摘要

Transition-metal-catalyzed C‒C bond formation reaction by uniting readily available π-components is an attractive strategy to synthesis biologically important compounds in a single operation with high atom-efficacy. Particularly, C H bond activation reactions are experienced method to synthesis of natural products and biologically important compounds in a highly regioselective manner. The C H functionalization of aryl aldehydes with amines and alkynes to afford highly substituted isoquinolines. On the other hand multiple C H activations of N-hyroxybenzamidines with alkynes afforded highly substituted hetroaromatic compounds in one-pot manner. For better understanding, I divided this thesis into four chapters. The first three chapters describe about rhodium-catalyzed inter and intramolecular C-H activation/annulation of aldehydes with amines and alkynes or (amino-alkynes). The final chapter describe about the multiple C H activations of N-hyroxybenzamidines or (aryl nitrile and amines) with alkynes using rhodium(III) as the catalyst.
 Chapter 1 describes a new method for the synthesis of isoquinolinium salts from the oxidative coupling/annulation of alkynes with aldehydes and amines via Rh(III) catalysis. The proposed mechanism is strongly supported by the isolation of a five-membered rhodacycle and an intermediate organic compound. This protocol successfully applied to the total synthesis of Oxychelerythrine with 66% overall yield.

 Chapter 2 deals with the synthesis of quaternary protoberberine alkaloids (QPA) from aldehydes and aminoalkynes with Rh(III)-salt complex. The reaction can be applied to a straight forward synthesis of 13-substituted protoberberine natural products.

 Chapter 3 illustrates a rhodium-catalyzed synthesis of N-heterocycles from aldehydes, amines and alkynes by C-H activation method. This is the first example of an imine-directed synthesis of highly substituted isoquinolones in one-pot.

 Chapter 4 is about the synthesis of polyhetreoaromatics from N-benzamidines and alkynes by multiple rhodium-catalyzed C H activation and annulation steps. A possible mechanism is proposed involving multi-step chelation-assisted ortho-C–H activation, alkyne insertion and reductive elimination

關鍵字

銠金屬 ； 碳氫鍵活化 ； 異喹啉 ； 醛 ； 炔 ； 胺 ； 苯亞胺

參考文獻

Chapter-1

1.8. References:

[1] K. M. Engle, D.-H. Wang, J.-Q. Yu, J. Am. Chem. Soc. 2010, 132, 14137.

[4] A. J. Canty, G. van Koten, Acc. Chem. Res. 1995, 28, 406.

[5] A. D. Ryabov, I. K. Sakodinskaya, A. K. Yatsimirsky, J. Chem. Soc., Dalton Trans. 1985, 2629.