A sequential one‐pot synthesis of Michael adducts of aroylmethylidenemalonates with activated aromatics is described. The method involves treatment of trans‐2‐aryl‐3‐nitro‐cyclopropane‐1,1‐dicarboxylates with boron trifluoride etherate to form aroylmethylidenemalonates in situ and then addition of activated aromatics such as indoles, carbazole, pyrrole, thiophenes, methoxybenzenes and benzodioxole followed by a catalytic amount of indium(III) triflate to the same reaction vessel. To prove the synthetic potential of the resulting Michael adducts, one of the adducts was transformed into a pharmaceutically interesting dihydropyridazinone derivative.
Product selectivity control for the synthesis of imidoylindoles and 4‐alkylidenedihydroquinazolines from N‐imidoyl‐o‐alkynylanilines via silver triflate‐catalyzed cycloisomerization or tetrabutylammonium fluoride‐promoted cyclization is described. The product selectivity depends mainly on the catalyst/promoter used, and on the substituents on the alkyne and amidine functions of the substrates.
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.
A method for copper‐catalyzed aryltrifluoromethylation of N‐phenylcinnamamides is reported. This method provides a straightforward route to a variety of CF3‐containing 3,4‐dihydroquinolin‐2(1 H)‐ones with excellent regioselectivity and diastereoselectivity.
Recent progress in asymmetric organocatalysis has led to the development of several asymmetric transformations that employ various substrates. Among these, cyanoacetates have emerged as excellent nucleophiles in conjugate addition, alkylation, Mannich and α‐heterofunctionalization reactions. In this review we discuss the enantioselective functionalization of 2‐cyanoacetates through organocatalytic reactions.
An efficient synthesis of (E)‐5‐aryl(halo)methylenebicyclo[2.2.2]oct‐2‐enes is reported. Lewis acid‐promoted carbohalogenation of 4‐(3‐arylprop‐2‐ynyl)‐cyclohex‐2‐enols in dichloromethane proceeds rapidly to afford the exo‐methylene‐bridged bicycles in good yields. This method also provides an easy access to (E)‐5‐aryl(halo)methylenebicyclo[2.2.1]hept‐2‐enes from the five‐membered ring 2,6‐enynols. The reactions are procedurally simple and high yielding, producing the aryl(halo)methylene‐bridged bicycles in minutes under air and mild conditions.
The skeletal rearrangement of ether tethered N‐sulfonyl‐1,2,3‐triazoles has been achieved by rhodium(II) catalysis. This method offers a rapid entry to 2‐aminoindanone and dihydroisoquinoline architectures which can be further transformed to other valuable building blocks, such as vicinal aminoindanols, isoquinolines and isoquinolinones. A pathway involving an azavinyl rhodium carbene intermediate was proposed according to a preliminary mechanistic study.
A simple and efficient domino protocol has been developed for the preparation of biologically important benzamides, 2,2‐diazidobenzofuran‐3(2H)‐ones and benzoxazolones from various structurally and electronically divergent acetophenones and ortho‐hydroxyacetophenones in the presence of molecular iodine, sodium azide and sodium bicarbonate at 100 °C in good to excellent yields.
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.
A novel method for the synthesis of 3‐iodoquinolines was developed by copper‐catalyzed tandem annulation from diaryliodoniums, nitriles, and 1‐iodoalkynes. It is a method that is characterized by the most convenient operation and wide molecular diversity.
A zinc diiodide (ZnI2)‐mediated direct synthesis of 2,3‐dihydroisoxazoles via a [3+2] cycloaddition reaction of the nitrones and non‐electron‐deficient terminal alkynes has been developed. This method was applied in the formal synthesis of HPA‐12 and aminoglucose.
The organocatalytic trichlorosilane reduction system has been successfully utilized to develop a multi‐step tandem approach for the easy preparation of chiral 2‐methyl‐3‐alkylindolines starting from simple 2‐methylindoles and aldehydes. A broad range of chiral 2‐methyl‐3‐alkylindoline products was obtained with high yields and enantioselectivities and excellent stereoselectivities by this approach.
A one‐pot, three‐component method for preparation of 1,4,5‐trisubstituted 5‐acyl‐1,2,3‐triazoles has been developed based on a highly selective acylation of the copper(I)‐carbon(sp2) bond with acyl chlorides in the presence of the copper(I)‐carbon(sp) bond. The procedure is characterized by high efficiency and simple conditions.
A general method to generate umpolung of aldimines with cyanide was developed via the addition of cyanide to aldimines followed by a proton transfer from the carbon atom to the nitrogen atom in the resulting cyanide adducts. This novel method was successfully applied to the first imino‐Stetter reaction of aldimines obtained from 2‐aminocinnamic acid derivatives and aromatic aldehydes with cyanide, affording 2‐aryl‐substituted indole‐3‐acetic acid derivatives. Furthermore, the usefulness of this method was successfully demonstrated by the synthesis of an FPTase inhibitor, one of the biologically important 2‐arylindole‐3‐acetic acid derivatives.
A practical synthesis yielding P‐perfluoroalkylated phosphines from triarylphosphines and perfluoroalkyl iodides has been developed. The photoinduced reaction involves the substitution of aryl groups on the phosphorus atom with perfluoroalkyl groups to successfully afford P‐perfluoroalkylated phosphines. In addition, the P‐perfluoroalkylated phosphines were found to promote the Cu‐free cross‐coupling reaction of acid chlorides with terminal alkynes.
A chemoselective reduction of α‐keto amides to biologically important α‐hydroxy amides (mandelamides) by polymethylhydrosiloxane (PMHS) using 5 mol% potassium phosphate (K3PO4) as catalyst has been developed. This transition metal‐free protocol discloses excellent chemoselectivity for the ketone reduction of α‐keto amides in the presence of other reducible functionalities like ketone, nitro, halides, nitrile and amide. Also, the chemoselectively reduced α‐hydroxy amide has been derivatized to isocyanide‐free Passerini adducts. The N‐alkyl‐α‐hydroxy amides have been successfully converted to 3‐phenyloxindole derivatives by treatment with methanesulfonyl cholride and triethylamine.
An N‐phthalimide‐protected (ortho‐aminophenyl)propiolate was prepared by the carboxylation of the corresponding silylalkyne precursor with carbon dioxide. The obtained propiolate was further transformed to various 3,4‐fused 2‐quinolones via cycloadditions and subsequent deprotection/lactam formation.
The asymmetric synthesis of a set of hydroxyphenyl γ‐valerolactones was achieved starting from 2‐silyloxyfuran and alkoxy‐substituted benzaldehydes as common precursors. Key synthesis steps included an enantioselective vinylogous Mukaiyama aldol reaction and a Barton–McCombie deoxygenation. Five enantioenriched γ‐valerolactone targets were obtained in 5–6 steps, 18–63% overall yields and 82–98 % ee, paving the way for the straightforward entry to this class of biologically effective and poorly available flavan‐3‐ol metabolites. In parallel, an unprecedented one‐pot reductive ring expansion process was fortuitously discovered, yielding racemic δ‐lactone analogues from phenolic butanolide precursors.
Grignard reagents are probably the best organometallics to develop large‐scale eco‐friendly cross‐couplings compatible with the requirements of sustainable development. This account aims to highlight some reactions having an interesting industrial potential and gives the personal point of view of the authors on some attractive fields of research in this area.
