anomeric o-arylation SI final draft
107
1 Electronic Supplementary Information Copper-mediated anomeric O-arylation with organoboron reagents Victoria Dimakos, Jih Way Liu, Zhenlu Ge and Mark S. Taylor Department of Chemistry, University of Toronto 80 St George Street, Toronto ON, Canada, M5S 3H6 Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry. This journal is © The Royal Society of Chemistry 2019
Transcript of anomeric o-arylation SI final draft
1
Electronic Supplementary Information
Copper-mediated anomeric O-arylation with organoboron reagents
Victoria Dimakos, Jih Way Liu, Zhenlu Ge and Mark S. Taylor
Department of Chemistry, University of Toronto
80 St George Street, Toronto ON, Canada, M5S 3H6
Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry.This journal is © The Royal Society of Chemistry 2019
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Table of Contents
General methods ........................................................................................................................... 4 Synthesis of Carbohydrate Substrates ........................................................................................ 4
S1 – Thiophenyl-2,3,4,6-tetra-O-benzyl-α- D-mannopyranoside ............................................... 4
1a –2,3,4,6-Tetra-O-benzyl- D-mannopyranoside ....................................................................... 4
1c –2,3,4,6-Tetra-O-acetyl- D-mannopyranoside ........................................................................ 5
1d – 2,3,4,6-Tetra-O-acetyl- D-glucopyranoside ........................................................................ 5
1e – 2,3,4,6-Tetra-O-acetyl- D-galactopyranoside ...................................................................... 5
1f – 2,3-Di-O-benzyl-4,6-O-benzylidene- D-glucopyranose ...................................................... 6
1g – 3,4,6-Tri-O-benzyl-2-deoxy-D-glucopyranose ................................................................... 6
Synthesis of Boronic Esters and Boroxines ................................................................................ 6
2b – 2-(4-methoxyphenyl)-1,3,2-dioxaborinane ......................................................................... 6
2c – 2-(4-methoxyphenyl)-5,5-dimethyl-1,3,2-dioxaborinane ................................................... 7
2d – Tri(4-methoxyphenyl)boroxine ........................................................................................... 7
2e – Triphenylboroxine ............................................................................................................... 7
2l – Tri(3-methoxyphenyl)boroxine ........................................................................................... 8
2m – Tri(3,5-dimethylphenyl)boroxine ...................................................................................... 8
2n – Tri(4-vinylphenyl)boroxine ................................................................................................ 8
2o – Tri(4-chlorophenyl)boroxine .............................................................................................. 9
Copper-Mediated O-Arylation .................................................................................................... 9 General procedure A: optimization of reaction conditions for O-arylation of hemiacetals. ...... 9
General procedure B: Preparation of O-aryl glycosides, phase-switching workup with sorbitol/NaOH. ............................................................................................................................ 9
General procedure C: Preparation of O-aryl glycosides, phase-switching workup with sorbitol/Na2CO3. ....................................................................................................................... 10
3a – 4-Methoxyphenyl-2,3,4,6-tetra-O-benzyl-D-mannopyranoside ........................................ 10
3b – Phenyl-2,3,4,6-tetra-O-benzyl-D-mannopyranoside ......................................................... 11
3c – Phenyl-2,3,4,6-tetra-O-acetyl-α-D-mannopyranoside ....................................................... 12
3d – Phenyl-2,3,4,6-tetra-O-acetyl-D-glucopyranoside ............................................................ 13
3e – Phenyl-2,3,4,6-tetra-O-acetyl-D-galactopyranoside .......................................................... 14
3f – Phenyl-2,3-di-O-benzyl-4,6-O-benzylidene-D-glucopyranoside ...................................... 15
3g – Phenyl-3,4,6-tri-O-benzyl-2-deoxy-D-glucopyranoside ................................................... 15
3h – Phenyl 2,3,5-O-benzyl- D-arabinofuranoside .................................................................... 16
3
3i – Phenyl-2,3:5,6-di-O-isopropylidene-α-D-mannofuranoside .............................................. 17
3k – 4-Methoxyphenyl-2,3:5,6-di-O-isopropylidene-α-D-mannofuranoside ........................... 17
3l – 3-Methoxyphenyl-2,3:5,6-di-O-isopropylidene-α-D-mannofuranoside ............................ 18
3m – 3,5-Dimethylphenyl-2,3:5,6-di-O-isopropylidene-α-D-mannofuranoside ....................... 19
3n – 4-Vinylphenyl-2,3:5,6-di-O-isopropylidene-α-D-mannofuranoside ................................. 19
3o – 4-Chlorophenyl-2,3:5,6-di-O-isopropylidene-α-D-mannofuranoside ............................... 20
References .................................................................................................................................... 21 1H, 13C and 2D NMR Spectra......................................................................................................22
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General methods
Screw cap tubes were purchased from Pyrex® (13 mm x 100 mm, mfr. no. = Corning, 9825-13). Schlenk flasks were dried at 140 °C for at least 24 hours prior to use. Acetonitrile and tetrahydrofuran were HPLC grade and purified using a solvent purification system equipped with columns of activated alumina under nitrogen. (Innovative Technology, Inc.). Acetonitrile was dried further over activated 4 Å molecular sieves prior to use. Anhydrous dimethylformamide and was purchased from Sigma Aldrich and used directly from the SureSeal bottle. Phenylboronic acid was purchased from Sigma Aldrich and recrystallized from water and dried under high vacuum prior to use. Other reagents and solvents were used without further purification. Flash column chromatography was carried out using neutral silica gel (60 Å, 230–400 mesh, Silicycle). Analytical thin layer chromatography was carried out using aluminum- backed silica gel 60 F254 plates (EMD), and compounds were visualized through the use of UV
light and aqueous basic KMnO4 stain. 1H and
13C NMR and 2D NMR spectra were recorded
using a Varian Mercury 400 MHz, Bruker Avance III 400 MHz, Agilent DD2 600, or Agilent
DD2-500 spectrometer equipped with a XSens cryoprobe. 1H NMR are reported in parts per
million (ppm) relative to tetramethylsilane and referenced to residual protium in the solvent. Spectral features are tabulated in the following order: chemical shift (δ, ppm); multiplicity (s-singlet, d-doublet, t-triplet, q-quartet, m-complex multiplet); number of protons; coupling constant(s) (J, Hz); assignment. Assignments were made on the basis of coupling constants and 2D NMR spectra. High-resolution mass spectra (HRMS) were obtained on a JEOL AccuTOF JMS- T1000LC mass spectrometer equipped with a DART (direct analysis in real time) ion source. Infrared (IR) spectra were obtained on a Perkin-Elmer Spectrum 100 instrument equipped with a single-bounce diamond/ZnSe ATR accessory as neat samples, or as thin film
from CH2Cl2 as indicated. Spectral features are tabulated as follows: wavenumber (cm–1
); intensity (s-strong, m-medium, w-weak).
Synthesis of Carbohydrate Substrates S1 – Thiophenyl-2,3,4,6-tetra-O-benzyl-α- D-mannopyranoside
Prepared from thiophenyl-α-D-mannopyranoside as previously reported.1
1H NMR (400 MHz, CDCl2): δ (ppm) = 7.52–7.45 (m, 2H), 7.43–7.20 (m, 23H), 5.67–5.63 (m, 1H), 4.94 (d, J = 10.8 Hz, 1H), 4.76 (d, J = 12.3 Hz, 1H), 4.71–4.65 (m, 2H), 4.64 (d, J = 2.0 Hz, 2H), 4.57 (d, J = 10.8 Hz, 1H), 4.52 (d, J = 11.9 Hz, 1H), 4.35–4.29 (m, 1H), 4.13–4.07 (m, 1H), 4.04 (dd, J = 3.1, 1.8 Hz, 1H), 3.93–3.85 (m, 2H), 3.78 (dd, J = 10.9, 2.0 Hz, 1H).
1a –2,3,4,6-Tetra-O-benzyl- D-mannopyranoside
OBnOBnOBnO OBn
SPh
OBnOBnOBnO OBn
OH
5
Prepared from thiophenyl-2,3,4,6-tetra-O-benzyl-α- D-mannopyranoside as previously reported.2
1H NMR (400 MHz, CDCl3): δ 7.40–7.26 (m, 18H), 7.16 (dd, J = 7.1, 2.6 Hz, 2H), 5.27 (dd, J = 3.5, 1.9 Hz, 1H), 4.88 (d, J = 11.0 Hz, 1H), 4.79–4.69 (m, 2H), 4.64 – 4.47 (m, 5H), 4.03 (ddd, J = 8.4, 5.7, 2.4 Hz, 1H), 3.96 (dd, J = 9.3, 3.0 Hz, 1H), 3.89 (d, J = 9.6 Hz, 1H), 3.81 (dd, J = 3.0, 2.0 Hz, 1H), 3.76–3.65 (m, 2H).
1c –2,3,4,6-Tetra-O-acetyl- D-mannopyranoside
Prepared from 1,2,3,4,6-penta-O-acetyl-D-mannopyranoside as previously reported.2
1H NMR (400 MHz, CDCl3): δ 5.42 (dd, J = 10.0, 3.4 Hz, 1H), 5.34–5.23 (m, 3H), 4.29–4.19
(m, 2H), 4.17– 4.07 (m, 1H), 2.16 (s, 3H), 2.10 (d, J = 1.9 Hz, 3H), 2.05 (s, 3H), 2.00 (s, 3H).
1d – 2,3,4,6-Tetra-O-acetyl- D-glucopyranoside
Prepared from 1,2,3,4,6-penta-O-acetyl-D-glucopyranoside as previously reported.3
1H NMR (400 MHz, CDCl3): δ 5.51 (dd, J = 10.2, 9.4 Hz, 1H), 5.45–5.39 (m, 1H), 5.22 (dd, J =
9.6 Hz, 0.26H), 5.10–5.01 (m, 1H), 4.88–4.84 (m, 1H), 4.73 (d, J = 8.0 Hz, 0.22H), 4.27–4.17 (m, 2H), 4.13–4.06 (m, 2H), 3.9–3.86 (m, 1H), 3.73 (ddd, J = 10.1, 4.8, 2.4 Hz, 0.19H), 2.07 (s, 4H), 2.06 (s, J = 0.7 Hz, 4H), 2.02 (d, J = 1.4 Hz, 1H), 2.01 (s, 3H), 2.00 (s, 1H), 1.99 (s, 3H).
1e – 2,3,4,6-Tetra-O-acetyl- D-galactopyranoside
Prepared from 1,2,3,4,6-penta-O-acetyl- D-glucopyranoside as previously reported.4
1H NMR (400 MHz, CDCl3): δ 5.53 (dd, J = 3.6, 3.6 Hz, 1H), 5.48 (dd, J = 3.4, 1.3 Hz, 1H),
5.42 (dd, J = 10.8, 3.4 Hz, 1H), 5.17 (ddd, J = 10.8, 3.6, 1.2 Hz, 1H), 5.09 – 5.04 (m, 0.55H), 4.69 (ddd, J = 9.1, 4.6, 3.3 Hz, 0.25H), 4.50–4.44 (m, 1H), 4.18–4.03 (m, 3H), 3.96 (dd, J = 6.5, 1.2 Hz, 0.31H), 3.47 (dd, J = 9.1, 0.7 Hz, 0.25H), 2.86 (dd, J = 3.5, 1.3 Hz, 1H), 2.16 (d, J = 0.6 Hz, 0.84H), 2.15 (d, J = 0.6 Hz, 3H), 2.11 (d, J = 0.6 Hz, 0.88H), 2.10 (d, J = 0.5 Hz, 3H), 2.06 (s, 4H), 2.00 (s, 0.87H), 2.00 (s, 2H).
OAcOAcOAcO OAc
OH
O
OHAcOAcO
AcO
OAc
O
OHAcOAcO
AcO OAc
6
1f – 2,3-Di-O-benzyl-4,6-O-benzylidene- D-glucopyranose
Prepared from 1,2,3,4,6-penta-O-acetyl-β- D-glucopyranoside as previously reported.5
1g – 3,4,6-Tri-O-benzyl-2-deoxy-D-glucopyranose
Prepared from 3,4,6-tri-O-benzyl-D-glucal as previously reported.6
1H NMR (400 MHz, CDCl3): δ 7.39–7.27 (m, 18H), 7.21 – 7.15 (m, 3H), 5.42 (s, 1H), 4.90 (d, J
= 10.9 Hz, 1H), 4.70–4.57 (m, 4H), 4.53 (d, J = 11.0 Hz, 3H), 4.09 –3.98 (m, 2H), 3.75–3.62 (m, 3H), 3.53 (dd, J = 9.9, 8.9 Hz, 1H), 2.45 (d, J = 4.0 Hz, 1H), 2.30 (ddd, J = 13.1, 5.1, 1.5 Hz, 1H), 1.77–1.66 (m, 1H).
