A metal-organic framework Cu2(BPDC)2(BPY) was synthesized and used as a heterogeneous catalyst for the copper-catalyzed A3 reaction of tetrahydroisoquinoline, aldehydes, and alkynes to form C1-alkynylated tetrahydroisoquinolines. High regioselectivity to the endo-yneproduct was achieved, with more than 99% of 2-benzyl-1-(phenylethynyl)-1,2,3,4-tetrahydroisoquinoline and less than 1% of 2-(1,3-diphenylprop-2-ynyl)-1,2,3,4-tetrahydroisoquinoline being observed in the product mixture. The Cu2(BPDC)2(BPY) also exhibited higher catalytic activity for the transformation than that of other Cu-MOFs such as Cu(BDC), Cu2(BDC)2(BPY), Cu2(EDB)2(BPY), Cu3(BTC)2 and Cu2(BDC)2(DABCO). No product was detected for the reaction using other MOFs including Mn(BDC), Co-MOF-74, Zn-IRMOF-61, and Ni2(BDC)2(DABCO). The Cu2(BPDC)2(BPY) catalyst could be recovered and reused several times without a significant degradation in catalytic activity.