Rapid and Efficient Copper‐Catalyzed Finkelstein Reaction of (Hetero)Aromatics under Continuous‐Flow Conditions

A general, rapid, and efficient method for the copper‐catalyzed Finkelstein reaction of (hetero)aromatics has been developed using continuous flow to generate a variety of aryl iodides. The described method can tolerate a broad spectrum of functional groups, including N‐H and O‐H groups. Additionally, in lieu of isolation, the aryl iodide solutions were used in two distinct multistep continuous‐flow processes (amidation and Mg–I exchange/nucleophilic addition) to demonstrate the flexibility of this method.     

Highly Efficient CSeCF3 Coupling of Aryl Iodides Enabled by an Air‐Stable Dinuclear PdI Catalyst

Building on our recent disclosure of catalysis at dinuclear Pd^I sites, we herein report the application of this concept to the realization of the first catalytic method to convert aryl iodides into the corresponding ArSeCF₃ compounds. Highly efficient C? SeCF₃ coupling of a range of aryl iodides was achieved, enabled by an air‐, moisture‐, and thermally stable dinuclear Pd^I catalyst. The novel SeCF₃‐bridged dinuclear Pd^I complex 3 was isolated, studied for its catalytic competence and shown to be recoverable. Experimental and computational data are presented in support of dinuclear Pd^I catalysis.     

Deoxyfluorination with CuF2: Enabled by Using a Lewis Base Activating Group

Deoxyfluorination is a primary method for the formation of C−F bonds. Bespoke reagents are commonly used because of issues associated with the low reactivity of metal fluorides. Reported here is the development of a simple strategy for deoxyfluorination, using first-row transition-metal fluorides, and it overcomes these limitations. Using CuF₂ as an exemplar, activation of an O-alkylisourea adduct, formed in situ, allows effective nucleophilic fluoride transfer to a range of primary and secondary alcohols. Spectroscopic investigations have been used to probe the origin of the enhanced reactivity of CuF₂. The utility of the process in enabling ¹⁸F-radiolabeling is also presented.     

Deoxyfluorination with CuF2: Enabled by Using a Lewis Base Activating Group

Deoxyfluorination is a primary method for the formation of C?F bonds. Bespoke reagents are commonly used because of issues associated with the low reactivity of metal fluorides. Reported here is the development of a simple strategy for deoxyfluorination, using first‐row transition‐metal fluorides, and it overcomes these limitations. Using CuF₂ as an exemplar, activation of an O‐alkylisourea adduct, formed in situ, allows effective nucleophilic fluoride transfer to a range of primary and secondary alcohols. Spectroscopic investigations have been used to probe the origin of the enhanced reactivity of CuF₂. The utility of the process in enabling ¹⁸F‐radiolabeling is also presented.     

A Practical and General Amidation Method from Isocyanates Enabled by Flow Technology

The addition of carbon nucleophiles to isocyanates represents a conceptually flexible and efficient approach to the preparation of amides. This general synthetic strategy has, however, been relatively underutilized owing to narrow substrate tolerance and the requirement for less favourable reaction conditions. Herein, we disclose a high‐yielding, mass‐efficient, and scalable method with appreciable functional group tolerance for the formation of amides by reaction of Grignard reagents with isocyanates. Through the application of flow chemistry and the use of substoichiometric amounts of CuBr₂, this process has been developed to encompass a broad range of substrates, including reactants found to be incompatible with previously published procedures.     

Copper‐Catalyzed Enantioselective 1,6‐Boration of para‐Quinone Methides and Efficient Transformation of gem‐Diarylmethine Boronates to Triarylmethanes

Presented is the first enantioselective copper‐catalyzed 1,6‐conjugate addition of bis(pinacolato)diboron to para‐quinone methides. The reaction proceeds with excellent yields and good to excellent enantioselectivities, and provides an attractive approach to the construction of optically active gem‐diarylmehtine boronic esters. Additionally, the subsequent conversion of the derived potassium trifluoroborates into triarylmethanes with highly enantiospecificity was realized.     

Nickel‐Catalyzed Csp2Csp3 Bond Formation by CarbonFluorine Activation

We report herein a general catalytic method for Csp²?Csp³ bond formation through C?F activation. The process uses an inexpensive nickel complex with either diorganozinc or alkylzinc halide reagents, including those with β‐hydrogen atoms. A variety of fluorine substitution patterns and functional groups can be readily incorporated. Sequential reactions involving different precatalysts and coupling partners permit the synthesis of densely functionalized fluorinated building blocks.     

Investigation of a Lithium–Halogen Exchange Flow Process for the Preparation of Boronates by Using a Cryo‐Flow Reactor

Conducting low‐temperature organometallic reactions under continuous flow conditions offers the potential to more accurately control exotherms and thus provide more reproducible and scalable processes. Herein, progress towards this goal with regards to the lithium–halogen exchange/borylation reaction is reported. In addition to improving the scope of substrates available on a research scale, methods to improve reaction profiles and expedite purification of the products are also described. On moving to a continuous system, thermocouple measurements have been used to track exotherms and provide a level of safety for continuous processing of organometallic reagents. The use of an in‐line continuous liquid–liquid separation device to circumvent labour intensive downstream off‐line processing is also reported.     

Sandmeyer‐Type Trifluoromethylthiolation and Trifluoromethylselenolation of (Hetero)Aromatic Amines Catalyzed by Copper

Aromatic and heteroaromatic diazonium salts were efficiently converted into the corresponding trifluoromethylthio‐ or selenoethers by reaction with Me₄NSCF₃ or Me₄NSeCF₃, respectively, in the presence of catalytic amounts of copper thiocyanate. These Sandmeyer‐type reactions proceed within one hour at room temperature, are applicable to a wide range of functionalized molecules, and can optionally be combined with the diazotizations into one‐pot protocols.     

Alkene Carboboration Enabled by Synergistic Catalysis

A synergistic Pd/Cu system for the coupling of alkenes, (Bpin)₂ (pin=pinacolate), and aryl/vinyl bromides is disclosed. This method allows for the catalytic generation of secondary Csp³?Cu nucleophiles in situ and subsequent Pd‐catalyzed cross‐coupling.     

Iron‐Catalyzed 1,2‐Addition of Perfluoroalkyl Iodides to Alkynes and Alkenes

Iron catalysis has been developed for the intermolecular 1,2‐addition of perfluoroalkyl iodides to alkynes and alkenes. The catalysis has a wide substrate scope and high functional‐group tolerance. A variety of perfluoroalkyl iodides including CF₃I can be employed. The resulting perfluoroalkylated alkyl and alkenyl iodides can be further functionalized by cross‐coupling reactions. This methodology provides a straightforward and streamlined access to perfluoroalkylated organic molecules.