Synthesis of Boronic Esters and Boroxines 2b – 2-(4-methoxyphenyl)-1,3,2-dioxaborinane
4-methoxyphenylboronic acid (303.9 mg, 2 mmol), 1,3-propane diol (152.2 mg, 2 mmol) and dichloromethane (6mL) were combined in a long screw-cap tube and stirred at room temperature for 16 hours. Upon completion, the reaction was concentrated under reduced pressure and dried by azeotropic removal of water with toluene (0.5 mL x 3). The product was then dried under high-vacuum to afford a white solid. Spectral data were in agreement with previous reports.7
1H NMR (400 MHz, CDCl2): δ (ppm) = 7.77 – 7.70 (m, 2H), 6.91 – 6.85 (m, 2H), 3.82 (s, 3H), 3.75 (s, 3H), 1.02 (s, 6H).
O
OHBnOBnOOOPh
O
OHBnO
BnOBnO
OMe
BOO
7
2c – 2-(4-methoxyphenyl)-5,5-dimethyl-1,3,2-dioxaborinane
4-methoxyphenylboronic acid (303.9 mg, 2 mmol), neopentyl glycol (208.3 mg, 2 mmol) and toluene (5mL) were combined in a long screw-cap tube and stirred at reflux for 16 hours. Upon completion, the reaction was concentrated under reduced pressure and dried by azeotropic removal of water with toluene (0.5 mL x 3). The product was then dried under high-vacuum prior to use to afford a white solid. Spectral data are in agreement with those previously reported.8
1H NMR (400 MHz, CDCl2): δ (ppm) 7.77–7.70 (m, 2H), 6.91–6.85 (m, 2H), 3.82 (s, 3H), 3.75 (s, 3H), 1.02 (s, 6H).
2d – Tri(4-methoxyphenyl)boroxine
4-methoxyphenylboronic acid was condensed through the use of the Kugelrohr Apparatus at 100 °C for 3 hours to afford the corresponding boroxine as a white solid.9
1H NMR (400 MHz, CDCl3): δ (ppm) = 8.20–8.14 (m, 6H), 7.05–6.99 (m, 6H), 3.90 (s, 9H).
2e – Triphenylboroxine
Phenylboronic acid was condensed through the use of the Kugelrohr Apparatus at 100 °C for 2 hours to afford the corresponding boroxine as a white solid.9
1H NMR (400 MHz, CDCl3): δ 8.27–8.23 (m, 6H), 7.64–7.58 (m, 3H), 7.54–7.49 (m, 6H).
OMe
BOO
Me Me
BO
BOB
OPMP
PMP
PMP
BO
BOB
OPh
Ph
Ph
8
2l – Tri(3-methoxyphenyl)boroxine
3-methoxyphenylboronic acid was condensed through the use of the Kugelrohr Apparatus at 110 °C for 8 hours to afford the corresponding boroxine as a white solid.9
1H NMR (400 MHz, CDCl3): δ 7.83 (d, J = 7.3 Hz, 3H), 7.79–7.71 (m, 3H), 7.45 (t, J = 7.7 Hz,
3H), 7.20–7.10 (m, 3H), 3.92 (s, 9H).
2m – Tri(3,5-dimethylphenyl)boroxine
3,5-dimethylphenylboronic acid was condensed through the use of the Kugelrohr Apparatus at 110 °C for 5 hours to afford the corresponding boroxine as a white solid.
1H NMR (400 MHz, CDCl3): 7.85 (s, 6H), 7.24 (s, 3H), 2.45 (s, 18H).
2n – Tri(4-vinylphenyl)boroxine
�
�
4-Vinylphenylboronic acid was condensed through the use of the Kugelrohr Apparatus at 100 °C for 4 hours to afford the corresponding boroxine as a white solid. Spectral data are in agreement with those previously reported.10
BO
BOB
O
OMe
OMe
MeO
BO
BOB
O
Me
Me
Me
Me
Me
Me
BO
BOB
O
9
1H NMR (400 MHz, CDCl3): δ 8.25–8.16 (m, 6H), 7.57–7.52 (m, 6H), 6.81 (dd, J = 17.6, 10.9 Hz, 3H), 5.91 (dd, J = 17.6, 0.9 Hz, 3H), 5.38 (dd, J = 10.9, 0.9 Hz, 3H).
2o – Tri(4-chlorophenyl)boroxine
4-Chlorophenylboronic acid was condensed through the use of the Kugelrohr Apparatus at 110 °C for 4 hours to afford the corresponding boroxine as a white solid. Spectral data are in agreement with those previously reported.10
1H NMR (400 MHz, CDCl3): δ 8.13 (d, J = 8.3 Hz, 6H), 7.53–7.43 (m, 6H).
Copper-Mediated O-Arylation
General procedure A: Optimization of reaction conditions for O-arylation of hemiacetals. Carbohydrate (0.2 mmol, 1 equiv.), Cu(OAc)2 (72.7 mg, 0.4 mmol, 2 equiv.) and aryl boron
reagent (1 mmol, 5 equiv. boron) were combined in an oven-dried long screw-cap tube charged with a magnetic stir bar. Anhydrous acetonitrile (2 mL) was then added, followed by triethylamine (0.11 mL, 0.8 mmol). The reaction tube was then capped and sealed with Teflon and parafilm and allowed to stir at 40 °C overnight. The crude mixture was then concentrated under reduced pressure, diluted with ethyl acetate and washed with a solution of 1M sorbitol/1M Na2CO3 (2x50mL). The aqueous phase was then backwashed with ethyl acetate three times. The organic layers were combined then dried over MgSO4 before being concentrated under reduced
pressure. 1,3,5-trimethoxybenzene was added to the crude mixture, which was then analyzed by 1H NMR spectroscopy in CDCl3.
General procedure B: Preparation of O-aryl glycosides, phase-switching workup with sorbitol/NaOH.*
Carbohydrate (0.2 mmol, 1 equiv.), Cu(OAc)2 (72.7 mg, 0.4 mmol, 2 equiv.) and aryl boroxine
(0.33 mmol, 1.67 equiv.) were combined in an oven-dried long screw-cap tube charged with a magnetic stir bar. Anhydrous acetonitrile (2 mL) was then added, followed by triethylamine (0.11 mL, 0.8 mmol). The reaction tube was then capped and sealed with Teflon and parafilm
* A sorbitol/NaOH solution was used to remove an aryl alcohol byproduct from the crude reaction mixture in cases where it was difficult to separate this byproduct from the desired product by column chromatography.
BO
BOB
O
Cl
Cl
Cl
10
and allowed to stir at 40 °C overnight. The crude mixture was then concentrated under reduced pressure, diluted with dichloromethane and and vigorously hand shaken with a solution of 1M sorbitol/1M NaOH (2x50mL). The aqueous phase was then backwashed with dichloromethane three times. The organic layers were combined then dried over MgSO4 before being concentrated
under reduced pressure. The crude reaction mixture was analyzed by crude 1H NMR to obtain anomeric ratios and was then purified by flash column chromatography on silica gel.
General procedure C: Preparation of O-aryl glycosides, phase-switching workup with sorbitol/Na2CO3.
Carbohydrate (0.2 mmol, 1 equiv.), Cu(OAc)2 (72.7 mg, 0.4 mmol, 2 equiv.) and aryl boroxine
(0.33 mmol, 1.67 equiv.) were combined in an oven-dried long screw-cap tube charged with a magnetic stir bar. Anhydrous acetonitrile (2 mL) was then added, followed by triethylamine (0.11 mL, 0.8 mmol). The reaction tube was then capped and sealed with Teflon and parafilm and allowed to stir at 40 °C overnight. The crude mixture was then concentrated under reduced pressure, diluted with ethyl acetate and vigorously hand shaken with a solution of 1M sorbitol/1M Na2CO3 (50mL) for 5 minutes. The aqueous phase was then backwashed with ethyl acetate three times. The organic layers were combined then dried over MgSO4 before being
concentrated under reduced pressure. The crude reaction mixture was analyzed by crude 1H NMR to obtain anomeric ratios and was then purified by flash column chromatography on silica gel.
3a – 4-Methoxyphenyl-2,3,4,6-tetra-O-benzyl-D-mannopyranoside
Synthesized according to general procedure B from 2,3,4,6-tetra-O-benzyl-D-mannopyranoside (108.1 mg, 0.2 mmol) and tri(4-methoxyphenyl)boroxine (103.9 mg, 0.33 mmol). The α anomer was isolated as light yellow oil, and the β anomer was isolated as a white solid after flash chromatography on silica gel, eluting with 10% to 40% diethyl ether in hexanes (α: 58.4 mg, β: 13.5 mg, combined yield: 56%).
α: β= 8:1 (determined through analysis of the crude 1H NMR spectrum)
α anomer:
1H NMR (400 MHz, CDCl3): δ 7.43–7.22 (m, 20H, ArH), 7.22–7.16 (m, 2H, ArH), 7.01–6.91 (m, 2H, ArH), 6.82–6.74 (m, 2H, ArH), 5.48 (d, J = 2.0 Hz, 1H, H-1), 4.91 (d, J = 10.8 Hz, 1H, PhCH2), 4.79 (m, 2H, PhCH2), 4.70 (m, 2H, PhCH2), 4.64 (d, J = 11.9 Hz, 1H, , PhCH2), 4.55 (d, J = 10.8 Hz, 1H, PhCH2), 4.47 (d, J = 12.0 Hz, 1H, PhCH2), 4.12–4.09 (m, 2H, H-3 and H-4), 3.97 (dd, J = 2.2, 2.2 Hz, 1H, H-2), 3.95–3.89 (m, 1H, H-5), 3.80 (dd, 11.0, 4.7 Hz, 1H, H-6a), 3.76 (s, 3H, OCH3), 3.71 (dd, J = 10.9, 2.0 Hz, 1H, H-6b).
OBnOBnOBnO OBn
OPMP
11
13C NMR (101 MHz, CDCl3): δ (ppm) = 155.1, 150.4, 138.6, 138.6, 138.5, 138.4, 128.5, 128.5, 128.5, 128.4, 128.1, 128.0, 127.9, 127.8, 127.8, 127.8, 127.7, 127.6, 118.0, 114.7, 97.31, 80.16, 75.3, 75.0, 74.8, 73.4, 72.9, 72.5, 72.5, 69.3, 55.8.
IR (thin film, cm-1
): 3031.1 (w), 2901 (w), 2873 (w), 2347 (w), 1598 (w), 1506 (s), 1454.00 (w), 1363 (w), 1291 (w), 1219 (m), 1132 (m), 1100 (m), 1033 (m), 1005 (m), 829(w), 801 (w), 739 (m).
HRMS (DART+, m/z): calculated for C41H46NO7 [M+NH4]
+: 664.3274, found 664.32727.
β anomer:
1H NMR (600 MHz, CDCl3): δ (ppm) = 7.55–7.51 (m, 2H, ArH), 7.35–7.21 (m, 20H, ArH), 7.01–6.97 (m, 2H, ArH), 6.80–6.76 (m, 2H, ArH), 5.08 (d, J = 12.4 Hz, 1H, PhCH2), 4.99 (d, J = 12.4 Hz, 1H, PhCH2), 4.93 (d, J = 10.8 Hz, 1H, PhCH2), 4.87 (d, J = 0.8 Hz, 1H, H-1), 4.63– 4.50 (m, 5H, PhCH2), 4.09 (dd, J = 3.1, 0.8 Hz, 1H, H-2), 3.95 (dd, J = 9.4, 9.4 Hz, 1H, H-4), 3.87 (dd, J = 10.9, 2.0 Hz, 1H, H-6a), 3.78 (d, J = 6.4 Hz, 1H, H-6b), 3.76 (s, 3H, OCH3), 3.58– 3.50 (m, 2H, H-3 and H-5). 13C NMR (151 MHz, CDCl3): δ (ppm) = 155.2, 151.6, 138.8, 138.7, 138.4, 138.2, 128.6, 128.5, 128.5, 128.4, 128.3, 128.2, 127.9, 127.8, 127.8, 127.8, 127.7, 127.6, 118.0, 114.6, 100.5, 82.4 76.3, 75.3, 75.0, 74.4, 74.3, 73.6, 71.9, 69.7, 55.8.
IR (thin film, cm-1
): 3063.62 (w), 3030 (w), 2915 (w), 2861 (w), 2346 (w), 1728 (w), 1601 (w), 1507 (s), 1454 (w), 1365 (w), 1312 (w), 1222 (m), 1177 (w), 1097 (s), 1065 (s), 1028 (m), 911 (w), 827 (w), 793 (w), 737 (m).
HRMS (DART+, m/z): calculated for C41H46NO7 [M+NH4]
+: 664.32743, found 664.32695.
3b – Phenyl-2,3,4,6-tetra-O-benzyl-D-mannopyranoside
Synthesized according to general procedure B from 2,3,4,6-tetra-O-benzyl-D-mannopyranoside (108.1 mg, 0.2 mmol) and triphenylboroxine (103.9 mg, 0.33 mmol). Both anomers were isolated as light yellow solids after flash chromatography on silica gel, eluting with 10% to 30% ethyl acetate in hexanes (α: 60.2 mg, β: 9.6mg, combined yield: 57%).
