CIC Employed in the Ugi Reaction

SCHEME 7.9 Modified TosMIC (If) in natural product synthesis. 

2 l-Oxy-2-picolyl Isocyanide l-Oxy-2-picolyl isocyanide (Ig) was first synthesized by Mizuno and coworkers in 1980 [33]. Commercially available 

2-pyridylmethyl alcohol (68) can be converted to the corresponding 2-picolylamine 1-oxide (6b) via meta-chloroperoxybenzoic acid (m-CPBA) oxidation followed by treatment with saturated NH4OH at 0°C and passing through DOWEX 1 (OH exchange resin). Refluxing 6b in a solution of ethyl formate provides A-(2-picolyl 

1- oxide) formamide (8a) exclusively. Refluxing the formamide 8a in the presence of CCI4, Et3N, and triphenylphosgene at 60°C for 3 h provides the desired 1-oxy- 

In 1981, Isenring and Hofheinz discovered that diphenylmethyl isocyanide can act as a CIC when the Ugi product was treated with N2O4 in CHCI3 at 0°C and warmed to room temperature [36]. The Ugi product a-acylaminoamide 71 forms a nitrosoamide intermediate 72, which converts slowly into the diazo species 73 

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