The Study On The Selective C-H Direct Arylation Reactions Of Thiophenes Catalyzed By Phosphine-free Pd-complexes

Heteroarenes equipped with aryl groups(heterobiaryls) are often found in pharmaceuticals, pesticides, biologically active compounds and organic matericals. With the development of organometallic chemistry, the direct C-H arylation of heteroarenes catalyzed by Palladium complex has emerged as a versatile protocal for the construction of heterobiaryls. Compared with traditional cross-coupling reactions, the prefunctionalization of starting materials are unnecessary and represents a more environmentally friendly and economic strategy. While the ubiquitous and divers nature of C-H bonds in complex organic compounds makes regioselective of this type a formidable challenge. Therefore, this paper take thiophene derivatives with selectivitives themselves as substrates, through the design of different kind of catalysts and optimization of the reaction conditions to obtain arylation products with high selectivity under low catalyst loading.(1) Direct C-H arylation of thiophenes at α-position. the bulky bis(imino)acenaphthene-supported(BIAN-IPr) N-heterocyclic carbine(NHC) Pdcomplexs bearing 12 different monodendtate ancillary ligands were synthesis, and their structures were characterized by 1H NMR, 13 C NMR, MS and elemental analysis. Among them, five single crystals were obtained, and their structures have been analysised. Then the activity of these Pd-N-heterocyclic carben(Pd-NHC) complexs and the reaction conditions were investigated, finally the optimized catalytic system is confirmed: using thiophenes(1.0 mmol) and aryl bromide(1.5 mmol) as staring materials, in the presence of(0.05 mol %) C1 as the catalyst,(2.0 mmol) KOAc as the base,(30mol %) Piv OH as the addictive and(3 m L) DMAc as the solvent at 130 oC for 24 h under aerobic condition. α-arylation of 44 kinds of thiophene derivatives were proceed smoothly, no mater electron-rich or electron-deficient substrates both exerted excellent activity, even sterically hindered substrates can proceed smoothly under the optimized conditions. To our delight, the catalyst loadings can declined to 0.01 mol % to some high active substrates.(2) Direct C-H arylation of thiophenes at β-position. we designed and synthesized six Pd-diimine complexes, and their structure has been characterized by 1H NMR and 13 C NMR. Then the activity of these complexes and the reaction conditions have been optimized, finally the the optimized catalytic system has been confirmed: using thiophene derivatives(1.0 mmol) and aryl boronic acid(2.0 mmol) as the substrates, in the presence of(2.0mol %) C2 as the catalyst,(4.0 mmol) TEMPO as the oxidant, glacial acetic acid as the solvent at 60 oC for 24 h under aerobic condition. β-arylation of 36 kinds of thiophene derivatives, especially electron-rich substrates, were proceeded smoothly under the optimized conditions, and high yields and selectivity were obtained.(3) Studies indicate that strong σ-donating NHC-Pd complexs are in favour of the direct arylation of thiophene derivatives at α-position, however, relatively electrondeficient Pd-diimine complexes showed more inclined to β-position. However, the selectivity not only related with the catalysts but also associated with the reaction conditions, thus resulted in two different mechanism.