Supporting Information

Transcription

1 Supporting Information Multi-Polymer Solution-Phase Reactions: Application to the Mitsunobu Reaction Andrew M. arned, elen Song e, Patrick. Toy,,* Daniel L. Flynn, Paul R. anson * Department of Chemistry, University of Kansas, 1251 Wescoe all Drive, Lawrence, KS and the KU Chemical Methodology and Library Development Center of Excellence, 1501 Wakarusa Drive, Lawrence, KS Deciphera Pharmaceuticals LLC, 1505 Wakarusa, Drive, Lawrence, KS, Department of Chemistry, The University of ong Kong, Pokfulam Road, ong Kong, People s Republic of China phanson@ku.edu, phtoy@hku.hk Experimental Section General Methods. All reactions were carried out under argon in oven-dried or flame-dried glassware. TF, toluene, acetonitrile, and C 2 Cl 2 were purified by passage through the Solv- Tek purification system employing activated Al 2 3. Flash column chromatography was performed with Merck silica gel (EM , mesh) or with the Biotage orizon PFC System with FLAS 12+ or FLAS 40+ cartridges. Thin layer chromatography was performed on silica gel 60F 254 plates (EM-5717, Merck). 1 and 13 C MR spectra were recorded in CDCl 3 (unless otherwise mentioned) on a Bruker DRX-400 spectrometer operating at 400 Mz and 100 Mz, respectively, or on a Bruker DRX-500 spectrometer operating at 500 Mz and 125 Mz, respectively and calibrated to the solvent peak. 31 P MR spectra were recorded in CDCl 3 (unless otherwise mentioned) on a Bruker DRX-400 spectrometer operating at 162 Mz and calibrated to external 85% 3 P 4. igh resolution mass spectrometry (RMS) and FAB spectra were obtained on a VG Instrument ZAB double-focusing mass spectrometer. S-1

2 + Br 1 mol% PdCl 2 (PPh 3 ) 2 Et 3, C 2, DMF, 50 o C Br I 5-exo-(4-bromophenyl)bicyclo[2.2.1]hept-2-ene: To 1-bromo-4-iodobenzene ( g, 24.4 mmol) and PdCl 2 (PPh 3 ) 2 (172.9 mg, mmol) in 10 ml DMF, was added norbornadiene (7.6 ml, 75.1 mmol), Et 3 (11 ml, 78.9 mmol), and formic acid (88%, 2.2 ml, 51.3 mmol). The solution was then heated to 50 o C for 1 hour with GC monitoring. The reaction was then transferred to a separatory funnel with 50 ml 10% Cl and 50 ml heptane. The organic phase was extracted two times with 50 ml 10% Cl, and the combined aqueous layers washed twice with 50 ml heptane. The combined organic layers were dried with a 2 S 4 and then filtered through a pad (2 cm x 4.5 cm) of silica which was then washed with heptane. After evaporation the residue was then subjected to flash chromatography, eluting with heptane, to afford 5-exo-(4- bromophenyl)bicyclo[2.2.1]hept-2-ene ( g, 91%) as a colorless oil: TLC (eptane) R f 0.51; IR (thin film) 3058, 2968, 1489, 1074, 1009 cm -1 ; 1 MR (400 Mz, CDCl 3 ) 7.40 (d, 2, J = 8.4 z), 7.15 (d, 2, J = 8.3 z), 6.24 (dd, 1, J = 5.6, 3.2 z), 6.17 (dd, 1, J = 5.6, 2.9 z), 2.97 (bs, 1), 2.87 (bs, 1), 2.66 (dd, 