Solvent-free reaction using a high-speed ball milling technique has been first applied to cross-dehydrogenative coupling (CDC) reactions between tetrahydroisoquinolines and three types of pronucleophiles such as nitroalkanes, alkynes, and indoles. All coupling products were obtained in good yields at short reaction times (no more than 40 min). When alkynes and indoles were used as pronucleophile, the reactions can be catalyzed efficiently by recoverable copper balls without any additional metal catalyst.

The effect of liquid-assisted grinding has been studied using mechanical Suzuki-Miyaura reaction of aryl chlorides as the model reaction. Catalytic systems of Davephos and PCy are tested respectively showing strong influences from different liquids. Unexpected improvement of yield over 55% is observed using alcohols as additives, which is explained by in situ formed alkoxides and their participation in oxidative addition. Further expansion of substrates using Pd(OAc)/PCy/MeOH system gives desired products in good to high yields.

Chiral propargylamines were prepared by a ball-milling promoted, fast, high yielding, and highly enantioselective solvent-free A3 reaction using a reusable catalyst.

No abstract

Construction of 3-vinylindoles (3) and β,β-diindolyl propionates (4) through solvent-free C-H functionalization has been explored under high-speed ball-milling conditions. The reaction selectivity is influenced by the catalyst dramatically: Pd(OAc)2 provides 3 in moderate to good yields, whereas PdX2 (X = Cl, I) affords 4 as the major products. The reaction mechanism has been further studied by using electrospray ionization mass spectrometry, implicating the dimeric palladium complex A as the key intermediate in an explanation of the selectivity.