Pyridine-Containing m-phenylene Ethynylene Oligomers Having Tunable Basicities

Transcription

1 Supporting nformation Pyridine-Containing m-phenylene Ethynylene ligomers Having Tunable Basicities Jennifer M. Heemstra and Jeffrey S. Moore* Departments of Chemistry and Materials Science & Engineering, 600 S. Mathews Ave, The University of llinois at Urbana-Champaign, Urbana, L moore@scs.uiuc.edu EXPERMETAL PRCEDURES General. Unless otherwise noted, all starting materials were obtained from commercial suppliers and were used without further purification. All air- or moisture-sensitive reactions were done under an atmosphere of dry nitrogen. Flash column chromatography was carried out with silica gel 60 ( mesh) from EM Science. Dry triethylamine and acetonitrile were obtained using a solvent-purification system from Anhydrous Engineering. The 1 H and 13 C MR spectra were recorded on a Varian Unity 400, Varian Unity 500, or Varian arrow Bore 500 spectrometer. Chemical shifts are expressed in parts per million (δ) using residual solvent protons as internal standard (δ 7.26 ppm for CH 3 ). Coupling constants, J, are reported in Hertz (Hz), and splitting patterns are designated as s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet), br (broad), and app (apparent). Mass spectra were obtained through the Mass Spectrometry Facility, School of Chemical Sciences, Universtiy of llinois. Low resolution fast atom bombardment (FAB) and low and high resolution electron impact (E) mass spectra were obtained on a Micromass 70-VSE spectrometer. High resolution fast atom bombardment (FAB) mass spectra were obtained on a Micromass 70-SE-4F spectrometer. Low resolution matrix assisted laser desorption (MALD) mass spectra were obtained using a Applied Biosystems Voyager-DE STR spectrometer. Elemental analyses were performed by the University of llinois Micro Analytical Service Laboratory. High pressure liquid chromatography (HPLC) analysis was performed with a Rainin Dynamax solvent delivery system, model SD-200, using a Microsorb Si C5 silica column and a UV detector operating at 290 nm. pka measurements using UV-vis spectroscopy. UV absorption spectra were recorded at room temperature on a Shimadzu (model UV-160A) spectrophotometer using 1-cm quartz cells. For the titration experiments, stock solutions of each of the oligomers and indicators 1 were prepared using spectrophotometric grade acetonitrile purchased from Fisher Scientific. A UV spectrum of each compound was obtained at a dilution such that the maximum absorbance was < 1. Concentrated H 4 was then added, and a UV spectrum of the protonated base acquired. To measure pk a values, a 1:1 mixture of two bases was prepared (c = 8-20 µm) in spectrophotometric grade acetonitrile, and small portions of H 4 added until no further change was observed in the UV spectrum. The initial concentrations of each base were verified using eq 1 for the UV spectrum prior to addition of any acid.

2 λ A B 2 λ λ = ε [B1] + ε [B ] (1) B1 2 pk a values were then calculated for each of the spectra over the course of the titration using methods outlined by Koppel and coworkers. 2 The final value of pk a represents the average of values obtained from spectra where each of the species present meets a threshold concentration. This concentration was typically 10% of the initial concentration, but for pk a > 1.7, a lower threshold concentration was invoked. Absolute pk a values were assigned to each compound by averaging all of the independent pathways to that compound in the acidity scale.