1, J = 8.0, 5.5 z), (m, 2), 1.52 (bd, 1, J = 8.5 z), 1.43 (bd, 1, J = 8.6 z); 13 C MR (100 Mz, CDCl 3 ) 145.1, 137.4, 137.1, 131.2, 129.3, 119.1, 48.0, 45.6, 43.2, 42.3, Br PPh 2 a) n-buli, TF, -78 o C b) Ph 2 PCl, -78 o to 0 o C (4-(exo-bicyclo[2.2.1]hept-5-en-2-yl)phenyl)diphenylphosphine (1): A flame-dried flask was charged with 5-exo-(4-bromophenyl)bicyclo[2.2.1]hept-2-ene ( g, 15 mmol) under a blanket of argon and 15 ml anhydrous TF were added and the solution cooled to -78 o C. n- BuLi (2.5M in hexanes, 6.2 ml, 15.5 mmol) was added slowly. After 1 hour at -78 o C, chlorodiphenylphosphine (4.2 ml, 22.7 mmol) in 5 ml TF was added via cannula. After 1 hour the reaction was warmed to RT and allowed to stir at this temperature for 11 hours at which time it was quenched with a saturated aq. 4 Cl. The mixture was portioned between water and Et 2, and the aqueous layer washed twice with Et 2. The combined organic layers were dried S-2

3 with a 2 S 4 and evaporated. The resulting oil was then subjected to flash chromatography eluting with heptane to afford (4-(exo-bicyclo[2.2.1]hept-5-en-2-yl)phenyl)diphenylphosphine ( g, 74%) as a white solid: mp o C, TLC (eptane) R f 0.17; IR (thin film) 3053, 2968, 1433, 1330, 1091, 821 cm -1 ; 1 MR (400 Mz, CDCl 3 ) (m, 10), (m, 4), 6.24 (dd, 1, J = 5.6, 3.1 z), 6.16 (dd, 1, J = 5.6, 2.9 z), 2.96 (bs, 1), 2.90 (bs, 1), 2.70 (dd, 1, J = 7.7, 4.8 z), 1.73 (ddd, 1, J = 11.8, 4.6, 3.6 z), 1.63 (ddd, 1, J = 11.4, 8.8, 2.3 z), 1.56 (bd, 1, J = 8.5 z), 1.42 (bd, 1, J = 8.4 z); 13 C MR (100 Mz, CDCl 3 ) 147.0, (J CP = 10.6 z), (J CP = 10.6 z), (J CP = 18.1 z), (J CP = 19.8 z), 133.7, 133.5, 128.5, (J CP = 6.9 z), (J CP = 7.2 z), 48.1, 45.8, 43.6, 42.2, 33.6; 31 P MR (162 Mz, CDCl 3 ) -5.56; RMS m/z (M+) (calcd for C P: ). PPh 2 PPh mol% 2nd G Grubbs cat C 2 Cl 2, 50 o C 30 Polymerization of (4-(exo-bicyclo[2.2.1]hept-5-en-2-yl)phenyl)diphenylphosphine: (4-(exo- Bicyclo[2.2.1]hept-5-en-2-yl)phenyl)diphenylphosphine ( g, 9.77 mmol) was dissolved in 98 ml degassed C 2 Cl 2 and 2nd generation Grubbs catalyst was added (274 mg, mmol). The solution was then heated to 50 o C. The reaction was monitored by TLC (3:1 heptane/etac) and upon completion (about 1 hour), the solution was cooled to RT and excess ethyl vinyl ether was added. After 30 min, sodium bicarbonate (0.6 g, 7.14 mmol) and tetrakishydroxymethyl phosphonium chloride (80% soln in water, 0.91 ml, 6.42 mmol) were added and the mixture heated to 50 o C overnight. After cooling to RT, the mixture was extracted three times with water and the combined aqueous layers washed with C 2 Cl 2. The combined organic layers were dried with a 2 S 4 and evaporated. The resulting residue was then dissolved in a 20 ml C 2 Cl 2 and slowly added by pipette into 400 ml Me with heavy stirring. The resulting precipitate was then filtered through a fritted funnel and collected to afford oligomer 2 ( g, 97%) as a freeflowing white solid: IR (thin film) 3068, 3051, 2941, 1597, 1433, 908, 733, 696 cm -1 ; 1 MR (400 Mz, CDCl 3 ) (m, 14), (m, 2), (m, 3), (m, 3), (m, 2); 31 P MR (162 Mz, CDCl 3 ) ppm (m). S-3

