Supporting Information Cascade Reactions with Grubbs’ Catalyst and AD-mix-α/β Using PDMS Thimbles Martin T. Mwangi, Michael D. Schulz, Ned B. Bowden* Chemistry Department University of Iowa Iowa City, IA 52242 e-mail:
[email protected] Materials. Grubbs’ second-generation catalyst was purchased from Aldrich and maintained in a glove box under nitrogen. Substrates and reagents were purchased from Acros/Fisher (4methoxystyrene, styrene, 4-methylstyrene, 1-chlorobutane, N-methylimidazole, hexafluorophosphoric acid, methane sulfonamide, europium tris[3-(heptafluoropropylhydroxymethylene)-(+)-camphorate] (Eu(hfc)3), diallyl sulfide, butyl acrylate, ethyl acrylate, diallylamine, and sodium sulfite) or from Aldrich (diethyl diallylmalonate, 1,6-heptadien-4-ol, AD-mix-α, ADmix-β, (R,R)- and (S,S)-1,2-diphenylethane-1,2-diol) and used as supplied. Organic solvents (except the ionic liquid) were purchased from Acros or Aldrich at the highest purity and used as supplied. The ionic liquid, 1-butyl-3-methylimidazolium hexafluorophosphate (BMIM), was prepared according to literature procedures.1,2 All solvents used for metathesis reactions were degassed and maintained under nitrogen. All solvent ratios are by volume (v/v) unless otherwise stated. Polydimethylsiloxane (PDMS) preparation kit (Sylgard 184) was purchased from Essex Brownell and used as supplied. PDMS thimbles were prepared according to literature.1 All olefin metathesis reactions were performed under a nitrogen atmosphere using either Schlenk flasks or a glove box.
S1
Characterization. 1H and 13C NMR spectra were recorded on a Bruker DPX 300 instrument using CDCl3 as solvent and TMS as an internal standard unless otherwise stated. For all compounds not reported in literature, a mass spectrum was run to obtain the molecular weight. Enantiomeric excesses (ee) were determined by running a 1H NMR spectrum of the pure products in presence of 0.65 molar equivalents Eu(hfc)3. Leaching of ruthenium and osmium across the thimble walls was determined by ICP-MS on a Varian Ultra mass 700 ICP-MS (EPA 200.8 heavy metal analysis protocol). (3S,4R)-diethyl 3,4-dihydroxycyclopentane-1,1-dicarboxylate. We provide the experimental procedure that was followed for the cascade reactions for this EtO2C
CO2Et
substrate. Any deviations from this method are given for all subsequent substrates. HO
OH
In a glove box, Grubbs’ second-generation catalyst (43 mg, 0.05 mmoles) was placed in a PDMS thimble contained in a Schlenk flask. The flask was sealed, removed from the glove box and placed under N2. Solvent mixture (1 mL of 1/1 CH2Cl2/BMIM) was added to the interior of the thimble followed by diethyl diallylmalonate (300 μL, 1.25 mmoles). The reaction mixture was allowed to stir at ambient conditions for 2 h. To the exterior of the thimble was added AD-mix-α (3.6 g, 0.0063 mmoles of osmium catalyst) and methane sulfonamide (0.238 g, 2.5 mmoles) in 10 mL of solvent (1/2/3 BMIM/H2O/acetone), and the reaction was allowed to stir vigorously for a further 36 h. To the reaction mixture on the exterior was added Na2SO3 (3.2 g, 25 mmoles). The product was extracted from the solvent on the interior and exterior with 3 x 50 mL Et2O, solvent was removed in vacuo, and the product was purified using a silica gel column eluting with 25% EtOAc in hexanes to give the target diol in 75 % yield. 1H NMR (CDCl3): δ 4.03-4.17 (m, 6H, overlapping signals), 3.47 (br S, 2H), 2.34 (m, 4H), 1.15-1.21 (m, 6H, overlapping triplets). 13
C NMR (CDCl3): δ 172.40, 172.12, 72.89, 61.75, 61.62, 56.34, 38.45, 30.89, 13.80, 13.77. Calcd
for C11H18O6 246.1103; Found, 247.1176 (M+1). S2
