Metal cyanides cycloadditions

The cycloaddition of ethoxycarbonyl azide to racemic O-acetyl cyanohydrin 21 was performed either at 40 °C in acetone or at room temperature and without solvent in the presence of a metal salt (zinc(II) acetate, nickel chloride or copper(I) cyanide) as catalyst54. The required dihydro-triazole 22 (isolated from the 2 1 mixture of regioisomers) was directly converted to the jS-acetoxy amine via migration of the endo-acetoxy group. The Ivans relationship of the hydrogen atoms at C-5 and C-6 was deduced from ll NMR. 

In the presence of potassium cyanide the N-methyl-C-phenylnitrone (112) takes part in yet a further cycloaddition reaction to give l-methyl-4,5-diphenylimidazole. With lithium metal the aldimine (113) forms a delocalized carbanion which will cyclize with aryl cyanides (Scheme 61) (80AHC(27)24l). See also Section 4.08.1.1.3. 

Originally, the pyridine construction reaction was based on cobalt catalysis and restricted to the use of acetonitrile or alkyl nitriles as one of the cycloaddition partners. However, recent advancements in this area have led to the development of certain ruthenium or rhodium catalysts, allowing the use of methylcyanoformate as an electron-deficient nitrile component in crossed [2 - - 2 - - 2]-cycloaddition reactions [39]. From the point of view of applications, the use of methylcyanoformate in transition-metal-catalyzed pyridine formation reaction is quite beneficial because the ester moiety might serve as a functional group for further manipulations. It might also serve as a protective group of the cyanide moiety, because cyanide itself cannot be used in this reaction. These considerations led to the design of a quite flexible approach to substituted 3-(130)- and y-carbolines (131) based on transition-metal-catalyzed [2 -f 2 -I- 2] cycloaddition reactions between functionalized yne-ynamides (129) and methylcyanoformate (Scheme 7.28) [40]. 

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