4 + 4 mol% PdCl 2 (PPh 3 ) 2 Et 3, C 2, DMF, 70 o C Br (4-(exo-bicyclo[2.2.1]hept-5-en-2-yl)phenyl)methanol (3): To 4-bromobenzyl alcohol ( g, 32.9 mmol) and PdCl 2 (PPh 3 ) 2 (967.6 mg, 1.38 mmol) in 11 ml DMF, was added norbornadiene (12 ml, 119 mmol), Et 3 (14 ml, 100 mmol), and formic acid (88%, 2.8 ml, 65.3 mmol). The solution was then heated to 80 o C for 6 hour with TLC (4:1 heptane/etac) monitoring. The reaction was then partitioned between benzene and 10% Cl. The aqueous layer was extracted twice with benzene and the organic layers washed with brine and dried with a 2 S 4. After evaporation, the residue was then subjected to flash chromatography in portions, eluting with 20% EtAc in heptane, to afford a yellow oil which was Kugelrohr distilled ( o C, 150 mtorr) to give (4-(exo-bicyclo[2.2.1]hept-5-en-2-yl)phenyl)methanol ( g, 74%) as a colorless oil: TLC (4:1 eptane/etac) R f 0.19; IR (neat) 3344, 3055, 2953, 1514, 1457, 1331, 1015, 813, 698 cm -1 ; 1 MR (400 Mz, CDCl 3 ) (m, 4), 6.25 (dd, 1, J = 5.6, 3.1 z), 6.17 (dd, 1, J = 5.6, 2.9 z), 4.66 (s, 2), 2.97 (bs, 1), 2.89 (bs, 1), 2.72 (dd, 1, J = 8.5, 4.7 z), 1.73 (ddd, 1, J = 11.8, 4.7, 3.6 z), 1.64 (ddd, 1, J = 11.3, 8.8, 2.2 z), (m, 2), 1.42, (ddd, 1, J = 8.5, 1.9, 1.9 z); 13 C MR (100 Mz, CDCl 3 ) 145.4, 138.0, 137.2, 137.1, 127.6, 127.0, 64.7, 48.1, 45.6, 43.3, 42.2, a) (CCl) 2, PhC 3, 0 o C b) 2 C 2 Et, DMAP Et 3, TF Et (4-(exo-bicyclo[2.2.1]hept-5-en-2-yl)phenyl)methyl ethyl hydrazinedicarboxylate: (4-(exobicyclo[2.2.1]hept-5-en-2-yl)phenyl)methanol ( g, 24.2 mmol) in 25 ml PhC 3 was added dropwise over 1 hour to a solution of phosgene in PhC 3 (~20 wt%, 26 ml, 49.2 mmol) cooled with an ice bath. The mixture was stirred cold for 45 min then warmed to RT for 3.5 hours. Argon was bubbled through the solution with exit to an aq. a trap for 1 hour to remove Cl and excess phosgene. The solution was then added via cannula to a solution of S-4

5 ethyl carbazate (4.16 g, 40.2 mmol), Et 3 (5.6 ml, 40.2 mmol), and DMAP (30 mg, mmol) in 20 ml TF at 0 o C. The mixture was stirred at RT for 12 hours. The reaction was then transferred to a separatory funnel and portioned between 10% Cl and EtAc. The aqueous layer was extracted four times with EtAc. The combined organic layers were dried with MgS 4, filtered and evaporated. The residue was then subjected to flash chromatography, eluting with 4:1 heptane/etac then 2:1 heptrane/etac. Mixed fractions were rechromatographed to afford (4-(exo-bicyclo[2.2.1]hept-5-en-2-yl)phenyl)methyl ethyl hydrazinedicarboxylate ( g, 55%) as a colorless viscous