One-Step Asymmetric Construction of 1,4-Stereocenters via Tandem Mannich-Isomerization Reactions Mediated by a Dual-Functional Betaine Catalyst.

The construction of chiral motifs containing nonadjacent stereocenters stands out as a major challenge as they are usually constructed in separate steps utilizing different chiral catalysts. Therefore, the development of new strategies to streamline the construction of such complex motifs has become a major focus of asymmetric synthesis. We report here an unprecedented asymmetric tandem Mannich-isomerization reaction that allows the direct construction of 1,4-stereocenters in a highly stereoselective manner. This asymmetric transformation demonstrated the potential of a tandem nucleophilic addition-isomerization reaction as a broadly useful strategy for the efficient construction of 1,4-stereocenters. Notably, this tandem reaction was mediated by a single chiral betaine as a dual-functional catalyst, promoting first an enantioselective intermolecular C-C bond forming reaction and next a stereoselective intramolecular 1,3-proton transfer reaction.

Synthesis of 9,9-Disubstituted Fluorenes from 2-Iodobiphenyls and α-Diazoesters under Palladium Catalysis.

9,9-Disubstituted fluorenes are widely employed in materials science. We have developed a straightforward approach for the synthesis of 9,9-disubstituted fluorenes from 2-iodobiphenyls and α-diazoesters. The reaction proceeds via a tandem palladium-catalyzed C(sp2)-H activation/carbenoid insertion sequence.

Synthesis of Fluorenes Starting from 2-Iodobiphenyls and CH2Br2 through Palladium-Catalyzed Dual C-C Bond Formation.

A facile and efficient approach is developed for the synthesis of fluorene and its derivatives starting from 2-iodobiphenyls and CH2Br2. A range of fluorene derivatives can be synthesized under relatively mild conditions. The reaction proceeds via a tandem palladium-catalyzed dual C-C bond formation sequence through the key dibenzopalladacyclopentadiene intermediates, which are obtained from 2-iodobiphenyls through palladium-catalyzed C-H activation.

Sequential Difunctionalization of 2-Iodobiphenyls by Exploiting the Reactivities of a Palladacycle and an Acyclic Arylpalladium Species.

A novel sequential difunctionalization reaction of 2-iodobiphenyl has been developed by exploiting the distinct reactivities of a palladacycle and an acyclic arylpalladium species. In this tandem reaction, an in situ formed dibenzopalladacyclopentadiene reacts selectively with an alkyl halide, after which the thus formed acyclic arylpalladium species selectively undergoes a Heck reaction with an alkene. This work demonstrates the strong relationship between the coordination mode of a transition metal complex and its reactivity, which could shed light on the mechanisms of other transition-metal-catalyzed reactions and offer the opportunity to develop other synthetically enabling organic transformations.

Palladium-catalyzed C-H ethoxycarbonyldifluoromethylation of electron-rich heteroarenes.

The first Pd-catalyzed C-H ethoxycarbonyldifluoromethylation with BrCF2CO2Et has been developed. The use of a bidentate phosphine ligand (Xantphos) is critical for the reaction to occur. A variety of electron-rich heteroarenes, including indoles, furans, thiophenes, and pyrroles, can be ethoxycarbonyldifluoromethylated in moderate to excellent yields. The reactions take place at the C-H bonds adjacent to the heteroatoms with high regioselectivity. This method provides a new protocol for the introduction of difuoroalkyl groups into electron-rich heteroarenes.

Ligand-promoted oxidative cross-coupling of aryl boronic acids and aryl silanes by palladium catalysis.

The first cross-coupling reaction between aryl silanes and aryl boronic acids is described. This transformation represents one of the very few examples of coupling reactions between two nucleophilic organometallic reagents and provides a new method for the formation of biaryl compounds. The successful development of this reaction was enabled by the use of commercially available 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (BINAP) as the ligand. A small amount of BINAP (3 mol %) was sufficient to suppress the formation of the homocoupling products, and the reaction yielded the cross-coupling products with high selectivity under mild conditions, even when the ratio of the two coupling partners was 1:1.

Silver-catalyzed C-H trifluoromethylation of arenes using trifluoroacetic acid as the trifluoromethylating reagent.

Direct trifluoromethylation of arenes using TFA as the trifluoromethylating reagent was achieved with Ag as the catalyst. This reaction not only provides a new protocol for aryl C-H trifluoromethylation, but the generation of CF3· from TFA may prove useful in other contexts and could potentially be extended to other trifluoromethylation reactions.

Copper-catalyzed highly efficient ester formation from carboxylic acids/esters and formates.

A highly efficient copper-catalyzed protocol for the synthesis of esters has been developed from formates. This protocol is applicable to reactions with either esters or acids as the substrates, and shows broad substrate scopes and high yields.

Palladium-catalyzed benzylation of carboxylic acids with toluene via benzylic C-H activation.

Direct benzylation of carboxylic acids with toluene has been developed via palladium-catalyzed C-H acyloxylation under 1 atm of oxygen. This reaction demonstrates good functional group tolerance and high yields, providing a facile, atom-economic, and efficient method for the synthesis of benzyl esters.