Copper‐Catalyzed Carbotrifluoromethylation of Unactivated Alkenes Driven by Trifluoromethylation of Alkyl Radicals

We report herein an unprecedented protocol for radical carbotrifluoromethylation of unactivated alkenes. With Cu(OTf)₂ as the catalyst, the reaction of unactivated alkenes, TMSCF₃ and activated alkyl chlorides at room temperature provides the corresponding carbotrifluoromethylation products in satisfactory yields. Directed by trifluoromethylation of alkyl radicals, the method exhibits an excellent regioselectivity that is opposite to those driven by CF₃ radical addition.     

Copper‐Catalyzed Intermolecular Carboetherification of Unactivated Alkenes by Alkyl Nitriles and Alcohols

A three‐component carboetherification of unactivated alkenes has been developed allowing the rapid building of complexity from simple starting materials. A wide range of α‐substituted styrenes underwent smooth reactions with unactivated alkyl nitriles and alcohols to afford γ‐alkoxy alkyl nitriles with concomitant generation of a quaternary carbon center. A radical clock experiment provided clear‐cut evidence that the reaction proceeds through a tertiary alkyl radical intermediate.     

Enantioselective Copper‐Catalyzed Carboetherification of Unactivated Alkenes

Chiral saturated oxygen heterocycles are important components of bioactive compounds. Cyclization of alcohols onto pendant alkenes is a direct route to their synthesis, but few catalytic enantioselective methods enabling cyclization onto unactivated alkenes exist. Herein reported is a highly efficient copper‐catalyzed cyclization of γ‐unsaturated pentenols which terminates in C? C bond formation, a net alkene carboetherification. Both intra‐ and intermolecular C? C bond formations are demonstrated, thus yielding functionalized chiral tetrahydrofurans as well as fused‐ring and bridged‐ring oxabicyclic products. Transition‐state calculations support a cis‐oxycupration stereochemistry‐determining step.     

Copper‐Catalyzed Alkynylboration of Alkenes with Diboron Reagents and Bromoalkynes

An efficient method for the synthesis of homopropargylboronates by copper‐catalyzed alkynylboration of alkenes with diboron reagents and bromoalkynes has been developed. The alkynylboration reaction features high selectivity and efficiency, mild reaction conditions, wide substrate scope, and functional‐group compatibility, and is a highly attractive complement to existing methods for the synthesis of homopropargylboronates. Both the boryl and alkynyl groups are good potential functional groups for the subsequent manipulations that provide access to a variety of important molecule structures.     

Copper‐Catalyzed Alkylarylation of Unactivated Alkenes: Synthesis of 3‐Alkyl Indolines from N‐Allyl Anilines and Alkanes

A rare example of C(sp³)?H functionalization of simple alkanes with unactivated alkenes is presented. In the presence of a copper salt and di‐tert‐butyl peroxide (DTBP), N‐allyl anilines underwent exo‐selective alkylation/cyclization cascade with unactivated alkenic bonds as radical acceptors and simple alkanes as radical precursors, providing a direct access to 3‐alkyl indolines. The present protocol features simple operation, broad substrate scope and great exo selectivity.     

Ligand‐Controlled Regiodivergent Copper‐Catalyzed Alkylboration of Alkenes

A novel copper‐catalyzed regiodivergent alkylboration of alkenes with bis(pinacolato)diboron and alkyl halides has been developed. The regioselectivity of the alkylboration was controlled by subtle differences in the ligand structure. The reaction thus enables the practical, regiodivergent synthesis of two different alkyl boronic esters with complex structures from a single alkene.     

Efficient Copper‐Catalyzed Direct Intramolecular Aminotrifluoromethylation of Unactivated Alkenes with Diverse Nitrogen‐Based Nucleophiles

A mild, convenient, and step‐economical intramolecular aminotrifluoromethylation of unactivated alkenes with a variety of electronically distinct, nitrogen‐based nucleophiles in the presence of a simple copper salt catalyst, in the absence of extra ligands, is described. Many different nitrogen‐based nucleophiles (e.g., basic primary aliphatic and aromatic amines, sulfonamides, carbamates, and ureas) can be employed in this new aminotrifluoromethylation reaction. The aminotrifluoromethylation process allows straightforward access to diversely substituted CF₃‐containing pyrrolidines or indolines, in good to excellent yields, through a direct difunctionalization strategy from the respective acyclic starting materials. Mechanistic studies were conducted and a plausible mechanism was proposed.     

Copper‐Catalyzed Stereoselective Aminoboration of Bicyclic Alkenes

A copper‐catalyzed aminoboration of bicyclic alkenes, including oxa‐ and azabenzonorbornadienes, has been developed. With this method, amine and boron moieties are simultaneously introduced at an olefin with exo selectivity. Subsequent stereospecific transformations of the boryl group can provide oxygen‐ and nitrogen‐rich cyclic molecules with motifs that may be found in natural products or pharmaceutically active compounds. Moreover, a catalytic asymmetric variant of this transformation was realized by using a copper complex with a chiral bisphosphine ligand, namely (R,R)‐Ph‐BPE.     