oil: TLC (4:1 eptane/etac) R f 0.052; IR (thin film) 3304, 3055, 2968, 1732, 1514, 1227, 1063 cm -1 ; 1 MR (400 Mz, CDCl 3 ) (m, 4), 6.56 (bs, 1), 6.48 (bs, 1), 6.24 (dd, 1, J = 5.6, 3.1 z), 6.16 (dd, 1, J = 5.7, 2.9 z), 5.15 (s, 2), 4.20 (bq, 2, J = 7.0 z), 2.96 (bs, 1), 2.88 (bs, 1), 2.70 (dd, 1, J = 8.2, 4.7 z), 1.72 (ddd, 1, J = 11.8, 4.7, 3.5 z), 1.63 (ddd, 1, J = 11.1, 8.8, 2.0 z), 1.55 (bd, 1, J = 8.5 z), 1.42, (ddd, 1, J = 8.5, 1.8, 1.8 z), 1.27 (bs, 3); 13 C MR (100 Mz, CDCl 3 ) (br), 146.4, 137.3, 137.1, 132.6, (br), 127.6, 67.5, 62.1, 48.0, 45.6, 43.4, 42.1, 33.5, 14.3; RMS m/z (M+) (calcd for C : ). Et 1) 3.3 mol% (3-BrPyr) 2 Cl 2 Ru=CPh TF, RT Et 2) 2 mol% (PCy 3 ) 2 Cl 2 Ru=CPh 1000 psi 2 40% Me/C 2 Cl 2 30 Polymerization of (4-(exo-bicyclo[2.2.1]hept-5-en-2-yl)phenyl)methyl ethyl hydrazinedicarboxylate: (4-(exo-bicyclo[2.2.1]hept-5-en-2-yl)phenyl)methyl ethyl hydrazinedicarboxylate ( g, 13.3 mmol) was dissolved in 140 ml TF and the solution degassed for 20 min. (IMes 2 )(3-BrPyr) 2 Cl 2 Ru=CPh (396.8 mg, mmol) was added under heavy stirring. The solution was stirred at RT and monitored by TLC (2:1 heptane/etac) and upon completion (about 60 min), the reaction quenched with 10 ml ethyl vinyl ether. After 30 min, the solvent was evaporated and the residue transferred to a Parr bomb with 100 ml 40% Me/C 2 Cl 2 and (PCy 3 ) 2 Cl 2 Ru=CPh (197.7 mg, mmol) was added. The vessel was sealed, flushed with 2, pressurized to 1000 psi, and heated to 50 o C. After 4 hours, the reaction was allowed to cool overnight and depressurized. The mixture was then evaporated and S-5

6 redissolved in 100 ml TF. Sodium bicarbonate ( g) and tetrakishydroxymethyl phosphonium chloride (80% soln in water, 2.4 ml) were added and the mixture heated to 70 o C for 48 hrs. After cooling to RT, the slightly yellow mixture was added to 800 ml 2 in order to precipitate the polymer which was filtered through a fritted funnel, washed with 2 and collected. Drying in a vacuum oven at 50 o C afforded the oligomer A ( g, 80%) as a freeflowing white solid: IR (thin film) 3298, 2930, 1728, 1514, 1225, 1063 cm -1 ; 1 MR (400 Mz, 4:1 CDCl 3 :CD 3 D) (rel intensities) (m, 4.4), 4.97 (s, 2), 4.80 (s, 0.47), 4.02 (s, 2), 3.94 (s, 2), (bs, 1.2), (m, 6.4), (m, 7.2), (m, 1.6). Et Br 2, Et 3 Et C 2 Cl xidation of oligomer X: To a solution of oligomer A ( g, 11.4 mmol) and pyridine (1.9 ml, 23.5 mmol) in 15 ml TF at 0 o C, was added Br 2 (590 µl, 11.5 mmol) dropwise over 5 min. The mixture was stirred cold for 20 min and then warmed to RT for 3 hours. The reaction was then transferred to a separatory funnel and extracted with 2 and C 2 Cl 2. The aqueous layer was washed four times with C 2 Cl 2. The combined organic layers were dried with a 2 S 4, filtered and evaporated. The residue was dissolved in 100 ml C 2 Cl 2 and slowly added to 1000 