The reaction was stirred at room temperature for 36 hours and monitored by TLC MeOH/DCM mixture 1/4.. Most of the solvent was evaporated, and the residue was directly loaded onto a silic
Trang 1Chapter 4
Experimental
Trang 24.1 General Procedures
All reactions were performed in oven-dried round bottom flasks or glass vials The flasks were fitted with rubber septa and reactions were conducted under a positive pressure of nitrogen, unless otherwise noted All solvent distillation was done at 760 Torr Toluene, THF, diethyl ether and diisopropyl ether were distilled from sodium wire; CH2Cl2 was distilled from calcium hydride Commercial reagents were purchased from Sigma Aldrich, Fluka, Alfa Aesar or Lancaster, and used as supplied without further purification Analytical thin layer chromatography (TLC) was performed with Merck pre-coated TLC plates, silica gel 60F-254, layer thickness 0.25mm Flash column chromatography was performed using Merck 60 (0.040 – 0.063 mm) mesh silica gel
Proton nuclear magnetic resonance (1H NMR) and carbon nuclear magnetic resonance (13C NMR) spectra were recorded on a Bruker ACF300 (300 MHz) or AMX500 (500 MHz) NMR spectrometer The residual solvent peak was used as an internal reference Low resolution mass spectra were obtained on a VG Micromass
7035 spectrometer in EI mode, a Finnigan/MAT LCQ spectrometer in ESI mode, and
a Finnigan/MAT 95XL-T mass spectrometer in FAB mode High resolution mass spectra were obtained on a Finnigan/MAT 95XL-T spectrometer Infrared spectra were recorded on a BIO-RAD FTS 165 FTIR spectrometer Enantiomeric excesses were determined by chiral HPLC analysis on Jasco HPLC units, including a Jasco DG-980-50 Degasser, a LG-980-02 Ternary Gradient Unit, a PU-980 Intelligient
Trang 3Sampler Optical rotations were recorded on a Jasco DIP-1000 polarimeter Melting points were determined on a BÜCHI B-540 melting point apparatus Single crystal X-Ray diffraction studies were obtained on a Bruker-AXS Smart Apex CCD single-crystal diffractometer
4.2 Preparation of the aminoindanol derived guanidines
4.2.1 General procedure for the preparation of the amonoindanol derived
guanidines
To a 10 mL flask containing O-protected 1-amino-2-indanol (1.1 mmol, 1.0 eq.)
and 1-(Chloro-1-pyrrolidinylmethylene)pyrrolidinium hexafluorophosphate (366 mg, 1.1 mmol, 1.0 eq.) was added 5 mL of DCM, then Et3N (0.77 mL, 5.5 mmol, 5.0 eq.) The reaction was stirred at room temperature for 36 hours and monitored by TLC (MeOH/DCM mixture 1/4) Most of the solvent was evaporated, and the residue was directly loaded onto a silica gel column, followed by flash column chromatography
