Selective Oxytrifluoromethylation of Allylamines with CO2

Reported is the first oxy‐trifluoromethylation of allylamines with carbon dioxide (CO₂) using copper catalysis, thus leading to important CF₃‐containing 2‐oxazolidones. It is also the first time CO₂, a nontoxic and easily available greenhouse gas, has been used to tune the difunctionalization of alkenes from amino‐ to oxy‐trifluoromethylation. Of particular note, this multicomponent reaction is highly chemo‐, regio‐, and diastereoselective under redox‐neutral and mild reaction conditions. Moreover, these reactions feature good functional‐group tolerance, broad substrate scope, easy scalability and facile product diversification. The important products could also be formed with either spirocycles or two adjacent tetrasubstituted carbon centers.     

Cooperative Ni/Cu‐Catalyzed Asymmetric Propargylic Alkylation of Aldimine Esters

A novel Ni/Cu dual catalysis gives rise to fundamentally new cooperative reactivity and enables the regio‐ and enantioselective propargylic alkylation reaction. A diverse set of α‐quaternary propargylated amino ester derivatives were synthesized in good yields with excellent enantioselectivity (up to 99 % ee). This work highlights the power of cooperative catalysis, which can be expected to have broad implications in homogeneous catalysis beyond the highly valuable synthetic intermediates.     

Redox‐Divergent Synthesis of Fluoroalkylated Pyridines and 2‐Pyridones through Cu‐Catalyzed N−O Cleavage of Oxime Acetates

Cu‐catalyzed redox‐divergent [3+3] coupling of oxime esters with β‐CF₃ enones and acrylates is described. This redox‐neutral coupling with enones and acrylates affords trifluoromethylated pyridines and pyridones, respectively. Under reductive conditions, difluoromethylated pyridines, difluoromethlated pyridones, and trifluoromethylated dihydropyridones are obtained. The reactions occur under mild conditions with broad substrate scope and regio/redox selectivity.     

Ligand‐Free,Cu‐ and Fe‐Catalyzed Selective Ring‐Opening Arylations of Benzoxazoles with Aryl Iodides

Cu‐ or Fe‐based catalyst systems have been reported to selectively catalyze the N,N‐diarylation or N‐monoarylation of benzoxazoles ring‐opening with aryl iodides in the absence of additional added ligand in polyethylene glycol under an inert atmosphere. Two types of coupling products (triphenylamines and diphenylamines) have been examined and the reaction routes can be simply controlled by changing the metal salts (Cu or Fe) as catalyst. A range of substrates have been investigated for the diverse reactions, and the corresponding arylation products were achieved in good to high yields. This selective, low‐cost, and environmentally friendly protocol displays great potential for replacing existing methodologies as well as extending the synthetic applications of benzoxazoles.     

Synthesis of Phenanthridine and Quinoxaline Derivatives via Copper-Catalyzed Radical Cyanoalkylation of Cyclobutanone Oxime Esters and Vinyl Azides

Main observation and conclusion A copper-catalyzed radical cyclization of cyclobutanone oxime esters and vinyl azide is described.This method provides facile ac...     

Cu‐Catalyzed Hydroxymethylation of Unactivated Alkyl Iodides with CO To Provide One‐Carbon‐Extended Alcohols

We have developed a reductive carbonylation method by which unactivated alkyl iodides can be hydroxymethylated to provide one‐carbon‐extended alcohol products under Cu‐catalyzed conditions. The method is tolerant of alkyl β‐hydrogen atoms, is robust towards a wide variety of functional groups, and was applied to primary, secondary, and tertiary alkyl iodide substrates. Mechanistic experiments indicate that the transformation proceeds by atom‐transfer carbonylation (ATC) of the alkyl iodide followed in tandem by two CuH‐mediated reductions in rapid succession. This radical mechanism renders the Cu‐catalyzed system complementary to precious‐metal‐catalyzed reductive carbonylation reactions.     

Iron‐Catalyzed Aminative Cyclization/Intermolecular Homolytic Aromatic Substitution Using Oxime Esters and Simple Arenes

Intermolecular C?H alkylation of simple arenes in the presence of an iron catalyst has been achieved in a cascade manner with an aminative cyclization triggered by N?O bond cleavage of an alkene‐tethered oxime ester. Various arenes, including electron‐rich and electron‐poor arenes, and heteroarenes can be employed in the reaction system. Regioselectivity and radical trapping experiments support the involvement of alkyl radical species, which undergo a homolytic aromatic substitution (HAS) to afford the arylation products.     