3 2 H pk a measured by titration pk a CH CH 3 Me 2 3e R 2 R 2 H 3 C CH 3 Me 2 2e R 1 R CH CH 3 Me R 2 R 2 Me R 1 R d d R 1 = C 2 Tg Si(Me) 3 R 2 R 2 2c R 1 R 1 2 3c R 2 = C 2 Tg C CH 3 3b R 2 R CH 3 2b 7.2 R 1 R 1 2 2a R 1 R 1 H R 2 R 2 3a 5.0

4 2 2,6-Dichloro-4-nitropyridine (4). To a 200 ml round bottom flask was added 2,6-dichloropyridine - oxide 3 (2.08 g, 12.7 mmol) and H 2 S 4 (concd, 40 ml). The solution was stirred, and H 3 (concd, 40 ml) added dropwise over 15 min. The flask was fitted with a reflux condenser, placed in an oil bath at 120 o C, and stirred for 15 h. The reaction mixture was chilled to 25 o C in an ice bath, then poured onto 300 g ice. The solution was extracted 3 x 300 ml CH 3, and the combined organic phase dried over a 2 S 4, filtered, and evaporated to give a yellow solid (1.51 g). The crude product was purified by silica gel chromatography (6:1 hexanes:etac) to give g (25%) of yellow solid. mp o C. 1 H MR (400 MHz, CD 3 ) δ 8.01 (s, 2H). 13 C MR (125.7 MHz, CD 3 ) δ 156.4, 153.0, HRMS (E) m/z (calcd [M] + = ). Anal. Calcd. for C 5 H (193.0): C, 31.12; H, 1.04;, Found: C, 30.88; H, 0.84;, itropyridine monomer (5). A 10 ml sealed tube was charged with 4 (0.359 g, 1.86 mmol), Pd 2 (dba) 3 ( g, mmol), Cu ( g, mmol), and PPh 3 ( g, mmol). The contents of the sealed tube were degassed by alternating three times between vacuum and 2, then Et 3 (6.2 ml) and triisopropylsilyl acetylene (1.67 ml, 7.44 mmol) were added. The solution was degassed, the tube sealed under an atmosphere of 2, and the solution stirred in an oil bath at 30 o C for 66 h. The reaction mixture was then filtered through a cotton plug, and evaporated to give a brown oil. Purification by silica gel chromatography (20:1 hexanes:etac) gave g (42%) of yellow oil. 1 H MR (500 MHz, CD 3 ) δ 8.01 (s, 2H), (m, 42H). 13 C MR (125.7 MHz, CD 3 ) δ 153.9, 146.0, 119.3, 103.9, 96.7, 18.7, HRMS (FAB) m/z (calcd [M + H] + = ). Anal. Calcd. for C 27 H Si 2 (484.8): C, 66.89; H, 9.15;, Found: C, 66.55; H, 9.31;, Me 4-Methoxypyridine monomer (6). To a 10 ml round bottom flask was added 5 (0.216 g, mmol), K 2 C 3 ( g, mmol) and MeH (4.5 ml). The reaction mixture was stirred in an oil bath at 65 o C for 25 min, then removed from the oil bath and 20 ml H 2 added. The mixture was extracted with 3 x 20 ml CH 2 2, and the combined organic phase dried over MgS 4, filtered, and concentrated to a brown

5 oil. Purification by silica gel chromatography (20:1 hexanes:etac) gave g (85%) of white solid. mp o C. 1 H MR (400 MHz, CD 3 ) δ 6.92 (s, 2H), 3.86 (s, 3H), (m, 42H). 13 C MR (125.7 MHz, CD 3 ) δ 165.6, 144.8, 113.8, 105.7, 91.8, 55.5, 18.8, HRMS (FAB) m/z (calcd [M + H] + = ). 2 H 2 4-Aminopyridine monomer (7). To a 3 ml vial was added 5 ( g, mmol), powdered iron ( g, 1.02 mmol) and glacial acetic acid (1.0 ml). The reaction mixture was stirred in an oil bath at 70 o C for 20 min, then neutralized with sat. aq. ahc 3 and extracted with 2 x 30 ml Et 2. The combined organic phase was dried over a 2 S 4, filtered, and evaporated to give an orange solid. Purification by silica gel chromatography (4:1 hexanes:etac) afforded the product as g (78%) of orange crystals. mp o C. 1 H MR (400 MHz, CD 3 ) δ 6.68 (s, 2H), 4.12 (br s, 2H), (m, 42H). 13 C MR (125.7 MHz, CD 3 ) δ 152.9, 143.9, 113.4, 106.1, 90.5, 18.7, HRMS (FAB) m/z (calcd [M + H] + = ). H 2 4-,-Dimethylaminopyridine monomer (8). To a 10 ml round bottom flask was added 7 (0.270 g, mmol), paraformaldehyde (0.195 g, 6.42 mmol), and glacial acetic acid (5.0 ml). While stirring the reaction mixture, abh 3 C (0.295 g, 4.69 mmol) was added. The reaction mixture was stirred in an oil bath at 35 o C for 20 h, then neutralized with ahc 3 (sat. aq.) and extracted with 3 x 50 ml EtAc. The combined organic phase was dried over a 2 S 4, filtered, and evaporated to give a pink solid. Purification by silica gel chromatography (9:1 hexanes:etac) afforded g of white solid (78%). mp o C. 1 H MR (400 MHz, CD 3 ) δ 6.63 (s, 2H), 3.00 (s, 6H), (m, 42 H). 13 C MR (125 MHz, CD 3 ) δ 154.2, 143.6, 110.5, 106.8, 89.7, 39.2, 18.8, HRMS (FAB) m/z (calcd [M + H] + = ).