α: β= 7:1 (determined through analysis of the crude 1H NMR spectrum)
α anomer:
OBnOBnOBnO OBn
OPh
12
1H NMR (400 MHz, CDCl3) δ: 7.46 – 7.27 (m, 20H, ArH), 7.25–7.18 (m, 2H, ArH), 7.09–6.99 (m, 3H, ArH), 5.64 (d, J = 2.0 Hz, 1H, H-1), 4.95 (d, J = 10.8 Hz, 1H, PhCH2), 4.88–4.79 (m,
2H, PhCH2), 4.79–4.71 (m, 2H, PhCH2), 4.69 (d, J = 12.0 Hz, 1H, PhCH2), 4.58 (d, J = 10.8 Hz,
1H, PhCH2), 4.49 (d, J = 12.0 Hz, 1H, PhCH2), 4.23–4.13 (m, 2H, H-3 and H-4), 4.01 (dd, J =
2.3, 2.3 Hz, 1H, H-2), 3.97–3.88 (m, 1H, H-5), 3.84 (dd, J = 11.0, 4.5 Hz, 1H, H-6a), 3.72 (dd, J = 11.0, 1.9 Hz, 1H, H-6b).
13C NMR (101 MHz, CDCl3) δ: 156.4, 138.6, 138.6, 138.7, 138.3, 129.6, 128.5, 128.5, 128.4, 128.4, 128.1, 128.0, 127.9, 127.8, 127.8, 127.7, 127.7, 127.5, 122.4, 116.6, 96.46, 80.11, 75.3, 74.9, 74.7, 73.4, 72.9, 72.6, 72.5, 69.1.
IR (thin film, cm-1): 3089 (w), 3063 (w), 3031 (w), 2908 (w), 2863 (w), 1598 (w), 1588 (w), 1495(m), 1454 (m), 1362 (w), 1290 (w), 1225 (m), 1130 (s), 1094 (s), 1050 (m), 1028 (s), 1008 (s), 989 (s), 908 (w), 846 (w), 740 (s).
HRMS (DART-TOF+, m/z): calculated for C40H44NO6 [M+NH4]+: 634.31686, found
634.31606.
β anomer:
1H NMR (600 MHz, CDCl3) δ:7.55–7.52 (m, 2H, ArH), 7.36–7.22 (m, 20H, ArH), 7.06–7.00 (m, 3H, ArH), 5.10 (d, J = 12.3 Hz, 1H, ArH), 5.03–4.98 (m, 2H, H-1 and PhCH2), 4.94 (d, J = 10.8 Hz, 1H, PhCH2), 4.62–4.52 (m, 5H, PhCH2), 4.10 (d, J = 2.9 Hz, 1H, H-2), 3.97 (dd, J = 9.5, 9.5 Hz, 1H, H-4), 3.88 (dd, J = 10.9, 1.9 Hz, 1H, H-6a), 3.77 (dd, J = 10.9, 6.3 Hz, 1H, H-6b), 3.65–3.59 (m, 2H, H-3 and H-5).
13C NMR (151 MHz, CDCl3) δ:157.3, 138.6, 138.4, 138.3, 138.0, 129.4, 128.4, 128.4, 128.4, 128.2, 128.2, 128.0, 127.7, 127.7, 127.6, 127.5, 127.4, 122.4, 116.4, 99.4, 82.2, 76.2, 75.2, 74.8, 74.2, 73.5, 71.8, 69.5, 65.9, 29.7.
IR (thin film, cm-1
): 3064(w), 3031 (w), 2912 (w), 2869 (w), 1602 (m), 1495 (m), 1454 (m), 1366 (w), 1316 (w), 1231 (m), 1098 (s), 1072 (s), 1027 (m) 909 (w), 840 (w), 752 (m), 737 (m).
HRMS (DART+, m/z): calculated for C40H44NO6 [M+NH4]
+: 634.31686, found 634.31670.
3c – Phenyl-2,3,4,6-tetra-O-acetyl-α-D-mannopyranoside
Synthesized according to general procedure C from 2,3,4,6-tetra-O-acetyl-D-mannopyranoside (69.7 mg, 0.2 mmol) and triphenylboroxine (103.9 mg, 0.33 mmol). Isolated as a light yellow solid after flash chromatography on silica gel, eluting with 10% to 30% ethyl acetate in hexanes (62.4 mg, 73% (isolated material contained 10% of the β anomer). Spectral data were in agreement with previous reports.12
OAcOAcOAcO OAc
OPh
13
α: β= 10:1 (determined through analysis of the crude 1H NMR spectrum)
1H NMR (400 MHz, CDCl3) δ:7.33–7.27 (m, 2H, ArH), 7.12–7.01 (m, 3H, ArH), 5.67 (dd, J = 3.3, 1.3 Hz, 0.1H, H-2 β), 5.57 (dd, J = 10.0, 3.5 Hz, 1H, H-3α), 5.52 (d, J = 1.9 Hz, 1H, H-1α), 5.44 (dd, J = 3.5, 1.9 Hz, 1H, H-2α), 5.36 (dd, J = 10.0, 10.0 Hz, 1H, H-4α), 5.22 (d, J = 1.3 Hz, 0.08H, H-1 β), 5.14 (dd, J = 9.9, 3.3 Hz, 0.1H H-3β), 4.33–4.22 (m, 1H, H-6aα), 4.15–4.03 (m, 2H, H-5, H-6bα), 2.19 (s, 3H, CH3α), 2.05 (s, 3H, CH3α), 2.03 (s, 3H, CH3α), 2.02 (s, 3H, CH3α).
13C NMR (100 MHz, CDCl3) δ: 170.6, 170.1, 170.0, 169.8, 155.7, 129.7, 123.1, 116.6, 95.9,
77.5, 77.2, 76.8, 69.6, 69.3, 69.0, 66.1, 62.3, 29.8, 21.0, 20.8, 20.8, 20.8.�
IR (neat, cm-1): 2921 (w), 2867 (w), 1743 (s), 1590 (m), 1493 (m), 1434 (m), 1368 (s), 1209 (s), 1126 (m), 1035 (s), 979 (m), 757 (m), 691 (m).
3d – Phenyl-2,3,4,6-tetra-O-acetyl-D-glucopyranoside
Synthesized according to general procedure C from 2,3,4,6-tetra-O-acetyl-D-glucopyranoside (69.7 mg, 0.2 mmol) and triphenylboroxine (103.9 mg, 0.33 mmol). The anomers ware isolated as light yellow solids after flash chromatography on silica gel, eluting with 10% to 30% ethyl acetate in hexanes (α: 30.5 mg, β: 16.8 mg, combined yield: 56%). Spectral data for both anomers were in agreement with previous reports.11,12
α: β= 1.2:1 (determined through analysis of the crude 1H NMR spectrum)
α anomer:
1H NMR (400 MHz, CDCl3) δ:7.36–7.28 (m, 2H, ArH), 7.10–7.04 (m, 3H, ArH), 5.73 (d, J=4.0
Hz, 1H, H-1), 5.70 (d, J=9.40 Hz, 1H, H-3), 5.15 (dd, J= 1.1, 10 Hz, 1H, H-4), 5.04 (dd, J= 10.2, 3.66 Hz, 1H, H-2), 4.24 (dd, J=12.0, 5.0 Hz, 1H, H-6a), 4.15–4.11 (m, 1H, H-5), 4.06 (dd, J= 12.0, 2.30 Hz, H-6b), 2.06 (s, 3H, CH3), 2.05(s, 3H, CH3), 2.04(s, 3H, CH3), 2.03 (s, 3H, CH3).
13C NMR (100 MHz, CDCl3) δ: 170.7, 170.3, 169.7, 156.2, 129.8, 123.2, 116.8, 94.4, 77.5,
77.2, 76.8, 70.6, 70.3, 68.5, 68.1, 61.8, 20.87, 20.80, 20.78, 20.76.
IR (neat, cm-1): 2920(w),2850(w),1736(s),1600(w),1494(m),1365(m),1218(s),1033(s),958(w),848(s)764(m),695(m).
β anomer:
1H NMR (400 MHz, CDCl3) δ: 7.31–7.27 (m, 2H, ArH), 7.09–7.05 (m, 1H, ArH), 7.01–6.98
(m, 2H, ArH), 5.30–5.27 (m, 2H, H-3, H-2), 5.17 (dd, J=9.8, 9.8 Hz, 1H, H-4), 5.08( d, J=7.4
O
OPhAcOAcO
AcO
OAc
14
Hz, 1H, H-1), 4.29 (dd, J=2.2, 5 Hz, 1H, H-6a), 4.18 (dd, J=2.4, 12.0 Hz, 1H,H-6b), 3.85 (ddd, J= 10.0, 5.4, 2.5 Hz, 1H, H-5), 2.07 (s, 3H, CH3), 2.06 (s, 3H, CH3), 2.04 (s, 3H, CH3), 2.03 (s, 3H, CH3).
13C NMR (100 MHz, CDCl3) δ: 170.7, 170.4, 169.5, 169.4, 157.0, 129.7, 123.5, 117.1, 99.3,
77.5, 77.4, 77.2, 76.8, 72.9, 72.2, 71.4, 68.5, 62.1, 20.82, 20.78, 20.77, 20.74.
IR (neat, cm-1): 2924 (m), 2856 (m), 1756 (s), 1596 (w), 1493 (w), 1378 (m), 1223 (s), 1074 (m), 1047 (m), 913 (w), 766 (w), 698(w).
3e – Phenyl-2,3,4,6-tetra-O-acetyl-D-galactopyranoside
Synthesized according to general procedure C from 2,3,4,6-tetra-O-acetyl-D-galactopyranoside (69.7 mg, 0.2 mmol) and triphenylboroxine (103.9 mg, 0.33 mmol). The anomers ware isolated as light yellow solids after flash chromatography on silica gel, eluting with 20% to 60% diethyl ether in hexanes (α: 25.5 mg, β: 22.1 mg). The β anomer was inseparable from an acyl transfer compound derived from 2,3,4,6-tetra-O-acetyl-D-galactopyranoside (20% by mass). The combined yield of the anomers of 3e was therefore 51%. Spectral data for both anomers were in agreement with previous reports. 12, 13
α: β= 1:1 (determined through analysis of the crude 1H NMR spectrum)
α anomer:
1H NMR (400 MHz, CDCl3) δ: 7.35–7.27 (m, 2H, ArH), 7.13–7.02 (m, 3H, ArH), 5.78 (d,
J=3.5 Hz, 1H, H-1), 5.58 (dd, J=10.8, 3.4 Hz, 1H, H-3), 5.53 (dd, J = 3.4, 1.3 Hz, 1H, H-4), 5.29 (dd, J=10.3, 3.4 Hz, 1H, H-2), 4.38–4.33 (m, 1H, H-5), 4.15–4.02 (m, 2H, H-6a, H-6b), 2.17 (s, 3H, CH3), 2.07 (s, 3H, CH3), 2.03 (s, 3H, CH3), 1.93 (s, 3H, CH3). 13
C NMR (126 MHz, CDCl3) δ:170.5, 170.4, 170.3, 170.2, 156.4, 129.8, 123.1, 116.9, 95.0, 68.0, 67.9, 67.7, 67.3, 61.6, 20.9, 20.87, 20.82, 20.7.
IR(neatcm-1)2923(w),1737(s),1603(m),1497(m),1358(s),1210(s),1064(s),987(m),909(m),848(m).
β anomer:
1H NMR (400 MHz, CDCl3) δ: 7.35–7.27 (m, 2H, ArH), 7.10–7.04 (m, 1H, ArH), 7.02–6.98
(m, 2H, ArH), 5.52–5.47 (m, 1H, H-2), 5.45 (dd, J = 3.5, 1.1 Hz, 1H, H-4), 5.11 (dd, J= 10,4, 3.1 Hz, 1H, H-3), 5.04 (d, J=8.0 Hz, 1H, H-1), 4.23 (dd, J = 11.3, 7.0 Hz, 1H, H-6a), 4.16 (dd, J = 11.3, 6.3 Hz, 1H, H-6b), 4.08–4.01 (m, 1H, H-5), 2.18 (s, 3H, CH3), 2.07 (s, 3H, CH3), 2.06 (s, 3H, CH3), 2.01 (s, 3H, CH3).
O
OPhAcOAcO
AcO OAc
15
13C NMR (100 MHz, CDCl3) δ:170.5, 170.4, 170.3, 169.5, 157.1, 129.7, 123.5, 117.1, 99.9,
71.2, 71.0, 68.8, 67.0, 61.5, 29.8, 20.88, 20.81, 20.79, 20.73.
Select peaks belonging to acyl transfer by-product: 6.38 (d, J = 1.7 Hz, 0.19H), 5.35–5.32 (m, 0.42H), 4.38–4.31 (m, 0.18H)
IR (neat cm-1): 2926 (w), 1737 (s), 1603 (w), 1496 (w), 1431 (w), 1367 (m), 1238 (s), 1186 (s), 1042 (s), 987 (s), 847 (m).
3f – Phenyl-2,3-di-O-benzyl-4,6-O-benzylidene-D-glucopyranoside
Synthesized according to general procedure C from 2,3-Di-O-benzyl-4,6-O-benzylidene-D-glucopyranose (89.7 mg, 0.2 mmol) and triphenylboroxine (103.9 mg, 0.33 mmol). A mixture of anomers was isolated as a white solid after flash chromatography on silica gel, eluting with 10% to 30% diethyl ether in hexanes (47.3 mg, 45%).
