Palladium(ii)-catalyzed synthesis of dibenzothiophene derivatives via the cleavage of carbon–sulfur and carbon–hydrogen bonds

Pd(ii)-catalyzed synthesis of dibenzothiophene derivatives has been developed. The reaction proceeds through the cleavage of carbon–hydrogen and carbon–sulfur bonds.


3-Nitrodibenzothiophene (6) [CAS: 94764-55-3].
General procedure was followed except that 2-Phenylthio-4'-nitrobiphenyl was used instead of All of other substrates bearing an electron-withdrawing group reacted smoothly to give the desired products in high yields. It was therefore considered that the low yield obtained in the NO2-containing substrate could be attributed to the poisoning of the catalyst by the NO2 group, most likely through the coordination of this group to the Pd(II) species. In this way, the NO2 group would inhibit the binding of the substrate to the catalyst, thereby inhibiting the reaction, which would explain the low yield. To test this hypothesis, we investigated the impact of adding a single equivalent of nitrobenzene to the reaction of another substrate. The result of this reaction showed that there was a 3-fold decrease in the yield of the cyclized product (see below). These results therefore clearly show that the presence of a nitro group in the reaction was detrimental to the catalytic process.

VI. Procedures for Experiments Shown in Scheme 2
The reaction of 1b in the presence of AgOAc. 8 An oven-dried 5 mL screw-capped vial was charged with 1b (79 mg, 0.30 mmol), Pd(tfa) 2 (10.0 mg, 0.03 mmol), AgOAc (200 mg, 1.2 mmol), K 2 CO 3 (42 mg, 0.3 mmol) and PivOH (1.0 mL), and the resulting mixture was stirred at rt for 10 min until the generation of CO 2 ceased. The cap was then closed, and the mixture was stirred at 130 °C for 24 h. The mixture was cooled to rt and filtered through a short pad of silica gel, eluting with CH 2 Cl 2 . The eluent was then evaporated to give a residue, which was purified by flash chromatography (hexane) to give a inseparable mixture of 4-phenyldibenzothiophene 19 and dibenzothiophene 2 (37 mg, 51% in total). The ratio of 19/2 was determined to be 82:18 by GC analysis. Further purification by GPC gave an analytically pure 19.
The separated organic extract was then dried over Na 2 SO 4 , filtered, and concentrated in vacuo to give a residue, which was purified by flash column chromatography to give SM-27 as a yellow solid (998 mg, 85%).
The spectroscopic date indicated that SM-28 existed as a mixture of two rotational isomers.

S27
A typical procedure was followed except that SM-28 was used as the substrate and 0.045 mmol of Pd(OAc) 2 and 0.135 mmol of 3 were used.
Rf 0.29 (hexane/CH 2 Cl 2 = 3/2). A two-necked flask was charged with dibenzpthiophene 5-oxide (2.0 g, 10.0 mmol) and benzene (20 mL), and the resulting solution was cooled to 0 °C. Conc. H 2 SO 4 (2.7 mL) was then added to the mixture, and the resulting mixture was stirred at rt for 24 h. The reaction mixture was added to ice water (50 mL) and extracted with benzene. The aqueous layer was collected, and added 70% HClO 4 (5.0 mL). Sparated out solid was collected, which was triturated with MeOH to give 5-phenyl-perchloratedibenzothiophenium (34) as a white solid (2.1g, 58%).

A procedure for the reaction of 34 with stoichiometric Pd(0) complexes.
An oven-dried 5 mL screw-capped vial was charged with a palladium complex (0.15 mmol), 5-phenyl-perchloratedibenzothiophenium (34) (54.1 mg, 0.15 mmol) and toluene (0.5 mL) under a gentle stream of nitrogen, and the resulting mixture was heated at the indicated temperature for 18 h. The mixture was cooled to rt and filtered through a short pad of silica gel, eluting with EtOAc. The eluent was evaporated to give a residue, which was purified by flash column chromatography over silica gel eluting with hexane. In some cases, the yield was too low to allow for the isolation of the product, and the yield was consequently determined by NMR using 1,1,2,2-tetrachloroethane as an internal standard. When Pd(PPh 3 ) 4 was used as the palladium(0) source, dibenzothiophene (2) was obtained in good yield, even at 80 °C (entries 1).
A similar result was also obtained with a phosphine-free palladium (0)  as an internal standard. The results of this analysis revealed that benzene was formed in 73% yield, along with the cyclized product (94% by NMR).

VIII-4. Product inhibition.
An oven-dried 5 mL screw-capped vial was charged with Pd(OAc) 2 (10.1 mg, 0.045 mmol), 1b The mixture was cooled to rt and filtered through a short pad of silica gel, eluting with EtOAc.
The filtrate was evaporated. The yield of 5 were determined by NMR using 1,1,2,2-tetrachloroethane as an internal standard. As shown below, the yields of the product decreased by 28-48 % following the addition of DBT derivatives. These results indicated that the magnitude of the inhibitory effect of the dibenzothiophene derivative was dependent on its structure, with the electron-rich derivative showing higher inhibition than the electron-neutral derivative. S35

VIII-5. Effect of the leaving group.
Several other SAr groups were also investigated in this reaction to determine the electronic effects on the outcome of the catalytic cyclization process. The results revealed that the use of an electron-rich phenyl ring (i.e., Ar = p-MeO-C 6 H 4 ) resulted in a similar yield of the cyclized product to that obtained using a naked phenyl ring (i.e., Ar = Ph). However, the use of an electron-deficient phenyl ring (i.e., Ar = p-F 3 C-C 6 H 4 ) led to a 6-fold decrease in the yield (see the table below). These electronic effects can be attributed to a delicate balance between the demands of the different steps involved in the ring-forming process. For example, the use of an electron-rich SAr group would be preferred during the reductive elimination step from 30', whereas an electron-deficient SAr group would better facilitate the subsequent oxidative addition step of 31'. Based on these considerations, it is clear to see why the use of an electron-neutral SPh group gave the highest yield of the product.