6 Me Me sonicotinic acid methyl ester monomer (9). A 50 ml sealed tube was charged with 10 (0.979 g, 4.75 mmol), Pd 2 (dba) 3 (0.175 g, mmol), Cu ( g, mmol), and PPh 3 (0.198 g, mmol). The contents of the sealed tube were degassed by alternating three times between vacuum and 2, then Et 3 (30 ml) added. The solution was degassed, then trimethylsilyl acetylene (6.7 ml, 47.4 mmol) added. The tube was sealed under an atmosphere of 2, and the solution stirred in an oil bath at 60 o C for 24 h. The reaction mixture was filtered through a cotton plug, and evaporated to a brown solid. Purification by silica gel chromatography (49:1 hexanes:etac) followed by recrystallization from MeH:H 2 gave g (41%) of white flakes. mp o C. 1 H MR (400 MHz, CD 3 ) δ 7.90 (s, 2H), 3.95 (s, 3H), 0.26 (s, 18H). 13 C MR (125.7 MHz, CD 3 ) d 164.6, 144.4, 138.2, 126.0, 102.6, 97.0, 53.1, HRMS (E) m/z (calcd [M] + = ). Pyridine monomer (10). A 50 ml sealed tube was charged with 2,6-dichloropyridine (0.997 g, 6.53 mmol), Pd 2 (dba) 3 (0.241 g, mmol), Cu ( g, mmol), and PPh 3 (0.278 g, 1.06 mmol). The contents of the sealed tube were degassed by alternating three times between vacuum and 2, then Et 3 (30 ml) added. The solution was degassed, then trimethylsilyl acetylene (9.0 ml, 63.7 mmol) added. The tube was sealed under an atmosphere of 2, and the solution stirred in an oil bath at 80 o C for 42 h. The reaction mixture was filtered through a cotton plug, and evaporated to a dark green solid. Purification by silica gel chromatography (19:1 hexanes:etac) followed by recrystallization from MeH:H 2 gave g (23%) of white needles. mp o C. 1 H MR (400 MHz, CD 3 ) δ 7.58 (dd, J = 8.1, 7.5 Hz, 1H), 7.38 (d, J = 7.9 Hz, 2H), 0.25 (s, 18H). 13 C MR (125.7 MHz, CD 3 ) δ 143.4, 136.4, 126.8, 103.2, 95.4, HRMS (E) m/z (calcd [M] + = ). Tg 2 2 Tg Tg 4-itropyridine trimer (2a). A vial was charged with 5 (0.116 g, mmol), AcH ( ml, mmol), and THF (2 ml). A solution of TBAF in THF (1.0 M, 0.48 ml) was added, and the reaction mixture stirred for 1 min. The solution was filtered through a plug of silica gel with EtAc, and