α: β= 1:1 (determined through analysis of the crude 1H NMR spectrum)
1H NMR (400 MHz, CDCl3) δ: 7.55–7.46 (m, 4H, ArH), 7.46–7.26 (m, 28H, ArH), 7.12–7.03
(m, 5H, ArH) 5.61 (s, 0.47H, CHPh), 5.58 (s, 1H, CHPh), 5.45 (d, J=5.5 Hz, 1H, H-1α), 5.15 (d, J= 7.4 Hz, 0.41H, H-1β), 5.01–4.83 (m, 6H, CH2Ph), 4.73 (d, J=11.9 Hz, 1H CH2Ph), 4.40 (dd, J= 10.5, 4.80 Hz, 0.26H, H-6β), 4.27 (dd, J= 9.3, 9.3, 1H, H-3α), 4.21 (dd, J= 10.3, 4.76 Hz, H-6α), 4.02 (dd, J=9.9, 4.6 Hz, 1H, H-5α), 3.92–3.64 (m, 5H, H-2β, H-3β, H-4β, H-6β, H-2α, H-4α, H-6α), 3.61–3.51 (m, 0.33H, H-5β). 13
C NMR (100 MHz, CDCl3) δ:157.2, 156.7, 138.9, 138.2, 137.5, 137.4, 129.8, 129.7, 129.1, 129.1, 128.6, 128.5, 128.5, 128.4, 128.4, 128.2, 128.1, 128.0, 127.9, 127.8, 127.8, 126.2, 126.2, 123.2, 122.8, 117.1, 117.1, 102.2, 101.5, 101.4, 96.6, 82.2, 81.9, 81.4, 81.0, 79.3, 78.6, 75.7, 75.5, 75.3, 73.8, 69.0, 68.9, 66.4, 63.3, 32.1, 30.3, 29.5, 26.9, 22.8, 14.3.
IR (neat, cm-1): 2922 (m), 2860 (m), 1603 (w), 1455 (m), 1495 (m), 1382 (m), 1224(w), 1090 (s), 1030 (m), 908 (m), 734 (s), 697 (s).
HRMS (DART-TOF+, m/z): Calculated for C33H36NO6[M+NH4]+ :525.22771, found
525.22776.
3g – Phenyl-3,4,6-tri-O-benzyl-2-deoxy-D-glucopyranoside
O
OPhBnOBnOOOPh
O
OPhBnO
BnOBnO
16
Synthesized according to general procedure C from 3,4,6-tri-O-benzyl-2-deoxy D-glucopyranoside (86.9 mg, 0.2 mmol) and triphenylboroxine (103.9 mg, 0.33 mmol). A mixture of anomers was isolated as a light yellow oil after flash chromatography on silica gel, eluting with 10% to 30% diethyl ether in hexanes (49 mg, 48%).
α: β= 1:1.3 (determined through analysis of the crude 1H NMR spectrum)
1H NMR (400 MHz, CDCl3) δ: 7.42–7.26 (m, 31H), 7.26–7.17 (m, 2H), 7.10–6.97 (m, 7H),
5.72 (dd, J = 2.0, 1.3 Hz, 1H, H-1α), 5.09 (dd, J = 9.7, 2.1 Hz, 1H, H-1β), 4.94 (dd, J = 10.9, 2.8 Hz, 2H), 4.79–4.69 (m, 3H), 4.69–4.52 (m, 7H), 4.45 (d, J = 12.1 Hz, 1H), 4.21 (ddd, J = 11.4, 8.7, 5.0 Hz, 1H), 3.91–3.69 (m, 7H), 3.65–3.56 (m, 4H), 2.57– 2.45 (m, 2H, H-2a), 2.02–1.86 (m, 2H, H-2b).
13C NMR (101 MHz, CDCl3) δ: 157.3, 156.6, 138.7, 138.6, 138.43, 138.42, 138.3, 138.2,
129.54, 129.53, 128.6, 128.55, 128.51, 128.45, 128.44 128.42, 128.1, 128.02, 128.01, 127.89, 127.87, 127.86, 127.8, 127.8, 127.8, 127.7, 127.7, 127.6, 122.4, 122.0, 116.7, 116.6, 97.8, 95.9, 79.3, 78.1, 78.0, 77.6, 75.6, 75.2, 75.1, 73.6, 73.5, 72.1, 71.7, 71.6, 69.4, 68.8, 36.7, 35.6.
IR (thin film, cm-1
): 3071 (w), 3031 (w), 2884 (w), 2864 (w), 1594 (m), 1495 (s), 1454 (m), 1364 (s), 1193 (w), 1089 (s), 1074 (s), 1027 (s), 974 (s), 908 (w), 850 (w), 751 (s), 732 (s), 693 (s).
HRMS (DART-TOF+, m/z): Calculated for C33H38NO5 [M+NH4]+ :528.27500, found
528.27475.
3h – Phenyl 2,3,5-O-benzyl- D-arabinofuranoside
Synthesized according to general procedure C from 2,3,5-O-benzyl- D-arabinofuranoside (84.1mg, 0.2 mmol) and triphenylboroxine (103.9 mg, 0.33 mmol). The anomers ware isolated as colourless oils after flash chromatography on silica gel, eluting with 10% to 40% diethyl ether in hexanes (56.8 mg combined yield: 57%).
α: β= 3:1 (determined through analysis of the crude 1H NMR spectrum)
α anomer:
1H NMR (400 MHz, CDCl3) δ7.40–7.25 (m, 17H, ArH), 7.12–7.06 (m, 2H, ArH), 7.06–7.00
(m, 1H, ArH), 5.74 (d, J = 1.5 Hz, 1H, H-1), 4.66–4.52 (m, 6H, CH2Ph), 4.40–4.32 (m, 2H, H-2 and H-4), 4.13 (dd, J = 6.8, 3.3 Hz, 1H, H-3), 3.73–3.62 (m, 2H, H-5).�13
C NMR (100 MHz, CDCl3) δ: 156.75, 138.2, 138.0, 137.5, 129.6, 128.6, 128.5, 128.5, 128.1, 128.8, 127.96, 127.91, 127.8, 122.2, 116.9, 104.7, 88.6, 83.3, 81.7, 73.5, 72.4, 72.3, 69.4.�
O OPhOBn
OBn
BnO
17
IR (thin film, cm
-1): 2925(w),2860(w),1599(w),1496(m),1455(m),1265(m),1226(m),
1079(s),909(m),735(s),697(m).HRMS (DART-TOF
+, m/z): CalculatedforC32H32O5[M+NH4]+:514.25935,found514.25895.
β anomer:
1H NMR (400 MHz, CDCl3) δ 7.34–7.11 (m, 17H, Ar-H), 7.06–6.92 (m, 3H, ArH), 5.50 (d, J =
4.2 Hz, 1H, H-1), 4.70–4.53 (m, 4H, CH2Ph), 4.44–4.33 (m, 2H, CH2Ph), 4.29–4.11 (m, 3H, H-2, H-3, H-4), 3.50 (d, J = 6.0 Hz, 2H, H5). 13
C NMR (100 MHz, CDCl3) δ: 157.2, 138.27, 138.20, 137.6, 129.6, 128.60, 128.52, 128.41, 128.19, 128.10, 127.88, 127.82, 127.7, 127.6, 122.4, 117.1, 99.2, 84.2, 83.2, 81.4, 73.5, 72.8, 72.6, 72.4.� IR (thin film, cm
-1): 2925(s),2860(m),1598(m),1495(s),1455(m),1225(s),1028(s),737(s),
697(s).HRMS (DART-TOF
+, m/z): CalculatedforC32H32O5[M+NH4]+:514.25935,found514.25895.
3i – Phenyl-2,3:5,6-di-O-isopropylidene-α-D-mannofuranoside
Synthesized according to general procedure C from 2,3:5,6-di-O-isopropylidene-α-D-mannofuranoside (52.1 mg, 0.2 mmol) and triphenylboroxine (103.9 mg, 0.33 mmol). Isolated as a white solid after flash chromatography on silica gel, eluting with 10% diethyl ether in hexanes (39.1 mg, 58%). Spectral data were in agreement with previous reports.14
1H NMR (500 MHz, CDCl3) δ: 7.31–7.26 (m, 2H), 7.04–6.98 (m, 3H), 5.64 (s, 1H), 4.92 (dd, J = 5.9, 3.5 Hz, 1H), 4.87 (d, J = 5.9 Hz, 1H), 4.43 (ddd, J = 8.0, 6.2, 4.2 Hz, 1H), 4.12–4.06 (m, 2H), 3.99 (dd, J = 8.8, 4.2 Hz, 1H), 1.52 (s, 3H), 1.43 (s, 3H), 1.38 (d, J = 1.8 Hz, 6H).
13C NMR (126 MHz, CDCl3) δ: 156.4, 129.6, 122.4, 116.8, 113.1, 109.5, 105.0, 85.6, 81.3, 79.7, 73.1, 67.1, 27.1, 26.1, 25.4, 24.8.
3k – 4-Methoxyphenyl-2,3:5,6-di-O-isopropylidene-α-D-mannofuranoside
O
OPh
OO
Me Me
O OMe Me
18
Synthesized according to general procedure C from 2,3:5,6-di-O-isopropylidene-α-D-mannofuranoside (52.1 mg, 0.2 mmol) and tri(4-methoxyphenyl)boroxine (132.6 mg, 0.33 mmol). Isolated as a white solid after flash chromatography on silica gel, eluting with 2.5% acetone in dichloromethane (45.5 mg, 62%).
1H NMR (500 MHz, CDCl3) δ: 6.98–6.89 (m, 2H, ArH), 6.84–6.78 (m, 2H, ArH), 5.51 (s, 1H, H-1), 4.90 (dd, J = 5.9, 3.5 Hz, 1H, H-3), 4.84 (d, J = 5.9 Hz, 1H, H-2), 4.42 (ddd, J = 8.0, 6.3, 4.2 Hz, 1H, H-5), 4.12 – 4.04 (m, 2H, H-6a, H-4), 3.98 (dd, J = 8.8, 4.3 Hz, 1H, H-6b), 3.76 (s, 3H, OMe), 1.50 (s, 3H, CH3), 1.43 (s, 3H, CH3), 1.37 (d, J = 4.1 Hz, 6H, CH3).
13C NMR (126 MHz, CDCl3) δ: 155.1, 150.3, 118.2, 114.7, 113.0, 109.5, 105.9, 85.5, 81.1, 79.7, 73.1, 67.1, 55.7, 27.0, 26.1, 25.3, 24.7.
IR (neat, cm–1): 2989 (w), 2943 (m), 2885 (w), 2842 (w), 1510 (s), 1463 (m), 1382 (m), 1370 (s), 1242 (s), 1214 (s), 1181 (m), 1163 (m), 980 (s), 1066 (s), 1033 (s), 1007 (s), 980 (s), 953 (s), 893 (m), 859 (m), 821 (s), 776 (m), 763 (m), 673 (m).
HRMS (DART-TOF+, m/z): Calculated for C19H27O7 [(M + H)+]: 367.17568. Found:
367.17615.
3l – 3-Methoxyphenyl-2,3:5,6-di-O-isopropylidene-α-D-mannofuranoside
Synthesized according to general procedure C from 2,3:5,6-di-O-isopropylidene-α-D-mannofuranoside (52.1 mg, 0.2 mmol) and tri(3-methoxyphenyl)boroxine (132.6 mg, 0.33 mmol). Isolated as a colourless oil after flash chromatography on silica gel, eluting with 2.5% acetone in dichloromethane (39.6 mg, 54%). 1H NMR (500 MHz, CDCl3) δ: 7.19–7.15 (m, 1H, Ar-H), 6.62–6.55 (m, 3H, Ar-H), 5.62 (s, 1H, H-1), 4.91 (dd, J = 5.9, 3.5 Hz, 1H, H-3), 4.86 (d, J = 5.9 Hz, 1H, H-2), 4.42 (ddd, J = 8.0, 6.2, 4.2 Hz, 1H, H-5), 4.12–4.05 (m, 2H, H-4, H-6a), 3.99 (dd, J = 8.8, 4.3 Hz, 1H, H-6b), 3.78 (s, 3H, OMe), 1.51 (s, 3H, CH3), 1.43 (s, 3H, CH3), 1.37 (s, 6H, CH3).
13C NMR (126 MHz, CDCl3) δ: 160.86, 157.58, 130.04, 113.11, 109.51, 108.86, 108.07, 105.00, 103.02, 85.60, 81.30, 79.70, 73.11, 67.07, 55.44, 27.08, 26.10, 25.37, 24.75.
O
OPMP
OO
Me Me
O OMe Me
O
O
OO
Me Me
O OMe Me
OMe
19
IR (thin film, cm–1): 2993 (w), 2942 (w), 1598 (m), 1492 (m), 1455 (w), 1374 (m), 1261 (m), 1202 (m), 1150 (s), 1114 (m), 1066 (s), 1050 (s), 1006 (s), 986 (a), 889 (w), 846 (s), 766 (m), 733 (m), 686 (m), 650 (w).
