Oxidative Addition Reactions of Primary Amines with Isocyanides

4 Oxidative Addition Reactions of Primary Amines with Isocyanides 

Formally, carbodiimides may be generated by the addition of a (nucleophilic) primary amine to an isocyanide (with an electron deficiency see constitutional formula 1515b and considerations on isocyanides in the introduction to Section 4.5.2) under release of a reduction equivalent (two electrons) and two protons. The required oxidation equivalent can be provided most easily with an oxygen atom. 

Reaction of isocyanides with primary amines in the presence of selenium and DBU, followed by the introduction of molecular oxygen in refluxing THF, affords unsymmetrical and symmetrical carbodiimides in isolated yields of 58-87% [1282] (see also Section 4.5.3.5, Table 4.48). The oxidation reaction is mediated by selenium with the assistance of base DBU. 

Typical procedure. N-tert-Butyi-N -n-butylcarbodiimide 1747 [1282] A mixture of fert-butyl isocyanide 1745 (2 mmol), n-butylamine 1746 (2 mmol), selenium (2 mmol), and DBU (8 mmol) was stirred for 1 h in refluxing THF (5 mL). Then, molecular oxygen was introduced by means of a peristaltic pump at 20 mL min for 5 h while maintaining reflux. After deposited selenium had been filtered off, the filtrate was diluted with Et20 (50 mL), washed with brine (3 x 50 mL), dried over MgS04, and concentrated in vacuo to give essentially pure 1747 in 82% yield. 

Another variation of the oxidation reaction with dioxygen can be efficiently accomplished by a catalytic condensation of amines and isonitriles using a palladium complex catalyst and iodine at 100 °C to give dialkylcarbodirmides in yields of 35-86% [1283]. Dicyclohexylcarbodirmide was obtained in 67% yield from cyclo-hexylisonitrile 1748 and cyclohexylamine 1749 (see Section 4.5.3.5, Table 4.48). 

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