7 evaporated to give a brown solid. To a 10 ml sealed tube was added 12 (0.224 g, mmol), Pd 2 (dba) 3 ( g, mmol), Cu ( g, mmol), and PPh 3 ( g, mmol). The contents of the sealed tube were degassed by alternating three times between vacuum and 2, then deprotected 5 transferred via syringe with 3 x 0.4 ml portions of CH 3 C. Triethylamine (0.4 ml) was added to the sealed tube, the solution degassed, the tube sealed under an atmosphere of 2, and the reaction mixture stirred in an oil bath at 50 o C for 22 h. The solvents were evaporated to give a black oil, which was purified by silica gel chromatography (EtAc) to give g of brown oil (41%). 1 H MR (400 MHz, CD 3 ) δ 8.34 (td, J = 1.7, 0.6 Hz, 2H), 8.19 (s, 2H), 8.12 (ddd, J = 7.9, 1.7, 1.3 Hz, 2H), 7.81 (ddd, J = 7.7, 1.5, 1.3 Hz, 2H), 7.50 (td, J = 7.8, 0.5 Hz, 2H), (m, 4H), (m, 4H), (m, 12H), (m, 4H), 3.36 (s, 6H). 13 C MR (125.7 MHz, CD 3 ) δ 165.5, 154.1, 145.9, 136.4, 133.6, 131.0, 130.8, 128.9, 121.6, 118.8, 91.5, 87.6, 71.9, 70.72, 70.68, 70.63, 69.1, 64.5, HRMS (FAB) m/z (calcd [M + H] + = ). HPLC (1.0 ml/min, 2.5% iprh/ch 3 20 min, retention time 5.6 min) indicated >96% purity. Me Tg Me Tg Tg sonicotinic acid methyl ester trimer (2b). A vial was charged with 11 (0.102 g, mmol), AcH ( ml, mmol) and THF (3 ml). A solution of TBAF in THF (1.0 M, ml) was added, and the reaction mixture stirred for 1 min. The solution was filtered through a plug of silica gel with EtAc, and evaporated to give a pale yellow solid. To a 5 ml sealed tube was added 12 (0.251 g, mmol), Pd 2 (dba) 3 ( g, mmol), Cu ( g, mmol), and PPh 3 ( g, mmol). The contents of the sealed tube were degassed by alternating three times between vacuum and 2, then deprotected 11 transferred via syringe with 2 x 0.75 ml portions of CH 3 C. Triethylamine (0.5 ml) was added to the sealed tube, the solution degassed, the tube sealed under an atmosphere of 2, and the reaction mixture stirred in an oil bath at 60 o C for 22 h. The solvents were evaporated to give a brown oil, which was purified by silica gel chromatography (EtAc) to give g of yellow oil (84%). 1 H MR (400 MHz, CD 3 ) δ 8.30 (td, J = 1.7, 0.5 Hz, 2H), 8.08 (ddd, J = 7.9, 1.7, 1.3 Hz, 2H), 8.04 (s, 2H), 7.79 (ddd, J = 7.7, 1.7, 1.3 Hz, 2H), 7.47 (td, J = 7.8, 0.5 Hz, 2H), (m, 4H), 4.00 (s, 3H), (m, 4H), (m, 12H), (m, 4H), 3.35 (s, 6H). 13 C MR (125.7 MHz, CD 3 ) δ 165.5, 164.3, 144.4, 138.3, 136.2, 133.3, 130.6, 130.5, 128.6, 125.7, 122.1, 89.6, 88.4, 71.9, 70.63, 70.57, 70.52, 69.1, 64.4, 59.0, HRMS (FAB) m/z (calcd [M + H] + = ). HPLC (1.0 ml/min, 2.5% iprh/ch 3 20 min, retention time 5.5 min) indicated 100% purity.