(MeOH/DCM mixture, 1/50 to 1/10) 79·HPF6 was obtained as white solid, and then
it was dissolved in 5 mL of 2 M NaOH (aq.), extracted three times with DCM, washed with brine, dried over Na2SO4, and concentrated to afford catalyst 79 as pale
yellow oil
4.2.2 Characterization of the amonoindanol derived guaidines
(79a) (1R,2R)-2-(tert-butyldimethylsilyloxy)-N-(dipyrrolidin-1-ylmethylene)-2,3-
dihydro-1H-inden-1-amine
Trang 4Pale yellow oil, 75% yield [α]27D -112.4 (c 0.89, CHCl3).1H NMR (500 MHz, CDCl3,
ppm): δ 0.10 (d, 6H, J = 15.15 Hz), 0.90 (s, 9H), 1.86 (br, 8H), 2.79 (dd, 1H, J = 8.83, 15.10 Hz), 3.11 (dd, 1H, J = 6.95, 15.1 Hz ), 3.31-3.39 (br, 8H), 4.42 (m, 1H), 4.74 (d, 1H, J = 7.55 Hz), 7.09-7.13 (m, 4H) 13C NMR (125 MHz, CDCl3, ppm): δ 18.9, 26.1,
26.6, 30.4, 40.0, 49.6, 70.3, 83.4, 124.5, 125.0, 127.3, 127.6, 139.9, 157.8 FTIR (film):
756, 1041, 1217, 1525, 3021 cm-1 LRMS (ESI) m/z 414.2 (M+H+), HRMS (ESI) m/z 414.2948 (M+H+), calc for C24H40N3OSi 414.2935
(79b) (1R,2R)-2-(tert-butyldiphenylsilyloxy)-N-(dipyrrolidin-1-ylmethylene)-2,3-
dihydro-1H-inden-1-amine
Pale yellow oil, 80% yield [α]26D -92.6 (c 2.69, CHCl3) 1H NMR (500 MHz, CDCl3,
ppm): δ 1.09 (d, 9H, J = 2.55 Hz), 1.87 (br, 8H), 2.70-2.80 (m, 2H), 3.33-3.40 (br, 8H), 4.58 (m, 1H), 4.98 (d, 1H, J = 6.95 Hz), 6.98 (d, 1H, J = 6.95 Hz), 7.07-7.13 (m, 3H),
7.33-7.43 (m, 6H), 7.71-7.76 (m, 4H) 13C NMR (125 MHz, CDCl3, ppm): δ 19.9, 26.1,
27.7, 39.8, 49.3, 70.4, 84.2, 124.5, 125.0, 127.2, 127.6, 128.0, 128.2, 130.0, 130.2,
Trang 5C NMR (125 MHz, CDCl3, ppm): δ 26.1, 37.3, 49.2, 69.2, 72.7, 90.2, 124.6, 125.1, 127.3, 127.6, 128.0, 128.3, 128.9, 139.8, 139.9, 145.2, 157.5.FTIR (film): 758, 929,
1047, 1216, 1422, 1525, 3020 cm-1 LRMS (ESI) m/z 390.2 (M+H+), HRMS (ESI) m/z 390.2533 (M+H+), calc for C25H32N3O 390.2540
(79d) (1R,2S)-2-(tert-butyldiphenylsilyloxy)-N-(dipyrrolidin-1-ylmethylene)-2,3-
dihydro-1H-inden-1-amine
Trang 6Yellow oil, 70% yield [α]27D +7.9 (c 1.31, CHCl3).1H NMR (500 MHz, CDCl3, ppm):
δ 1.04 (s, 9H), 1.83 (br, 8H), 2.66 (d, 1H, J = 11.3 Hz), 3.12 (dd, 1H, J = 6.35, 14.45
Hz), 3.27-3.38 (br, 8H), 4.48 (br, 1H), 4.81 (d, 1H, J = 5.05 Hz), 7.07 (t, 1H, J = 4.1 Hz), 7.12 (s, 2H), 7.21-7.23 (m, 1H), 7.34 (t, 4H, J = 7.25 Hz), 7.38-7.42 (m, 2H),
7.66-7.71 (m, 4H) FTIR (film): 760, 928, 1045, 1215, 1427, 1521, 3019 cm-1.LRMS (ESI) m/z 538.3 (M+H+), HRMS (ESI) m/z 538.3237 (M+H+), calc for C34H44N3OSi 538.3248
4.3 Desymmetrization of meso N-acyl aziridines with thiols
4.3.1 Typical procedure for the desymmetrization of meso N-acyl azirid-
ines with thiols
To a 10 ml flask containing catalyst 79b (0.27 mg, 0.0005 mmol, 1 mol %) and a
stirring bar, meso-aziridine 12a (14.6 mg, 0.05 mmol, 1.0 eq.) was added, followed by
