Pyrroles, ubiquitous bioactive heterocycles in nature, are readily prepared via a palladium‐catalyzed oxidative annulation of cyclic trans‐enamines to various internal alkynes in the absence of a directing group.
By using N,N‐dimethylformamide (DMF) as a methylenating reagent, the copper‐catalyzed C H activation of indole was demonstrated as an efficient and facile protocol for synthesizing 3,3′‐diindolylmethane (DIM) and its derivatives. The results indicate that copper chloride was the best catalyst among the investigated transition metal salts, which affords an excellent regioselectivity and good yield when tert‐butyl hydroperoxide (TBHP) was used as an oxidant.
A synthetic strategy has been developed for the synthesis of 2‐dialkylaminoquinolines from easily available quinoline N‐oxides, tertiary amines, diisopropyl H‐phosphonate and carbon tetrachloride (CCl4) in one pot under metal‐free conditions at room temperature.
A transition metal‐free, regioselective C‐5 trifluoromethylation of 2,3‐dihydropyridin‐4(1H)‐ones (cyclic enaminones) with trimethyl(trifluoromethyl)silane (TMSCF3) was developed that proceeds under mild conditions at room temperature. This direct transformation was successful with both electron‐rich and electron‐deficient cyclic enaminones. This method bypasses substrate prefunctionalization and transition metal catalysis, and allows the convenient and direct access to a variety of medicinally important 3‐trifluoromethylpiperidine derivatives. This chemistry also represents a rare example of a direct trifluoromethylation of an internal olefinic C H bond. A radical mechanism is proposed for this reaction.
An efficient strategy for the regioselective ortho‐acylation of azoxybenzenes with various aldehydes in the presence of palladium catalysts has been developed and furnishes good to excellent yields. The reaction proceeds smoothly and can tolerate a variety of functional groups.
A wide range of imidazo[1,2‐a]pyridines are accessible from cheap and readily available 2‐aminopyridines and 1,3‐dicarbonyl compounds using a unique CBrCl3/2‐aminopyridine system for bromination at the α‐carbon. 2‐Aminopyridine is not only the substrate but also acts as a bromination shuttle, transferring the bromine atom from CBrCl3 to the α‐carbon of the 1,3‐dicarbonyl. The reaction mechanism involves a series of reversible steps, including an addition reaction with cyclic transition state, to form a bromo‐hemiaminal intermediate. Isolated yields of up to 97% were obtained under mild conditions and at short reaction times in this transition metal‐free, one‐pot synthesis.
A nickel‐catalyzed facile synthesis of structurally diverse five‐membered lactams from aliphatic amides and terminal acetylenes with the assistance of an 8‐aminoquinolyl auxiliary has been achieved. A broad range of terminal acetylenes and aliphatic amides proved to be the efficient coupling partners, furnishing the corresponding lactams in moderate to good yields. The transformation is proven to undergo an oxidative alkynylation followed by the intramolecular annulation process. The methodology can be extended to aromatic amides and acrylamides, which provides an efficient and straightforward protocol for the construction of a variety of isoindolinone and pyrrolidinone derivatives.
We disclose herein an efficient enantioselective conjugate addition reaction between coumarin‐3‐carboxylic acids and malonic acid half thioesters (MAHTs). The reaction was catalyzed by N‐heteroarenesulfonyl Cinchona alkaloid amides to afford double‐decarboxylative conjugate addition products in good yield with high enantioselectivity. The reaction of various coumarin‐3‐carboxylic acids with MAHTs gave products in high yield with high enantioselectivity.
Polysubstituted furans were obtained with excellent yields via the electrophilic alkynylation of 1,3‐dicarbonyl compoundsws with phenyl‐ or ester‐substituted brominated alkynes. The reaction is catalyzed by the inexpensive and readily available catalyst, cobalt(II) chloride, and has a wide substrate scope. The C(sp) C(sp3) coupling occurs under mild conditions with short reaction times and does not require an inert atmosphere or ligands. It is proposed that the reaction proceeds through a chelation complex of cobalt(II) with the deprotonated 1,3‐dicarbonyl compound.
The 8‐aminoquinoline‐directed, nickel(II)‐mediated ortho‐iodination of benzamides using molecular iodine has been developed. The process is highly regioselective and furnishes only monoiodinated products. A broad range of arenes and heteroarenes with diverse functional groups provided monoiodinated products in good to excellent yields.
A rhodium(III)‐catalyzed selective olefination of picolinamide derivatives has been developed. The reaction shows high regioselectivity, low catalyst loading (0.5 mol%), high yield and good functional group tolerance, providing a convenient strategy for the synthesis of 3‐alkenylpicolinamides.
Direct functionalization of the ubiquitous C H bond is receiving much attention because complex structures can be formed from simple precursors. This paper reports a useful method for the direct hydroxylation of 2‐phenylpyridines using palladium(II) chloride and aqueous hydrogen peroxide. In this method, hydrogen peroxide, which has high atom efficiency, is employed as the oxidant and phenol derivatives are generated via C H activation.
An efficient regioselective synthesis of 2‐acylpyrroles via palladium‐catalyzed addition of pyrroles with benzonitriles and subsequent hydrolysis is developed. The direct acylation reaction of protected as well as (NH)‐free pyrroles proceeded smoothly to afford 2‐acylpyrrole scaffolds of high biological interest.
A general and efficient palladium‐catalyzed intermolecular direct C‐2 alkenylation of indoles using oxygen as the oxidant has been developed. The reaction is of complete regio‐ and stereoselectivity. All products are E‐isomers at the C‐2‐position with no Z‐isomers and 3‐substituted products were detected.
The last decades have seen a tremendous expanse in the application of C H activation of many different substrate classes, including the invaluable indole scaffold. Following the exciting emergence of C H activation as a multi‐faceted platform for functionalization, a versatile tool box has been developed for the preparation of structurally diverse indoles. This review article discusses recent advances and strategies for transition metal‐catalyzed C H activation of indoles.
An efficient and concise one‐pot strategy for the direct alkylation of quinoline N‐oxides via palladium‐catalyzed dual C H bonds activation has been developed. This methodology provides quinoline‐containing heterocyclic molecules in moderate to excellent yields.
An efficient method for the synthesis of 3‐alkylated indoles is described. The oxidative cross‐coupling reaction of diphenylmethane derivatives with indoles at the C‐3 position was achieved employing the N,N‐dimethylcarbamoyl moiety as an auxiliary group in the presence of iron(II) chloride (FeCl2) and 2,3‐dichloro‐5,6‐dicyanoquinone (DDQ).
The palladium‐catalyzed acylation of 2‐aryl‐1,2,3‐triazoles with aldehydes via C H bond activation is described. A wide variety of products was isolated in good to excellent yields. This finding provides a new and useful strategy for the synthesis of aromatic ketones.
