Sulfenate anions as organocatalysts for benzylic chloromethyl coupling polymerization via C=C bond formation

Organocatalytic polymerization reactions have a number of advantages over their metal-catalyzed counterparts, including environmental friendliness, ease of catalyst synthesis and storage, and alternative reaction pathways. Here we introduce an organocatalytic polymerization method called benzylic chloromethyl-coupling polymerization (BCCP). BCCP is catalyzed by organocatalysts not previously employed in polymerization processes (sulfenate anions), which are generated from bench-stable sulfoxide precatalysts. The sulfenate anion promotes an umpolung polycondensation via step-growth propagation cycles involving sulfoxide intermediates. BCCP represents an example of an organocatalyst that links monomers by C=C double bond formation and offers transition metal-free access to a wide variety of polymers that cannot be synthesized by traditional precursor routes.


1,3-Bis(hydroxymethyl)-5-(octadecyloxy)benzene
An oven-dried 100 mL Schlenk tube equipped with a stir bar was charged with dimethyl 5-(octadecyloxy)benzene-1,3-dioate (2.4 g, 5.2 mmol). The Schlenk tube was sealed with a rubber septum, connected to a Schlenk line, and evacuated and refilled with nitrogen (repeated three times). Anhydrous THF (15 mL) was added under nitrogen via syringe through the rubber septum and the solution was stirred at 0 o C for 30 min. Next, 10.4 mL of LiAlH4 (20.8 mmol, 2.0 M solution in THF) was added dropwise into the Schlenk tube via syringe. The mixture was warmed to room temperature and stirred for 24 h under nitrogen.

1,3-Bis(chloromethyl)-5-(octadecyloxy)benzene (M1)
An oven-dried 250 mL round bottom flask equipped with a stir bar was charged with 1,3-bis(hydroxymethyl)-5-(octadecyloxy)benzene (1.4 g, 3.45 mmol). Chloroform (50 mL) was added via syringe and the solution was cooled to 0 o C. Methane sulfonyl chloride (0.8 mL, 10.35 mmol) and triethylamine (1.5 mL, 10.35 mmol) was added dropwise into the round bottom flask via syringe at 0 o C. The, reaction vessel was sealed with a septum, put in an oil bath, stirred at 50 o C for 16 h and cooled to room temperature. After quenching the reaction mixture with water (20 mL) the layers were separated. The reaction mixture was then extracted with chloroform (10 mL × 3). The combined organic phases was, dried over anhydrous Na2SO4 and concentrated.
Anhydrous THF (15 mL) was added under nitrogen via syringe through the rubber septum and the solution was stirred at 0 o C for 30 min. Next, 10.0 mL of LiAlH4 (20.0 mmol, 2.0 M solution in THF) was added dropwise into the Schlenk tube via syringe. The mixture was warmed to room temperature and stirred for 24 h under nitrogen. After cooling to 0 o C, an aqueous solution of HCl (22 mL, 1 M) was added slowly. The mixture was diluted with ethyl acetate (20 mL), the layers were separated, the organic layer was washed with saturated brine (20 mL), dried over anhydrous Na2SO4 and mixture was concentrated in a 250 mL round bottom flask. The mixture was next dried under vacuum for 12 h and used as obtained in the next step.
A stir bar was added to the round bottom flask. Chloroform (50 mL) was added via syringe and the solution was cooled to 0 o C. Methane sulfonyl chloride (1.2 mL, 15.1 mmol) and triethylamine (2.2 mL, 15.1 mmol) was added dropwise into the round bottom flask via syringe at 0 o C. The resulting mixture was sealed, then put in an oil bath and stirred at 50 o C for 16 h and then cooled to room temperature. After quenching the reaction with water (20 mL), the layers were separated. The reaction mixture was extracted with chloroform (10 mL × 3). The combined organic phase was dried over anhydrous Na2SO4 and concentrated. The residue was purified by column chromatography (silica gel, hexanes) to afford 1.30 g of the momomer 2 (65% yield over 2 steps).  An oven-dried 250 mL three-neck round-bottom flask equipped with a stir bar was charged with 2,7-dibromo-9,9-dihexylfluorene (9.8 g, 20 mmol), 3-carboxymethylphenylboronic acid (10.8 g, 60 mmol), Pd(PPh3)4 (1.2 g, 1 mmol) and K2CO3 (8.3 g, 60 mmol). The round-bottom flask was equipped with a condenser (connected with circulating water). The top of the condenser were sealed by a rubber septum fitted with a balloon attached with a needle. The entire apparatus was connected to a Schlenk line, and evacuated and refilled with nitrogen (repeated three times). THF (120 mL) and H2O (60 mL) were added under nitrogen via syringe through the rubber septum and the solution was heated to 80 o C and stirred for 24 h. After this time, the reaction mixture was cooled to room temperature and extracted with ethyl acetate (40 mL × 3). The combined organic phases was washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The resulting residue was purified by column chromatography (silica gel, hexanes : ethyl acetate = 20 : 1) to afford the product dimethyl 3,3'-(9,9-dihexylfluorene-2,7-diyl)dibenzoate (7.7 g, 64% yield) as a white solid.  152.0, 142.0, 140.6, 139.3, 131.9, 130.9, 129.1, 128.4, 128.3, 126.4, 121.6, 120.4, 55.6, 52.4, 40.6, 31.6, 29.8, 23.9, 22.7