5 mL of diethyl ether The reaction mixture was placed in a cryobath preset at -50 oC and allowed to stir for 0.5 hour before 2,6-dichlorobenzenethiol (17.9 mg, 0.1 mmol, 2.0 eq.) was added The reaction was stirred at -50 oC and monitored by TLC for 48 hours The solvent was removed under reduced pressure and the residue was purified
by flash column chromatography (silica gel, gradient elution with hexane/EA mixture,
8/1 to 4/1 and then DCM) to afford the product 81c (21.6 mg) as a white solid in 92%
yield and 94% ee
Trang 74.3.2 Characterization of the ring-opened products
(81c) N-((1R,2R)-2-(2,6-dichlorophenylthio)cyclohexyl)-3,5-dinitrobenzamide
White solid, 92% yield, 94% ee.Mp = 210.9-212.0 oC.[α]26D -33.3 (c 1.0, CHCl3).1H NMR (500 MHz, CDCl3, ppm): δ 1.27-1.32 (m, 1H), 1.40-1.54 (m, 2H), 1.63-1.83 (m, 3H), 2.12-2.14 (m, 1H), 2.36-2.39 (m, 1H), 3.30-3.35 (m, 1H), 4.04-4.10 (m, 1H), 6.65 (d, 1H, J = 6.95 Hz), 7.20 (t, 1H, J = 8.2 Hz), 7.38 (d, 2H, J = 7.55 Hz), 8.90 (d, 2H, J = 1.9 Hz), 9.17 (t, 1H, J = 1.9 Hz) 13C NMR (125 MHz, CDCl3, ppm): δ 24.5, 25.8, 32.4, 33.4, 52.9, 55.3, 120.9, 127.1, 128.9, 130.2, 132.2, 138.1, 141.5, 148.5, 162.1.FTIR (film): 929, 1045, 1215, 1424, 1520, 1633, 3020, 3428 cm-1 LRMS (ESI) m/z 468.1 (M-H+), HRMS (ESI) m/z 468.0201 (M-H+), calc for C19H16Cl2N3O5S 468.0193
The enantiomeric excess was determined by chiral HPLC; Phenomenex Lux 5u
Cellulose-2 (4.6 mm i.d x 250 mm);hexane/2-propanol 80/20; flow rate 1.0 mL/min; temp 25 °C; detection UV 230 nm; retention time: 18.6 min (major) and 22.4 min (minor)
Trang 8(82a) N-((1R,6R)-6-(2,6-dichlorophenylthio)cyclohex-3-enyl)-3,5-dinitro-
benzamide
White solid, 93% yield, 90% ee Mp = 207.5-209.1 oC.[α]28D-44.5 (c 0.53, CHCl3).1H NMR (500 MHz, CDCl3, ppm): δ 2.19-2.24 (m, 1H), 2.45-2.60 (m, 2H), 2.90-2.95 (m, 1H), 2.41-2.48 (m, 1H), 3.69-3.75 (m, 1H), 4.29-4.36 (m, 1H), 5.69 (t, 2H, J = 11.5 Hz), 6.69 (d, 1H, J = 7.0 Hz), 7.19 (t, 1H, J = 8.2 Hz), 7.37 (d, 2H, J = 7.6 Hz), 8.88 (d, 2H,
J = 1.9 Hz), 9.15 (t, 1H, J = 1.9 Hz) 13C NMR (125 MHz, CDCl3, ppm): δ 32.03, 34.5, 48.5, 51.7, 121.7, 125.0, 126.0, 127.8, 129.6, 131.0, 132.6, 138.6, 142.1, 149.3, 163.0
Trang 9FTIR (film): 929, 1046, 1216, 1426, 1519, 1602, 2976, 3020, 3443 cm-1.LRMS (ESI) m/z 466.3 (M-H+), HRMS (ESI) m/z 466.0031 (M-H+), calc For C19H14Cl2N3O5S 466.0037
The enantiomeric excess was determined by chiral HPLC; CHIRALPAK AD-H (4.6
mm i.d x 250 mm); hexane/2-propanol 90/10; flow rate 1.0 mL/min; temp 25 °C; detection UV 230 nm; retention time: 10.9 min (major) and 12.9 min (minor)
(82b) N-((1R,2R)-2-(2,6-dichlorophenylthio)cyclopentyl)-3,5-dinitrobenzamide
