Direct Synthesis of Tri-/Difluoromethyl Ketones from Carboxylic Acids by Cross-Coupling with Acyloxyphosphonium Ions.

A simple and straightforward approach to the synthesis of trifluoromethyl and difluoromethyl ketones from widely available carboxylic acids is disclosed. The transformation utilizes an acyloxyphosphonium ion as the active electrophile, conveniently generated in situ from the carboxylic acid substrate by using commodity chemicals. The utility of the reaction system is exemplified by its chemoselectivity, with tolerance to a variety of important functional groups.

Direct Access to Acyl Fluorides from Carboxylic Acids Using a Phosphine/Fluoride Deoxyfluorination Reagent System.

A fast and simple method for deoxyfluorination of carboxylic acids is presented. The protocol employs commodity chemicals (PPh, NBS, fluoride), affording products in excellent yields under mild conditions. Acyloxyphosphonium ion, the key reaction intermediate, was identified by NMR spectroscopic methods.

Mechanistic Insights into Ruthenium-Pincer-Catalyzed Amine-Assisted Homogeneous Hydrogenation of CO to Methanol.

Amine-assisted homogeneous hydrogenation of CO to methanol is one of the most effective approaches to integrate CO capture with its subsequent conversion to CHOH. The hydrogenation typically proceeds in two steps. In the first step the amine is formylated via an in situ formed alkylammonium formate salt (with consumption of 1 equiv of H).

C(sp)-H Trifluoromethylation of enamides using TMSCF: access to trifluoromethylated isoindolinones, isoquinolinones, 2-pyridinones and other heterocycles.

A method for the direct C(sp2)-H trifluoromethylation of enamides, including biologically relevant isoindolinones, isoquinolinones and 2-pyridinones using TMSCF3 under oxidative conditions is presented. The protocol is convenient, operationally simple and exhibits high tolerance across a multitude of relevant handles and functional groups.

Direct Difluorination-Hydroxylation, Trifluorination, and C(sp)-H Fluorination of Enamides.

A direct double functionalization involving both difluorination and hydroxylation of enamides is reported. With the appropriate combination of an electrophilic fluorinating reagent and HO, the most convenient and ecofriendly hydroxylating agent, the preparation of 3-(difluoroalkyl)-3-hydroxyisoindolin-1-ones was achieved under basic or Brønsted acidic conditions. Suitable conditions for trifluorination as well as C(sp)-H fluorination were also identified.

Synthesis of 3-substituted isoindolin-1-ones via a tandem desilylation, cross-coupling, hydroamidation sequence under aqueous phase-transfer conditions.

A simple and expedient method for the synthesis of 3-methylene-isoindolin-1-ones 4 under aqueous phase-transfer conditions has been developed. Starting from 2-iodobenzamides 1 and (silyl)alkynes, the products are obtained in high yields and short reaction times (30 min) with the use of inexpensive CuCl/PPh3 catalyst system in the presence of n-Bu4NBr (TBAB) as a phase-transfer agent. Terminal alkynes are conveniently "unmasked" upon in situ desilylation under the reaction conditions.

Lewis Acid Catalyzed Condensation-Cyclization Cascade: Direct Synthesis of Di/Trifluoromethyl-1,2,3,4-tetrahydroquinazolines.

Condensed heterocycles such as quinazolines constitute the framework of many promising drugs. The great impact of the dramatic fluorine effect in pharmaceuticals prompted a great surge in the quest for fluorinated drug design resulting in over 20 % fluorine-containing drugs in the market today. Therefore, finding an efficient and cost-effective method for the direct synthesis of fluorine-tagged quinazoline systems is of great significance in the pharmaceutical arena.

Unique reactivity of fluorinated molecules with transition metals.

Organofluorine and organometallic chemistry by themselves constitute two potent areas in organic synthesis. Thus, the combination of both offers many chemical possibilities and represents a powerful tool for the design and development of new synthetic methodologies leading to diverse molecular structures in an efficient manner. Given the importance of the selective introduction of fluorine atoms into organic molecules and the effectiveness of transition metals in C-C and C-heteroatom bond formation, this review represents an interesting read for this aim.

Nucleophilic trifluoromethylation of carbonyl compounds: trifluoroacetaldehyde hydrate as a trifluoromethyl source.

A feasible nucleophilic trifluoromethylating protocol has been developed using trifluoroacetaldehyde hydrate as an atom-economical trifluoromethyl source. The reaction was found to be applicable to the nucleophilic trifluoromethylation of a broad spectrum of carbonyl compounds with satisfactory yields in general. DFT calculations have been performed to provide mechanistic insight into the present and related reactions employing 2,2,2-trifluoro-1-methoxyethanol and hexafluoroacetone hydrate.