External Flash Generation of Carbenoids Enables Monodeuteration of Dihalomethanes.

In this study, incorporation of one deuterium atom was achieved by H-D exchange of one of the two identical methylene protons in various dihalomethanes (halogen=Cl, Br, and I) through a rapid-mixing microflow reaction of lithium diisopropylamide as a strong base and deuterated methanol as a deuteration reagent. Generation of highly unstable carbenoid intermediate and suppression of its decomposition were successfully controlled under high flow-rate conditions. Monofunctionalization of diiodomethane afforded various building blocks composed of boryl, stannyl, and silyl groups. The monodeuterated diiodomethane, which served as a deuterated C1 source, was subsequently subjected to diverted functionalization methods to afford various products including biologically important molecules bearing isotope labelling at specific positions and homologation products with monodeuteration.

Synthesis of ß-Fluorovinyliodonium Salts by the Reaction of Alkynes with Hypervalent Iodine/HF Reagents.

The reaction of alkynes with PhIO and Py·HF followed by treatment with BF3·OEt2 gave ß-fluorovinyliodonium tetrafluoroborates in good to high yields. More conveniently, the reaction using PhI and Py·HF in the presence of m-CPBA also afforded ß-fluorovinyliodonium tetrafluoroborates in good yields. These methods have the advantages that ß-fluorovinyliodonium salts can be prepared without ArIF2.

Hypervalent Iodine/HF Reagents for the Synthesis of 3-Fluoropyrrolidines.

The intramolecular aminofluorination of homoallylamine derivatives using a reagent system of PhI(OAc)2 and Py·HF in CH2Cl2 at room temperature for 5 h gave N-tosyl-3-fluoropyrrolidines in good to high yields. Furthermore, the catalytic aminofluorination was furnished by the reaction using p-iodotoluene as a catalyst in the presence of Py·HF as a fluorine source and mCPBA as a terminal oxidant.

Hypervalent Iodine-Mediated Fluorination of Styrene Derivatives: Stoichiometric and Catalytic Transformation to 2,2-Difluoroethylarenes.

Fluorination of styrene derivatives with a reagent system composed of µ-oxo-bis[trifluoroacetato(phenyl)iodine] and a pyridine·HF complex gave the corresponding (2,2-difluoroethyl)arenes in good yields. Similarly, the reagent of PhI(OCOCF3)2 and the pyridine·HF complex acted as a fluorinating agent for styrene derivatives. The fluorination of styrene derivatives with the pyridine·HF complex underwent under catalytic conditions using 4-iodotoluene as a catalyst and m-CPBA as a terminal oxidant.

Hypervalent iodine-promoted α-fluorination of acetophenone derivatives with a triethylamine·HF complex.

The direct fluorination reaction of acetophenone using iodosylarenes and TEA·5HF was conducted under mild conditions except for use of a HF reagent. The fluorination reaction was applied to acetophenone derivatives, acetonaphthones, benzyl phenyl ketone, propiophenone, butyrophenone, 1-indanone, and phenacyl chloride, giving selectively the corresponding α-fluoroketone derivatives in good yields.