The first example of a nickel‐catalyzed C–H trifluoromethylation of electron‐rich heteroarenes, including imidazopyridines, indoles and thiophenes, has been developed with the commercially available and relatively inexpensive industrial raw material iodotrifluoromethane (CF3I) as the trifluoromethylating reagent. The synthetic potential of this method is demonstrated by its successful application to the direct trifluoromethylation of the biologically active molecules melatonin and zolmitriptan.
A new synthetic method for α‐alkynyl‐α,β‐unsaturated esters is presented herein. The method is based on a copper(I)‐catalyzed three‐component reaction of a terminal alkyne, diazoesters and aldehydes. The reaction is featured by mild conditions, high yields and excellent stereoselectivity. Cu(I) carbene migratory insertion is proposed as the key step in the transformation.
An asymmetric total synthesis of ent‐ancistrocladinium A was developed via chiral phosphoric acid‐catalyzed asymmetric reductive amination of 1‐aryl‐2‐propanone and naphthylamine followed by a Bischler–Napieralski reaction. Direct use of the naphthyl moiety in the amine as a key building block in the natural product allowed us to achieve the total synthesis of ancistrocladinium A in only three steps from the known starting materials.
The introduction of a trifluoromethyl group into the 2′‐position of spiro‐pyrrolidine‐3,3′‐oxindoles is described. By using 1 mol% of a quinine‐derived squaramide as catalyst, the 2,2,2‐trfluoroethylamine (CF3CH2NH2)‐derived ketimine is transformed initially into a trifluoromethylimine through an umpolung reaction. The subsequent 1,3‐dipolar cycloaddition gives the pharmaceutical important target compounds in excellent yields, enantioselectivities and diastereoselectivies.
1‐Alkynylcyclopropyl tosylates react with alkylmagnesium halides in the presence of catalytic ferric acetylacetonate [Fe(acac)3] under net propargylic substitution; allene formation, which is the prevalent reactivity mode of propargylic substrates otherwise, was noticed as a side reaction only when branched alkyl‐ or aryl‐Grignard reagents were used. These transformations represent the first successful iron‐catalyzed cross‐coupling reactions of tert‐alkyl electrophiles.
Commercial gold nanoparticles supported on titanium dioxide (TiO2) were found to be a highly efficient catalyst for alkyne hydroamination. Terminal alkynes could easily undergo intermolecular hydroamination with low catalyst loadings (0.2 mol% Au) under solvent‐free conditions. Indoles were efficiently synthesized using microwave heating through intramolecular hydroamination.
Aryl carbamates were for the first time applied as electrophiles in the cross‐coupling with arylsilanes via nickel or iron catalysis to construct valuable biaryl compounds. This new coupling reaction features a good group tolerance and non‐sensitivity to steric hindrance on both aryl carbamates and arylsilanes.
A highly efficient chiral N,N′‐dioxide‐zinc(II) complex catalytic system has been developed for the enantioselective aza‐Friedel–Crafts reaction of isatin‐derived ketimines with indoles. A series of enantiomerically enriched 3‐indolyl‐3‐aminooxindoles containing a tetrasubstituted stereocenter were obtained in up to 99% yield with up to 96% ee. Furthermore, control experiments provide a fundamental sight into the mechanism of the reaction.
A facile method to synthesize 3‐halobenzo‐heterocyclic‐2‐carbonyl compounds is described. Mechanistic studies suggested that a halo‐cyclization process, which generated the unstable spiro‐acetal transition state and readily convertible to the corresponding carbonyl compound might be involved. Diverse 3‐halobenzo‐heterocyclic‐2‐carbonyl compounds could be synthesized with up to 95 % yield in mild conditions with inexpensive starting materials.
N‐Tosylhydrazone‐yne‐ene substrates are satisfactorily prepared and their cyclization under rhodium catalysis is evaluated. A cascade process involving rhodium vinyl carbene formation – through carbene/alkyne metathesis – and cyclopropanation has been developed to stereoselectively afford vinylcyclopropanes.
A novel one‐pot reaction which combines halogenation, decarboxylation/desulfonamidation with oxidation has been developed. Diverse valuable 3,3‐dihalo‐2‐oxindole compounds can be produced rapidly and safely with isolated yields of up to 98% under mild conditions.
A copper‐catalyzed new domino reaction allowed the facile and direct construction of the dibenzo‐fused azepinone ring leading to an array of novel small molecules. The co‐catalyst, ligand or additive free one‐pot method afforded a unique class of functionalized derivatives, one of which showed encouraging PDE4 inhibition in vitro and apoptosis in vivo.
An efficient and easy method for C −C homocoupling was developed using cobalt bromide as catalyst. A series of functionalized alkyl bromides and alkyl chlorides were coupled in high yields under mild conditions. This reaction seems to involve a radical intermediate.
A novel iron‐catalyzed direct alkylamination reaction of phenols has been achieved with O‐benzoyl‐N‐alkylhydroxylamines as aminating agents. This protocol provides a facile access to N‐alkyl‐substituted aminophenols though a radical reaction from phenols. The catalytic direct alkylamination operates at room temperature without the need of any ligands and additives to afford the desired products with excellent regioselectivity and functional group tolerance.
An efficient asymmetric synthesis of spirocyclohexenone β‐lactams bearing three contiguous stereocenters has been achieved in moderate to good yields and high stereoselectivities. The protocol involves the combination of a squaramide‐catalyzed sulfa‐Michael addition under desymmetrization via a dynamic kinetic resolution of racemic 2,5‐cyclohexadienones.
A manganese(II) acetate‐catalyzed domino reaction of vinyl azides and 4‐hydroxycoumarin has been developed for the synthesis of polyfunctionalized spirofuranone‐lactams. A wide range of vinyl azides are capable of providing the desired spirofuranone‐lactams in good to excellent yields. The reaction was achieved via thermal decomposition of vinyl azides to 2H‐azirines, followed by an intramolecular nucleophilic attack and stereoselective cyclization. The mild reaction conditions and easy operation make this reaction advantageous for the synthesis of spirofuranone‐lactams.
The first facile one‐pot synthesis of sulfone‐containing oxindoles with easily accessible disulfides as the sulfonylating precursors is described. This reaction occurs smoothly under transition metal‐free conditions and shows excellent functional group tolerance, allowing the facile and efficient green synthesis of various sulfone‐containing oxindoles in aqueous solution. Preliminary mechanistic studies reveal that both water (H2O) and potassium persulfate (K2S2O8) can be the oxygen source of the sulfone groups in the products.
N‐Propargyl‐ and N‐homoallenyl‐2‐bromo‐β‐tryptamines undergo gold(I)‐catalyzed dearomatizing cyclizations to afford 2‐bromospiroindolenines that are in situ hydrolyzed to furnish spirooxindoles in a one‐pot process. Tryptophane derivatives (R2=CO2Et) led upon cyclization to chiral spirooxindoles in excellent diastereoselectivities.
The formation of an amide bond via incorporation of two isocyanide units during a palladium‐catalyzed construction of the indoloquinoline ring afforded N‐substituted 6H‐indolo[2,3‐b]quinoline‐11‐carboxamides as new cytotoxic agents. The solvent and base play a key role in the selective and unprecedented synthesis of this class of amides.
