C–H arylation of triphenylene, naphthalene and related arenes using Pd/C

A highly selective arylation of a number of polyaromatic hydrocarbons (PAHs) with aryliodonium salts and Pd/C as the only reagent is reported.


S4
T 0 = 50 °C, T 1 = 290 °C, ramp = 40 °C/min, t = 10 min). Exact ESI mass spectra were recorded on a Bruker Daltonics MicroTof. High resolution ESI mass spectra were recorded on a Thermo-Fisher Scientific Orbitrap LTQ XL. Exact EI mass spectra were recorded on a Waters-Micromass GC-Tof. Major signals are quoted in m/z. Infrared spectra were recorded neat on a Shimadzu FTIR-8400S. The wave numbers (υ) of recorded IR-signals are quoted in cm -1 .

Preparation of Iodonium Salts Diphenyliodonium tetrafluoroborate
Diphenyliodonium tetrafluoroborate was synthesised according to the procedure of Bielawski et al. 1 Reaction of iodobenzene (5.56 g, 3.00 mL, 27.3 mmol, 1 eq) and phenylboronic acid Data is in accordance with the literature. 1

Experimental and characterization of reaction products
3.1 Arylation of Naphthalene: General procedure A Note: Efficient stirring is crucial to obtaining reproducible yields and therefore we strongly recommend the use of cross-shaped stirring bars. Alternatively, we found that using 3 small 'standard' linear bars rather than 1 larger bar produced reproducible results. Stirring plates were set at >1000 rpm.
Unless otherwise noted, to the iodonium salt (0.500 mmol, 1.0 eq), naphthalene (2.0 eq) and Pd/C (5 wt% Pd/C, <3% H 2 O, Heraeus type K-0219, 27 mg, 12.5 µmol, 2.5 mol%) was added 1,2-dimethoxyethane (5.00 mL), and the reaction stirred at the reported temperature for 16 h. The reaction mixture was allowed to cool to room temperature and then filtered through a pad of silica, washing with EtOAc (60 mL). The filtrate was concentrated in vacuo and the crude material purified by flash column chromatography.

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Data is in accordance with the literature. 11

Arylation of triphenylene: General procedure B
To the iodonium salt (0.400 mmol, 1.0 eq), triphenylene (182 mg, 0.800 mmol, 2.0 eq) and Pd/C (5 wt% Pd/C, <3% H 2 O, Heraeus type K-0219, 42 mg, 5 mol%) was added 1,2-dimethoxyethane (2.00 mL), and the reaction stirred at 100 °C for 24 h. The reaction mixture was allowed to cool to room temperature and then filtered through a pad of silica, washing with EtOAc (60 mL). The filtrate was concentrated in vacuo and the crude material purified by flash column chromatography. S18

4-Phenylpyrene (7a)
According to general procedure A: Reaction of pyrene (202 mg, 1.00 mmol, 2 eq) and bis ( Data is in accordance with the literature. 12

5-Phenylacenapthene (9a)
According to general procedure A: Reaction of acenaphthene (154 mg, 1.00 mmol, 2 eq) and Data is in accordance with the literature. 14

Solvent Screen
Reactions were performed exactly as described for the substrate scope.

Triphenylene Optimization
Reactions were performed exactly as described for the substrate scope.

Additive Screen
We extensively screened additives in an attempt to increase both the yield and selectivity of reactions. In each case we observed either no effect or a detrimental effect on the reaction. 72 Standard conditions: Triphenylene (0.30 mmol), Ph 2 IBF 4 (0.5 eq), Catalyst 5 mol%, DME (0.5 mL), 100 °C, 24 h. a Determined by GC-FID b Isolated yield.

Discussion
The catalyst screen demonstrated that Pd/C (Hereaus) and Pd/Al 2 O 3 are equally proficient catalysts. As in our previous studies, it is also very clear that the source of Pd/C has an impact on yield. While homogeneous Pd(0) catalysts also show reactivity, Pd(II) catalysts (homogeneous or heterogeneous) are ineffective. Comparative studies of Pd/C, Pd/Al 2 O 3 and Pd(OAc) 2 provided some insight to the different reactivity of these systems. showed excellent reactivity in the standard reaction, no product formation was observed with S27 electron rich iodonium salts. Interestingly, this is consistent with a Pd(II)/(IV) manifold as proposed by Sanford. 'Poisoning' reactions of electron-rich iodonium salts using Pd/C as catalyst by the addition of Pd/Al 2 O 3 did not occur, suggesting that the composition of the support alone does not account for the inhibition of the reaction. Pd(OAc) 2 generally proved less efficient that Pd/C, which may be accounted for by the reduced stability of the nanoparticles in the absence of a support.

