Copper chloride‐catalyzed aerobic oxidative annulation of N‐furfuryl‐β‐enaminones provides access to polysubstituted pyrroles and indoles. This protocol involves an unprecedented copper chloride‐catalyzed oxidative chlorination of furan and pyrrole rings with oxygen as the terminal oxidant.
In the presence of sodium carbonate, the [4+3] cycloadditions of α‐halogeno hydrazones with nitrones were performed efficiently, and affording 2,3,4,7‐tetrahydro‐1,2,4,5‐oxatriazepines in moderate to high yields.
Potassium hydroxide‐catalyzed hydrosilylation exhibits excellent activity and chemoselectivity for the reduction of cyclic imides under mild reaction conditions. The chemoselectivity of the reduction system may be readily tuned by changing the identity and stoichiometry of the hydrosilanes: a polymethylhydrosiloxane (PMHS)/potassium hydroxide reduction system resulted in the reduction of various cyclic imides to the corresponding ω‐hydroxylactams in 70–94% yield, while the diphenylsilane (Ph2SiH2)/potassium hydroxide reduction system selectively afforded the aryl lactams in 33–95% yield. These catalytic protocols tolerate diverse functional groups and are easy to scale up.
The dynamic kinetic resolution of α‐substituted racemic β‐lactams by alcoholytic ring‐opening, catalyzed by immobilized lipase B from Candida antarctica is described. With this process, a variety of racemic α‐substituted N‐Cbz‐azetidinones (Cbz=benzyloxycarbonyl) was transformed to the corresponding N‐Cbz‐protected β2‐amino acid allyl esters with high enantioselectivity (up to 99%) and high yields (up to quantitative) at room temperature.
A new enantioselective synthetic method for the synthesis of α,α‐dialkylmalonates with a quaternary carbon center was developed via α‐alkylation of prochiral malonates by phase‐transfer catalysis (PTC). Asymmetric α‐alkylation of benzylideneamino tert‐butyl α‐methylmalonates under phase‐transfer catalytic conditions in the presence of (S,S)‐3,4,5‐trifluorophenyl‐NAS bromide afforded the corresponding α,α‐dialkylmalonates in high yields (up to 97%) with excellent enantioselectivities (up to 98% ee). The products were then selectively hydrolyzed to chiral malonic monoacids under basic, acidic, or catalytic hydrogenation conditions.
The Wittig reaction of isatin derivatives with Morita–Baylis–Hillman bromides of cinnamaldehydes afforded 3‐dienylidene‐2‐oxindoles. These trienes were converted into the corresponding spirooxindoles in a stereoselective manner in refluxing toluene in good yields. The diastereomeric spirooxindoles could be obtained stereoselectively by adding a catalytic amount of palladium(II) acetate via the palladium‐catalyzed isomerization of EEE‐trienes to ZEE‐trienes followed by a more facile 6π‐electrocyclization process. The obtained spirooxindoles could be further functionalized by palladium‐catalyzed oxidative arylation, thionation with Lawesson’s reagent, catalytic hydrogenation and Friedel–Crafts‐type reaction.
Silver‐catalyzed three‐component, tandem reactions of 4‐alkynyl‐2‐oxo‐2H‐chromene‐3‐carbaldehydes, amines and various nucleophiles result in the formation of highly functionalized chromeno[3,4‐c]pyridin‐5‐ones in high yields. Gold‐catalyzed [4+2] cycloadditions of 4‐alkynyl‐2‐oxo‐2H‐chromene‐3‐carbaldehydes with alkynes or alkenes have also been achieved to afford benzo[c]chromen‐6‐ones efficiently.
A straightforward approach for the chemodivergent synthesis of quinolines is described through site‐selective coupling of ortho‐aminoaryl ketones with α‐enolic dithioesters (DTEs) under solvent‐free conditions. The operationally and user‐simple one‐pot methodology is based on the trifunctional nature of DTEs. Both the carbonyl and the thiocarbonyl moiety in α‐enolic dithioesters were employed for the efficient construction of three differently substituted quinolines in a chemoselective manner simply by variation of an easy to handle acid catalyst.
Efficient one‐step syntheses of α,β‐ and β,β‐dihaloenones were achieved by ruthenium(II)‐catalyzed reactions between cyclic or acyclic diazodicarbonyl compounds and oxalyl chloride or oxalyl bromide in moderate to good yields. This methodology offers several significant advantages, which include ease of handling, mild reaction conditions, one‐step reaction, and the use of an effective and non‐toxic catalyst. The synthesized compounds were further transformed into highly functionalized novel molecules bearing aromatic rings on the enone moiety using the Suzuki reaction.
A practical and novel process for the decarboxylative fluorination of β‐ketoacids in water in the presence of phase transfer catalyst has been developed, affording a series of α‐fluoroketones in good to excellent yields. Furthermore, a preliminary investigation for the catalytic asymmetric transformation was performed and a proposed mechanistic pathway for this catalytic process was proposed.
