Cobalt‐catalyzed C−H amination of arenes with alkylamines by the assistance of 8‐aminoquinoline as auxiliary through sp2 C−H bond functionalization has been achieved. Attractive features of this protocol include the low loading of the cobalt catalyst and the readily available reagents.
The synthesis of biologically relevant homophthalimide and 3‐aminoisocoumarin nuclei via palladium‐catalyzed carbonylation of 2‐(2‐iodoaryl)acetamides has been developed. The degree of N‐substitution on the starting amide substrate dictates whether C−N or C−O coupling takes place in the final step of the catalytic cycle giving rise to each type of heterocycle. The introduction of a second C−halogen bond in the starting acetamides allows a catalytic cascade double carbonylation involving a C−H activation step to give fused heterocyclic structures.
A copper(I)‐catalyzed, (diacetoxyiodo)benzene [PhI(OAc)2]‐mediated ring‐expansion/thiolactonization of α‐oxo ketene dithioacetals was efficiently realized via azidation of the internal olefinic C−H bond with sodium azide under mild conditions. Sequential amination, ring‐expansion rearrangement, and thiolactonization occurred to form aminated thiolactones in the presence of acetic anhydride as the additive, while only C−H amination to afford the unprotected enamines occurred when using ammonium sulfide as a reducing additive. The in situ generated vinyl azides were confirmed as the reactive intermediates, which were captured by phenylacetylene to produce triazoles. This protocol provides a concise route to thiolactone derivatives and unprotected enamines.
The palladium(II)‐catalyzed hydroarylation of diphenylphosphorylallenes (via 1,2‐addition of the allenic double bond) with arylboronic acids in the presence of sodium hydroxide and oxygen is developed. The regioselectivities turn out to be well controlled, affording 2‐aryl‐3‐(diphenylphosphinyl)alkenes as the only product. Moreover, the stereoselectivities for reactions of γ‐substituted allenes can also be nicely controlled, resulting in the formation of Z‐alkenes. The reaction shows high substituent loading capability and tolerance of various substituents. A mechanism, including transmetalation of arylboronic acid with palladium halides, insertion of the 1,2‐allenic double bond to the Pd−Ar bond, and protonation to afford the final hydroarylation product is proposed.
A novel and selective method for the simple copper‐catalyzed α‐amination of α‐aminocarbonyl compounds to afford 2‐amino‐2‐iminocarbonyl and 2‐amino‐2‐oxocarbonyl compounds is reported. This transformation is achieved by C(sp3)−H and N−H bond oxidative cross‐coupling and selective C−N bond oxidative cleavage. This reaction system has a broad reaction scope, providing a facile pathway for the α‐functionalization of α‐amino ketones.
The first highly enantioselective intramolecular N−H bond insertion was realized by using copper catalysts modified with chiral spirobisoxazoline ligands, which provides a novel strategy for the synthesis of chiral 2‐carboxytetrahydroquinolines. This reaction features fast reaction rate, high yield, high enantioselectivity, and mild reaction conditions.
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.
An efficient ligand‐free copper‐manganese (Cu‐Mn) spinel oxide‐catalyzed direct tandem C−H oxygenation and N‐arylation of benzylamines has been developed. The method has been utilized for the synthesis of medicinally important 2‐arylquinazolin‐4(3H)‐ones. Salient features of this method include recyclable catalyst, no ligand, excellent product yields, shorter reaction times and a broad substrate scope.
Under indium Lewis acid catalysis, a nitrogen atom of N‐unsubstituted pyrroles was replaced with a nitrogen atom of primary amines, thereby producing N‐aryl‐ and N‐alkylpyrroles. This system formally introducing such carbon frameworks to the pyrrole nitrogen atom shows unique selectivity: only the H−N(pyrrolyl) unit undergoes the N‐arylation and N‐alkylation even in the coexistence of a similar H−N(indolyl) part; and an aryl–halogen bond remains intact. These are clearly different from the typical method depending on the C−N(pyrrolyl) bond‐forming reaction with organic halides as substrates. From a viewpoint of pyrrole N‐protection–deprotection chemistry, worth noting is that a methyl group on the pyrrole nitrogen atom can be removed, albeit in a formal way.
