39894-71-8

Gold-catalyzed oxidative coupling of alkynes was developed as an efficient approach for the synthesis of challenging cyclic conjugated diynes (CCD). Compared with the classic copper-promoted oxidative coupling reaction of alkynes, this gold-catalyzed process exhibited a faster reaction rate due to rapid reductive elimination from the Au(III) intermediate. This unique reactivity thus allowed a challenging diyne macrocyclization to take place with high efficiency. Condition screening revealed an [(n-Bu)4N]+[Cl-Au-Cl]? salt as the optimal pre-catalyst. Macrocycles with ring size between 13 and 28 atoms were prepared in moderate to good yields, which highlighted the broad substrate scope of this new strategy. Furthermore, the synthetic utilities of the CCDs for copper-free click chemistry have been demonstrated, showcasing the potential application of this strategy in biological systems. Macrocycles are important structural moieties in medicinal and biological research, and efficient methods for macrocyclization are always in high demand. With the unique conformation having six carbon atoms in a linear geometry, the cyclic conjugated diynes (CCD) present greater synthetic challenges and have been much less explored. Therefore, application of these unique macrocycles in biological studies is largely unexplored. Here, we describe the discovery of gold-catalyzed Glaser-Hay type oxidative coupling of terminal alkynes to achieve CCD under diluted conditions with broad substrate scope and great functional group compatibility. Taking advantage of the 14-member cyclic diyne, a copper-free click chemistry was achieved, which provided an effective alternative strategy for the traditional cyclooctyne-based azide-alkyne cycloaddition, suggesting a promising future for this method in tackling challenging problems in related biological and medicinal research. Gold-catalyzed oxidative coupling of alkynes was developed as an efficient approach for the synthesis of challenging cyclic conjugated diyne. Compared with copper-promoted oxidative coupling, this protocol allowed macrocyclization under dilute conditions with good overall reactivity and high functional group tolerance. The success in achieving copper-free click chemistry on cyclic conjugated diyne highlights its potential application in biological and medicinal research.

The development of an asymmetric gold-catalysed dihydroalkoxylation strategy for the synthesis of the 3′H-spiro[chroman-2,1′- isobenzofuran] spiroacetal ring system 5 is described. Spiroacetal was generated in up to 87:13 enantiomeric ratio using chiral gold-phosphine complexes and chiral silver phosphate Ag(S)-TRIP.

Click chemistry is used to construct ligand scaffolds for a series of chiral diphosphites. Enantioselectivity as high as 97% ee is obtained using these click ligands in rhodium-catalyzed asymmetric hydrogenation. Control experiments and spectroscopic data suggest that a 16-membered P,P-macrocyclic Rh(1) chelate is formed.

Treatment of 2-alkynylphenol with an alkyl Grignard reagent in the presence of a catalytic amount of manganese(II) chloride provided 2-(2-alkyl-1-alkenyl)phenol in good yield. Alkylmagnesation proceeded with high regio-and stereoselectivities.