8 Tg Tg Tg Pyridine trimer (2c). A vial was charged with 9 (0.101 g, mmol) and THF (4 ml). A solution of TBAF in THF (1.0 M, 0.75 ml) was added, and the reaction mixture stirred for 1 min. The solution was filtered through a plug of silica gel with EtAc, and evaporated to give a dark yellow solid. To a 10 ml sealed tube was added 12 (0.425 g, mmol), Pd 2 (dba) 3 ( g, mmol), Cu ( g, mmol), and PPh 3 ( g, mmol). The contents of the sealed tube were degassed by alternating three times between vacuum and 2, then deprotected 9 transferred via syringe with 3 x 0.7 ml portions of CH 3 C. Triethylamine (0.7 ml) was added to the sealed tube, the solution degassed, the tube sealed under an atmosphere of 2, and the reaction mixture stirred in an oil bath at 50 o C for 24 h. The solvents were evaporated to give a brown solid, which was purified by silica gel chromatography (19:1 EtAc: i-prh) to give g of yellow oil (66%). 1 H MR (400 MHz, CD 3 ) δ 8.30 (td, J = 1.7, 0.6 Hz, 2H), 8.07 (ddd, J = 7.8, 1.7, 1.3 Hz, 2H), 7.79 (ddd, J = 7.7, 1.7, 1.3 Hz, 2H), 7.73 (dd, J = 8.2, 7.5 Hz, 1H), 7.52 (d, J = 8.0 Hz, 2H), 7.46 (td, J = 7.8, 0.5 Hz, 2H), (m, 4H), (m, 4H), (m, 12H), (m, 4H), 3.36 (s, 6H). 13 C MR (125.7 MHz, CD 3 ) δ 165.5, 143.4, 136.6, 136.1, 133.2, 130.4, 130.1, 128.5, 126.5, 122.4, 88.8, 88.4, 71.8, 70.56, 70.49, 70.45, 69.0, 64.3, HRMS (FAB) m/z (calcd [M + H] + = ). HPLC (1.0 ml/min, 2.5% iprh/ch 3 20 min, retention time 8.9 min) indicated 99.6% purity. Me Tg Me Tg Tg 4-Methoxypyridine trimer (2d). A vial was charged with 6 (0.104 g, mmol) and THF (2 ml). A solution of TBAF in THF (1.0 M, 0.44 ml) was added, and the reaction mixture stirred for 1 min. The solution was filtered through a plug of silica gel with EtAc, and evaporated to give a brown solid. To a 5 ml sealed tube was added 12 (0.230 g, mmol), Pd 2 (dba) 3 ( g, mmol), Cu ( g, mmol), and PPh 3 ( g, mmol). The contents of the sealed tube were degassed by alternating three times between vacuum and 2, then deprotected 6 transferred via syringe with 3 x 0.5 ml portions of CH 3 C. Triethylamine (0.5 ml) was added to the sealed tube, the solution degassed, the tube sealed under an atmosphere of 2, and the reaction mixture stirred in an oil bath at 50 o C for 20 h. The solvents were evaporated to give a brown oil, which was purified by silica gel chromatography (EtAc) to give g of yellow oil (48%). 1 H MR (400 MHz, CD 3 ) δ 8.29 (t, J = 1.7 Hz, 2H), 8.06 (dt, J = 7.9, 1.4 Hz, 2H), 7.78 (dt, J = 7.8, 1.5 Hz, 2H), 7.45 (td, J = 7.8, 0.4 Hz, 2H), 7.08 (s, 2H), (m,

9 4H), 3.93 (s, 3H), (m, 4H), (m, 12H), (m, 4H), 3.36 (s, 6H). 13 C MR (125.7 MHz, CD 3 ) δ 166.0, 165.8, 144.6, 136.3, 133.4, 130.6, 130.3, 128.7, 122.6, 113.2, 89.1, 88.1, 72.0, 70.8, 70.72, 70.69, 69.2, 64.5, 59.1, HRMS (FAB) m/z (calcd [M + H] + = ). HPLC (1.0 ml/min, 2.5% iprh/ch 3 20 min, retention time 8.5 min) indicated 100% purity. Tg Tg Tg 4-,-Dimethylaminopyridine trimer (2e). A vial was charged with 8 ( g, mmol) and THF (2 ml). A solution of TBAF in THF (1.0 M, 0.38 ml) was added, and the reaction mixture stirred for 1 min. The solution was filtered through a plug of silica gel with EtAc, and evaporated to give a brown oil. To a 4 ml sealed