This reaction was repeated using 1/1 t-BuOH/H2Ofor the dihydroxylation step to give the target diol in 68% yield. The characterization was identical. (1S,2R)-4-phenythylcyclopentane-1,2-diol. Reaction of 4-benzyloxy heptaOBn
1,6-diene (0.51 g, 2.5 mmoles) with Grubbs’ second-generation catalyst (85 mg, 0.1 HO
OH
mmoles) for 4 h, followed by reaction of the subsequent product with site-isolated AD-
mix-α (7.2 g, 0.012 mmoles of osmium catalyst) for 19 h gave title compound in 82 % yield and 63% diastereoselectivity. NMR data agreed with those reported in literature.3 1H NMR (CDCl3): δ 7.40 (m, 5H), 4.52 (s, 0.8H), 4.47 (s, 1.2H), 4.23 (m, 1H), 4.18 (m, 1H), 3.38 (br s, 1.7 H), 3.04 (s, 0.4H), 2.01- 2.06 (m 4H). 13C NMR (CDCl3): δ 138.41, 137.84, 128.60, 128.53, 127.95, 127.93, 127.81, 127.73, 77.89, 77.64, 73.26, 72.65, 71.10, 71.02, 38.52, 38.43. (1S,2S)-Diphenylethane-1,2-diol. Reaction of styrene (0.13 g, 1.25 mmoles) with Grubbs’ second-generation catalyst (42.5 mg, 0.05 mmoles) for 6 h, followed by reaction OH
of the subsequent product with site-isolated AD-mix-α (1.75 g, 0.003 mmoles of OH
13
osmium) for 13 h, gave the title compound in 72% yield and 85% ee. The 1H and
C NMR spectra agreed with those reported in the literature.4,5 1H NMR (CDCl3): δ 7.23-7.25 (m,
3H), 7.12-7.15 (m, 2H), 4.72 (s, 1H), 2.87 (s, 1H)
13
C NMR (CDCl3): δ 128.11, 127.92, 126.90,
79.10.
S3
Figure 1. NMR spectra of the product from our cascade reaction (top) and the 1:2 mixture of pure (R,R) : (S,S)-isomers showing the resolution of the enantiomeric benzylic protons at 27.11 and 28.02 ppm. The ratio of these two peaks was used to determine the ee. To determine the enantiomeric excess, the product diol (8.8 mg, 0.041 mmoles) and Eu(hfc)3 (31.9 mg, 0.027 mmoles) were dissolved in CDCl3 in a glove box and mixed well. The mixture was then analyzed by 1H NMR spectroscopy and the ratio of the peaks at 28.02 and 27.11 ppm was used to determine the enantiomeric excess. To confirm the peak assignment, commercially available (R,R)- and (S,S)-diphenylethane-1,2-diol were used. A stock solution made of a mixture of the (R,R) isomer (21 mg, 0.098 mmoles) and the (S,S) isomer (39.5 mg, 0.184 mmoles) was prepared using 3 ml of CDCl3 in the glove box. To 1 ml of the stock was added Eu(hfc)3 (67 mg, 0.056 mmoles) and the mixture was analyzed by 1H NMR spectroscopy. Our 1H NMR spectra are given above (Figure 1). The data showed that we obtained the (S,S) enantiomer in our cascade reaction using AD-mix-α as previously reported.5,6 This result agreed with literature precedence. The chiral diols below were assigned by inference from this experiment and literature.5
S4
Similarly, the reaction was repeated using AD-mix-β for the dihydroxylation step to give the antipode in 72 % yield and >98% ee.
OH OH
35
30
25
20
15
PPM
Figure 2. NMR spectrum showing how we determined the ee for (1R,2R)-diphenylethane-1,2-diol. (1S,2S)-di-p-tolylethane-1,2-diol. Reaction of 4-methyl styrene (0.15g, 1.25 mmoles) with Grubbs’ second generation catalyst (42.5 mg, 0.05 mmoles) for 8 h, followed OH
by reaction of the subsequent product with site-isolated AD-mix-α (1.75 g, OH
0.003 mmoles of osmium) for 12 h gave the title compound in 86% yield and 84% ee. The 1H and 13
C NMR spectra agreed with those reported in the literature.4,7 1H NMR (CDCl3): δ 7.05 (m, 4H),
4.69 (s, 1H), 2.30 (s, 3H) CDCl3): δ 137.51, 136.96, 128.83, 126.82, 78.80, 21.14
S5
Figure 3. NMR spectrum showing how we determined the ee for the (1S,2S)-di-p-tolylethane-1,2diol. Similarly, the reaction was repeated using AD-mix-β for the dihydroxylation step to give the
13.429 13.407
27.263
35.236
antipode in 95 % yield and >98% ee.