HRMS (DART-TOF+, m/z): Calculated for C19H27O7 [(M + H)+]: 367.17568. Found:
367.17505.
3m – 3,5-Dimethylphenyl-2,3:5,6-di-O-isopropylidene-α-D-mannofuranoside
�
Synthesized according to general procedure C from 2,3:5,6-di-O-isopropylidene-α-D-mannofuranoside (52.1 mg, 0.2 mmol) and tri(3,5-dimethylphenyl)boroxine (130.6 mg, 0.33 mmol). Isolated as a colourless oil after flash chromatography on silica gel, eluting with 2.5% acetone in dichloromethane (46 mg, 63%).
1H NMR (500 MHz, CDCl3) δ: 6.67 (s, 1H, ArH), 6.64 (s, 2H, ArH), 5.62 (s, 1H, H-1), 4.91 (dd, J = 5.9, 3.5 Hz, 1H, H-3), 4.84 (d, J = 5.9 Hz, 1H, H-2), 4.43 (ddd, J = 8.0, 6.3, 4.2 Hz, 1H, H-5), 4.14–4.05 (m, 2H, H-4 and H-6a), 4.01 (dd, J = 8.8, 4.2 Hz, 1H, H-6b), 2.28 (s, 6H Ar-Me), 1.52 (s, 3H, CH3), 1.44 (s, 3H, CH3), 1.38 (s, 3H, CH3), 1.37 (s, 3H, CH3).
13C NMR (126 MHz, CDCl3) δ: 156.4, 139.4, 124.1, 114.4, 113.0, 109.5, 104.9, 85.6, 81.2, 79.7, 77.4, 77.2, 76.9, 73.1, 67.0, 27.0, 26.1, 25.4, 24.7, 21.5.
IR (thin film, cm–1): 2989 (w), 2946 (w), 1618 (w), 1596 (m), 1465 (w) 1375 (m), 1297 (m), 1261 (m), 1210 (m), 1153 (s), 1114 (m), 1088 (s), 1064 (s), 1025 (s), 1004 (s), 994 (s), 981 (s), 953 (m), 890 (m)< 843 (s), 733 (s), 687 (m), 650 (w).
HRMS (DART-TOF+, m/z): Calculated for C20H29O6 [(M + H)+]: 365.19641. Found:
365.19643.
3n – 4-Vinylphenyl-2,3:5,6-di-O-isopropylidene-α-D-mannofuranoside
Synthesized according to general procedure C from 2,3:5,6-di-O-isopropylidene-α-D-mannofuranoside (52.1 mg, 0.2 mmol) and tri(4-vinylphenyl)boroxine (128.7 mg, 0.33 mmol). Isolated as a white solid after flash chromatography on silica gel, eluting with 10% ether in hexane (41.5 mg, 57%).
O
O
OO
Me Me
O OMe Me
Me
Me
O
O
OO
Me Me
O OMe Me
20
1H NMR (500 MHz, CDCl3) δ: 7.36–7.31 (m, 2H, ArH), 6.98–6.94 (m, 2H, ArH), 6.66 (dd, J = 17.6, 10.9 Hz, 1H, CHCH2), 5.66–5.60 (m, 2H, H-1, CHCH2), 5.16 (dd, J = 10.9, 0.9 Hz, 1H, CHCH2), 4.91 (dd, J = 5.9, 3.5 Hz, 1H, H-3), 4.86 (d, J = 5.9 Hz, 1H, H-2), 4.43 (ddd, J = 8.0, 6.3, 4.2 Hz, 1H, H-5), 4.12 – 4.05 (m, 2H, H-4, H-6a), 3.98 (dd, J = 8.8, 4.2 Hz, 1H, H-6b), 1.52 (s, 3H, CH3), 1.43 (s, 3H, CH3), 1.37 (s, 6H,CH3).
13C NMR (126 MHz, CDCl3) δ: 156.1, 136.2, 132.0, 127.5, 116.7, 113.1, 112.5, 109.5, 105.0, 85.6, 81.3, 79.7, 73.1, 67.0, 27.1, 26.1, 25.3, 24.7. IR (neat, cm–1): 2988 (m), 2951 (w), 2902 (w), 1630 (w) 1606 (m), 1510 (s), 1455 (q), 1376 (m), 1367 (m), 1283 (w), 1238 (m), 1206 (s), 1177 (w), 1159 (s), 1109 (s), 1078 (s), 1049 (s), 994 (s), 981 (s), 920 (s), 896 (w), 863 (s), 842 (s), 819 (s), 775 (w), 737 (w), 692 (w). HRMS (DART-TOF+, m/z): Calculated for C20H27O6 [(M + H)
+]: 363.18076. Found:
363.18048.
3o – 4-Chlorophenyl-2,3:5,6-di-O-isopropylidene-α-D-mannofuranoside
Synthesized according to general procedure C from 2,3:5,6-di-O-isopropylidene-α-D-mannofuranoside (52.1 mg, 0.2 mmol) and tri(4-chlorophenyl)boroxine (137 mg, 0.33 mmol). Isolated as a light yellow oil after flash chromatography on silica gel, eluting with 2.5% acetone in dichloromethane (26 mg, 35%).
1H NMR (500 MHz, CDCl3) δ: 7.25–7.20 (m, 2H, ArH), 6.95–6.90 (m, 2H, ArH), 5.57 (s, 1H, H-1), 4.90 (dd, J = 5.9, 3.5 Hz, 1H, H-3), 4.85 (d, J = 5.8 Hz, 1H, H-2), 4.42 (ddd, J = 7.8, 6.2, 4.2 Hz, 1H, H-5), 4.11–4.03 (m, 2H, H-4, H-6a), 3.96 (dd, J = 8.8, 4.2 Hz, 1H, H-6b), 1.50 (s, 3H, CH3), 1.42 (s, 3H, CH3), 1.37 (s, 6H, CH3). 13C NMR (126 MHz, CDCl3) δ: 154.9, 129.5, 127.4, 118.1, 113.2, 109.5, 105.2, 85.5, 81.4, 79.7, 73.1, 67.0, 27.0, 26.1, 25.3, 24.7. IR (thin film, cm–1): 2993 (w), 2939 (w), 1596 (w), 1490 (s), 1457 (w), 1375 (m), 1229 (s), 1208 (s), 1161 (m), 1115 (m), 1088 (s), 1067 (s), 998 (s), 981 (s), 891 (w), 845 (s), 825 (s), 732 (m), 643 (m). HRMS (DART-TOF+, m/z): Calculated for C18H24ClO6[(M + H)
+]: 371.12614 Found:
371.12633.
O
O
OO
Me Me
O OMe Me
Cl
21
References
1 T.G. Frihed, M. T. C Walvoort, J. D. C. Codée, G. A. Van Der Marel, M. Bols, and C. M. Pedersen, J. Org. Chem. 2013, 78, 2191–2205. 2 P. Rohse and V. Wittmann, Chem.: Eur. J. 2016, 22, 9724–9733. 3 M. M. Sim, H. Kondo and C-H. Wong, J. Am. Chem. Soc. 1993, 115, 2260–2267. 4 S. A. Allman, H. H. Jensen, B. Vijayakrishnan, J. A. Garnett, E. Leon, Y. Liu, D. C. Anthony, N. R. Sibson, T. Feizi, S. Matthews and B. G. Davis, ChemBioChem. 2009, 10, 2522–2529. 5 K. A. D’Angelo and M. S. Taylor, J. Am. Chem. Soc. 2016, 138, 11058–11066. 6 US Pat., WO 2010/005799 A2, 2010. 7 N. Dastbaravardeh, M. Schnürch and M. D. Mihovilovic, Org. Lett. 2012, 14, 1930–1933. 8 G.A. Molander, S. L. J. Trice and S. D. Dreher, J. Am. Chem. Soc. 2010, 132, 17701–17703. 9 A. Antoft-Finch, T. Blackburn and V. Snieckus, J. Am. Chem. Soc. 2009, 131, 17750–17752. 10 C. Bomio, M. A. Kabeshov, A. R. Lit, S-H. Lau, J. Ehlert, C. Battilocchio and S.V. Ley, Chem. Sci. 2017, 8, 6071– 6075. 11 E. J. Concinero, D. P. Gamblin, B. G. Davis and J. P. Simons, J. Am. Chem. Soc. 2009, 131, 11117–11123. 12 M. Matsui and M. Okada, Chem. Pharm. Bull. 1972, 20, 1033–1040. 13 I. J. Talisman, V. Kumar, J. R. Deschamps, M. Frisch and S. V. Malhotra, Carbohydr. Res. 2011, 346, 2337–2341. 14 G. L. Tolnai, U. J. Nilsson and B. Olofsson, Angew. Chem. Int. Ed. 2016, 55,11226–11230.
22
1H, 13C and 2D NMR Spectra
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23
0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.01H (ppm)
17
.72
3.0
0
5.8
2
2.4
5
7.2
47
.26
CD
Cl3
7.8
57
.85
7.8
5
2m – 1H NMR (400 MHz, CDCl3)
BO
BOB
O
Me
Me
Me
Me
Me
Me
24
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.011.51H (ppm)
1.3
03
.84
4.2
01
.15
1.4
12
.04
1.0
81
.05
1.3
01
.89
2.0
81
.00
1.0
1
2.2
52
.10
2.0
22
0.4
7
3.7
23
.72
3.7
63
.76
3.7
83
.79
3.9
73
.97
4.1
04
.10
4.1
14
.11
4.1
24
.45
4.4
84
.53
4.5
64
.63
4.6
64
.70
4.7
04
.78
4.7
94
.90
4.9
35
.48
5.4
86
.77
6.7
76
.79
6.7
96
.95
6.9
56
.96
6.9
77
.18
7.1
87
.19
7.2
07
.26
CD
Cl3
7.2
87
.28
7.2
87
.29
7.2
97
.29
7.3
07
.30
7.3
17
.31
7.3
27
.32
7.3
27
.33
7.3
37
.34
7.3
57
.35
7.3
67
.37
7.3
87
.38
7.3
87
.39
7.3
97
.40
7.4
07
.41
3aα – 1H NMR (400 MHz, CDCl3)
OBnOBnOBnO OBn
OPMP
25
-10010203040506070809010011012013014015016017018019020021013C (ppm)
55
.86
9.3
72
.57
2.5
72
.97
3.4
74
.87
5.0
75
.37
6.8
CD
Cl3
77
.2 C
DC
l37
7.5
CD
Cl3
80
.29
7.3
11
4.7
11
8.0
12
7.6
12
7.7
12
7.8
12
7.8
12
7.8
12
7.9
12
8.0
12
8.1
12
8.4
12
8.5
12
8.5
12
8.5
13
8.4
13
8.5
13
8.6
13
8.6
15
0.4
15
5.1
3aα – 13C NMR (101 MHz, CDCl3)
OBnOBnOBnO OBn
OPMP
26
3.54.04.55.05.56.06.57.07.51H (ppm)
3.5
4.0
4.5
5.0
5.5
6.0
6.5
7.0
7.5
1H
(ppm
)
3aα – COSY (400 MHz, CDCl3)
OBnOBnOBnO OBn
OPMP
27
2.83.03.23.43.63.84.04.24.44.64.85.05.25.45.65.86.06.26.46.66.87.07.27.47.67.81H (ppm)
50
60
70
80
90
100
110
120
130
140
150
13
C (
ppm
)
3aα – HSQC (400 MHz, CDCl3)
OBnOBnOBnO OBn
OPMP
28
3.54.04.55.05.56.06.57.07.51H (ppm)
0
10
20
30
40
50
60
70
80
90
100
110
120
130
140
150
160
170
180
13
C (
ppm
)
3aα – HMBC (400 MHz, CDCl3)
OBnOBnOBnO OBn
OPMP
29
-1.00.01.02.03.04.05.06.07.08.09.010.011.01H (ppm)
2.1
14
.33
1.0
71
.03
1.0
5
5.2
51
.02
1.0
31
.03
1.0
0
2.1
42
.11
2.3
51
8.7
01
.99
3.5
83
.59
3.6
03
.60
3.7
53
.76
3.7
63
.77
3.8
63
.87
3.9
54
.09
4.0
94
.09
4.0
94
.52
4.5
44
.57
4.5
84
.59
4.6
04
.60
4.8
74
.87
4.9
24
.94
4.9
85
.00
5.0
75
.09
6.7
86
.79
6.7
96
.99
6.9
97
.00
7.2
27
.22
7.2
37
.24
7.2
6 c
dcl3
7.2
77
.27
7.2
87
.28
7.2
87
.29
7.2
97