A straightforward and efficient method for the synthesis of nitrogen‐functionalized cyclopentane derivatives via [3+2] cycloaddition of enamines with donor‐acceptor cyclopropanes in the presence of catalytic amounts of various Lewis acids at room temperature has been developed; furthermore, the corresponding β‐amino acid was synthesized by monodecarboxylation and hydrogenolysis. An enantioenriched synthesis of nitrogen‐functionalized cyclopentane derivatives through dynamic kinetic asymmetric transformation of racemic donor‐acceptor cyclopropanes has also been achieved employing a copper complex [Cu(OTf)2‐ L1 ] as the catalyst affording an enantiomeric ratio up to 8:1.
Catalytic asymmetric reduction of N‐unsubstituted β‐enamino esters represents a major challenge for asymmetric catalysis. In this paper, the first organocatalytic system that could be used for the asymmetric hydrosilylation of N‐unsubstituted β‐enamino esters has been developed. Using N‐tert‐butylsulfinyl‐L ‐proline‐derived amides and L ‐pipecolinic acid‐derived formamides as catalyst, a broad range of β‐aryl‐ and β‐alkyl‐substituted free β‐amino esters could be prepared with high yields and enantioselectivities. The practicality was illustrated by the gram‐scale asymmetric synthesis of ethyl (R)‐3‐amino‐3‐phenylpropanoate and isopropyl (S)‐3‐amino‐4‐(2,3,5‐trifluorophenyl)butanoate. The resulting product can be smoothly transformed to the FDA approved medicines dapoxetine and sitagliptin in a short synthetic route.
One class of potential Lewis acids that has received negligible attention as a catalyst is the carbocation. Here we show the potential of triarylmethylium ions as highly powerful Lewis acid catalysts for organic reactions. The Lewis acidity of the triarylmethylium ion can be easily tuned by variation of the electronic properties of the aromatic rings and the catalytic activity of the carbocation is shown to correlate directly to the level of stabilization of the empty pC‐orbital at the cationic carbon. The versatility of triarylmethylium ions as efficient Lewis acid catalysts for organic reactions is demonstrated in Diels–Alder, aza‐Diels–Alder, conjugate addition, halogenation, epoxide rearrangement and intramolecular hetro‐ene reactions.
A practically simple and direct α‐alkylation of unactivated ketones using benzylic alcohols has been achieved. The in situ formed acetals are the key for the success of the reaction. The catalyst, silver hexafluoroantimonate(V) (AgSbF6) provides double activation by converting the ketone into an enol ether via acetal and generation of carbocationic center at the benzylic position of the benzylic alcohol. The alcohols include benzylic propargyl alcohols, cinnamyl alcohols, and diarylmethanols.
An intramolecular imination/azidation sequence has been realized through the tetrakis(acetonitrile)copper(I) hexafluorophophate [Cu(CH3CN)4PF6]‐catalyzed reaction of γ,δ‐unsaturated ketone O‐benzoyl oximes with trimethylsilyl azide (TMSN3). The reaction proceeds via the copper‐mediated N O cleavage and subsequent C N forming 5‐exo cyclization. The thus formed intermediate is then azidated to afford the corresponding dihydropyrrole product. Preliminary mechanistic investigations suggest that the cyclization step does not involve a radical intermediate.
Diynes bearing one terminal and one triarylmethyl‐substituted alkyne were converted into complex benzofluorenone derivatives via a one‐pot process involving a gold‐catalyzed step followed by a photocyclization/oxidation. In the first step an N‐oxide was used to position‐selectively generate an α‐oxo carbenoid at the terminal alkyne which after a regioselective 1,6‐carbene transfer along the tethered tritylalkyne and a subsequent aryl 1,2‐shift furnished tetraphenylethylene‐like derivatives. These intermediates were successfully transformed to fluorenones via oxidative photocyclization.
An asymmetric Michael addition of 5H‐oxazol‐4‐ones to vinyl sulfones has been developed. In the presence of 10 mol % of quinine‐based benzyl‐substituted thiourea as catalyst at 0 °C, the products could be obtained with excellent enantio‐ and diastereoselectivity (up to>99 % ee and>20:1 dr). 1.0 mol % of catalyst also produced the corresponding adducts with similar stereoselective results when the temperature was increased to 25 °C. The obtained adducts have been demonstrated as significant synthetic fragments to conveniently access the monofluorinated analogs of biologically important 2‐tertiary hydroxyl‐3‐methyl‐substituted carboxylic acid derivatives.
A simple and efficient ligand‐free nickel‐based catalytic system has been developed for the 1,4‐addition of arylboronic acids to α,β‐unsaturated carbonyl compounds. With catalyst loadings of 1–2 mol%, a series of 1,4‐adducts from chalcones and cinnamates was obtained in moderate to excellent yields within 5–30 min under a nitrogen atmosphere and microwave irradiation. The 1,4‐addition of arylboronic acids to acrylates is less efficient.
An efficient and practical decarboxylative double benzylation method for various 2‐picolinic acids has been established by using a bimetallic catalytic system of palladium(II) chloride (PdCl2) and silver(I) oxide (Ag2O), which offered a variety of diarylmethane derivatives with moderate to good yields.
