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

Abstract

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. The successful integration of an oxidative Strecker reaction, thio-Michael addition, and neutral-alumina-promoted hydrolysis of β-mercapto-α-iminonitriles into a three-component one-pot process allowed us to develop the direct conversion of amines, aldehydes, and thiols into β-mercaptoamides. All of these procedures were applicable to aromatic and aliphatic amines and aldehydes.

N‐Heterocyclic Carbene/Cobalt Cooperative Catalysis for the Chemo‐ and Regioselective C−N Bond Formation between Aldehyde and Amines/Amides

“…Therefore, the development of newer alternative synthetic strategies to this ubiquitous functional group has attracted attention over the years. [3][4][5][6][7][8][9][10][11][12][13] Different reactions have been investigated including Schmidt reaction, Staudinger ligation, [4] Beckmann rearrangement of oximes, [5] aminocarbonylation of alkenes, haloarenes and alkynes, [6] oxidative amidation of aldehydes and alcohols [7] hydrative amide synthesis with alkynes, [8] and amidation of thioacids and ketones with azides/amines [9] including the recent high atom economic systems: transition-metal-catalyzed oxidative amidation of aldehyde with primary amines using Fe, Cu, Ru, Rh, Pd, lanthanide and Ag-based catalysts. [10] These synthetic methods require heated reaction conditions and prolonged time, and the substrate scope is limited.…”

External-Oxidant-Based Multicomponent Reactions

“…The in situ oxidation of alcohols has also been widely explored to broaden the scope of other already existing multicomponent reactions, varying from the Bienaymé-Blackburn-Groebke construction of the imidazopyridine ring 31 to the Biginelli pyrimidine synthesis, 32 and to a less common Wittig/Diels-Alder combination. 33 Also, the type of external oxidant employed is extremely variable, from the 'evergreen' IBX employed by Zhu in a Strecker reaction followed by a second oxidation step (see section 3.2 for further details) 34 to the graphene oxide supported on gold nanoparticles employed by Dabiri in an A 3 (amine-alkynealdehyde) coupling. 35 Scheme 11 summarizes all the examples taken from the recent literature together with the corresponding oxidant employed.…”

Oxidative activation of dihydropyridine amides to reactive acyl donors

“…The product was purified by flash column chromatography using EtOAc-pentane (20 : 80 to 40 : 60). 61 The general procedure C was followed. 59 The general procedure C was followed.…”