OH
OH
35
30
25
20
15
PPM
Figure 4. NMR spectrum showing how we determined the ee for the (1S,2S)-di-p-tolylethane-1,2diol. S6
(1S,2S)-1,2-bis(4-methoxyphenyl) ethane-1,2-diol. Reaction of 4-methoxy styrene (0.34 g, OH
MeO
OH
OMe
2.5 mmoles) with Grubbs’ second generation catalyst (85 mg, 0.1 mmoles) for 6 h, followed by reaction of the subsequent product with
site-isolated AD-mix-α (7.2 g, 0.012 mmoles of osmium) for 12 h gave the title compound in 61% yield and 94% ee. The 1H and 13C NMR spectra agreed with those reported in the literature.7-9 1H NMR (CDCl3): δ 7.05 (d, 2H), 6.76 (d, 2H), 4.63 (s, 1H), 3.77 (s, 3H), 2.78 (br s, 1H) 13C NMR (CDCl3): δ 159.15, 132.04, 128.14, 113.46, 78.76, 55.17
Figure 5. NMR spectrum showing how we determined the ee for the (1S,2S)-1,2-bis(4methoxyphenyl) ethane-1,2-diol.
Similarly, the reaction was repeated using AD-mix-β for the dihydroxylation step to give the antipode in 87 % yield and >98% ee.
S7
13.809 13.784
28.129
36.261
OMe
OH OH
MeO
40
35
30
25
20
15
PPM
Figure 6. NMR showing how we determined the ee for the (1S,2S)-1,2-bis(4-methoxyphenyl) ethane-1,2-diol. (2S,3R)-Ethyl 2,3-dihydroxy-3-phenylpropanoate. Reaction of ethyl acrylate (0.5 g, 5 mmoles) and styrene (0.26 g, 2.5 mmoles) with Grubbs’ second generation
OH O OEt OH
catalyst (85 mg, 0.1 mmoles) was allowed to proceed for 9 h followed by
pumping off the excess acrylate and reaction of the subsequent product with site-isolated AD-mix-β (7.2 g, 0.012 mmoles of osmium catalyst) for 12 h gave title compound in 82% yield and >98% ee. The 1H and 13C NMR spectra agreed with those reported in the literature.5,10,11 1H NMR (CDCl3): δ 7.26-7.42 (m, 5H), 5.00 (d, J= 3 Hz, 1H), 4.36 (d, J= 3, 1Η), 4.26 (q, J= 7.1Hz, 2H), 3.16 (br S, 1H), 2.84 (br S, 1H), 1.27 (t, J= 7.1 Hz, 3H) 13C NMR (CDCl3): δ 172.70, 139.92, 128.42, 128.04, 126.24, 74.63, 62.20, 14.06.