tube was added 12 (0.199 g, mmol), Pd 2 (dba) 3 ( g, mmol), Cu ( g, mmol), and PPh 3 ( g, mmol). The contents of the sealed tube were degassed by alternating three times between vacuum and 2, then deprotected 8 transferred via syringe with 3 x 0.4 ml portions of CH 3 C. Triethylamine (0.4 ml) was added to the sealed tube, the solution degassed, the tube sealed under an atmosphere of 2, and the reaction mixture stirred in an oil bath at 50 o C for 20 h. The solvents were evaporated to give a brown oil, which was purified by silica gel chromatography (98:2 EtAc:Et 3 ) to give g of yellow oil (66%). 1 H MR (400 MHz, CD 3 ) δ 8.29 (td, J = 1.7, 0.4 Hz, 2H), 8.05 (ddd, J = 7.9, 1.7, 1.3 Hz, 2H), 7.81 (d, J = 7.9 Hz, 2H), 7.44 (t, J = 7.8 Hz, 2H), 6.78 (s, 2H), (m, 4H), (m, 4H), (m, 12H), (m, 4H), 3.36 (s, 6H), 3.10 (s, 6H). 13 C MR (125.7 MHz, CD 3 ) δ 165.8, 154.5, 143.1, 136.2, 133.3, 130.5, 130.0, 128.6, 122.9, 109.8, 90.0, 86.7, 71.9, 70.73, 70.66, 70.63, 69.2, 64.4, 59.1, HRMS (FAB) m/z (calcd [M + H] + = ). HPLC (1.0 ml/min, 2.5% iprh/ch 3 20 min, retention time 3.6 min) indicated >95% purity. Tg Tg Tg itropyridine tridecamer (3a). A vial was charged with 5 ( g, mmol), AcH ( ml, mmol) and THF (0.2 ml). A solution of TBAF in THF (1.0 M, ml) was added, and the reaction mixture stirred for 1 min. The solution was filtered through a plug of silica gel with EtAc, and evaporated to give a pale brown solid. To a 4 ml sealed tube was added Pd 2 (dba) 3 (0.959 mg, 1.05 µmol),

10 Cu ( mg, 1.20 µmol), and PPh 3 (0.999 mg, 3.81 µmol). The contents of the sealed tube were degassed by alternating three times between vacuum and 2, then 13 ( g, mmol) transferred with 2 x 0.25 ml portions of CH 3 C and deprotected 5 transferred with 2 x 0.25 ml portions of CH 3 C. Triethylamine (0.33 ml) was added to the sealed tube, the solution degassed, the tube sealed under an atmosphere of 2, and the reaction mixture stirred in an oil bath at 50 o C for 22 h. The solvents were evaporated to give a brown wax, which was purified by silica gel chromatography (97:3, 92:8 CH 3 : i- PrH) to give g of yellow wax (47%). 1 H MR (400 MHz, CD 3 ) δ 8.30 (t, J = 1.6 Hz, 2H), 8.26 (t, J = 1.6 Hz, 2H), (m, 16H), 8.17 (t, J = 1.6 Hz, 2H), 8.14 (t, J = 1.7 Hz, 2H), 8.10 (t, J = 1.6 Hz, 2H), 7.97 (t, J = 1.6 Hz, 2H), (m, 6H), 7.87 (t, J = 1.6 Hz, 2H), 7.81 (t, J = 1.6 Hz, 2H), (m, 24H), (m, 24H), (m, 72H), (m, 24H), 3.35 (s, 6H), 3.34 (s, 30H), 0.25 (s, 18H). MS (MALD) m/z (calcd [M + a] ). HPLC (1.0 ml/min, 4% iprh/ch 3 10 min, ramp to 7% iprh/ch 3 over 10 min, hold at 7% iprh/ch 3 20 min, retention time 20.2 min) indicated >97% purity. Tg Me Me 6 Tg Tg 6 6 sonicotinic acid methyl ester tridecamer (3b). A vial was charged with 11 ( g, mmol), AcH ( ml, mmol) and THF (0.2 ml). A solution of TBAF in THF (1.0 M, ml) was added, and the reaction mixture stirred for 1 min. The solution was filtered through a plug of silica gel with EtAc, and evaporated to give a white solid. To a 4 ml sealed tube was added Pd 2 (dba) 3 (0.817 mg, µmol), Cu ( mg, 1.19 µmol), and PPh 3 (0.856 mg, 3.26 µmol). The contents of the sealed tube were degassed by alternating three times between vacuum and 2, then 13 ( g, mmol) transferred with 2 x 0.25 ml portions of CH 3 C and deprotected 11 transferred with 2 x 0.25 ml portions of CH 3 C. Triethylamine (0.33 ml) was added to the sealed tube, the solution degassed, the tube sealed under an atmosphere of 2, and the reaction mixture stirred in an oil bath at 60 o C for 26 h. The solvents were evaporated to give a brown wax, which was purified by silica gel chromatography (97:3, 93:7 CH 3 : i- PrH) to give g of pale brown wax (51%). 