.29
7.2
97
.29
7.3
07
.30
7.3
07
.30
7.3
17
.31
7.3
17
.32
7.3
27
.33
7.3
37
.34
7.5
27
.52
7.5
27
.53
7.5
4
OBnOBnOBnO OBn
OPMP
3aβ – 1H NMR (600 MHz, CDCl3)
30
-10010203040506070809010011012013014015016017018019020021022013C (ppm)
55
.86
9.7
71
.97
3.6
74
.37
4.4
75
.07
5.3
76
.37
6.9
cdcl3
77
.2 c
dcl3
77
.4 c
dcl3
82
.41
00
.51
14
.61
18
.01
27
.61
27
.71
27
.81
27
.81
27
.81
27
.91
28
.21
28
.31
28
.41
28
.51
28
.51
28
.61
38
.21
38
.41
38
.71
38
.8
15
1.6
15
5.2
OBnOBnOBnO OBn
OPMP
3aβ – 13C NMR (151 MHz, CDCl3)
31
3.43.63.84.04.24.44.64.85.05.25.45.65.86.06.26.46.66.87.07.27.47.67.81H (ppm)
3.0
3.5
4.0
4.5
5.0
5.5
6.0
6.5
7.0
7.5
1H
(ppm
)
OBnOBnOBnO OBn
OPMP
3aβ – COSY (600 MHz, CDCl3)
32
2.02.53.03.54.04.55.05.56.06.57.07.58.08.59.01H (ppm)
50
60
70
80
90
100
110
120
130
140
150
13
C (
ppm
)
OBnOBnOBnO OBn
OPMP
3aβ – HSQC (600 MHz, CDCl3)
33
2.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.01H (ppm)
40
50
60
70
80
90
100
110
120
130
140
150
160
170
13
C (
ppm
)
OBnOBnOBnO OBn
OPMP
3aβ – HMBC (600 MHz, CDCl3)
34
-0.50.51.52.53.54.55.56.57.58.59.510.511.51H (ppm)
1.1
21
.08
1.1
11
.07
2.0
91
.10
1.0
61
.08
2.1
12
.07
1.0
3
1.0
0
3.1
12
.02
20
.71
3.7
03
.71
3.7
33
.74
3.8
23
.83
3.8
64
.00
4.0
14
.01
4.1
64
.17
4.1
74
.19
4.4
84
.51
4.5
74
.60
4.6
74
.70
4.7
44
.75
4.8
34
.84
4.9
34
.96
5.6
45
.64
7.0
37
.04
7.0
57
.05
7.0
67
.07
7.0
77
.08
7.2
17
.21
7.2
27
.22
7.2
37
.27
7.2
87
.29
7.3
07
.31
7.3
17
.32
7.3
27
.33
7.3
37
.34
7.3
57
.35
7.3
67
.36
7.3
77
.38
7.3
87
.39
7.4
07
.40
7.4
27
.42
7.4
37
.44
7.4
47
.45
OBnOBnOBnO OBn
OPh
3bα – 1H NMR (400 MHz, CDCl3)
35
203040506070809010011012013014015016017018019020013C (ppm)
69
.17
2.5
72
.67
2.9
73
.47
4.7
74
.97
5.3
76
.8 C
DC
l37
7.2
CD
Cl3
77
.5 C
DC
l38
0.1
96
.51
16
.61
22
.31
27
.51
27
.71
27
.71
27
.81
27
.81
27
.91
28
.01
28
.11
28
.41
28
.41
28
.51
28
.51
29
.61
38
.31
38
.51
38
.61
38
.6
15
6.4
OBnOBnOBnO OBn
OPh
3bα – 13C NMR (101 MHz, CDCl3)
36
3.03.23.43.63.84.04.24.44.64.85.05.25.45.65.86.06.26.46.66.87.07.27.47.61H (ppm)
3.0
3.5
4.0
4.5
5.0
5.5
6.0
6.5
7.0
7.5
1H
(ppm
)
OBnOBnOBnO OBn
OPh
3bα – COSY (400 MHz, CDCl3)
37
3.03.23.43.63.84.04.24.44.64.85.05.25.45.65.86.06.26.46.66.87.07.27.47.67.81H (ppm)
50
60
70
80
90
100
110
120
130
140
150
13
C (
ppm
)
OBnOBnOBnO OBn
OPh
3bα – HSQC (400 MHz, CDCl3)
38
2.62.83.03.23.43.63.84.04.24.44.64.85.05.25.45.65.86.06.26.46.66.87.07.27.47.61H (ppm)
50
60
70
80
90
100
110
120
130
140
150
160
170
180
13
C (
ppm
)
OBnOBnOBnO OBn
OPh
3bα – HSQC (400 MHz, CDCl3)
39
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.011.51H (ppm)
1.7
51
.00
1.0
71
.16
0.9
1
4.6
31
.00
1.8
20
.95
2.9
22
.78
15
.39
1.7
2
3.6
03
.61
3.6
23
.62
3.7
83
.79
3.8
73
.87
3.9
63
.97
4.1
04
.10
4.5
34
.55
4.5
54
.57
4.5
84
.59
4.6
04
.61
4.6
24
.93
4.9
44
.99
5.0
05
.02
5.0
95
.11
7.0
27
.02
7.0
37
.03
7.0
57
.05
7.2
27
.23
7.2
47
.24
7.2
57
.26
7.2
67
.27
7.2
77
.27
7.2
87
.28
7.2
87
.28
7.2
97
.29
7.2
97
.30
7.3
07
.30
7.3
07
.31
7.3
27
.32
7.3
27
.33
7.3
37
.34
7.3
57
.53
7.5
37
.53
7.5
47
.55
3bβ – 1H NMR (600 MHz, CDCl3)
OBnOBnOBnO OBn
OPh
40
3040506070809010011012013014015016017018019013C (ppm)
69
.77
1.9
73
.67
4.3
74
.97
5.3
76
.37
6.9
cdcl3
77
.2 c
dcl3
77
.4 c
dcl3
82
.3
99
.51
16
.51
22
.51
27
.61
27
.71
27
.81
27
.81
27
.91
28
.11
28
.31
28
.41
28
.51
28
.61
28
.61
29
.6
13
8.2
13
8.4
13
8.6
13
8.7
15
7.5
3bβ – 13C NMR (151 MHz, CDCl3)
OBnOBnOBnO OBn
OPh
41
3.03.23.43.63.84.04.24.44.64.85.05.25.45.65.86.06.26.46.66.87.07.27.47.67.88.01H (ppm)
2.5
3.0
3.5
4.0
4.5
5.0
5.5
6.0
6.5
7.0
7.5
8.0
1H
(ppm
)
3bβ – COSY (600 MHz, CDCl3)
OBnOBnOBnO OBn
OPh
42
2.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.51H (ppm)
60
70
80
90
100
110
120
130
140
150
160
13
C (
ppm
)
3bβ – HSQC (600 MHz, CDCl3)
OBnOBnOBnO OBn
OPh
43
3.23.43.63.84.04.24.44.64.85.05.25.45.65.86.06.26.46.66.87.07.27.47.67.81H (ppm)
70
80
90
100
110
120
130
140
150
160
13
C (
ppm
)
3bβ – HMBC (600 MHz, CDCl3)
OBnOBnOBnO OBn
OPh
44
-1012345678910111213141H (ppm)
6.8
69
.31
6.8
63
.32
2.2
11
.19
0.1
10
.08
1.1
91
.05
1.2
71
.47
0.1
0
3.2
32
.38
2.0
22
.03
2.0
52
.18
2.1
92
.19
4.0
54
.06
4.0
94
.10
4.1
04
.11
4.1
14
.12
4.1
34
.25
4.2
54
.25
4.2
64
.28
4.2
94
.29
4.3
04
.30
5.2
25
.22
5.3
45
.34
5.3
65
.39
5.3
95
.44
5.4
45
.44
5.4
55
.52
5.5
35
.55
5.5
65
.58
5.5
87
.03
7.0
37
.04
7.0
57
.05
7.0
67
.06
7.0
77
.07
7.0
87
.08
7.0
97
.09
7.0
97
.09
7.1
07
.26
cdcl3
7.2
77
.28
7.2
87
.29
7.3
07
.30
7.3
17
.31
7.3
27
.32
3c – 1H NMR (400 MHz, CDCl3)
OAcOAcOAcO OAc
OPh
45
-10010203040506070809010011012013014015016017018019020021022023013C (ppm)
20
.82
0.8
20
.82
1.0
29
.8
62
.36
6.1
69
.06
9.3
69
.67
6.8
cdcl3
77
.2 c
dcl3
77
.5 c
dcl3
95
.9
11
6.6
12
3.1
12
9.7
15
5.7
16
9.8
17
0.0
17
0.1
17
0.6
3c – 13C NMR (100 MHz, CDCl3)
OAcOAcOAcO OAc
OPh
46
3c– COSY (400 MHz, CDCl3)
2.02.53.03.54.04.55.05.56.06.57.07.58.0
1H (ppm)
2.0
2.5
3.0
3.5
4.0
4.5
5.0
5.5
6.0
6.5
7.0
7.5
1H
(ppm
)
OAcOAcOAcO OAc
OPh
47
-10123456789101112131H (ppm)
0
10
20
30
40
50
60
70
80
90
100
110
120
130
140
150
160
170
180
13
C (
ppm
)
3c– HSQC (400 MHz, CDCl3)
OAcOAcOAcO OAc
OPh
48
0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.51H (ppm)
20
30
40
50
60
70
80
90
100
110
120
130
140
150
160
170
180
13
C (
ppm
)
3c– HMBC (400 MHz, CDCl3)
OAcOAcOAcO OAc
OPh
49
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.011.51H (ppm)
2.8
12
.85
3.0
22
.82
1.0
51
.04
1.0
1
1.0
11
.00
0.7
61
.24
3.0
5
2.1
5
2.0
42
.04
2.0
52
.06
4.0
44
.05
4.0
74
.08
4.1
14
.12
4.1
24
.12
4.1
34
.14
4.1
44
.15
4.1
54
.16
4.2
34
.24
4.2
64
.27
5.0
25
.03
5.0
55
.06
5.1
35
.15
5.1
65
.18
5.6
85
.71
5.7
15
.73
5.7
47
.04
7.0
57
.05
7.0
67
.06
7.0
67
.07
7.0
77
.07
7.0
87
.08
7.0
87
.08
7.0
97
.09
7.1
07
.10
7.1
07
.10
7.2
6 c
dcl3
7.2
87
.29
7.2
97
.29
7.3
07
.31
7.3
17
.32
7.3
27
.33
7.3
37
.33
O
OPhAcOAcO
AcO
OAc
3dα – 1H NMR (400 MHz, CDCl3)
50
-10010203040506070809010011012013014015016017018019020021022023013C (ppm)
20
.82
0.8
20
.82
0.9
61
.86
8.1
68
.57
0.3
70
.67
6.8
cdcl3
77
.2 c
dcl3
77
.5 c
dcl3
94
.4
11
6.8
12
3.2
12
9.8
15
6.2
16
9.7
17
0.3
17
0.7
O
OPhAcOAcO
AcO
OAc
3dα – 13C NMR (100 MHz, CDCl3)
51
1.01.52.02.53.03.54.04.55.05.56.06.57.07.58.01H (ppm)
1.0
1.5
2.0
2.5
3.0
3.5
4.0
4.5
5.0
5.5
6.0
6.5
7.0
7.5
8.0
1H
(ppm
)
O
OPhAcOAcO
AcO
OAc
3dα – COSY (400 MHz, CDCl3)
52
1.01.52.02.53.03.54.04.55.05.56.06.57.07.58.01H (ppm)
10
20
30
40
50
60
70
80
90
100
110
120
130
140
150
160
170
13
C (
ppm
)
O
OPhAcOAcO
AcO
OAc
3dα – HSQC (400 MHz, CDCl3)
53
1.01.52.02.53.03.54.04.55.05.56.06.57.07.58.01H (ppm)
20
30
40
50
60
70
80
90
100
110
120
130
140
150
160
170
180
190
13
C (
ppm
)
O
OPhAcOAcO
AcO
OAc
3dα – HMBC (400 MHz, CDCl3)
54
-1.00.01.02.03.04.05.06.07.08.09.010.011.01H (ppm)
8.7
41
0.0
81
1.5
77
.13
1.0
31
.07
1.0
6
1.0
71
.08
2.3
8
2.1
11
.10
5.7
8
2.0
42
.05
2.0
62
.06
2.0
73
.84
3.8
43
.85
3.8
63
.86
3.8
73
.87
3.8
84
.15
4.1
64
.18
4.1
94
.27
4.2
84
.30
4.3
15
.07
5.0
85
.08
5.0
95
.09
5.0
95
.15
5.1
75
.19
5.1
95
.27
5.2
75
.28
5.2
85
.29
5.2
95
.30
5.3
05
.30
6.9
86
.98
6.9
86
.99
7.0
07
.00
7.0
07
.00
7.0
17
.06
7.0
77
.07
7.0
77
.08
7.0
97
.09
7.1
07
.26
cdcl3
7.2
87
.28
7.2
87
.29
7.3
07
.30
7.3
07
.31
7.3
27
.32
OOPh
AcOAcO
AcO
OAc
3dβ – 1H NMR (400 MHz, CDCl3)
55
OOPh
AcOAcO
AcO
OAc
-10010203040506070809010011012013014015016017018019020021022023013C (ppm)