Z‐Selective Copper(I)‐Catalyzed Alkyne Semihydrogenation with Tethered Cu–Alkoxide Complexes

A highly stereoselective alkyne semihydrogenation with copper(I) complexes is reported. Copper–N‐heterocyclic carbene complex catalysts, bearing an intramolecular Cu?O bond, allow for the direct transfer of both hydrogen atoms from dihydrogen to the alkyne. The corresponding alkenes can be isolated with high Z selectivity and negligible overreduction to the alkane.     

High‐Density DNA Functionalization by a Combination of Cu‐Catalyzed and Cu‐Free Click Chemistry

We report the regioselective Cu‐free click modification of styrene functionalized DNA with nitrile oxides. A series of modified oligodeoxynucleotides (nine base pairs) was prepared with increasing styrene density. 1,3‐Dipolar cycloaddition with nitrile oxides allows the high density functionalization of the styrene modified DNA directly on the DNA solid support and in solution. This click reaction proceeds smoothly even directly in the DNA synthesizer and gives exclusively 3,5‐disubstituted isoxazolines. Additionally, PCR products (300 and 900 base pairs) were synthesized with a styrene triphosphate and KOD XL polymerase. The click reaction on the highly modified PCR fragments allows functionalization of hundreds of styrene units on these large DNA fragments simultaneously. Even sequential Cu‐free and Cu‐catalyzed click reaction of PCR amplicons containing styrene and alkyne carrying nucleobases was achieved. This new approach towards high‐density functionalization of DNA is simple, modular, and efficient.     

Cu‐Catalyzed Cross‐Dehydrogenative ortho‐Aminomethylation of Phenols

A highly selective Cu^II‐catalyzed cross‐dehydrogenative ortho‐aminomethylation of phenols with aniline derivatives is described. The corresponding C(sp²)?C(sp³) coupling products were obtained in moderate to excellent yields under mild reaction conditions and with a broad substrate scope. A radical mechanism is proposed.     

Pd‐Catalyzed Selective Carbonylation of gem‐Difluoroalkenes: A Practical Synthesis of Difluoromethylated Esters

The first catalyst for the alkoxycarbonylation of gem‐difluoroalkenes is described. This novel catalytic transformation proceeds in the presence of Pd(acac)₂/1,2‐bis((di‐tert‐butylphosphan‐yl)methyl)benzene (btbpx) ( L4 ) and allows for an efficient and straightforward access to a range of difluoromethylated esters in high yields and regioselectivities. The synthetic utility of the protocol is showcased in the practical synthesis of a Cyclandelate analogue using this methodology as the key step.     

Rhodium‐Complex‐Catalyzed Hydroformylation of Olefins with CO2 and Hydrosilane

A rhodium‐catalyzed one‐pot hydroformylation of olefins with CO₂ , hydrosilane, and H₂ has been developed that affords the aldehydes in good chemoselectivities at low catalyst loading. Mechanistic studies indicate that the transformation is likely to proceed through a tandem sequence of poly(methylhydrosiloxane) (PMHS) mediated CO₂ reduction to CO and a conventional rhodium‐catalyzed hydroformylation with CO/H₂. The hydrosilylane‐mediated reduction of CO₂ in preference to aldehydes was found to be crucial for the selective formation of aldehydes under the reaction conditions.     

Palladium‐Catalyzed Oxidative Carbonylation of N‐Allylamines for the Synthesis of β‐Lactams

β‐Lactam scaffolds are considered to be ideal building blocks for the synthesis of nitrogen‐containing compounds. A new palladium‐catalyzed oxidative carbonylation of N‐allylamines for the synthesis of α‐methylene‐β‐lactams is reported. DFT calculations suggest that the formation of β‐lactams via a four‐membered‐ring transition state is favorable.     

Cu‐Mediated Selective N‐Arylation of Aminotriazole Acyclonucleosides

Novel N‐aryltriazole nucleosides were synthesized via a Cu‐mediated C? N cross‐coupling reaction, using 3‐aminotriazole acyclonucleosides and various boronic acid reagents. Interestingly, N‐arylation proceeded much more rapidly on the amide group than on the amine group, leading to selective N‐arylation of the amide functionality on nucleosides containing both groups on the triazole nucleobase.     

Kinetic Resolution of α‐Hydroxy‐Substituted Oxime Ethers by Enantioselective Cu−H‐Catalyzed Si−O Coupling

A catalyst‐controlled enantioselective alcohol silylation by Cu?H‐catalyzed dehydrogenative Si?O coupling of hydroxy groups α to an oxime ether and simple hydrosilanes is reported. The selectivity factors reached in this kinetic resolution are generally high (s≈50), and these reactions thereby provide reliable access to highly enantioenriched α‐hydroxy‐substituted oxime ethers. The synthetic usefulness of these compounds is also demonstrated.