2,7-Bis(3-(chloromethyl)phenyl)-9,9-dihexylfluorene (M3-1)
An oven-dried 100 mL Schlenk tube equipped with a stir bar was charged with dimethyl 3,3'-(9,9dihexylfluorene-2,7-diyl)dibenzoate (2.4 g, 4 mmol). The Schlenk tube was sealed with a rubber septum, connected to a Schlenk line, and evacuated and refilled with nitrogen (repeated three times). Anhydrous THF (15 mL) was added under nitrogen via syringe through the rubber septum, the solution was cooled to 0 o C and then was stirred at 0 o C for 30 min. Next, 4 mL of LiAlH4 (8 mmol, 2.0 M solution in THF) was added dropwise into the Schlenk tube via syringe over 5 min. The mixture was stirred for 40 min under nitrogen at 0 o C. Next, 16 mL HCl solution in water (1 M) was slowly added to quench the reaction and the reaction mixture was extracted with ethyl acetate (20 mL × 3). The combined organic phases were washed with brine, dried over anhydrous Na2SO4, and mixture was concentrated in a 100 mL round bottom flask under reduced pressure.
The product mixture was next dried under vacuum for 12 h and used as obtained in the next step.
The above mentioned 100 mL round bottom flask was next charged with a stir bar. Dichloromethane (60 mL) was added via syringe and the solution was cooled to 0 o C. Thionyl chloride (1.8 mL, 24 mmol) and triethylamine (0.08 mL, 0.6 mmol), respectively, were added dropwise into the flask via syringes over 5 min at 0 o C. After all reagents were added, the flask was equipped with a condenser (connected with circulating water). The top of the condenser were sealed by a rubber septum fitted with a balloon attached with a needle.

2-(2,5-Bis((E)-3-(chloromethyl)styryl)phenyl)-5-hexylthiophene :
An oven-dried 100 mL Schlenk tube equipped with a stir bar was charged with dimethyl 3,3'-((1E,1'E)-(2-(5hexylthiophen-2-yl)-1,4-phenylene)bis(ethene-2,1-diyl))dibenzoate (2.8 g, 5 mmol). The Schlenk tube was sealed with a rubber septum, connected to a Schlenk line, and evacuated and refilled with nitrogen (repeated three times). Anhydrous THF (20 mL) was added under nitrogen via syringe through the rubber septum, the solution was cooled to 0 o C, and the reaction mixture was stirred at 0 o C for 30 min. Next, 5 mL of LiAlH4 (10 mmol, 2.0 M solution in THF) was added dropwise into the Schlenk tube via syringe over 5 min. The mixture was stirred for 40 min under nitrogen at 0 o C. 18 mL 1 M HCl was slowly added to quench the reaction and then the reaction mixture was extracted with ethyl acetate (30 mL × 3). The combined organic phases were washed with brine, dried over anhydrous Na2SO4, and mixture was concentrated in a 100 mL round bottom flask. The mixture was next dried under vacuum for 12 h and the resulting compound used as obtained in the next step.

