Achieving site-selectivity and chemoselectivity is enormously challenging for substrates with multi-reactive sites in organic reactions. One kind of model substrates, 5-benzyl-1-(2-halobenzyl)-2-phenyl-1H-pyrazol-3(2H)-ones with six reactive sites were chosen as the examples to probe their intramolecular four kinds of five reactions including C(sp3 )-H arylation, C(sp2 )-H arylation, reductive Heck reaction, and domino Heck reaction/alkylation of aryl C(sp2 )-H bonds through variation of the reaction conditions. Screening of the reaction conditions showed that the different bases controlled the palladium-catalyzed intramolecular site-selectivity and chemoselectivity of the substrates: (i) Cesium carbonate (Cs2 CO3 ) promoted the benzyl C(sp3 )-H arylation of the substrates providing dihydropyrazolo[1,5-b]isoquinolin-2(1H)-ones at 100 °C, and isomerization of the dihydropyrazolo[1,5-b]isoquinolin-2(1H)-ones gave isoquinoline derivatives at a higher temperature (140 °C); (ii) Sodium acetate (NaOAc) mediated the aryl C(sp2 )-H arylation of the substrates affording seven-membered biphenyl N-heterocycles; (iii) Sodium dichloroacetate (Cl2 HCCO2 Na) facilitated occurrence of the reductive Heck reaction of the substrates affording 1H-pyrazolo[5,1-a]isoindol-2(8H)-ones; (iv) Sodium trifluoroacetate (F3 CCO2 Na) assisted performance of the domino Heck reaction/aryl C(sp2 )-H alkylation of the substrates leading to the spiro heterocycles. The 'one substrate - multiple reactions - multiple products' strategy greatly reduces cost, increases diversity of products, provides more opportunity for screening of pharmaceutical molecules, and enriches modern organic synthetic chemistry.
Keywords: C−H functionalization; base-controlled; chemoselectivity; palladium-catalyzed; site-selectivity.
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