Copper‐Catalyzed Trifluoromethylation of Trisubstituted Allylic and Homoallylic Alcohols

An efficient copper‐catalyzed trifluoromethylation of trisubstituted allylic and homoallylic alcohols with Togni’s reagent has been developed. This strategy, accompanied by a double‐bond migration, leads to various branched CF₃‐substituted alcohols by using readily available trisubstituted cyclic/acyclic alcohols as substrates. Moreover, for alcohols in which β‐H elimination is prohibited, CF₃‐containing oxetanes are isolated as the sole product.     

Copper‐Promoted Conversion of Aromatic Amines into Trifluoromethylated Arenes: One‐Pot Sandmeyer Trifluoromethylation

A simple copper‐promoted one‐pot Sandmeyer trifluoromethylation of aromatic amines with Langlois’ reagent has been demonstrated. The reaction is performed in mild reaction conditions under an air atmosphere with good substrate scope and functional group compatibility. It provides an alternative and straightforward synthetic approach to access a variety of trifluoromethylated arenes.     

Iron‐Catalyzed Trifluoromethylation of Enamide

Herein the first example of the iron(II)‐catalyzed trifluoromethylation of enamide using mild and simple reaction conditions is reported. The method is cost‐effective and uses the easy‐to‐handle Togni’s reagent as the electrophilic CF₃ source. This transformation is totally regioselective at the C3 position of enamides and exhibits broad substrate scope, good functional group tolerance and thus demonstrates its useful application in a late‐stage fluorination strategy.     

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 Difunctionalization of Activated Alkynes by Radical Oxidation–Tandem Cyclization/Dearomatization to Synthesize 3‐Trifluoromethyl Spiro[4.5]trienones

A copper‐catalyzed difunctionalizing trifluoromethylation of activated alkynes with the cheap reagent sodium trifluoromethanesulfinate (NaSO₂CF₃ or Langlois’ reagent) has been developed incorporating a tandem cyclization/dearomatization process. This strategy affords a straightforward route to synthesis of 3‐(trifluoromethyl)‐spiro[4.5]trienones, and presents an example of difunctionalization of alkynes for simultaneous formation of two carbon–carbon single bonds and one carbon–oxygen double bond.     

Copper‐Catalyzed Highly Stereoselective Trifluoromethylation and Difluoroalkylation of Secondary Propargyl Sulfonates

It is challenging to stereoselectively introduce a trifluoromethyl group (CF₃) into organic molecules. To date, only limited strategies involving direct asymmetric trifluoromethylation have been reported. Herein, we describe a new strategy for direct asymmetric trifluoromethylation through the copper‐catalyzed stereospecific trifluoromethylation of optically active secondary propargyl sulfonates. The reaction enables propargylic trifluoromethylation with high regioselectivity and stereoselectivity. The reaction could also be extended to stereospecific propargylic difluoroalkylation. Transformations of the resulting enantiomerically enriched fluoroalkylated alkynes led to a variety of chiral fluoroalkylated compounds, thus providing a useful protocol for applications in the synthesis of fluorinated complexes.     

Copper‐Catalyzed Oxyboration of Unactivated Alkenes

The first regiodivergent oxyboration of unactivated terminal alkenes is reported, using copper alkoxide as a catalyst, bis(pinacolato)diboron [(Bpin)₂] as a boron source, and (2,2,6,6‐tetramethylpiperidin‐1‐yl)oxyl (TEMPO) as an oxygen source. The reaction is compatible with various functional groups. Two regioisomers are selectively produced by selecting the appropriate ligands on copper. The products may be used as a linchpin precursor for various other functionalizations, and net processes such as carbooxygenation, aminooxygenation, and dioxygenation of alkenes can be achieved after C?B bond transformations. Mechanistic studies indicate that the reaction involves the following steps: 1) Transmetalation between CuOtBu and (Bpin)₂ to generate a borylcopper species; 2) regiodivergent borylcupration of alkenes; 3) oxidation of the thus‐generated C?Cu bond to give an alkyl radical; 4) trapping of the resulting alkyl radical by TEMPO.     

Photoinduced Copper‐Catalyzed Asymmetric Decarboxylative Alkynylation with Terminal Alkynes

We describe a photoinduced copper‐catalyzed asymmetric radical decarboxylative alkynylation of bench‐stable N‐hydroxyphthalimide(NHP)‐type esters of racemic alkyl carboxylic acids with terminal alkynes, which provides a flexible platform for the construction of chiral C(sp³)?C(sp) bonds. Critical to the success of this process are not only the use of the copper catalyst as a dual photo‐ and cross‐coupling catalyst but also tuning of the NHP‐type esters to inhibit the facile homodimerization of the alkyl radical and terminal alkyne, respectively. Owing to the use of stable and easily available NHP‐type esters, the reaction features a broader substrate scope compared with reactions using the alkyl halide counterparts, covering (hetero)benzyl‐, allyl‐, and aminocarbonyl‐substituted carboxylic acid derivatives, and (hetero)aryl and alkyl as well as silyl alkynes, thus providing a vital complementary approach to the previously reported method.     

Phosphine‐Catalyzed Remote β‐CH Functionalization of Amines Triggered by Trifluoromethylation of Alkenes: One‐Pot Synthesis of Bistrifluoromethylated Enamides and Oxazoles

An unprecedented phosphine‐catalyzed remote β‐C? H functionalization of amine derivatives triggered by trifluoromethylation of an alkene with Togni’s reagent was disclosed. This reaction proceeded through the highly selective and concomitant activation of an unactivated alkene and the β‐C? H bond of an amine derivative, providing bistrifluoromethylated enamides in excellent yields with good regio‐, chemo‐, and stereoselectivity. Furthermore, the newly developed one‐pot protocol provides a facile and step‐economical access to valuable trisubstituted 5‐(trifluoromethyl)oxazoles. Mechanistic studies showed that this reaction may initiate with a novel phosphine‐catalyzed radical trifluoromethylation of unactivated alkene via a phosphorus radical cation.     

A Facile Route to Aryl Boronates: Room‐Temperature,Copper‐Catalyzed Borylation of Aryl Halides with Alkoxy Diboron Reagents

A simple but effective copper‐catalyzed borylation of aryl halides, including electron‐rich and sterically hindered aryl bromides, with alkoxy diboron reagents occurs under mild conditions (see scheme). Preliminary DFT studies of the mechanism suggest that σ‐bond metathesis between a copper–boryl intermediate and the aryl halide generates the aryl boronate product.

     

Copper‐Catalyzed Decarboxylative Radical Silylation of Redox‐Active Aliphatic Carboxylic Acid Derivatives

A decarboxylative silylation of aliphatic N ‐hydroxyphthalimide (NHPI) esters using Si−B reagents as silicon pronucleophiles is reported. This C(sp³)−Si cross‐coupling is catalyzed by copper(I) and follows a radical mechanism, even with exclusion of light. Both primary and secondary alkyl groups couple effectively, whereas tertiary alkyl groups are probably too sterically hindered. The functional‐group tolerance is generally excellent, and α‐heteroatom‐substituted substrates also participate well. This enables, for example, the synthesis of α‐silylated amines starting from NHPI esters derived from α‐amino acids. The new method extends the still limited number of C(sp³)−Si cross‐couplings of unactivated alkyl electrophiles.