Marios Kidonakis

Synopsis: We report a simple electrochemical protocol to prepare 2-amino-dihydrobenzofurans from enamides. In contrast to previously reported approaches relying on stoichiometric chemical oxidants or transition metal catalysis of prefunctionalized compounds, the present method directly couples 4-(Boc-amino)phenol through anodic activation to a wide range of enamides, using inexpensive graphite electrodes in an undivided cell.

An operationally simple protocol for the electrochemical oxidation of the primary hydroxy group in glycopyranosides is presented. The strategy uses aqueous ammonia as a base and electrolyte, reticulated vitreous carbon (RVC) electrodes, and TEMPO as a mediator. Under these conditions, the ammonium salts of the corresponding uronic acids are obtained in excellent yield upon evaporation of the volatiles, rendering an exceptionally simple protocol.

Supported Au nanoparticles on TiO₂ (1 mol%) are capable of catalyzing the reduction of the carbene-like diazo functionality of α-diazocarbonyl compounds into a methylene group [C=(N₂) → CH₂] by NH₃BH₃ or NaBH₄ in methanol as solvent. The Au-catalyzed reduction that occurs within a few minutes at room temperature formally requires one hydride equivalent (B-H) and one proton that originates from the protic solvent. This pathway is in contrast to the Pt/CeO₂-catalyzed reaction of α-diazocarbonyl compounds with NH₃BH₃ in methanol, which leads to the corresponding hydrazones instead. Under our stoichiometric Au-catalyzed reaction conditions, the ketone-type carbonyls remain intact, which is in contrast to the uncatalyzed conditions where they are selectively reduced by the boron hydride reagent. It is proposed that the transformation occurs via the formation of chemisorbed carbenes on Au nanoparticles, having proximally activated the boron hydride reagent. This protocol is the first general example of catalytic transfer hydrogenation of the carbene-like α -ketodiazo functionality.

Diethylsilane (Et₂SiH₂), a simple and readily available dihydrosilane, that exhibits superior reactivity, as compared to monohydrosilanes, in a series of reductive transformations catalyzed by recyclable and reusable Au nanoparticles (1 mol‐%) supported on TiO₂. It reduces aldehydes or ketones almost instantaneously at ambient conditions. It can be used in a one pot rapid reductive amination procedure, in which premixing of aldehyde and amine is required prior to the addition of the reducing agent and the catalyst, even in a protic solvent. An unprecedented method for the synthesis of N‐arylisoindolines is also shown in the reductive amination between o‐phthalaldehyde and anilines. In this transformation, it is proposed that the intermediate N,2‐diphenylisoindolin‐1‐imines are reduced stepwise to the isoindolines. Finally, Et₂SiH₂ readily reduces amides into amines in excellent yields and shorter reaction times relative to previously known analogous nano Au⁽⁰⁾‐catalyzed protocols.

Recyclable supported Au nanoparticles on TiO₂ catalyze the cyclization of N‐propargyl or N‐homopropargyl β‐enaminones followed by dehydrogenation (aromatization) leading to substituted 3‐keto pyridines or 4‐picolines in very good yields. This pathway is in contrast to their known cyclization in the presence of Au(I) or Au(III) catalysts which provides 1,4‐oxazepines, instead. The enaminones are formed in situ upon mixing a conjugated allenone or allenyl ester with the alkynylamine, thus the pyridine‐forming transformation is typically a one pot process. magnified image

2‐Aryl‐substituted cyclopropyl aldehydes undergo an unprecedented Au nanoparticle‐catalyzed silaboration leading to rearranged linear β‐boronate‐bearing silyl enol ethers. Formation of these products is attributed to the ring opening radical clock rearrangement of the intermediate α‐cyclopropyl radical into a benzyl radical.

Au nanoparticles supported on TiO₂ (1 mol %) catalyze the quantitative cycloisomerization of conjugated allenones into furans under very mild conditions. The reaction rate is accelerated by adding acetic acid (1 equiv), but the acid does not participate in the protodeauration step as in the corresponding Au(III)-catalyzed transformation. The process is purely heterogeneous, allowing thus the recycling and reuse of the catalyst effectively in several runs.

Supported Au nanoparticles on TiO₂ catalyze the unprecedented dehydrogenative disilylation of monosubstituted and 1,1‐disubstituted allenes by Et₂SiH₂ exclusively on the terminal double bond in a stereoselective manner. Treatment of the disilylation products with H₂O, in a one‐pot operation also catalyzed by Au/TiO₂, leads to 3‐alkylidene‐1,2,5‐oxadisilolanes, an unknown class of heterocyclic compounds, which are excellent scaffolds for the stereoselective synthesis of alkenes under Hiyama‐type cross‐coupling conditions.

Aromatic aldehydes and acetophenones undergo silylative pinacol-type reductive dimerization in their reaction with silylborane pinB-SiMe2Ph (pin: pinacolato) catalyzed by supported Au nanoparticles on TiO2. It is proposed that after initial activation of silylborane by Au nanoparticles and addition to the carbonyl functionality of an aromatic aldehyde or ketone, an aryl silyloxy radical is generated from the collapse of the intermediate adduct, which then dimerizes through a chain process. The silyloxy radical was almost quantitatively trapped, in the presence of TEMPO.

Supported Au nanoparticles on TiO₂ catalyze the insertion of carbenes from α-diazocabonyl compounds into hydrosilanes. It is proposed that the transformation involves two modes of catalytic activation: formation of nucleophilic Au carbenes on the surface of nanoparticle via expulsion of N₂ and activation of the Si–H bond of hydrosilane on Au nanoparticle, followed by coupling of the chemisorbed species. No external ligands or additives are required, while the process is purely heterogeneous, thus allowing the recycling and reuse of the catalyst.