S8
OH
O OEt
OH
35
30
25
20
PPM
Figure 7. NMR spectrum showing how we determined the ee for the (2S,3R)-Ethyl 2,3-dihydroxy3-phenylpropanoate. (2S,3R)-Butyl 2,3-dihydroxy-3-phenylpropanoate. Reaction of butyl acrylate (0.64 g, 5 mmoles) and styrene (0.26 g, 2.5 mmoles) with Grubbs’ second generation
OH O OBu OH
catalyst (43 mg, 0.05 mmoles) was allowed to proceed for 8 h followed by
pumping off the excess acrylate and reaction of the subsequent product with site-isolated AD-mix-α (3.6 g, 0.0063 mmoles of osmium catalyst) for 20 h gave title compound in 78% yield and >98% ee. The 1H and 13C NMR spectra agreed with those reported in the literature. 1H NMR (CDCl3): δ 7.317.43 (m, 5H), 5.01 (dd, J= 7.2, 3 Hz, 1H), 4.38 (dd, J= 5.7, 3, 1Η), 4.22 (t, J= 7.2 Hz, 2H), 3.11 (d, J= 6 Hz, 1H), 2.71 (d, J= 7.2 Hz,1H), 1.61 (m, 2H), 1.33 (m, 2H), 0.93 (t, J= 7.2 Hz, 3H) 13C NMR (CDCl3): δ 172.74, 139.90, 128.27, 127.87, 126.25, 74.81, 74.60, 30.33, 18.85, 13.53
S9
14.785 14.724 14.643
OH
O OBu
OH
28
26
24
22
20
18
16
14
PPM
Figure 8. NMR spectrum showing how we determined the ee for the (2S,3R)-Butyl 2,3-dihydroxy3-phenylpropanoate. 1,1-Dioxido-(3R,4S)-tetrahydrothiophene-3,4-diol. In a glove box, Grubbs’ second O
HO
S
O
generation catalyst (85 mg, 0.01 mmoles) was placed in a PDMS thimble contained in a Schlenk flask. The flask was sealed, removed from the glove box and placed under N2.
OH
Solvent mixture (1 mL of 1/1 CH2Cl2/BMIM) was added to the interior of the thimble followed by diallyl sulfide (322 μL, 2.5 mmoles). The reaction mixture was allowed to stir at 35 °C for 6 h after which the walls of the glass flask were rinsed with 1 mL CH2Cl2 and the washes put into the thimble. To the exterior of the thimble was placed a mixture of K2Os(OH)6 (2 mg, 0.005 mmoles) and citric acid (0.72 g, 3.76 mmoles) in 15 mL 1/1 t-BuOH/H2O. To the exterior was also added 1/1 (w/w) aqueous N-methylmorpholine N-oxide (NMO) (1.3 mL, 4.5 mmoles NMO) and the reaction was allowed to stir vigorously for a further 15 h. Solvent was distilled off and the resulting residue was purified using a silica gel column eluting with 25% hexanes in EtOAc to give the title
S10
compound in 79 % yield. 1H NMR (d6-DMSO): δ 4.7-4.9 (br, s, 2H), 4.51 (m, 2H), 3.20 (m, 4H). 13
C NMR (CDCl3): δ 70.93, 57.70. Calcd for C4H8O4S 152.0143; Found, 153.0222 (M+1) (3S, 4R)–Pyrrolidine-3,4-diol. The reaction of diallylamine (0.48 g, 5 mmoles) with Grubbs’ second generation catalyst (170 mg, 0.02 mmoles) in presence of p-
H N HO
toluenesulfonic acid (0.95 g, 5 mmoles) was allowed to proceed for 6 h. Subsequent OH
addition of 0.5 mL saturated NaOH in 1/1 MeOH/H2O gave the intermediate 2,5-dihydro-1Hpyrrole. The intermediate was reacted with site-isolated of K2Os(OH)6 (2 mg, 0.005 mmoles) as described above for 24 h. The crude product was distilled under reduced vacuum, the distillate was pumped dry, residue dissolved in MeOH then filtered over celite to give a light yellow solution. The yellow filtrate was concentrated in vacuo and passed through a short alumina column eluting with 1:1 MeOH: CH2Cl2 to give the title compound as a white solid in 80 % yield. The 1H and 13C NMR spectra agreed with those reported in the literature.12,13 1H NMR (d6-Acetone): δ 3.52 (ddd, J= 1.8, 11.5, 11.7 2H), 3.05-3.08 (br, m, 2H), 2.82 (ddd, J= 3.6, 11.4, 11.7, 2H), 2.371 (dm, J= 10.8 Hz, 1H). 