Modified Stephen reduction

L.-M. Yang and co-workers designed and synthesized a new series of frans-stilbene benzenesulfonamide derivatives as potential antitumor agents.A common precursor diethylphosphonate was prepared from commercially available sulfanilamide in six steps. The aromatic nitrile-to-aldehyde reduction was affected by the modified Stephen reduction using Raney nickel alloy in aqueous formic acid. The corresponding aldehyde was obtained in high yield. 

Research by P. Scrimin and U. Toneiiato et ai. showed that Zn " was an aiiosteric reguiator of liposomal membrane permeability induced by synthetic template-assembled tripodal polypeptides. Several copies of peptide sequences from the peptaibol family were connected to fr/s(2-aminoethyl)amine (TREN), which is a tripodal metal ion ligand. The resulting tripodal polypeptides were capable of modifying the permeability of liposomal membranes, and their activity was tunable upon metal ion coordination of the TREN subunit. The synthesis of the TREN-based template began with the Stephen reduction of 4-cyanomethylbenzoate followed by the reductive amination of the resulting aldehyde with TREN. 

Another noteworthy example of a modified Stephens-Castro reaction is the key step in the total synthesis of the natural product oximidine II (5) with distinct anticancer properties (Scheme 9.4) [12]. The Cu acetylide generated in situ from the terminal alkyne 6 using K2CO3 and Cul, underwent intramolecular cychzation followed by partial reduction of the acetylene unit to give the required macrocycUc triene skeleton 7. 

The reduction of PAN according to Stephen in dioxane at 60 to 100 °C made it possible, practically without any side reactions, to obtain modified PAN derivatives whose composition is close to that of copolymers from AN and acrolein. 

The procedure outlined above describes the selective, retentive, p-coupling of (Z)-2,3-dibromopropenoic acid ethyl ester with (trimethylsilyl)acetylene employing the palladium-modified version of the Castro-Stephens reaction.4 5 The dibromide starting material is readily available by bromination of ethyl propiolate (Procedure A), as described by Trippett and Hall.2 The coupling product has been shown to be a versatile precursor for the synthesis of variously substituted enynes and enediynes. For example, a second acetylene may be introduced into the a-position under modified coupling conditions. Alternatively, reduction of the ester with diisobutylaluminum hydride and protection of the resultant alcohol with tert-butyldiphenylsilyl chloride affords a vinyl bromide that can be metalated and trapped with various electrophiles. These procedures have been used on the gram and multigram scale.5... 

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