White solid, 94% yield, 94% ee.Mp = 183.7-185.2 oC.[α]27D-30.1 (c 1.0, CHCl3).1H
Trang 10NMR (500 MHz, CDCl3, ppm): δ 1.59-1.69 (m, 1H), 1.77-1.95 (m, 3H), 2.20-2.28 (m, 1H), 2.41-2.48 (m, 1H), 3.65 (q, 1H, J = 7.7 Hz), 4.29-4.36 (m, 1H), 6.35 (d, 1H, J = 5.7 Hz), 7.15 (t, 1H, J = 8.2 Hz), 7.36 (d, 2H, J = 8.2 Hz), 8.75 (d, 2H, J = 1.9 Hz), 9.12 (t, 1H, J = 1.9 Hz) 13C NMR (125 MHz, CDCl3, ppm): δ 22.6, 31.8, 32.3, 53.0, 59.9, 121.7, 127.7, 129.5, 131.0, 132.9, 138.5, 142.3, 149.2, 163.0 FTIR (film): 928,
1046, 1216, 1425, 1520, 1633, 3020, 3459 cm-1 LRMS (ESI) m/z 454.2 (M-H+), HRMS (ESI) m/z 454.0019 (M-H+), calc for C18H14Cl2N3O5S 454.0037
The enantiomeric excess was determined by chiral HPLC; CHIRALCEL OD-H (4.6
mm i.d x 250 mm); hexane/2-propanol 80/20; flow rate 1.0 mL/min; temp 25 °C; detection UV 230 nm; retention time: 29.5 min (major) and 37.1 min (minor)
Trang 11(82c) N-((1R,2R)-2-(2,6-dichlorophenylthio)cycloheptyl)-3,5-dinitrobenzamide
White solid, 91% yield, 95% ee Mp = 222.5-225.0 oC [α]29D +14.2 (c 0.57, CHCl3)
1
H NMR (500 MHz, CDCl3, ppm): δ 1.53-1.94 (m, 11H), 2.09-2.14 (m, 1H), 3.44-3.49 (m, 1H), 4.13-4.15 (m, 1H), 6.65 (d, 1H, J = 6.4 Hz), 7.19 (t, 1H, J = 7.6 Hz), 7.38 (d, 2H, J = 7.6 Hz), 8.89 (d, 2H, J = 1.9 Hz), 9.15 (t, 1H, J = 1.9 Hz) 13C NMR (125 MHz, CDCl3, ppm): δ 24.6, 25.0, 28.2, 32.2, 33.0, 55.4, 57.8, 120.9, 127.1, 128.9, 130.4, 132.3, 138,2, 141.7, 148.6, 162.0 FTIR (film): 928, 1045, 1216, 1425, 1520, 1631,
2978, 3020, 3435 cm-1.LRMS (ESI) m/z 482.0 (M-H+), HRMS (ESI) m/z 482.0327 (M-H+), calc for C20H18Cl2N3O5S 482.0350
The enantiomeric excess was determined by chiral HPLC; CHIRALPAK IA(4.6 mm i.d x 250 mm); hexane/2-propanol 90/10; flow rate 1.0 mL/min; temp 25 °C; detection UV 230 nm; retention time: 16.9 min (minor) and 18.9 min (major)
Trang 12(82d) N-((2R,3R)-3-(2,6-dichlorophenylthio)-1,2,3,4-tetrahydronaphthalen-2-yl)-
3,5- dinitrobenzamide
White solid, 90% yield, 90% ee.Mp = 231.7-234.0 oC.[α]29D -62.7 (c 0.47, CHCl3) 1H NMR (500 MHz, CDCl3, ppm): δ 2.95 (dd, 1H, J = 8.2, 16.4 Hz), 3.19 (dd, 1H, J = 8.83, 17.0 Hz), 3.29 (dd, 1H, J = 5.68, 17.0 Hz), 3.65 (dd, 1H, J = 5.05, 17.0 Hz),
3.85-3.90(m, 1H), 4.46-4.52 (m, 1H), 6.79 (d, 1H, J = 6.9 Hz), 7.09-7.17 (m, 4H), 7.23 (t, 1H, J = 7.7 Hz), 7.37 (d, 2H, J = 8.2 Hz), 8.88 (s, 2H), 9.15 (s, 1H) 13C NMR (125 MHz, CDCl3, ppm): δ 35.0, 35.4, 48.5, 51.8, 121.1, 126.7, 127.2, 128.6, 129.0, 129.0, 130.6, 131.7, 132.8, 133.5, 137.8, 141.5, 148.6, 162.5 FTIR (film): 757, 928, 1046,
Trang 131215, 1424, 1519, 1631, 2977, 3019, 3460 cm-1 LRMS (ESI) m/z 516.2 (M-H+), HRMS (FAB) m/z 517.0271 (M), calc for C23H17Cl2N3O5S 517.0266.
