A new copper‐catalyzed, efficient method for the synthesis of heterodiarylmethanes through the coupling of imidazo[1,2‐a]pyridines with indoles employing N,N‐dimethylformamide as a methylenating reagent has been developed. A library of 3‐(1H‐indol‐3‐ylmethyl)‐imidazo[1,2‐a]pyridine derivatives has been synthesized under aerobic reaction conditions. This protocol is also applicable for the synthesis of (4‐imidazo[1,2‐a]pyridin‐3‐ylmethyl)(phenyl)dimethylamines. The method is highly selective for the hetero‐coupling.
Readily available iron(III)‐based imidazolium salts have proven to be very versatile catalysts for the allylic substitution reaction of alcohols with anilines, allowing the synthesis of quinolines, 2‐allylanilines and 4‐allylanilines just by modulating the reaction conditions. Noteworthy, the formation of quinoline derivatives proceeds by ortho‐allylation of the corresponding aniline and subsequent oxidative cyclization mediated by atmospheric oxygen. The reaction using anilines as nucleophiles is selective to the C‐alkylation versus the N‐alkylation, under any reaction conditions studied.
A simple and mild copper‐catalyzed sulfonylation of 8‐aminoquinolines with sodium and lithium sulfinates is reported. In the presence of manganese(III) acetate [Mn(OAc)3] as cooxidant a highly site‐selective C−H functionalization at the C‐5 position takes place. The reaction proceeds readily at room temperature in air and various sulfones were synthesized in moderate to high yields. Moreover, a straightforward procedure for the conversion of organolithium reagents and sulfur dioxide into C‐5 sulfonylated quinolines was developed.
A simple and practical method of fluoroalkylthiolation using fluoroalkylsulfonyl chlorides (RfSO2Cl, Rf=CF3, C4F9, C8F17, CF2H and CH2CF3) has been developed. These easy‐to‐handle reagents are powerful and can be used for electrophilic fluoroalkylthiolation of electron‐rich arenes and thiols using diethyl phosphite as reducing agent.
4H‐Pyran units are frequently present in molecules with significant biological and pharmaceutical activities. Herein, we present the first enantioselective formal [3+3] cycloaddition between 2‐(1‐alkynyl)‐2‐alken‐1‐ones and β‐keto esters catalyzed by a cyclohexyldiamine‐based thiourea‐tertiary amine bifunctional catalyst. Under the mild and eco‐friendly conditions, a wide range of polysubstituted 4H‐pyrans were obtained in moderate yields with good enantioselectivities.
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.
Introduction of oxygen and nitrogen into organic molecules is one of the fundamental strategies for their functionalization. Traditional approaches rely on the formation of an activated intermediate, which is then modified in a subsequent step. Here we report a simple direct oxidative α‐acetoxylation and azidation of α‐C−H bonds in Tröger's base analogues promoted by N‐bromosuccinimide (NBS) and palladium(II)acetate [Pd(OAc)2] under mild conditions. This approach is pivotal on NBS oxidizing the carbon atoms next to the nitrogen atoms in the presence of Pd(OAc)2 followed by a reaction with oxygen‐ or nitrogen‐centred nucleophiles such as KOAc or NaN3 to yield either the mono‐ and bisacetoxylated or azidated Tröger's base derivatives in a stereo‐ and chemoselective manner. The obtained products can be efficiently modified to access synthetically meaningful structures.
Direct strategies for the iodothiocyanation and iodonitration of allenes have been developed. In this process, potassium thiocyanate/silver nitrite and molecular iodine are used as the source of SCN, ONO2 and iodine to provide the desired products in moderate to good yields with high stereoselectivity.
The sodium iodide/hydrogen peroxide‐mediated oxidation/lactonization of indolepropionic acids was achieved, affording the corresponding spirocyclic oxindole‐lactones in moderate to high yields. This metal‐free procedure features mild reaction conditions, non‐toxicity and easy handling, with hydrogen peroxide (H2O2) as a clean oxidant.
The bis(N‐heterocyclic carbene)(diphenylacetylene)palladium complex [Pd(ITMe)2(PhC≡CPh)] (ITMe=1,3,4,5‐tetramethylimidazol‐2‐ylidene) acts as a highly active pre‐catalyst in the diboration and silaboration of azobenzenes to synthesize a series of novel functionalized hydrazines. The reactions proceed using commercially available diboranes and silaboranes under mild reaction conditions.
A novel N‐iodosuccinimide‐mediated decarboxylative (4+1) oxidative annulation between 2‐vinylpyridine derivatives and malonate monoesters was developed. It offers a new way to construct indolizine derivatives by utilizing malonate monoesters as a C1 unit. The alkyl 2,2‐diiodoacetate was found to be the active reaction intermediate during the transformation.
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.
Aluminum(III) complexes derived from aminotriphenolate ligands are shown to be excellent catalysts for the formation of cyclic sulfites from a range of (functionalized) terminal and internal epoxides, and ex situ generated sulfur dioxide. The developed catalytic protocol is characterized by its operational simplicity, wide scope in epoxide reaction partners, good to excellent isolated yields and mild reaction conditions [50–70 °C, p(SO2) <1 bar]. The synthetic potential of these cyclic sulfites in organic synthesis is demonstrated in the preparation of N‐substituted aziridines through a three‐step protocol.
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.
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.
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.
An inexpensive ruthenium‐catalyzed direct C–H olefination of aromatic carboxamides with allyl acetate was developed. This external oxidant‐free protocol provided an efficient route for the synthesis of useful trans‐styrene derivatives in high to excellent yields. The olefination reaction exhibited excellent regioselectivities and allowed the presence of a wide range of functional groups, such as OMe, F, Cl, Br, I, CF3, NMe2, as well as NO2.