13C NMR (CDCl3): δ 65.40, 61.68. Recycling of Grubbs’ catalysts followed by dihydroxylation. In a glove box, Grubbs’ second generation catalyst (85 mg, 0.01 mmoles) was placed in a PDMS thimble contained in a Schlenk flask (A). The flask was sealed, removed from the glove box and placed under N2. Solvent mixture (1 mL of 1/1 CH2Cl2/BMIM) was added to the interior of the thimble followed by diethyl diallylmalonate (300 μL, 1.25 mmoles). The reaction mixture was allowed to stir at ambient conditions for 1 h. For each cycle an aliquot was removed and a 1H NMR spectrum was obtained to check the conversion of the metathesis reaction. Degassed 1/2/3 BMIM/H2O/acetone (15 mL) was added to the exterior of the thimble and the metathesis product was allowed to flux to the exterior for 1 h. Solvent on the exterior of the thimble was removed and placed in a clean flask (B) containing AD-mix-α (3.6 g, 0.0063 mmoles of osmium catalyst) and methane sulfonamide (0.238 S11
g, 2.5 mmoles) and the reaction was allowed to stir vigorously for 12 h. Na2SO3 (3.2 g, 25 mmoles) was then added and the product was extracted with 3 x 50 mL Et2O and purified using a silica gel column eluting with 25% EtOAc in hexanes to give the target diol. To the thimble in flask (A) was added 0.5 mL CH2Cl2 and diethyl diallylmalonate and the procedure above repeated for a total of 7 cycles. Solvent removed from the exterior of the thimble was placed in a new flask for each cycle. Table 1. Isolated yields of the cis-diol in recycling experiments. Cycle number 1 2 3 4 5 6 7
Isolated yield (%) 59 78 88 83 91 86 72
Control reactions to investigate if Grubbs’ catalyst interferes with dihydroxylation and vice-versa. a) Does Grubbs’ catalyst poison the AD-mixes? In a glove box, Grubbs’ secondgeneration catalyst (21 mg, 0.025 mmoles) in 1 ml CH2Cl2 was placed in a Schlenk flask. The flask was sealed, removed from the glove box and placed under N2. Diethyl diallylmalonate (150 μL, 0.62 mmoles) was added to the flask under nitrogen and allowed to stir for 3.5 h. To the reaction mixture was then added degassed 1/2/3 BMIM/H2O/acetone (5 mL), AD-mix-α (1.8 g, 0.0025 mmoles of osmium catalyst) and methane sulfonamide (0.06 g, 0.62 mmoles) and the reaction was allowed to stir vigorously for a further 16 h. The reaction mixture was then extracted with 3 x 15 mL Et2O, dried over MgSO4, solvent removed in vacuo, and residue analyzed by 1H NMR spectroscopy. Similarly, the above reaction was repeated using 5.3 mg and 0.53 mg of Grubbs’ catalyst.
S12
b) Is the Grubbs’ catalyst poisoning the K2Os(OH)6? In a glove box, Grubbs’ secondgeneration catalyst (5.3 mg, 0.0062 mmoles) in 1 ml CH2Cl2 was placed in a Schlenk flask. The flask was sealed, removed from the glove box and placed under N2. Diethyl diallylmalonate (150 μL, 0.62 mmoles) was added to the flask under nitrogen and allowed to stir for 3.5 h. To the reaction mixture was added degassed 1/2/3 BMIM/H2O/acetone (5 mL), K2Os(OH)6 (0.228 g, 0.62 mmoles), (DHQ)2PHAL (0.483g, 0.62 mmoles), K2CO3 (0.308 g, 2.23 mmoles), and methane sulfonamide (0.06 g, 0.62 mmoles). The reaction was allowed to stir vigorously for a further 16 h. The reaction mixture was then extracted with 3 x 15 mL Et2O, dried over MgSO4, and solvent removed in vacuo and residue analyzed by 1H NMR spectroscopy. ICP-MS analysis to investigate if Grubbs’ catalyst was leaching to the exterior and the Sharpless catalyst to the interior. The amount of ruthenium and/or osmium leaching into or out of the thimbles was studied for the three solvent systems we used for our reactions. The metathesis reaction was run to 100% conversion before adding the reagents for dihydroxylation. The dihydroxylation step was run for 10 and 25 h to see if the catalysts leached on prolonged reaction times. 