The enantiomeric excess was determined by chiral HPLC; CHIRALPAK AD-H (4.6
mm i.d x 250 mm); hexane/2-propanol 90/10; flow rate 1.0 mL/min; temp 25 °C; detection UV 230 nm; retention time: 18.1 min (major) and 23.9 min (minor)
(82e) N-((2R,3R)-3-(2,6-dichlorophenylthio)butan-2-yl)-3,5-dinitrobenzamide
White solid, 91% yield, 93% ee.Mp = 184.1-186.1oC.[α]29D +53.5 (c 0.40, CHCl3).1H NMR (500 MHz, CDCl3, ppm): δ 1.29-1.33 (m, 6H), 3.84-3.90 (m, 1H), 4.45-4.52 (m,
Trang 141H), 7.06 (d, 1H, J = 8.2 Hz), 7.29 (d, 1H, J = 9.5 Hz), 7.47 (d, 2H, J = 8.2 Hz), 9.04 (d, 2H, J = 1.9 Hz), 9.21 (t, 1H, J = 1.9 Hz) 13C NMR (125 MHz, CDCl3, ppm): δ 18.5, 19.1, 48.9, 51.1, 121.1, 127.1, 128.9, 130.5, 131.6, 138.0, 141.4, 148.7, 162.1 FTIR (film): 928, 1045, 1216, 1425, 1520, 1643, 2977, 3020, 3446 cm-1.LRMS (ESI) m/z 442.1 (M-H+), HRMS (ESI) m/z 442.0044 (M-H+), calc for C17H14Cl2N3O5S 442.0037
The enantiomeric excess was determined by chiral HPLC; Phenomenex Lux 5u
Cellulose-1 (4.6 mm i.d x 250 mm); hexane/2-propanol 90/10; flow rate 1.0 mL/min; temp 25 °C; detection UV 230 nm; retention time: 64.8 min (minor) and 70.5 min (major)
Trang 15(82f) N-((1R,2R)-2-(2,6-dichlorophenylthio)-1,2-diphenyl-ethyl)-3,5-dinitrobenz-
amide
White solid, 93% yield, 88% ee.Mp = 213.5-215.2 oC.[α]29D +4.7 (c 1.60, CHCl3).1H NMR (500 MHz, CDCl3, ppm): δ 5.14 (d, 1H, J = 8.2 Hz), 5.77 (t, 1H, J = 8.2 Hz), 7.02-7.21 (m, 15H), 7.84 (d, 1H, J = 8.2 Hz), 9.09 (d, 2H, J = 1.9 Hz), 9.17 (t, 1H, J =
1.9 Hz) 13C NMR (125 MHz, CDCl3, ppm): δ 58.7, 59.4, 121.9, 127.3, 128.1, 128.5, 128.7, 128.9, 129.0, 129.1, 129.4, 131.0, 131.7, 138.1, 138.2, 139.3, 141.7, 149.4, 162.8 FTIR (film): 746, 919, 1046, 1215, 1425, 1527, 1642, 2977, 3020, 3431 cm-1.LRMS (ESI) m/z 566.3 (M-H+), HRMS (FAB) m/z 566.0349 (M-H+), calc for
C27H18Cl2N3O5S 566.0344
The enantiomeric excess was determined by chiral HPLC; CHIRALPAK AD-H (4.6
mm i.d x 250 mm); hexane/2-propanol 90/10; flow rate 1.0 mL/min; temp 25 °C; detection UV 230 nm; retention time: 20.5 min (major) and 24.7 min (minor)
Trang 164.4 Preparation of chiral allylic amide
(83c) N-((1R,2R)-2-(2,6-dichlorophenylsulfinyl)cyclohexyl)-3,5-dinitrobenzamide
To a solution of 81c (94.0 mg, 0.20 mmol, 1.0 eq.) in CH2Cl2 2 mL was added
mCPBA (70% W/W, 49.3 mg, 0.20 mmol, 1.0 eq.) The reaction mixture was stirred at
room temperature for 15 minutes Most of the solvent was evaporated, and the residue was directly loaded onto a silica gel column, followed by flash column
chromatography (hexane/EA mixture, 8/1 to 1/1) to afford 83 (97.0 mg, 0.2 mmol) as a
white solid in quantitative yield Mp = 139.9-142.6 oC [α]28D +24.2 (c 0.50, CHCl3)
Trang 17H NMR (500 MHz, CDCl3, ppm): δ 1.32-1.50 (m, 5H), 1.82-1.85 (m, 2H), 2.65 (d, 1H,
J = 10.1 Hz), 3.90-3.96 (m, 1H), 4.39-4.42 (m, 1H), 7.41 (d, 2H, J = 4.5 Hz), 7.87 (s,
1H), 9.07 (d, 2H, J = 2.5 Hz), 9.10 (d, 1H, J = 1.9 Hz) 13C NMR (125 MHz, CDCl3, ppm): δ 24.7, 26.0, 26.8, 34.0, 55.5, 64.1, 121.6, 128.3, 134.0, 135.6, 139.1, 149.3, 163.7 FTIR (film): 753, 1045, 1215, 1344, 1427, 1543, 1669, 2976, 3020, 3442 cm-1.LRMS (ESI) m/z 508.0 (M+Na+), HRMS (ESI) m/z 508.0108 (M+Na+), calc for