High-Throughput Experimentation screenings for polymerization:
Parallel High-throughput Experimentation Screening was accomplished in an MBraun glovebox operating with a constant N2-purge (oxygen typically <5 ppm). The experimental design was accomplished using Accelrys Library Studio. Screening reactions were carried out in 1 mL vials (30 mm height×8 mm diameter) in 24-well plate aluminum reactor block. Liquid chemicals were dosed using multi-channel or single-channel pipettors. Solid chemicals were dosed manually as solutions or slurries in appropriate solvents. Undesired additional solvent was removed using a GeneVac system located inside the glovebox. The reactions were heated and stirred on a heating block with a tumble-stirrer (V&P Scientific) using 1.98 mm diameter×4.80 mm length parylene stir bars. The tumble stirring mechanism helped to insure uniform stirring throughout the 96well plate. The reactions were sealed in the 96-well plate during reaction. Below each reactor vial in the aluminum 96-well plate was a 0.062 mm thick silicon-rubber gasket. Directly above the glass vial reactor tops was a Teflon perfluoroalkoxy copolymer resin sealing gasket and above that, two more 0.062 mm thick silicon-rubber gaskets. The entire assembly was compressed between an aluminum top and the reactor base with 9 evenly-placed screws.

Set up:
Experiments were set up inside a glovebox under a nitrogen atmosphere. A 96-well aluminum block containing 1 mL glass vials was dosed with sulfoxide catalyst in THF. The solvent was removed to dryness using a GeneVac. Monomer 1 (10 μmol) and the corresponding base (30 μmol) were separately dosed into each reaction vial with the corresponding solvent (100 μL each, total volume 200 μL , 0.05 M). The plate was then sealed with screwdriver and stirred for 24 h at 80 o C.

work up:
Upon cooling to room temperature, the plate was opened in the glovebox, water (10 µL) was added into each vial with a pipetman to quench the reactions and then solvent was removed to dryness using a GeneVac. Next, CHCl3 (200 µL) was added into each vial and the slurry solution was allowed to stir for 10 min. Cold methanol (600 µL) was added into each vial to precipitate the polymer and the slurry solution was allowed to stir for 10 min. The slurry is then transferred with a multichannel pipetman onto a filter plate positioned on the vacuum slot of a Freeslate CM2 reaction deck. After the MeOH/CHCl3 solution was filtered, the polymer remains on the filter plate. Finally, a 96-well collection plate was put beneath the filter plate and 800 µL THF was added into the filter plate well to dissolve the polymer. The polymer solution was transferred into a 96-well LC-block and analyzed by GPC. Figure 19. Work-flow of High-Throughput-Screening in polymerization study. Note: Catalyst loading to 2.5 mol % led to incomplete polymerization and data were not further processed.

Supplementary
General procedure for the 0.1 mmol lab-scale BCCP.
An oven-dried 8 mL microwave vial equipped with a stir bar was charged with monomer M1 (44.4 mg, 0.10 mmol) under a nitrogen atmosphere in a glove box. A solution of precatalyst 10 (1.73 mg, 0.075 mmol) in 1.0 mL anhydrous CPME was added by syringe. Next, a solution of KOtBu (33.6 mg, 0.30 mmol) in 1.0 mL anhydrous CPME was added by syringe. The reaction was stirred for 24 h at 80 ºC, quenched with 2 drops of H2O via syringe, cooled to room temperature and opened to air. After the volatile materials were removed with rotary evaporator, CHCl3 (2 mL) was added into each vial and the slurry solution was allowed to stir for 10 min. Cold methanol (6 mL) and H2O (0.5 mL) was then added into each vial to precipitate the polymer and the slurry solution with polymer suspension was allowed to stir for 10 min. The mixture was then transferred with a pipette onto a Whatman autovial syringeless filter (5 mL, 0.45 µm PTFE membrane). After the MeOH/CHCl3/H2O solution was filtered, polymer that remained in the filter was washed sequentially with 5 mL MeOH and 5 mL pentane. Finally, the polymer remaining in the filter was transferred into a 20 mL vial with spatula and dried in under vacuum to yield a pale yellow solid in 33.8 mg, 91% yield.  Table 1, entry 1.