20
.72
0.8
20
.82
0.8
62
.16
8.5
71
.47
2.2
72
.97
6.8
cdcl3
77
.2 c
dcl3
77
.5 c
dcl3
99
.3
11
7.1
12
3.5
12
9.7
15
7.0
16
9.4
16
9.5
17
0.4
17
0.7
3dβ – 13C NMR (100 MHz, CDCl3)
56
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.51H (ppm)
0
1
2
3
4
5
6
7
8
1H
(ppm
)
OOPh
AcOAcO
AcO
OAc
3dβ – COSY (400 MHz, CDCl3)
57
0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.51H (ppm)
20
30
40
50
60
70
80
90
100
110
120
130
140
150
160
170
13
C (
ppm
)
OOPh
AcOAcO
AcO
OAc
3dβ – HSQC (400 MHz, CDCl3)
58
OOPh
AcOAcO
AcO
OAc
3dβ – HMBC (400 MHz, CDCl3)
-1012345678910111213
f2 (ppm)
0
20
40
60
80
100
120
140
160
180
200
220
f1 (
ppm
)
59
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.01H (ppm)
2.7
72
.80
2.7
92
.92
2.1
3
1.0
2
0.9
91
.03
0.9
81
.00
3.0
1
2.0
4
1.9
32
.03
2.0
72
.17
4.0
44
.05
4.0
64
.08
4.0
84
.09
4.1
04
.11
4.1
24
.13
4.1
44
.34
4.3
44
.34
4.3
44
.35
4.3
54
.36
4.3
64
.37
4.3
74
.37
5.2
75
.28
5.3
05
.30
5.5
25
.52
5.5
35
.53
5.5
65
.57
5.5
95
.60
5.7
75
.78
7.0
47
.04
7.0
47
.05
7.0
57
.05
7.0
67
.06
7.0
67
.06
7.0
77
.07
7.0
77
.07
7.0
87
.08
7.2
6 C
DC
l3-in
sert
7.2
87
.29
7.3
07
.30
7.3
07
.31
7.3
17
.31
7.3
27
.32
7.3
23eα – 1H NMR (400 MHz, CDCl3)
O
OPhAcOAcO
AcO OAc
60
-10010203040506070809010011012013014015016017018019020021022023013C (ppm)
20
.72
0.8
20
.82
0.9
61
.66
7.3
67
.76
7.9
68
.07
6.9
77
.27
7.4
95
.0
11
6.9
12
3.1
12
9.8
15
6.4
17
0.2
17
0.3
17
0.4
17
0.5
3eα – 13C NMR (126 MHz, CDCl3)
O
OPhAcOAcO
AcO OAc
61
3eα – COSY (400 MHz, CDCl3)
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5
1H (ppm)
0
1
2
3
4
5
6
7
8
1H
(ppm
)
O
OPhAcOAcO
AcO OAc
62
0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.01H (ppm)
0
10
20
30
40
50
60
70
80
90
100
110
120
130
140
150
13
C (
ppm
)
3eα – HSQC (500 MHz, CDCl3)
O
OPhAcOAcO
AcO OAc
63
OOPh
AcOAcO
AcO OAc
-1.00.01.02.03.04.05.06.07.08.09.010.011.012.01H (ppm)
0.5
32
.93
0.9
80
.73
2.9
53
.58
1.2
63
.27
1.3
81
.01
1.0
50
.18
0.9
91
.02
0.4
21
.01
1.0
5
0.1
9
2.1
01
.13
2.2
4
2.0
02
.01
2.0
22
.04
2.0
42
.06
2.0
72
.07
2.1
62
.16
2.1
82
.18
2.1
94
.06
4.0
64
.06
4.0
64
.07
4.0
74
.14
4.1
54
.16
4.1
84
.22
4.2
34
.24
4.2
55
.04
5.0
55
.09
5.1
05
.12
5.1
25
.33
5.3
45
.34
5.4
55
.45
5.4
65
.46
5.4
75
.49
5.4
95
.51
6.9
96
.99
7.0
07
.00
7.0
17
.01
7.0
17
.01
7.0
67
.07
7.0
77
.07
7.0
87
.09
7.2
6 c
dcl3
7.2
87
.28
7.2
97
.30
7.3
07
.30
7.3
07
.31
7.3
13eβ – 1H NMR (500 MHz, CDCl3)
64
-10010203040506070809010011012013014015016017018019020021022013C (ppm)
20
.72
0.8
20
.82
0.9
61
.56
7.0
68
.87
1.0
71
.17
6.9
cdcl3
77
.2 c
dcl3
77
.4 c
dcl3
99
.8
11
7.1
12
3.5
12
9.7
15
7.1
16
9.5
17
0.3
17
0.4
17
0.5
OOPh
AcOAcO
AcO OAc
3eβ – 13C NMR (126 MHz, CDCl3)
65
1.52.02.53.03.54.04.55.05.56.06.57.07.58.01H (ppm)
1.5
2.0
2.5
3.0
3.5
4.0
4.5
5.0
5.5
6.0
6.5
7.0
7.5
1H
(ppm
)
OOPh
AcOAcO
AcO OAc
3eβ – COSY (500 MHz, CDCl3)
66
1.01.52.02.53.03.54.04.55.05.56.06.57.07.51H (ppm)
10
20
30
40
50
60
70
80
90
100
110
120
130
140
150
160
170
180
13
C (
ppm
)
OOPh
AcOAcO
AcO OAc
3eβ – HSQC (400 MHz, CDCl3)
67
-10123456789101112131H (ppm)
0
20
40
60
80
100
120
140
160
180
200
220
13
C (
ppm
)
OOPh
AcOAcO
AcO OAc
3eβ – HMBC (400 MHz, CDCl3)
68
-1.00.01.02.03.04.05.06.07.08.09.010.011.01H (ppm)
0.3
35
.38
0.8
71
.03
0.9
70
.26
1.2
15
.55
0.4
11
.00
1.0
40
.47
5.1
92
7.5
84
.12
3.6
93
.71
3.7
23
.72
3.7
33
.73
3.7
43
.74
3.7
53
.78
3.8
04
.19
4.2
04
.22
4.2
54
.28
4.7
24
.75
4.8
64
.86
4.8
94
.89
4.9
04
.93
4.9
54
.98
4.9
85
.01
5.1
55
.17
5.4
55
.46
5.5
85
.61
7.0
67
.07
7.0
87
.09
7.2
87
.28
7.2
97
.30
7.3
07
.31
7.3
27
.33
7.3
47
.34
7.3
57
.36
7.3
77
.37
7.3
87
.39
7.3
97
.40
7.4
17
.42
7.4
27
.44
7.4
47
.49
7.4
97
.50
7.5
17
.51
7.5
27
.53
O
OPhBnOBnOOOPh
3f – 1H NMR (400 MHz, CDCl3)
69
-10010203040506070809010011012013014015016017018019020021022023013C (ppm)
14
.32
2.8
26
.92
9.5
30
.33
2.1
63
.36
6.4
68
.96
9.0
73
.87
5.3
75
.57
5.7
76
.8 c
dcl3
77
.2 c
dcl3
77
.5 c
dcl3
78
.67
9.3
81
.08
1.4
81
.98
2.2
96
.61
01
.41
01
.51
02
.21
17
.11
17
.11
22
.81
23
.21
26
.21
26
.21
27
.81
27
.81
27
.91
28
.01
28
.11
28
.21
28
.41
28
.41
28
.51
28
.51
28
.61
29
.11
29
.11
29
.71
29
.81
37
.41
37
.51
38
.21
38
.91
56
.71
57
.2
O
OPhBnOBnOOOPh
3f – 13C NMR (100 MHz, CDCl3)
70
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.01H (ppm)
0
1
2
3
4
5
6
7
8
9
1H
(ppm
)
O
OPhBnOBnOOOPh
3f – COSY (400 MHz, CDCl3)
71
2.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.51H (ppm)
10
20
30
40
50
60
70
80
90
100
110
120
130
140
150
160
170
13
C (
ppm
)
O
OPhBnOBnOOOPh
3f – HSQC (400 MHz, CDCl3)
72
1.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.51H (ppm)
0
10
20
30
40
50
60
70
80
90
100
110
120
130
140
150
160
170
13
C (
ppm
)
O
OPhBnOBnOOOPh
3f – HMBC (400 MHz, CDCl3)
73
-0.50.51.52.53.54.55.56.57.58.59.510.511.51H (ppm)
2.4
4
2.3
3
3.7
2
7.1
0
1.0
91
.18
7.4
23
.48
2.2
41
.18
1.0
0
7.0
62
.29
31
.89
3.5
93
.60
3.6
13
.75
3.7
73
.78
3.7
83
.80
3.8
23
.83
4.4
44
.47
4.5
54
.56
4.5
74
.59
4.6
04
.62
4.6
24
.65
4.6
74
.72
4.7
44
.75
4.7
54
.92
4.9
34
.95
4.9
57
.00
7.0
27
.04
7.0
47
.04
7.0
67
.06
7.0
77
.08
7.0
87
.20
7.2
17
.26
CD
Cl3
7.2
77
.27
7.2
87
.28
7.2
97
.29
7.3
07
.30
7.3
17
.31
7.3
27
.32
7.3
37
.33
7.3
47
.34
7.3
57
.35
7.3
67
.36
7.3
67
.37
7.3
77
.38
7.3
87
.39
O
OPhBnO
BnOBnO
3g –1H NMR (400 MHz, CDCl3)
74
-10010203040506070809010011012013014015016017018019020021022013C (ppm)
36
.77
1.6
71
.77
2.1
73
.57
3.6
75
.17
5.2
75
.67
6.8
cdcl3
77
.2 c
dcl3
77
.5 c
dcl3
77
.67
8.0
78
.17
9.3
95
.99
7.8
11
6.6
11
6.7
12
2.0
12
2.4
12
7.6
12
7.7
12
7.7
12
7.8
12
7.8
12
7.8
12
7.9
12
7.9
12
7.9
12
8.0
12
8.0
12
8.1
12
8.4
12
8.4
12
8.5
12
8.5
12
8.6
12
8.6
12
9.5
12
9.5
13
8.2
13
8.3
13
8.4
13
8.4
13
8.6
13
8.7
15
6.6
15
7.3
O
OPhBnO
BnOBnO
3g –13C-NMR (101 MHz, CDCl3)
75
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.51H (ppm)
0
1
2
3
4
5
6
7
8
1H
(ppm
)
O
OPhBnO
BnOBnO
3g – COSY (400 MHz, CDCl3)
76
0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.01H (ppm)
20
30
40
50
60
70
80
90
100
110
120
130
140
150
160
13
C (
ppm
)
O
OPhBnO
BnOBnO
3g – HSQC (400 MHz, CDCl3)
77
-1.00.01.02.03.04.05.06.07.08.09.010.011.012.01H (ppm)
2.1
3
1.0
52
.11
6.2
9
1.0
0
1.1
21
.95
17
.39
3.6
33
.64
3.6
53
.66
3.6
73
.67
3.6
83
.68
3.6
94
.12
4.1
34
.13
4.1
44
.33
4.3
44
.34
4.3
44
.35
4.3
64
.36
4.3
74
.37
4.5
34
.54
4.5
54
.57
4.5
74
.58
4.6
04
.61
4.6
24
.63
4.6
44
.65
5.7
45
.74
7.0
17
.01
7.0
37
.04
7.0
57
.07
7.0
87
.09
7.0
97
.26
7.2
87
.29
7.3
07
.32
7.3
27
.32
7.3
37
.33
7.3
57
.35
7.3
67
.37
7.3
87
.38
7.3
9O
OPh
OBn
OBn
BnO
3hα – 1H NMR (400 MHz, CDCl3)
78
-10010203040506070809010011012013014015016017018019020021022023013C (ppm)
69
.47
2.3
72
.47
3.5
76
.8 c
dcl3
77
.2 c
dcl3
77
.5 c
dcl3
81
.78
3.3
88
.61
04
.71
16
.91
22
.21
27
.81
27
.91
28
.01
28
.11
28
.11
28
.51
28
.51
28
.61
29
.51
37
.51
38
.01
38
.2
15
6.7
O
OPh
OBn
OBn
BnO
3hα – 13C NMR (100 MHz, CDCl3)
79
-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.01H (ppm)
-1
0
1
2
3
4
5
6
7
8
9
1H
(ppm
)
O
OPh
OBn
OBn
BnO
3hα – COSY (400 MHz, CDCl3)
80
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.01H (ppm)
20
30
40
50
60
70
80
90
100
110
120
130
140
150
160
170
13
C (
ppm
)
O
OPh
OBn
OBn
BnO
3hα – HSQC (400 MHz, CDCl3)
81
2.02.53.03.54.04.55.05.56.06.57.07.58.08.51H (ppm)
50
60
70
80
90
100
110
120
130
140
150
160
170
13