1 H MR (400 MHz, CD 3 ) d 8.28 (t, J = 1.6 Hz, 2H), 8.23 (t, J = 1.6 Hz, 2H), (m, 14H), 8.14 (t, J = 1.6 Hz, 2H), 8.10 (t, J = 1.6 Hz, 2H), 8.07 (s, 2H), 7.95 (t, J = 1.6 Hz, 2H), (m, 8H), 7.87 (t, J = 1.6 Hz, 2H), 7.81 (t, J = 1.6 Hz, 2H), (m, 24H), 4.01 (s, 3H), (m, 24H), (m, 72H), (m, 24H), 3.35 (s, 6H), 3.34 (s, 30H), 0.25 (s, 9H). MS (MALD) m/z (calcd [M + a] ). HPLC (1.0 ml/min, 4% iprh/ch 3 10 min, ramp to 7% iprh/ch 3 over 10 min, hold at 7% iprh/ch 3 20 min, retention time 21.9 min) indicated >97% purity.

11 Tg SiMe 3 6 Tg Tg 6 6 Pyridine tridecamer (3c). A vial was charged with 9 ( g, mmol), AcH ( ml, mmol) and THF (1 ml). A solution of TBAF in THF (1.0 M, ml) was added, and the reaction mixture stirred for 1 min. The solution was filtered through a plug of silica gel with EtAc, and evaporated to give a white solid. To a 5 ml sealed tube was added Pd 2 (dba) 3 (1.24 mg, 1.36 µmol), Cu ( mg, 1.21 µmol), and PPh 3 (1.28 mg, 4.88 µmol). The contents of the sealed tube were degassed by alternating three times between vacuum and 2, then 13 ( g, mmol) transferred with 2 x 0.3 ml portions of CH 3 C and deprotected 9 transferred with 1 x 0.3 ml portions of CH 3 C. Triethylamine (0.3 ml) was added to the sealed tube, the solution degassed, the tube sealed under an atmosphere of 2, and the reaction mixture stirred in an oil bath at 60 o C for 18 h. The solvents were evaporated to give a brown wax, which was purified by silica gel chromatography (97:3, 92:8 CH 3 : i-prh) to give g of white wax (84%). 1 H MR (400 MHz, CD 3 ) δ 8.28 (t, J = 1.6 Hz, 2H), 8.22 (t, J = 1.6 Hz, 2H), (m, 14H), 8.18 (t, J = 1.6 Hz, 2H), 8.15 (t, J = 1.6 Hz, 2H), 8.11 (t, J = 1.6 Hz, 2H), 7.94 (t, J = 1.6 Hz, 2H), (m, 6H), 7.88 (t, J = 1.6 Hz, 2H), 7.82 (t, J = 1.6 Hz, 2H), 7.76 (t, J = 7.9 Hz, 1H), 7.55 (d, J = 7.9 Hz, 2H), (m, 24H), (m, 24H), (m, 72H), (m, 24H), 3.37 (s, 6H), 3.36 (s, 30H), 0.26 (s, 18H). MS (MALD) m/z (calcd [M + a] ). HPLC (1.0 ml/min, 4% iprh/ch 3 10 min, ramp to 7% iprh/ch 3 over 10 min, hold at 7% iprh/ch 3 20 min, retention time 22.7 min) indicated >95% purity. Tg CH 3 Me 6 Tg Tg Methoxypyridine tridecamer (3d). A vial was charged with 6 ( g, mmol), AcH ( ml, mmol) and THF (0.2 ml). A solution of TBAF in THF (1.0 M, ml) was added, and the reaction mixture stirred for 1 min. The solution was filtered through a plug of silica gel with EtAc, and evaporated to give a pale yellow solid. To a 5 ml sealed tube was added Pd 2 (dba) 3 (0.768 mg, µmol), Cu ( mg, 1.08 µmol), and PPh 3 (0.906 mg, 3.45 µmol). The contents of the sealed tube were degassed by alternating three times between vacuum and 2, then 13 ( g, mmol) transferred with 2 x 0.25 ml portions of CH 3 C and deprotected 6 transferred with 2 x 0.25 ml portions of CH 3 C.