General procedure for the scale-up (1 mmol ) polymerization.
An oven-dried 100 mL Schlenk tube equipped with a stir bar was charged with monomer 1 (444.0 mg, 1.0 mmol) and precatalyst 10 (17.3 mg, 0.75 mmol). The Schlenk tube was sealed with a rubber septum and was connected to a Schlenk line, evacuated, and refilled with nitrogen (repeated three times). Next, a solution of KOtBu (336 mg, 3.0 mmol) in 20 mL anhydrous CPME was added by syringe. The reaction was stirred for 24 h at 80 ºC, cooled to room temperature, opened to air and quenched with 1 mL of H2O. The reaction mixture was firstly transferred to a 250 mL round bottom flask and the volatile materials were removed with rotary evaporator. Next, CHCl3 (20 mL) was added into flask and the slurry solution was allowed to stir for 10 min.
Cold methanol (60 mL) was added into the flask to precipitate the polymer and the slurry solution with polymer suspension was allowed to stir for 10 min. The mixture was then filtered on a glass fritted filter funnel (75 mL), After the MeOH/CHCl3 solution was filtered, solid was washed by H2O (5 mL 1 mmol Scale synthesis and characterization of co-polymer P3-1, P4-1.

General Information
UV-Vis absorption spectra were recorded on a Shimadzu UV-2500 spectrophotometer. Photoluminescence (PL) spectra were measured on a Hitachi F-4600 fluorescence spectrophotometer. Thermogravimetric analysis (TGA) was carried out using a NETZSCH STA 449C instrument. The thermal stability of the samples under a nitrogen atmosphere was determined by measuring their weight loss while heating at a rate of 20 o C min -1 from 25 to 500-600 o C. Differential scanning calorimetry (DSC) was performed on a NETZSCH DSC 200 PC unit at a heating rate of 10 o C min -1 from 40 to 200-300 o C under a nitrogen atmosphere. The glass transition temperature (Tg) was determined from the second heating scan. Cyclic voltammetry (CV) was measured in nitrogen-purged dichloromethane for oxidation scan using a CHI voltammetric analyzer. Tetrabutylammonium hexafluorophosphate (TBAPF6) (0.1 M) was used as a supporting electrolyte. The conventional three-electrode configuration is employed, which consists of a platinum working electrode, a platinum wire auxiliary electrode and an Ag wire pseudo-reference electrode with ferrocenium-ferrocene (Fc + /Fc) as the internal standard. Cyclic voltammograms were obtained at a scan rate of 100 mV s -1 . The onset potential of the new compounds was determined from the intersection of two tangents drawn at rising and background current of the cyclic voltammongram at first circle. The half-wave potential (E1/2) value for Fc + /Fc are calculated as the average of cyclic voltammetric anodic and cathodic peaks. The HOMO energy levels were calculated from the oxidation curves according to the formula: -[4.8 eV + (Eonset -E1/2(Fc/Fc + ))]. The LUMO energy level was deduced from the energy band gap (Eg) and HOMO level. Where J is the current density, εr is the relative dielectric constant of active layer material usually 2-4 for organic semiconductors, herein we use a relative dielectric constant of 4, ε0 is the permittivity of empty space, μ is the mobility of hole or electron and L is the thickness of the active layer, V is the internal voltage in the device, and V = Vapp-Vbi, where Vapp is the voltage applied to the device, and Vbi is the built-in voltage resulting from the relative work function difference between the two electrodes (in the hole-only and the electron-only devices, the Vbi values are 0.2 V and 0 V respectively).