C (
ppm
)
O
OPh
OBn
OBn
BnO
3hα – HMBC (400 MHz, CDCl3)
82
-1.00.01.02.03.04.05.06.07.08.09.010.011.012.01H (ppm)
2.0
5
3.1
72
.07
4.0
8
1.0
0
3.0
4
17
.71
3.4
93
.51
4.1
44
.16
4.1
74
.18
4.1
94
.19
4.2
04
.23
4.2
44
.24
4.2
64
.35
4.3
84
.40
4.4
34
.55
4.5
84
.60
4.6
04
.63
4.6
34
.66
4.6
95
.50
5.5
16
.96
6.9
86
.98
7.0
07
.00
7.0
07
.01
7.0
27
.02
7.0
37
.03
7.1
27
.13
7.1
47
.15
7.1
57
.16
7.1
77
.17
7.1
87
.19
7.1
97
.20
7.2
27
.22
7.2
27
.23
7.2
47
.24
7.2
57
.26
7.2
77
.27
7.2
87
.28
7.2
97
.30
7.3
07
.31
7.3
27
.32
3hβ – 1H NMR (400 MHz, CDCl3)
OOPhBnO
OBn
BnO
83
-10010203040506070809010011012013014015016017018019020021022023013C (ppm)
72
.47
2.6
72
.87
3.5
76
.8 c
dcl3
77
.2 c
dcl3
77
.5 c
dcl3
81
.48
3.2
84
.29
9.2
11
7.1
12
2.3
12
7.6
12
7.7
12
7.8
12
7.9
12
8.1
12
8.2
12
8.4
12
8.5
12
8.6
12
9.6
13
7.6
13
8.2
13
8.3
15
7.2
3hβ – 13C NMR (100 MHz, CDCl3)
OOPhBnO
OBn
BnO
84
2.42.62.83.03.23.43.63.84.04.24.44.64.85.05.25.45.65.86.06.26.46.66.87.07.27.47.67.81H (ppm)
3.0
3.5
4.0
4.5
5.0
5.5
6.0
6.5
7.0
7.5
1H
(ppm
)
3hβ – COSY (400 MHz, CDCl3)
OOPhBnO
OBn
BnO
85
1.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.01H (ppm)
20
30
40
50
60
70
80
90
100
110
120
130
140
150
160
13
C (
ppm
)
3hβ – HSQC (400 MHz, CDCl3)
OOPhBnO
OBn
BnO
86
-10123456789101112131H (ppm)
0
20
40
60
80
100
120
140
160
180
200
220
13
C (
ppm
)
3hβ – HMBC (400 MHz, CDCl3)
OOPhBnO
OBn
BnO
87
-2-1012345678910111213141H (ppm)
6.4
93
.10
3.0
8
1.0
82
.18
1.0
51
.03
1.0
6
1.0
0
3.1
1
2.0
3
1.3
71
.38
1.3
91
.43
1.5
23
.97
3.9
83
.99
4.0
04
.07
4.0
84
.08
4.0
94
.09
4.1
04
.11
4.4
14
.42
4.4
24
.43
4.4
34
.44
4.4
44
.45
4.8
74
.88
4.9
14
.92
4.9
24
.93
5.6
46
.98
6.9
96
.99
7.0
07
.00
7.0
07
.00
7.0
07
.01
7.0
17
.01
7.0
17
.02
7.0
27
.03
7.0
37
.03
7.2
77
.27
7.2
87
.28
7.2
87
.28
7.2
97
.29
7.2
97
.30
7.3
07
.30
7.3
1
3i – 1H NMR (500 MHz, CDCl3)
O
OPh
OO
Me Me
O OMe Me
88
3i – 13C NMR (126 MHz, CDCl3)
-100102030405060708090100110120130140150160170180190200210220
13C (ppm)
24
.82
5.4
26
.12
7.1
67
.17
3.1
76
.9 c
dcl3
77
.2 c
dcl3
77
.4 c
dcl3
79
.78
1.3
85
.6
10
5.0
10
9.5
11
3.1
11
6.8
12
2.4
12
9.6
15
6.4
O
OPh
OO
Me Me
O OMe Me
89
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.01H (ppm)
0
1
2
3
4
5
6
7
8
1H
(ppm
)
3i – COSY (500 MHz, CDCl3)
O
OPh
OO
Me Me
O OMe Me
90
3i – HSQC (500 MHz, CDCl3)
-2-101234567891011121314
1H (ppm)
0
10
20
30
40
50
60
70
80
90
100
110
120
130
140
150
160
170
180
13
C (
ppm
)
O
OPh
OO
Me Me
O OMe Me
91
-2-101234567891011121314f2 (ppm)
0
20
40
60
80
100
120
140
160
180
200
220
f1 (
ppm
)
3i – HMBC (500 MHz, CDCl3)
O
OPh
OO
Me Me
O OMe Me
92
-1.00.01.02.03.04.05.06.07.08.09.010.011.012.01H (ppm)
6.5
73
.71
3.5
4
3.3
71
.14
2.2
31
.11
1.0
71
.18
1.0
0
2.1
82
.25
1.3
61
.37
1.4
31
.50
3.7
23
.74
3.7
63
.97
3.9
83
.99
4.0
04
.08
4.0
84
.09
4.0
94
.10
4.1
14
.40
4.4
14
.41
4.4
24
.42
4.4
34
.43
4.4
44
.83
4.8
44
.89
4.9
04
.90
4.9
15
.51
6.7
96
.80
6.8
16
.81
6.8
26
.83
6.9
26
.92
6.9
36
.94
6.9
46
.95
7.2
6
3k – 1H NMR (500 MHz, CDCl3)
O
OPMP
OO
Me Me
O OMe Me
93
-10010203040506070809010011012013014015016017018019020021022013C (ppm)
24
.72
5.3
26
.12
7.0
55
.7
67
.17
3.1
76
.9 c
dcl3
77
.2 c
dcl3
77
.4 c
dcl3
79
.78
1.1
85
.5
10
5.9
10
9.5
11
3.0
11
4.7
11
8.2
15
0.3
15
5.1
3k – 13C NMR (126 MHz, CDCl3)
O
OPMP
OO
Me Me
O OMe Me
94
1.01.52.02.53.03.54.04.55.05.56.06.57.07.51H (ppm)
1.0
1.5
2.0
2.5
3.0
3.5
4.0
4.5
5.0
5.5
6.0
6.5
7.0
7.5
1H
(ppm
)
3k – COSY (500 MHz, CDCl3)
O
OPMP
OO
Me Me
O OMe Me
95
-1.00.01.02.03.04.05.06.07.08.09.010.011.01H (ppm)
6.4
73
.31
3.2
6
3.1
71
.06
2.1
51
.04
1.0
51
.09
1.0
1
3.0
8
1.0
5
1.3
71
.39
1.4
31
.51
3.7
73
.78
3.7
93
.98
3.9
94
.00
4.0
04
.06
4.0
74
.08
4.0
84
.08
4.0
84
.09
4.1
04
.11
4.4
14
.41
4.4
24
.42
4.4
34
.43
4.4
34
.44
4.8
54
.86
4.9
04
.91
4.9
14
.92
5.6
26
.56
6.5
66
.57
6.5
76
.57
6.5
86
.58
6.5
96
.59
6.5
96
.60
6.6
06
.61
6.6
16
.62
6.6
27
.15
7.1
57
.16
7.1
67
.17
7.1
77
.18
7.1
97
.19
7.1
97
.26
3l – 1H NMR (500 MHz, CDCl3)
O
O
OO
Me Me
O OMe Me
OMe
96
3l – 13C NMR (126 MHz, CDCl3)
-100102030405060708090100110120130140150160170180190200210220
13C (ppm)
24
.72
5.4
26
.12
7.1
55
.4
67
.17
3.1
76
.9 c
dcl3
77
.2 c
dcl3
77
.4 c
dcl3
79
.78
1.3
85
.6
10
3.0
10
5.0
10
8.1
10
8.9
10
9.5
11
3.1
13
0.0
15
7.6
16
0.9
O
O
OO
Me Me
O OMe Me
OMe
97
-2.0-1.00.01.02.03.04.05.06.07.08.09.01H (ppm)
-2
-1
0
1
2
3
4
5
6
7
8
9
1H
(ppm
)
3l – COSY (500 MHz, CDCl3)
O
O
OO
Me Me
O OMe Me
OMe
98
-1.00.01.02.03.04.05.06.07.08.09.010.011.012.01H (ppm)
2.5
33
.39
3.2
23
.35
6.1
2
1.0
62
.10
1.0
2
1.0
50
.99
1.0
0
1.9
80
.97
1.3
71
.38
1.4
41
.52
2.2
84
.00
4.0
04
.01
4.0
24
.06
4.0
74
.08
4.0
94
.10
4.1
04
.12
4.4
14
.42
4.4
34
.43
4.4
34
.44
4.4
44
.45
4.8
44
.85
4.8
94
.90
4.9
04
.91
4.9
25
.62
6.6
46
.67
7.2
6
3m – 1H NMR (500 MHz, CDCl3)�
O
O
OO
Me Me
O OMe Me
Me
Me
99
-10010203040506070809010011012013014015016017018019020021022013C (ppm)
21
.52
4.7
25
.42
6.1
27
.0
67
.07
3.1
76
.9 c
dcl3
77
.2 c
dcl3
77
.4 c
dcl3
79
.78
1.2
85
.6
10
4.9
10
9.5
11
3.0
11
4.4
12
4.1
13
9.4
15
6.4
3m – 13C NMR (126 MHz, CDCl3)�
O
O
OO
Me Me
O OMe Me
Me
Me
100
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.51H (ppm)
-1
0
1
2
3
4
5
6
7
1H
(ppm
)
3m – COSY (500 MHz, CDCl3)�
O
O
OO
Me Me
O OMe Me
Me
Me
101
-1.00.01.02.03.04.05.06.07.08.09.010.011.012.01H (ppm)
5.7
42
.92
2.8
8
1.0
52
.03
1.0
4
1.0
21
.11
1.0
3
2.0
2
1.0
81
.95
1.9
9
1.3
71
.39
1.4
31
.52
3.9
63
.97
3.9
83
.99
4.0
64
.07
4.0
84
.08
4.0
84
.09
4.1
04
.11
4.4
14
.42
4.4
24
.42
4.4
34
.43
4.4
44
.45
4.8
64
.87
4.9
14
.91
4.9
24
.92
5.1
45
.15
5.1
75
.17
5.6
05
.60
5.6
15
.61
5.6
35
.65
5.6
55
.65
5.6
66
.63
6.6
56
.67
6.6
96
.94
6.9
46
.95
6.9
56
.96
6.9
76
.97
7.2
67
.31
7.3
27
.32
7.3
37
.34
7.3
47
.35
7.3
5
3n – 1H NMR (500 MHz, CDCl3)��
O
O
OO
Me Me
O OMe Me
102
-10010203040506070809010011012013014015016017018019020021022013C (ppm)
24
.72
5.3
26
.12
7.1
67
.07
3.1
76
.9 c
dcl3
77
.2 c
dcl3
77
.4 c
dcl3
79
.78
1.3
85
.6
10
5.0
10
9.5
11
2.5
11
3.1
11
6.7
12
7.5
13
2.0
13
6.2
15
6.1
3n – 13C NMR (126 MHz, CDCl3)��
O
O
OO
Me Me
O OMe Me
103
1.01.52.02.53.03.54.04.55.05.56.06.57.07.51H (ppm)
1.0
1.5
2.0
2.5
3.0
3.5
4.0
4.5
5.0
5.5
6.0
6.5
7.0
7.5
1H
(ppm
)
3n – COSY (500 MHz, CDCl3)��
O
O
OO
Me Me
O OMe Me
104
0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.51H (ppm)
10
20
30
40
50
60
70
80
90
100
110
120
130
140
150
160
13
C (
ppm
)
3n – HSQC (500 MHz, CDCl3)��
O
O
OO
Me Me
O OMe Me
105
-1.00.01.02.03.04.05.06.07.08.09.010.011.012.01H (ppm)
6.4
03
.21
3.2
0
1.0
42
.14
1.0
3
1.0
10
.99
1.0
0
2.0
7
2.0
0
1.3
71
.42
1.5
03
.95
3.9
53
.96
3.9
74
.04
4.0
54
.06
4.0
64
.07
4.0
84
.09
4.1
04
.40
4.4
14
.41
4.4
14
.42
4.4
24
.43
4.4
44
.84
4.8
54
.89
4.9
04
.90
4.9
15
.57
6.9
16
.91
6.9
26
.93
6.9
36
.94
6.9
56
.95
7.2
17
.22
7.2
27
.23
7.2
47
.24
7.2
6
3o –1H NMR (500 MHz, CDCl3)
O
O
OO
Me Me
O OMe Me
Cl
106
-10010203040506070809010011012013014015016017018019020021022013C (ppm)
24
.72
5.3
26
.12
7.0
67
.07
3.1
76
.9 c
dcl3
77
.2 c
dcl3
77
.4 c
dcl3
79
.78
1.4
85
.5
10
5.2
10
9.5
11
3.2
11
8.1
12
7.4
12
9.5
15
4.9
3o –13C NMR (126 MHz, CDCl3)
O
O
OO
Me Me
O OMe Me
Cl
107
1.01.52.02.53.03.54.04.55.05.56.06.57.07.51H (ppm)
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
4.5
5.0
5.5
6.0
6.5
7.0
7.5
8.0
1H
(ppm
)
O
O
OO
Me Me
O OMe Me
Cl
3o – COSY (500 MHz, CDCl3)
