PDF《Supporting Information》

S1 Nickel-Catalyzed Thiolation of Unactivated Aryl CCH Bonds: An Efficient Access to Diverse Aryl Sulfides Sheng\Yi?Yan,? ?Yue\Jin?Liu,? ?Bin?Liu,?Yan\Hua?Liu,? Bing\Feng?Shi* ? Department?of?Chemistry,?Zhejiang?University,?Hangzhou?310027,?China? Supporting Information Table of Contents: 1.

General information S2 2. Experimental Section S2 2.1 Preparation of substrate S2 2.2 Optimization of Reaction Conditions S5 2.3 Screening of Other Directing Groups S6 2.4 General Procedure for the Thiolation S6 2.5 Gram-Scale Experiment S19 2.6 Mechanistic Investigation S19 3. References S22 4. Spectra S23 S2 1. General Information All the materials and solvents were purchased from Adamas-beta and other commercial suppliers and used without additional purification. NMR spectra were recorded on a Bruke Avance operating for

1 H NMR at

400 MHz,

13 C NMR at

100 MHz, using TMS as internal standard. The peaks were internally referenced to TMS (0.00 ppm) or residual undeuterated solvent signal (77.16 ppm for

13 C NMR). The following abbreviations (or combinations thereof) were used to explain multiplicities: s = singlet, d = doublet, t = triplet, m = multiplet, b = broad. Mass spectroscopy data of the products were collected on an HRMS-TOF instrument or a low-resolution MS instrument using EI ionization. 2. Experimental Section 2.1 Preparation of Substrates Compounds 1a-1h, 1j-1p, 1a-d5, were known compounds.[1, 2, 3] Compounds 1i, 1q, 1r were prepared following typical method A or method B. Preparation of 2-(Pyridin-2-yl)isopropyl (PIP) Amine An improvement of the work-up procedure to the literature [4] was used: To a solution of 2-cyanopyridine (33.0 g, 0.32 mol) in

500 ml of toluene was added CH3MgBr (3.2M in 2-methyl tetrahydrofuran, 300ml, 0.96 mol) dropwise at

0 o C in a nitrogen atmosphere by vigorous magnetometric stirring. Upon completion of addition, the mixture was refluxed overnight. The reaction was quenched by adding saturated aqueous NH4Cl dropwise at

0 o C until the dark mixture changed to yellow. The suspension was filtrated through a pad of celite and the filtration was acidified by aqueous HCl (6 M,

10 ml). The resulting water phase combined with the filter residue was basified by saturated aqueous NaOH until the yellow colored mixture turned dark S3 brown with slurry sticky to the bottom. The mixture was washed with dichloromethane (500 ml * 4) carefully and the organic phase was combined and concentrated using a rotary evaporator. The crude product was further purified by distillation under reduced pressure. The target product was obtained as a light yellow liquid (>

98% purity.

24 g, 55%).

1 H NMR (400 MHz, CDCl3) δ 8.55 (d, J = 4.2 Hz,

1 H), 7.63 (td, J = 7.8, 1.8 Hz,

1 H), 7.45 (d, J = 8.0 Hz,

1 H), 7.12 (ddd, J = 7.4, 4.8, 0.8 Hz,

1 H), 1.87 (s,

2 H), 1.50 (s,

6 H);

13 C NMR (100 MHz, CDCl3) δ 168.32, 148.78, 136.55, 121.41, 118.53, 54.14, 31.35. General Procedure for the Preparation of Starting Materials (Method A): A solution of an acid (5 mmol) was refluxed in

5 mL SOCl2 for 2h and cooled to RT. The excess of SOCl2 was removed under vacuum to give corresponding acid choloride. The acid choloride was then re-dissolved in

5 mL dry CH2Cl2 and added dropwiseto a

20 mL dry CH2Cl2 solution containing amine (5 mmol) and Et3N (10 mmol) at

0 o C. After stirring for 6h at ambient temperature, the resulting mixture was washed with brine, dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography to give the desired product. General Procedure for the Preparation of Starting Materials (Method B): A mixture of amine (5 mmol), 6-bromohexanoic acid (5 mmol), EDCI (5.5 mmol) and HOBT (5.5 mmol) in anhydrous DMF (20 mL) was stirred at room temperature overnight. Water was added and the mixture was extracted with diethyl ether. The combined organic layer was washed with brine, dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography to give the desired product. S4 4-(dimethylamino)-N-(2-(pyridin-2-yl)propan-2-yl)benzamide 1i The title compound 1i was prepared according to the general procedure (Method A).