Copper‐Catalyzed Intramolecular Oxidative Amination of Unactivated Internal Alkenes

A copper‐catalyzed oxidative amination of unactivated internal alkenes has been developed. The Wacker‐type oxidative alkene amination reaction is traditionally catalyzed by a palladium through a mechanism involving aminopalladation and β‐hydride elimination. Replacing the precious and scarce palladium with a cheap and abundant copper for this transformation has been challenging because of the difficulty associated with the aminocupration of internal alkenes. The combination of a simple copper salt, without additional ligand, as the catalyst and Dess–Martin periodinane as the oxidant, promotes efficiently the oxidative amination of allylic carbamates and ureas bearing di‐ and trisubstituted alkenes leading to oxazolidinones and imidazolidinones. Preliminary mechanistic studies suggested a hybrid radical–organometallic mechanism involving an amidyl radical cyclization to form the key C?N bond.     

Copper‐Mediated/Catalyzed Oxyalkylation of Alkenes with Alkylnitriles

A copper‐promoted oxyalkylation of alkenes with alkylnitriles has been developed. The protocol provides rapid access to phthalides (γ‐lactones) or isochromanones (δ‐lactones) via the formation of a C(sp³)?C(sp³) and a C(sp³)?O bond with the generation of up to two quaternary carbon atoms. Mechanistic studies suggest that this reaction is initiated by the formation of the C(sp³)?C(sp³) bond rather than the C(sp³)?O bond. Catalytic conditions were subsequently developed using carboxylic acid as an internal nucleophile.     

Manganese‐Catalyzed Hydroarylation of Unactivated Alkenes

Transition‐metal‐catalyzed hydroarylation of unactivated alkenes with strategic use of remote coordinating functional groups has received significant attention recently to address the issues of both low reactivity and poor selectivity. The bidentate 8‐aminoquinoline amide group is the most successfully adopted in unactivated alkenes for Pd and Ni catalysis. We describe the first manganese‐catalyzed hydroarylation of unactivated alkenes bearing diverse simple functionalities with arylboronic acids. A series of δ‐ and γ‐arylated amides, ketones, pyridines, and amines was accessed with excellent regioselectivity and in high yields. Hydroalkenylation of unactivated alkenes was also shown to be applicable under this manganese‐catalysis regime. The method features earth‐abundant manganese catalysis, easily available substrates, broad functional‐group tolerance, and excellent regioselective control.     

Copper‐Catalyzed Ritter‐Type Reaction of Unactivated Alkenes with Dichloramine‐T

It was shown that dichloramine‐T ( 1 ) reacted with cyclohexene in acetonitrile to give N¹‐(2‐chlorocyclohexyl) amidine 2a and N‐(2‐chlorocyclohexyl)acetamide ( 3 ) via the competitive addition of acetonitrile and N‐chloro‐N‐tosylamino anion to cyclohexenechloronium ion. This reaction can be catalyzed by Cu(OAc)₂, primarily affording 2a . Furthermore, the resulting 2a can be cyclized to benzimidazol 14a in good yield by treating with KOH in dioxane.     

Zirconium‐Catalyzed Atom‐Economical Synthesis of 1,1‐Diborylalkanes from Terminal and Internal Alkenes

A general and atom‐economical synthesis of 1,1‐diborylalkanes from alkenes and a borane without the need for an additional H₂ acceptor is reported for the first time. The key to our success is the use of an earth‐abundant zirconium‐based catalyst, which allows a balance of self‐contradictory reactivities (dehydrogenative boration and hydroboration) to be achieved. Our method avoids using an excess amount of another alkene as an H₂ acceptor, which was required in other reported systems. Furthermore, substrates such as simple long‐chain aliphatic alkenes that did not react before also underwent 1,1‐diboration in our system. Significantly, the unprecedented 1,1‐diboration of internal alkenes enabled the preparation of 1,1‐diborylalkanes.     

Microwave‐Assisted Copper‐Catalyzed Oxidative Cyclization of Acrylamides with Non‐Activated Ketones

An operationally simple and efficient microwave‐assisted protocol for the oxidative cyclization of acrylamide derivatives with non‐activated ketones to generate 3,3‐disubstituted oxindoles is described. The reaction proceeds by a copper‐catalyzed tandem radical addition/cyclization strategy and tolerates a series of functional groups with moderate to excellent yields.     

Copper‐Catalyzed Aerobic Decarboxylation/Ketooxygenation of Electron‐Deficient Alkenes

A copper‐catalyzed ketooxygenation of electron‐deficient alkenes was developed. This approach combines O?H alkylation, aerobic decarboxylation, and oxygenation in one transformation. Mechanistic investigation of this reaction showed that the copper salt is responsible for both generating the amidoxyl radical and promoting aerobic decarboxylation.