2-Hydroxyalkyl isocyanide

Much simpler than the template-controlled generation of p-functionalized isocyanides is their direct use. 2-Hydroxyalkyl isocyanide 59, where the nucleophilic group and the isocyanide are linked together, spontaneously cyclizes upon activation of the isocyanide by coordination to an electron-poor metal center under... 

SchOllkopf et al. reacted lithiated isocyanides with epoxides to obtain 3-hydroxyalkyl isocyanides. The reaction was also performed with cyclohexene oxide, and the hydroxyisocyanate formed was cyclized to oxazines with copper(I) oxide, resulting in a diastereomeric mixture of 174 and 175 (76LA2105 86AG755). Irradiation of aliphatic dieneamides yielded a variety of dihydrooxazines of type 167 (88T1959). 

Isocyanides react with 2-phthalimidosulfanylphenols to give 2-imino-l,3-benzoxathioles (Equation 63) <2003S662>, and water-soluble 4-imino-l,3-oxathiolane derivatives have been formed by reaction with diiodo-methane followed by a silver or lead salt (Equation 64) <2005S2946>. A convenient route to oxathiolanes from 2-hydroxyalkyl /t-butyl sulfides and aldehydes has appeared (Equation 65) <2006T931>. 

Furthermore, multicomponent reactions, as represented by Ugi reaction and Biginelli reaction, are attractive strategies for the selective construction of complex organic molecules from several simple starting materials in a single operation. Recently, Wang and Zhu et al. reported asymmetric synthesis of 5-(l-hydroxyalkyl)tetrazoles 60 from aldehydes, isocyanide, and hydrazoic acid via chiral salen-organoaluminum complex 59 catalyzed asymmetric Passerlni-type reaction (Scheme 43) [76]. 

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