ml heptane. The cloudy supernatant was decanted and fresh heptane added to the yellow precipitate. Filtration through a fritted funnel afforded oligomer 4 ( g, 86%) as a yellow solid: IR (thin film) 2918, 1770, 1223, 1204, 1020 cm -1 ; 1 MR (400 Mz, CDCl 3 ) (rel. intensities) (m, 4), 5.38 (s, 2), 4.47 (s, 2), (bs, 2), (m, 8), (m, 8.7), (m, 2.6). Determination of load for oligomer 4: Triphenylphosphine (58.9 mg, mmol) was dissolved in 1 ml TF and 100 µl 2. ligomer 4 was added and the mixture stirred for 2 hours. An aliquot was added to an MR tube and CDCl 3 was added. Intergration of the peaks at S-6

7 29 ppm and -4.5 ppm gave the ratio of Ph 3 P:PPh 3. The load of 4 was calculated with the following equations: integral of XX ppm (integral of XX ppm + integral of XX ppm) = % Ph 3 P %Ph 3 P x mmol PPh 3 = mmol 4 mmol 4 grams 4 = load of 4 (mmol/g) General procedure for Mitsunobu reaction: An oven-dried vial was charged with 3-phenyl-1-propanol (20.7 mg, mmol), 4- nitrobenzoic acid (29.6 mg, mmol) and oligomer 2 (2.8 mmol/g, 110 mg, mmol) and dissolved in 0.75 ml TF. ligomer 4 (1.5 mmol/g, 202 mg, mmol) was added and the mixture stirred for 2 hours. The polymers were precipitated by the addition of ~2 ml EtAc and the mixture filtered through a 4 cm x 1 cm plug of silica and washed with 4 x 1 ml EtAc. The filtrate was evaporated and the residue filtered through a second plug of silica, eluting with 4:1 heptane/etac to afford 3-phenylpropyl 4-nitrobenzoate (30.3 mg, 70%) as a white solid: mp o C (lit o C), TLC (4:1 eptane/etac) R f 0.46; IR (thin film) 3120, 2958, 1716, 1602, 1523, 1352, 1286, 1103, 870, 746, 717, 700 cm -1 ; 1 MR (400 Mz, CDCl 3 ) 8.28 (d, 2, J = 9.0 z), 8.15 (d, 2, J = 9.0 z) (m, 2), (m, 3), 4.40 (t, 2, J = 6.5 z), 2.80 (t, 2, J = 7.4 z), 2.15 (dt, 2, J = 6.5, 7.4 z); 13 C MR (125 Mz, CDCl 3 ) 164.6, 150.5, 140.9, 135.7, 130.7, 128.5, 128.4, 126.1, 123.5, 65.3, 32.3, Methoxybenzyl benzoate: The general procedure above was followed, using 4- methoxybenzyl alcohol (15.5 mg, mmol), benzoic acid (15.3 mg, mmol), oligomer 2 (81.1 mg, mmol), and oligomer 4 (2.6 mmol/g, 86.1 mg, mmol) in 0.56 ml TF. Filtration through a plug of silica with 4:1 heptane/etac afforded 4-methoxylbenzyl benzoate 1 Kirner, W. R. J. Am. Chem. Soc. 1926, 48, S-7

8 (24.7 mg, 91%) as a white solid: mp o C (lit o C), TLC (4:1 eptane/etac) R f 0.43; IR (thin film) 3062, 2957, 1715, 1614, 1514, 1271, 1247, 827, 711 cm -1 ; 1 MR (400 Mz, CDCl 3 ) 8.06 (d, 2, J = 8.7 z), (m, 1), (m, 4), 6.92 (d, 2, J = 8.7 z), 5.30 (s, 2), 3.82 (s, 3); 13 C MR (100 Mz, CDCl 3 ) 166.5, 159.6, 132.9, 130.2, 130.0, 129.6, 128.3, 128.1, 113.9, 66.5, 55.3; MS m/z (M+) (rel intensity) 242 (98), 121 (100), 105 (35), 77 (21). 