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Remarkable progress has been made in solvent-free cross-dehydrogenative coupling (CDC) reactions under high-energy ball milling conditions. This chapter will show the CDC and asymmetry CDC reaction between tetrahydroisoquinolines and several kinds of pronucleophiles, including active methylene compounds (sp3), terminal alkynes (sp) and indoles (aryl-sp2). Further attention is paid to the influence of the milling parameters, especially the influence of milling frequency on yield and enantioselectivity.

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