The reaction mechanism for difluoromethylation of lithium enolates with fluoroform was analyzed computationally (DFT calculations with the artificial force induced reaction (AFIR) method and solvation model based on density (SMD) solvation model (THF)), showing an S_N2-type carbon–carbon bond formation; the “bimetallic” lithium enolate and lithium trifluoromethyl carbenoid exert the C−F bond “dual” activation, in contrast to the monometallic butterfly-shaped carbenoid in the Simmons–Smith reaction. Lithium enolates, generated by the reaction of 2 equiv. of lithium hexamethyldisilazide (rather than 1 or 3 equiv.) with the cheap difluoromethylating species fluoroform, are the most useful alkali metal intermediates for the synthesis of pharmaceutically important α-difluoromethylated carbonyl products.

A chiral dicationic palladium complex is found to be an efficient Lewis acid catalyst for the synthesis of α-fluoromethyl-substituted tertiary alcohols using a three-component coupling reaction. The reaction transforms three simple and readily available components (terminal alkyne, arene, and fluoromethylpyruvate) to valuable chiral organofluorine compounds. This strategy is completely atom-economical and results in perfect regioselectivities and high enantioselectivities of the corresponding tertiary allylic alcohols in good to excellent yields.

The aromatic perfluoroalkylation catalyzed by a copper(I) salt with bis(perfluoroalkyl)zinc reagents Zn(R_F)₂(DMPU)₂, which were prepared and then isolated as a stable white powder from perfluoroalkyl iodide and diethylzinc, was accomplished to provide the perfluoroalkylated products in good-to-excellent yields. The advantages of this reliable and practical catalytic reaction are 1) air-stable and easy-to-handle bis(perfluoroalkyl)zinc reagents can be utilized, 2) the reagent is reactive and hence the operation without activators and ligands is simple, and 3) not only trifluoromethylation but also perfluoroalkylation can be attained.

The direct α-siladifluoromethylation of lithium enolates with the Ruppert–Prakash reagent (CF₃TMS) is shown to construct the tertiary and quaternary carbon centers. The Ruppert–Prakash reagent, which is versatile for various trifluoromethylation as a trifluoromethyl anion (CF₃⁻) equivalent, can be employed as a siladifluoromethyl cation (TMSCF₂⁺) equivalent by CF bond activation due to the strong interaction between lithium and fluorine atoms.

Perfluoroalkyl (R_F) titanocene reagents [Cp₂Ti^IIIR_F] synthesized via [Cp₂Ti^IIICl] rather than [Cp₂Ti^II] show new types of perfluoroalkylation reactions. The [Cp₂Ti^IIIR_F] reagents exhibit a wide variety of reactivity with carbonyl compounds including esters and nitriles, and selectivities far higher than those reported for conventional R_FLi and R_FMgX reagents.

The direct synthesis of trifluoromethylindium reagents prepared from trifluoromethyl iodide by using just one equivalent each of indium, lithium chloride or sodium iodide, and ferrocene is reported. The weak In···F interaction is suitable to prepare stable but nucleophilic perfluoroalkyl reagents, which were successfully employed in the perfluoroalkylation of aldehydes. Notably, the nucleophilic trifluoromethylation of various aldehydes took place with trifluoromethyl iodide by utilizing just one equivalent each of indium, lithium chloride, and ferrocene.

Chiral dicationic Pd-complex-catalyzed enantioselective ene and aldol reactions with various isatin derivatives are shown to produce the corresponding 3-hydroxy-2-oxindole products in good yields with high enantioselectivities. These catalytic processes are effective not only with isatins but also with keto esters and diketones derivatives. Even with unprotected isatin, high yields and enantioselectivities were obtained to produce convolutamydine A as a naturally occurring compound. Sequentially, α-oxidation by m-CPBA and α-fluorination by selectfluor of the ene product could be achieved to give the corresponding α-hydroxy and α-fluoro ketones, respectively.

A synergistic effect is observed for the combination of a neutral dinuclear gold complex with a chiral silver phosphate in the intramolecular hyroalkoxylation of allenes to give furan derivatives in high yields and enantioselectivities. The monocationic dinuclear gold complex affords higher catalytic activity and enantioselectivity than the neutral or dicationic digold complexes. The synergistic effect is thus highly promising to provide a guiding principle in designing an efficient chiral environment for creating an asymmetric catalyst.

The development of efficient methods for the synthesis and purification of chiral organic compounds is a challenge in modern science and technology. Pharmaceutically and agrochemically important compounds are especially required in optically pure form. We report the racemic mixture synthesis of β-perfluoroalkyl α-amino acids, which is based on the In-mediated addition of perfluoroalkyl radicals to dehydroamino acids followed by asymmetric protonation. All the enantiomers can be separated by using a single chiral HPLC column, without orthogonal use of a fluorous column.

Optically active 3,3′-dimethyl-2,2′-diamino-1,1′-binaphthyl (DM-DABN) and 3,3′-dimethyl-2-amino-2′-hydroxybinaphthyl (DM-NOBIN) derivatives were synthesized by Cu-(−)-sparteine complex-catalyzed enantioselective homo- and hetero-coupling of 2-naphthylamine, respectively. The difference in enantioselectivity was observed by changing the concentration of oxygen. Chirality, 2010. © 2009 Wiley-Liss, Inc.