3-Phenylpropyl 2,4,5-trimethoxybenzoate: The general procedure above was followed, using 3-phenyl-1-propanol (13.3 mg, mmol), 2,4,5-trimethoxybenzoic acid (20.9 mg, mmol), oligomer 2 (71.3 mg, mmol), and oligomer 4 (1.5 mmol/g, mg, mmol) in 0.49 ml TF. Filtration through a plug of silica with 4:1 heptane/etac afforded 3- phenylpropyl 2,4,5-trimethoxybenzoate (24.7 mg, 76%) as a white solid: mp o C, TLC (4:1 eptane/etac) R f 0.088; IR (thin film) 3024, 2952, 1715, 1612, 1520, 1454, 1408, 1250, 1215, 1161, 1080, 1030 cm -1 ; 1 MR (400 Mz, CDCl 3 ) 7.42 (s, 1), (m, 2), (m, 3), 6.54 (s, 1), 4.31 (t, 2, J = 6.5 z), 3.94 (s, 3), 3.91 (s, 3), 3.88 (s, 3), 2.79 (t, 2, J = 7.4 z), 2.08 (dt, 2, J = 6.5, 7.4 z); 13 C MR (125 Mz, CDCl 3 ) 165.7, 155.6, 153.5, 142.6, 141.4, 128.4, 128.4, 125.9, 114.4, 111.0, 97.8, 63.8, 57.0, 56.4, 56.0, 32.2, 30.4; MS m/z (M+) (rel intensity) 330 (20), 212 (100), 195 (36), 91 (30). 2-Methylbenzyl (4-methoxyphenyl)acetate: The general procedure above was followed, using 2-methylbenzyl alcohol (12.6 mg, mmol), 4-methoxyphenylacetic acid (17.5 mg, mmol), oligomer 2 (76.1 mg, mmol), and oligomer 4 (1.5 mmol/g, mg, mmol) in 0.53 ml TF. Filtration through a plug of silica with 4:1 heptane/etac afforded 2- methylbenzyl (4-methoxyphenyl)acetate (19.5 mg, 70%) as a colorless oil: TLC (4:1 eptane/etac) R f 0.43; IR (thin film) 3024, 2956, 1732, 1612, 1514, 1464, 1248, 1148, 1034, 820, 748 cm -1 ; 1 MR (400 Mz, CDCl 3 ) (m, 6), 6.86 (d, 2, J = 8.7 z), 5.14 (s, 2), 3.80 (s, 3), 3.61 (s, 2), 2.29 (s, 3); 13 C MR (125 Mz, CDCl 3 ) 171.7, 158.7, 137.0, 133.8, 130.3, 130.3, 129.2, 128.5, 126.0, 126.0, 114.0, 65.0, 55.2, 40.4, 18.8; MS m/z (M+) (rel intensity) 270 (15), 121 (100), 105 (36). 2 hishi, T.; Yamada, J.; Inui, Y.; Sakagucki, T.; Yamashita, M. J. rg. Chem. 1994, 59, S-8

9 (E)-3,7-Dimethylocta-2,6-dienyl cyclopentanecarboxylate: The general procedure above was followed, using geraniol (15.5 mg, mmol), cyclopentanecarboxylic acid (12.1 mg, mmol), oligomer 2 (71.5 mg, mmol), and oligomer 4 (2.6 mmol/g, 78.1 mg, mmol) in 0.50 ml TF. Filtration through a plug of silica with 10:1 heptane/etac afforded (E)-3,7- Dimethylocta-2,6-dienyl cyclopentanecarboxylate (21.2 mg, 84%) as a colorless oil: TLC (4:1 eptane/etac) R f 0.60; IR (thin film) 2964, 1732, 1452, 1180, 1161 cm -1 ; 1 MR (400 Mz, CDCl 3 ) 5.34 (m, 1), 5.08 (m, 1), 4.58 (d, 2, J = 7.0 z), 2.72 (dddd, 1, J = 8.2, 8.2, 8.2, 8.2 z), 2.09 (m, 2), 2.12 (m, 2), (m, 2), (m, 4), 1.70 (s, 3), 1.68 (s, 3), 1.60 (s, 3), (m, 2); 13 C MR (125 Mz, CDCl 3 ) 176.8, 141.9, 131.8, 123.8, 118.6, 61.2, 43.9, 39.5, 30.0, 26.3, 25.8, 25.6, 17.7, 16.4; MS m/z (M+) (rel intensity) 250 (0.7), 136 (21), 97 (28), 69 (100). (S)-Allyl 2-(tert-butoxycarbonyl)-3-phenylpropanoate: The general procedure above was followed, using allyl alcohol (7 µl, mmol), -Boc-phenylalanine (26.7 mg, mmol), oligomer 2 (73.3 mg, mmol), and oligomer 4 (2.1 mmol/g, 97.3 mg, mmol) in 0.50 ml TF. Filtration