Imidoyl chloride, Passerini reactions

A stereochemical control of the Ugi reaction can be effected with carbohydrates as chiral templates (e.g. tetrakis(O-pivaloyl)galactosylamine), which gives rise to easily separable amides. From these a variety of non-natural amino acids can be derived after acidic hydrolysis. The Passerini reaction, related to the Ugi rearrangement, gives a-hydroxyamides. A modification of this reaction using titanium tetrachloride gives a-branched amides in high yields via C-metalated imidoyl chlorides (equation 38). 

Denmark has described several chiral bis-phosphoramides as Lewis base activators of weak Lewis acid SiCL and demonstrated their ability to mediate an enantioselective Passerini-type reaction. Catalytic bis-phosphoramide 36 and stoichiometric SiCU, in the presence of a proton scavenger (Htinig s base), promoted the formation of a-hydroxyamides with remarkably good enantioselectivity and yield. A variety of aromatic and unsaturated aldehydes and aryl, alkyl, and functionalized alkyl isocyanides proved to be useful and effective starting materials. High yields of Passerini products were attributed to the production of imidoyl chloride 37, which reduced the prevalence of the nitrilium intermediate and prevented the addition of a second equivalent of isonitrile. 

Lewis acid catalysis serves for the Passerini-type reaction of aldehydes with isocyanides forming a-hydroxyamides. The catalytic system consisting of SiCU and (107) provides high yield and good to excellent enantioselectivity for the addition of t-butyl isocyanide to a wide range of aldehydes [167]. The amide product is formed from the imidoyl chloride intermediate (110) by hydrolysis (Scheme 9.78). Treatment of the intermediate product with methanol followed by hydrolysis gives a-hydroxyesters with the retention of enantioselectivity. 

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See also in sourсe #XX -- [ ]

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