12 Triethylamine (0.33 ml) was added to the sealed tube, the solution degassed, the tube sealed under an atmosphere of 2, and the reaction mixture stirred in an oil bath at 55 o C for 22 h. The solvents were evaporated to give a brown wax, which was purified by silica gel chromatography (97:3, 92:8 CH 3 : i- PrH) to give g of yellow wax (51%). 1 H MR (400 MHz, CD 3 ) d 8.26 (t, J = 1.5 Hz, 2H), (m, 18H), 8.13 (t, J = 1.6 Hz, 2H), 8.10 (t, J = 1.6 Hz, 2H), 7.92 (t, J = 1.6 Hz, 2H), (m, 6H), 7.87 (t, J = 1.6 Hz, 2H), 7.81 (t, J = 1.5 Hz, 2H), 7.08 (s, 2H), (m, 24H), 3.93 (s, 3H), (m, 24H), (m, 72H), (m, 24H), 3.34 (s, 6H), 3.33 (s, 30H), 0.25 (s, 18H). MS (MALD) m/z (calcd [M + a] ). HPLC (1.0 ml/min, 4% iprh/ch 3 10 min, ramp to 7% iprh/ch 3 over 10 min, hold at 7% iprh/ch 3 20 min, retention time 20.3 min) indicated >99% purity. Tg 6 Tg Tg ,-Dimethylaminopyridine tridecamer (3e). A vial was charged with 8 ( g, mmol), AcH ( ml, mmol) and THF (0.2 ml). A solution of TBAF in THF (1.0 M, ml) was added, and the reaction mixture stirred for 1 min. The solution was filtered through a plug of silica gel with EtAc, and evaporated to give a pale brown solid. To a 4 ml sealed tube was added Pd 2 (dba) 3 (0.993 mg, 1.09 µmol), Cu ( mg, 1.98 µmol), and PPh 3 (1.18 mg, 4.50 µmol). The contents of the sealed tube were degassed by alternating three times between vacuum and 2, then 13 ( g, mmol) transferred with 2 x 0.25 ml portions of CH 3 C and deprotected 9 transferred with 2 x 0.25 ml portions of CH 3 C. Triethylamine (0.33 ml) was added to the sealed tube, the solution degassed, the tube sealed under an atmosphere of 2, and the reaction mixture stirred in an oil bath at 50 o C for 24 h. The solvents were evaporated to give a brown wax, which was purified by silica gel chromatography (97:3, 93:7 CH 3 : i-prh) to give g of pale yellow wax (48%). 1 H MR (400 MHz, CD 3 ) d 8.26 (t, J = 1.6 Hz, 2H), (m, 18H), 8.14 (t, J = 1.6 Hz, 2H), 8.10 (t, J = 1.6 Hz, 2H), 7.94 (t, J = 1.6 Hz, 2H), (m, 6H), 7.87 (t, J = 1.6 Hz, 2H), 7.81 (t, J = 1.6 Hz, 2H), 6.77 (s, 2H), (m, 24H), (m, 24H), (m, 72H), (m, 24H), 3.36 (s, 6H), 3.35 (s, 30H), 3.09 (s, 6H), 0.26 (s, 18H). MS (MALD) m/z (calcd [M + H] ). HPLC (1.0 ml/min, 8% iprh/ch 3 10 min, ramp to 15% iprh/ch 3 over 5 min, hold at 15% iprh/ch 3 25 min, retention time 17.9 min) indicated >95% purity. 1 Heemstra, J. H.; Moore, J. S. To be submitted for publication, Kaljurand,.; Rodima, T.; Leito,.; Koppel,. A.; Schwesinger, R. J. rg. Chem. 2000, 65,

13 3 Kaneko, C.; Uchiyama, K.; Sato, M.; Katagiri,. Chem. Pharm. Bull. 1986, 34,