Amidation of aldehydes and alcohols through α-iminonitriles and a sequential oxidative three-component Strecker reaction/thio-Michael addition/alumina-promoted hydrolysis process to access β-mercaptoamides from aldehydes, amines, and thiols.

Mild and general alumina-promoted hydrolysis conditions for converting α-iminonitriles into carboxamides have been developed. In combination with the oxidative three-component Strecker reaction, the one-pot direct amidation of aldehydes and alcohols is reported. Subsequently, an Yb(OTf)(3)-catalyzed Michael addition of thiols to α,β-unsaturated α-iminonitriles is reported for the synthesis of β-mercapto-α-iminonitriles.

Synthesis of pyrroles by consecutive multicomponent reaction/[4 + 1] cycloaddition of alpha-iminonitriles with isocyanides.

[4 + 1] Cycloaddition of alpha,beta-unsaturated imidoyl cyanide (2-cyano-1-azadienes) with isocyanides in the presence of a catalytic amount of AlCl(3) afforded polysubstituted 2-amino-5-cyanopyrroles in good to excellent yields. In combination with the IBX/TBAB-mediated oxidative Strecker reaction, this important heterocycle is readily synthesized in two steps from simple starting materials.

One-pot three-component synthesis of alpha-iminonitriles by IBX/TBAB-mediated oxidative Strecker reaction.

The reaction of aldehydes, amines, and TMSCN in the presence of 2-iodoxybenzoic acid (IBX) and tetrabutylammonium bromide (TBAB) afforded alpha-iminonitriles in good to excellent yields under mild conditions. The presence of TBAB is essential for this transformation. The methodology was applied to a two-step synthesis of indolizidine via a microwave-assisted intramolecular cycloaddition of alpha-iminonitrile.