Palladium/TY-Phos-Catalyzed Asymmetric Intermolecular α-Arylation of Aldehydes with Aryl Bromides.

Despite much progress has been made in the asymmetric α-arylation reactions of cyclic ketones, lactones and lactams, the enantioselective α-arylation of acyclic carbonyl compounds lagged much behind due to the in situ generated Z/E-enolate intermediates leading to opposite enantiomers. Especially, the asymmetric α-arylation of acyclic aldehydes is a long-standing challenge, because of the highest activity among carbonyl compounds leading to various competitive side reactions. Herein we reported an efficient Pd-catalyzed asymmetric intermolecular α-arylation reaction of α-alkyl-α-aryl disubstituted aldehydes with aryl bromides, which provides a rapid access to chiral aldehydes bearing an α-all-carbon quaternary stereocenter in moderate to good yields with good er in most cases. In addition, a pair of enantiomers could be easily prepared with the use of the same ligand by exchanging the aryl groups of aldehyde and aryl bromide.

Design and Synthesis of TY-Phos and Application in Palladium-Catalyzed Enantioselective Fluoroarylation of gem-Difluoroalkenes.

The first example of highly enantioselective fluoroarylation of gem-difluoroalkenes with aryl halides is presented by using a new chiral sulfinamide phosphine (Sadphos) type ligand TY-Phos. N-Me-TY-Phos can be easily synthesized on a gram scale from readily available starting materials in three steps. Salient features of this work including readily available starting materials, good yields, high enantioselectivities as well as broad substrate scope make this approach very practical and attractive. Notably, the asymmetric synthesis of an analogue of a biologically active molecule is also reported.

Copper-Catalyzed Aerobic 6-Endo-Trig Cyclization of ß,γ-Unsaturated Hydrazones for the Divergent Synthesis of Dihydropyridazines and Pyridazines.

A divergent synthetic strategy to 1,6-dihydropyridazines and pyridazines through Cu(II)-catalyzed controllable aerobic 6-endo-trig cyclization was developed. The selectivity can be rationally tuned via the judicious choice of reaction solvent. It was found that the 1,6-dihydropyridazines were obtained in moderate to high yields with CH3CN as the reaction solvent, whereas employment of AcOH directly afforded pyridazines in up to 92% yields, probably arising from the oxidation of the in situ generated 1,6-dihydropyridazines.