Mechanistic Investigation
Studies were undertaken on both naphthalene and triphenylene in a number of instances, to confirm the same mechanism is in operation. If not considered essential, mechanistic studies were only undertaken on one substrate. More extensive studies were typically undertaken employing naphthalene for economic considerations. Experiments demonstrate catalyst is essential for reactivity and rule out air as an oxidant.

3-Phase tests
Preparation of compounds

2-(Naphthalen-2-yl)ethanol
To a solution of 2-vinylnaphthalene (1.00 g, 6.50 mmol, 1 eq) in THF (5 mL The resin was dried in vacuo to afford Wang-resin II. To determine the loading, 50 mg of Wang-resin II was stirred in TFA/CH 2 Cl 2 3:1 (8 mL) at room temperature for 2 h. The reaction mixture was filtered, the residue washed with CH 2 Cl 2 (20 mL) and the filtrate washed with saturated aqueous NaHCO 3 (2x 30 mL), dried over MgSO 4 and the solvent removed in vacuo. The mass of the isolated material allowed for determination of the loading of the Wang resin. The material was analysed by GCMS and gave a loading of 0.45 mmol/g.

3-Phase tests
Reactions were undertaken as per general procedure A, substituting naphthalene (1)  analysis of the reaction yield showed the reaction is inhibited by the introduction of Hg(0).

Hot filtration test
As per general procedure B, triphenylene (4)

Kinetic profile with preactivation of catalyst
As per general procedure A: PhI 2 BF 4 (0.100 mmol, 1 equiv) and Pd/C (2.5 % mol) in DME (1.0 mL) were heated at 80 °C for 2h. Naphthalene (2 equiv) was then added to the reaction mixture and stirring at 80 °C continued. Aliquots were taken to determine the yield of reaction. Results are the average of 3 different experiments. Preheating the catalyst in the absence of an oxidant for 2 h prior to the introduction of the reagents did not negate the induction period. After the addition of the reagents, the yield of the reaction was determined to be 4% after 4 h. This is consistent with the kinetic profile of the standard reaction.

Determination of KIE
Via initial rate constants: As per general procedure A, reaction of naphthalene (1) (0.200 mmol, 2.0 eq) or naphthalene- S37 Initial rates of standard reaction with naphthalene (blue) and naphthalene-d 8 (red)

Competition experiment
To ensure formation of the active catalyst did not consume any reagent and affect the results, Pd/C (21 mg, 5 mol%) was pre-treated with PIDA (13 mg, 20 mol%) at 100 °C in DME (0.5 ml) for 2 h to form the active catalytic species. To the active catalyst solution was then added triphenylene (4) (46 mg, 0.200 mmol, 1 eq) PhI 2 BF 4 (74 mg, 0.200 mmol, 1 eq) and m-CO 2 EtPh 2 IBF 4 (102 mg, 0.200 mmol, 1 eq) and the reaction stirred for 4 h. Yields were determined at 2 h and 4h using GC-FID and indicated reaction of PhI 2 BF 4 is more rapid than m-CO 2 EtPh 2 IBF 4 .

Product Yield % a 2h
Yield % a 3h 5a 5d 8 3 19 10 a Yields determined by GC of crude reaction mixture, mesitylene as internal standard.

Order in palladium
Reactions were undertaken as per general procedure A. Catalyst loadings of 2.5 mg, 5 mg, 10 mg and 20 mg were undertaken. The induction period was established to be dependent on catalyst concentration, hence preliminary experiments were undertaken to establish the duration of the induction period and hence establish when measurement should begin. Initial reaction rates were determined by measuring the rate of product formation between ~3 and ~12 % yield, with a minimum of 5 data points. Plotting the initial rates (gradient) vs. catalyst S38 amount showed a linear correlation indicative of 1 st order reaction kinetics. Surprisingly, no product formation was observed after 16 h with 2.5 mg of catalyst.