Interrupted Click Reaction with CuCF2CF3 Reagent: Synthesis of 5-Pentafluoroethyl 1,2,3-Triazoles.

We herein describe a three-component interrupted click reaction to synthesize novel 5-pentafluoroethyl 1,2,3-triazoles in one step from readily available terminal alkynes and azides. The key reagent [CuCF2CF3], prepared from the low-cost gas pentafluoroethane, demonstrates an orthogonal reactivity in facilitating cycloaddition rather than previously reported radical reactions. Reaction conditions are mild by using air as a green oxidant.

Copper-Catalyzed Visible-Light-Induced Allylic Difluoromethylation of Unactivated Alkenes Using Difluoroacetic Acid.

We herein describe a straightforward allylic difluoromethylation reaction of unactivated alkenes. Compared to cross-couplings of prefunctionalized allylic substrates for the construction of allylic CF2H bonds, this reaction employs readily available alkenes as substrates under mild conditions. Difluoroacetic acid is used as an inexpensive and easy-to-handle source of CF2H radical under visible light irradiation with PIDA. The copper catalyst plays an important role of diverting the reaction pathway toward allylic difluoromethylation as opposed to previously found hydrodifluoromethylation.

Perfluoroalkylation of Thiosulfonates: Synthesis of Perfluoroalkyl Sulfides.

A practical synthesis of perfluoroalkyl sulfides is described. The method employs stable and readily accessible thiosulfonates as new electrophiles with commercial nucleophilic perfluoroalkylating reagents. The mild reaction conditions allow access to a wide variety of both aryl- and alkyl-substituted perfluoroalkyl sulfides amenable to pharmaceutical development. Furthermore, the reaction operation is straightforward, odorless, does not produce toxic wastes, and, therefore should appeal to practitioners in industrial-scale productions.

Radical Pentafluoroethylation of Unactivated Alkenes Using CuCF2CF3.

We have found that the CuCF2CF3 complex generated from low-cost pentafluoroethane is a convenient and practical source for the CF2CF3 radical under aerobic conditions at room temperature. Using this system, readily available unactivated alkenes can be pentafluoroethylated to provide novel allylic CF2CF3 compounds with excellent E-selectivity and functional group tolerability. Mechanistic studies including TEMPO-CF2CF3 trapping and radical clock experiments provided strong evidence for radical pathways, offering a new opportunity for copper-mediated radical perfluoroalkylation.

Trifluoromethylation of Anthraquinones for n-Type Organic Semiconductors in Field Effect Transistors.

This study puts forth a new design of n-type organic semiconductors, which has trifluoromethylethynyl groups attached to 9,10-anthraquinone at different positions. These electron-deficient anthraquinones are synthesized by trifluoromethylation of the corresponding trimethylsilyl-protected alkynes with fluoroform-derived CuCF3, and their π-π stacking in the crystals is tunable by varying the positions of trifluoromethylethynyl groups. It is found that most of these trifluoromethylated anthraquinones function as n-type semiconductors in solution-processed field effect transistors with electron mobility of up to 0.28 cm2 V-1 s-1.

Silver-Catalyzed Trifluoromethylalkynylation of Unactivated Alkenes with Hypervalent Iodine Reagents.

A catalytic method for the trifluoromethylalkynylation of unactivated alkenes is presented. The reaction is catalyzed by silver(I) trifluoroacetate for the simultaneous construction of two C-C bonds (alkyl-alkyne and alkyl-CF3). By employing versatile hypervalent iodine reagents, ethynylbenziodoxolones, useful trifluoromethylalkynylated compounds can be prepared from simple alkenes displaying excellent functional group tolerability. A radical mechanism is proposed with supporting evidence, providing a new entry to silver(I)-catalyzed trifluoromethylation reactions.

Trifluoromethylation of Unactivated Alkenes with Me3SiCF3 and N-Iodosuccinimide.

A novel approach to the trifluoromethylation of unactivated alkenes is presented. This reaction is promoted by N-iodosuccinimide (NIS) under visible light irradiation without the need for photocatalysts. The mild conditions allow the direct synthesis of useful trifluoromethylated ( E)-alkenes from readily available alkene feedstocks with excellent functional group tolerability. In addition, using easy-to-handle and commercial Me3SiCF3 instead of gaseous CF3I as the CF3 source is highly attractive for industrial-scale applications.

Copper-Mediated Trifluoromethylation-Allylation of Arynes.

An unprecedented three-component copper-mediated vicinal trifluoromethylation-allylation of arynes is described. A wide range of structurally diverse trifluoromethylated allylarenes can be quickly assembled in one step. The application of the method has been demonstrated in the expedient synthesis of the CF3-containing analogue of the antispasmodic drug papaverine. The new reactivity of the [CuCF3] reagent, which is generated from the inexpensive industrial byproduct fluoroform, is revealed with unique advantages.

Divergent Total Syntheses of (-)-Daphnilongeranin†B and (-)-Daphenylline.

(-)-Daphnilongeranin B and (-)-daphenylline are two hexacyclic Daphniphyllum alkaloids, each containing a complex cagelike backbone. Described herein are the first asymmetric total synthesis of (-)-daphnilongeranin B and a bioinspired synthesis of (-)-daphenylline with an unusual E ring embedded in a cagelike framework. The key features include an intermolecular [3+2] cycloaddition, a late-stage aldol cyclization to install the F ring of daphnilongeranin B, and a bioinspired cationic rearrangement leading to the tetrasubstituted benzene ring of daphenylline.

Copper-mediated 1,2-bis(trifluoromethylation) of arynes.

We herein describe an unprecedented 1,2-bis(trifluoromethylation) of arynes with [CuCF3] in the presence of an oxidant DDQ. The method allows the rapid construction of a new class of 1,2-bis(trifluoromethyl)arenes in one-step from aryne precursors under mild conditions. Its synthetic utility has been demonstrated in the preparation of bis(trifluoromethylated) molecules with potential pharmaceutical and materials science applications. Mechanistic studies indicated the presence of an o-trifluoromethyl aryl radical intermediate via CF3 group transfer from [CuCF3] to the aryne.

Domino Hydroboration/Trifluoromethylation of Alkynes Using Fluoroform-Derived [CuCF3].

A domino hydroboration/trifluoromethylation (formal hydrotrifluoromethylation) of alkynes using the fluoroform-derived [CuCF3] reagent is achieved. Synthetically useful (E)-alkenyl-CF3 building blocks and 1,1-bis(trifluoromethyl)-substituted alkenes can be prepared under ambient conditions in one pot/one step from alkynes. The ultimate source of CF3 is the inexpensive industrial waste fluoroform.

Hydroxytrifluoromethylation of Alkenes Using Fluoroform-Derived CuCF3.

Hydroxytrifluoromethylation of alkenes using the fluoroform (CF3H)-derived [CuCF3] reagent is described. In the presence of additive B2Pin2 and air, this reagent effectively facilitates the addition of hydroxy and trifluoromethyl groups across an alkene double bond, a formal hydroxytrifluoromethylation process. Various ß-trifluoromethyl alcohols can be synthesized from simple alkenes where the ultimate CF3 source is the industrial byproduct fluoroform.

Expedient construction of the [5-6-7] tricyclic core of calyciphylline a-type alkaloids.

An efficient synthetic route toward the highly congested [5-6-7] tricyclic core of calyciphylline A-type alkaloids has been developed. This approach features a highly efficient intramolecular Diels-Alder cycloaddition to establish the aza-five-membered C ring as well as the C1 all-carbon quaternary center, and a subsequent cyclopropanation together with a ring-expansion reaction of the resulted adduct to construct the seven-membered D ring.