through a plug of silica with 4:1 heptane/etac afforded (S)-Allyl 2-(tertbutoxycarbonyl)-3-phenylpropanoate (22.3 mg, 73%) as a colorless oil: [α] 22 D = (c = 1.07, Me) (lit 3 [α] 29 D = (c = 1.1, Me), TLC (4:1 eptane/etac) R f 0.39; IR (thin film) 3369, 3064, 2978, 1745, 1714, 1497, 1367, 1169 cm -1 ; 1 MR (400 Mz, CDCl 3 ) (m, 4), (m, 2), 5.86 (dddd, 1, J = 16.3, 10.4, 5.9, 5.9), 5.30 (dd, 1, J = 17.2, 1.4 z), 5.25 (dd, 1, J = 10.4, 1.4 z), 4.97 (d, 1, J = 7.4 z), 4.60 (m, 3), 3.13 (dd, 1, J = 13.8, 5.8 z), 3.07 (dd, 1, J = 13.8, 6.3 z), 1.42, (s, 9); 13 C MR (125 Mz, CDCl 3 ) 171.6, 155.0, 135.9, 131.5, 129.3, 128.5, 127.0, 118.9, 79.9, 65.9, 54.4, 38.3, 28.3; MS m/z (M+) (rel intensity) 305 (0.03), 232 (2), 204, (6), 189 (5), 91 (47), 57 (100). 1-itro-4-(3-phenylpropoxy)benzene: The general procedure above was followed, using 3- phenyl-1-propanol (16.4 mg, mmol), 4-nitrophenol (18.1 mg, mmol), oligomer 2 (88 mg, mmol), and oligomer 4 (2.1 mmol/g, mg, mmol) in 0.6 ml TF. Filtration through a plug of silica with 4:1 heptane/etac afforded (22.5 mg, 73%) of an 3 Takeda, K.; Akiyama, A.; akamura,.; Takizawa, S.-i.; Mizuno, Y.; Takayanagi,.; arigaya, Y. Synthesis, 1994, S-9

10 inseparable mixure of 1-itro-4-(3-phenylpropoxy)benzene and 3-phenylpropyl ether (85:15) as an off-white solid: TLC (4:1 eptane/etac) R f 0.45; IR (thin film) 3109, 3085, 2939, 1606, 1593, 1514, 1497, 1340, 1269, 1109, 845, 754 cm -1 ; 1 MR (400 Mz, CDCl 3 ) 1-itro-4-(3- phenylpropoxy)benzene: 8.19 (d, 2, J = 9.3 z), (m, 2), (m, 3), 6.93 (d, 2, J = 9.3 z), 4.05 (t, 2, J = 6.3 z), 2.83 (t, 2, J = 7.4 z), 2.17 (dt, 2, J = 7.4, 6.3 z); 3-phenylpropyl ether: (m, 0.7), (m, 1.1), 3.40 (t, 0.71, J = 6.6 z), 2.78 (t, 0.76, J = 7.2 z), 2.17 (dt, 0.71, J = 7.2, 6.6 z); 13 C MR (100 Mz, CDCl 3 ) 164.1, 141.4, 140.9, 140.5, 128.5, 128.5, 128.5, 128.4, 126.1, 125.9, 67.7, 34.1, 34.0, 33.1, 31.9, (E)-2-(3,7-dimethylocta-2,6-dienyl)isoindoline-1,3-dione: The general procedure above was followed, using geraniol (17.2 mg, mmol), phthalimide (17.3 mg, mmol), oligomer 2 (81.2 mg, mmol), and oligomer 4 (2.6 mmol/g, 88.8 mg, mmol) in 0.56 ml TF. Filtration through a plug of silica with 5:1 heptane/etac afforded (E)-2-(3,7-dimethylocta-2,6- dienyl)isoindoline-1,3-dione (22 mg, 69%) as a white solid: mp o C (lit o C), TLC (4:1 eptane/etac) R f 0.42; IR (thin film) 3059, 2922, 1770, 1715, 1614, 1393, 1111, 1076, 947, 719 cm -1 ; 1 MR (400 Mz, CDCl 3 ) 7.84 (m, 2), 7.70 (m, 2), 5.26 (m, 1), 5.04 (m, 1), 4.28 (d, 2, J = 7.1 z), 2.06 (m, 2), 1.99 (m, 2), 1.82 (s, 3), 1.63 (s, 3), 1.56 (s, 3); 13 C MR (125 Mz, CDCl 3 ) 168.1, 140.6, 133.8, 132.3, 131.7, 123.8, 123.1, 118.0, 39.5, 35.8, 26.3, 25.6, 17.6, 16.3; MS m/z (M+) (rel intensity) 283 (6), 160 (100), 123 (35), 69 (70). 4 Inoue, Y.; Taguchi, M.; Toyofuku, M.; ashimoto,. Bull. Chem. Soc. Jpn. 1984, 57, S-10