General approaches for fluorination, trifluoromethylation, and trifluoromethylthiolation were developed based on the electrophilic nature of arynes. In these reactions, the addition of fluorine-containing nucleophiles onto aryne intermediates was efficiently promoted by either silver catalysts or silvercontaining stoichiometric reagents. Contrary to known methods that require aromatic precursors, our new approach enables efficient non-traditional synthesis of Ar-F, Ar-CF 3 and Ar-SCF 3 from nonaromatic building blocks under relatively mild conditions.Scheme 1 Unprecedented reactivity of arynes in the presence of a silver complex.

Arynes generated directly from alkyne building blocks in the presence of silver catalysts effectively activate primary, secondary, and tertiary alkane C-H bonds. This C-H insertion requires only a catalytic amount of silver complex and modest heating compared to harsh conditions and extra promoters including directing groups, oxidants, and bases in typical transition-metal-based C-H bond functionalizations. Preliminary mechanistic studies suggest that the C-H bond-breaking and new bond-forming events take place in a concerted manner, rendering a formal 1,2-addition of C-H bond across the π-bond of arynes.

The regioselectivity in nucleophile trapping is investigated with arynes generated directly from bis-1,3-diynes. The regioselectivity is profoundly influenced by not only the nature of nucleophiles but also the substituents on the arynes, which is the consequence of both the unfavorable steric interaction between the incoming nucleophile and the nearby substituent and the inherent electronic bias induced by different substituents on the arynes.

In stark contrast to the effective 1°, 2°, and 3° C–H bond insertion of alkyl groups tethered to arynes, the 2° and 3° C–H bonds on the β-carbon of silyl groups show high tendency for hydride transfer rather than C–H insertion, whereas the corresponding 1° C–H bonds exclusively undergo C–H insertion.

The cross-metathesis of terminal alkyne and alkene using Ru-based Grubbs catalyst generally undergoes alpha-insertion. In this study, excellent control over alpha- and beta-insertion of ruthenium alkylidene into terminal alkynes has been achieved by using a substituent at a remote site from the reaction center. While the origin of this regioselectivity of insertion and metallotropic shift remains to be established, the trend indicates that the alpha-insertion with a concomitant metallotropic shift is favored with small substituents whereas the beta-insertion without a metallotropic shift is favored with bulky substituents such as tert-butyl and trialkyl silyl groups.