So far, the direct C−H alkenylation of aromatic nitriles with alkynes has not been achieved. Herein, we discribe the first manganese‐catalyzed C−H alkenylation of aromatic N−H imidates to access mono‐alkenylated aromatic nitriles. The reaction is accelerated by the presence of a catalytic amount of sodium pivalate. This protocol is also highlighted by the simple catalytic system, good compatibility of functional groups, and excellent mono‐/dialkenylation selectivity as well as E/Z stereoselectivity.
A regio‐ and stereoselective method for the synthesis of (E)‐α,β‐unsaturated carbonyls has been developed via a silver‐catalyzed tandem epoxide rearrangement/intermolecular carbonyl‐heteroalkyne metathesis. Various heteroalkynes including ynol ethers, ynamides, and thioalkynes work well for this transformation, leading to the production of (E)‐α,β‐unsaturated esters, amides, and thioesters in moderate to excellent yields with good functional group compatibility. It represents one of the rare examples of regio‐ and stereoselective intermolecular alkyne‐carbonyl metathesis (ACM).
N‐Alkenylated triazolinone ylides were generated through copper‐catalyzed oxy‐N‐alkenylation of triazolopyridines. The mechanistic course of this aerobic tandem reaction has been experimentally elucidated and primary photophysical data of the ylide products are also given.
The nickel‐catalyzed borylation of aryl 2‐pyridyl ethers via the loss of a 2‐pyridyloxy group is described. This method allows a 2‐pyridyloxy group to be used as a convertible directing group in C−H bond functionalization reactions. The nickel catalyst can also borylate arylmethyl 2‐pyridyl ethers, in which the stereochemistry at the benzylic position is retained in the case of chiral secondary benzylic substrates.
A cobalt‐catalyzed regioselective C‐3 alkylation of coumarins was realized under mild reaction conditions, during which a variety of substituted coumarins including those containing sensitive functional groups could smoothly undergo the selective C(sp2)−C(sp3) bond formation with a series of cyclic or straight‐chain alkyl ethers.
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.
A simple and efficient one‐pot approach has been developed for a copper‐catalyzed phosphorylation of glycine derivatives under air and at room temperature. The present cross‐dehydrogenative coupling allows various methoxyphenyl‐protected glycine derivatives to be phosphorylated using diverse alkyl and aryl phosphites through an oxidative coupling between Csp3−H and P−H bonds catalyzed by copper iodide. This method provides a new synthetic tool to obtain biologically active α‐aminophosphonates.
The rhodium‐catalyzed asymmetric allenylation of sulfonylimines is disclosed providing silyl homoallenylamide products in up to 99:1 er. Through subsequent activation of the C−N bond of the silyl homoallenyl sulfonamide, palladium‐catalyzed stereospecific allylic allenylation could be achieved giving C−C bond formation with high chirality transfer. The synthetic utility of both the silyl homoallenyl sulfonamides and the silyl homoallenyl malonates as bis(nucleophiles) is demonstrated.
An efficient protocol for the direct sulfanylation of various 4‐hydroxycoumarins and 4‐hydroxyquinolinones in good yield with arylsulfonylhydrazides as sulfanylating agents was developed via copper(I) bromide⋅dimethyl sulfide‐catalyzed S–O, S–N bond cleavage and C–S cross‐coupling reactions. A highly selective fluorescence turning‐on sensing of cadmium(II) ions in water using the synthesized 3‐sulfanyl‐4‐hydroxycoumarin derivative was also investigated.
The copper‐catalyzed reaction of 5‐substituted penta‐1,4‐diyn‐3‐yl acetates with P(O)H compounds to efficiently give a new class of phosphonyl diynes is reported. The reaction may take place through a regioselective nucleophilic attack of phosphorus nucleophiles on Cu‐allenylidene intermediates to form allenyl intermediates followed by a rapid allene‐alkyne isomerization process. The synthetic utility of the obtained products is demonstrated.
2,3‐Dihydroindenes and isoindolines are important skeletons present in medicinal and synthetic chemistry. In this paper, an acetyl bromide promoted metal‐free construction of 2,3‐dihydroindenes and isoindolines with high synthetic efficiency is developed.