C19H17Cl2N3O6SNa 508.0107
(84) (R)-N-(cyclohex-2-enyl)-3,5-dinitrobenzamide
To a 5 mL flask containing 83 (38.8 mg, 0.08 mmol, 1.0 eq.) was added 1 mL of
toluene, then K2CO3 (331 mg, 2.4 mmol, 30.0 eq.) The reaction was stirred under N2
and heated under reflux for 3 days The reaction mixtue was filtered and most of the solvent was evaporated under reduced pressure The residue was directly loaded onto a silica gel column, followed by flash column chromatography (hexane/EA mixture,
20/1 to 8/1) to afford 84 (13.9 mg, 0.048 mmol) as a white solid in 60% yield and 95%
ee Mp = 154.2-155.8 oC [α]29D +58.3 (c 0.30, CHCl3) 1H NMR (500 MHz, CDCl3,
ppm): δ 1.69-1.77 (m, 3H), 2.04-2.10 (m, 3H), 4.74 (br, 1H), 5.69 (dd, 1H, J = 2.5, 9.5 Hz), 6.00-6.02 (m, 1H), 6.25 (d, 1H, J = 5.7 Hz), 8.93 (d, 2H, J = 2.5 Hz), 9.16 (t, 1H,
Trang 18J = 1.9 Hz) 13C NMR (125 MHz, CDCl3, ppm): δ 20.3, 25.5, 29.9, 46.8, 121.7, 127.0, 127.8, 133.3, 138.9, 149.3, 162.7 FTIR (film): 767, 928, 1045, 1216, 1344, 1424, 1528,
1643, 2976, 3020, 3434 cm-1 LRMS (ESI) m/z 290.2 (M-H+), HRMS (ESI) m/z 290.0773 (M-H+), calc for C13H12N3O5 290.0782
The enantiomeric excess was determined by chiral HPLC; CHIRALPAK AD-H (4.6
mm i.d x 250 mm); hexane/2-propanol 90/10; flow rate 1.0 mL/min; temp 25 °C; detection UV 230 nm; retention time: 9.1 min (major) and 10.5 min (minor)
4.5 Preparation and desymmetrization of cis-aziridine-2,3-dicabo-
xylates
4.5.1 Typical procedure for the synthesis of cis-aziridine-2,3-dicarboxylate
Trang 19(89b) cis-di-tert-butyl 1-benzhydrylaziridine-2,3-dicarboxylate
To a dichloromethane solution of the oxo-acetic acid tert-butyl ester 87b (650 mg,
5.0 mmol) and MgSO4 at 0 oC was added diphenylmethyl amine (0.86 mL, 5.0 mmol, 1.0 eq.) The solution was allowed to warm to room temperature and stirred until complete conversion was achieved, as evidenced by TLC Filtering the mixture, and
the removal of the solvent afforded 1.46 g (99% yield) of the aldimine 88b as white
solid, which was used without further purification
To a propionitrile solution of 88b at -78 oC, was added triflic acid (0.14 mL, 1.25
mmol, 0.25 eq.) After 5 minutes, tert-butyl dizaoacetate (0.68 mL, 6.0 mmol, 1.2 eq.)
was added dropwise to the cold solution The reaction mixture was stirred at -78 oC for
6 hours, and then quenched by the addition of a saturated sodium carbonate solution The layers were separated, and the aqueous layer was extracted with ethyl acetate The combined organic layers were dried over Na2SO4, filtered, and concentrated to give the crude product, which was loaded onto a silica gel column, followed by flash column
chromatography (hexane/EA mixture, 8/1 to 2/1) to afford 89b (1.22 g, 3.0 mmol) as a
white solid in 60% yield.Mp = 198.0-202.2 oC 1H NMR (500 MHz, CDCl3, ppm): δ
1.46 (s, 18H), 2.52 (s, 2H), 3.83 (s, 1H), 7.22-7.26 (m, 2H), 7.28-7.44 (m, 4H), 7.57 (d,
4H, J = 6.95 Hz) 13C NMR (125 MHz, CDCl3, ppm): δ 28.0, 44.4, 76.7, 81.6, 127.3,