1/2/3 BMIM/H2O/acetone. In a glove box, Grubbs’ second generation catalyst (43 mg, 0.05 mmoles) was placed in a PDMS thimble contained in a Schlenk flask. The flask was sealed, removed from the glove box and placed under N2. Solvent mixture (1 mL of 1/1 CH2Cl2/BMIM) was added to the interior of the thimble followed by diethyl diallylmalonate (300 μL, 1.25 mmoles). The reaction mixture was allowed to stir at ambient conditions for 1 h. To the exterior of the thimble was added AD-mix-α (3.6 g, 0.0126 mmoles of osmium catalyst) and methane sulfonamide (0.119 g, 1.25 mmoles) in 15 mL of solvent (1/2/3 BMIM/H2O/acetone), and the reaction was allowed to stir vigorously for a further 10 h. All solvent from the exterior of the thimble was
S13
removed and amount of osmium and ruthenium quantified by ICP-MS. Similarly, all contents of the thimble were removed and amount of ruthenium and osmium present quantified by ICP-MS. The above experiment was repeated but the dihydroxylation step was allowed to run for 25 h. amount of ruthenium and osmium in the interior and exterior of the thimbles were similarly quantified. Using 1/1 t-BuOH/H2O under basic conditions (AD-mix-α). In a glove box, Grubbs’ second generation catalyst (43 mg, 0.05 mmoles) was placed in a PDMS thimble contained in a Schlenk flask. The flask was sealed, removed from the glove box, and placed under N2. Solvent mixture (1 mL of 1/1 CH2Cl2/BMIM) was added to the interior of the thimble followed by diethyl diallylmalonate (300 μL, 1.25 mmoles). The reaction mixture was allowed to stir at ambient conditions for 1 h. To the exterior of the thimble was added AD-mix-α (3.6 g, 0.0126 mmoles of osmium catalyst) and methane sulfonamide (0.119 g, 1.25 mmoles) in 15 mL of solvent (1/1 tBuOH/H2O), and the reaction was allowed to stir vigorously for a further 10 h. All solvent from the exterior of the thimble was removed and amount of osmium and ruthenium quantified by ICP-MS. Similarly, all contents of the thimble were removed and amount of ruthenium and osmium present quantified by ICP-MS. The above experiment was repeated but the dihydroxylation step was allowed to run for 25 h. The amounts of ruthenium and osmium in the interior and exterior of the thimbles were similarly quantified. References (1) Mwangi, M. T.; Runge, M. B.; Hoak, K. M.; Schulz, M. D.; Bowden, N. B. Chem. Eur. J.l 2008, 14, 6780-6788. (2) Miller II, A. L.; Bowden, N. B. Chem. Commun. 2007, 25, 2051-2053. (3) Mwangi, M. T.; Runge, M. B.; Bowden, N. B. J. Am. Chem. Soc. 2006, 128, 1443414435. (4) Yang, H.; Wang, H.; Zhu, C. J. Org. Chem. 2007, 72, 10029-10034. (5) Kobayashi, S.; Ishida, T.; Akiyama, R. Org. Lett. 2001, 3, 2649-2652. (6) Kobayashi, Y.; William, A. D.; Tokoro, Y. J. Org. Chem. 2001, 66, 7903-7906. (7) Chatterjee, A. K.; Bennur, T. H.; Joshi, N. N. J. Org. Chem. 2003, 68, 5668-5671. S14
(8) Andrus, M. B.; Meredith, E. L.; Hicken, E. J.; Simmons, B. L.; Glancey, R. R.; Ma, W. J. Org. Chem. 2003, 68, 8162-8169. (9) Khartulyari, A. S.; Kapur, M.; Maier, M. E. Org. Lett. 2006, 8, 5833-5836. (10) Han, H.; Janda, K. M. Angew. Chem. Int. Ed. 1997, 36, 1731-1733. (11) Ho, C.-M.; Yu, W.-Y.; Che, C.-M. Angew. Chem. Int. Ed. 2004, 43, 3303-3307. (12) Tian, Z.-Q.; Liu, Y.; Zhang, D.; Wang, Z.; Dong, S. D.; Carreras, C.; Zhou, Y.; Rastelli, G.; Santi, D. V.; Myles, D. C. Bioorg. Med. Chem. 2004, 12, 5317-5329. (13) Popowycz, F.; Gerber-Lemaire, S.; Demange, R.; Rodriguez-Garcia, E.; Asenjo, A. T. C.; Robina, I.; Vogel, P. Bioorg. Med. Chem. Lett. 2004, 11, 2489-2493.
S15
4.5
77.423 77.000 76.569 72.890
172.399 172.125
4.0
EtO2C
HO
160 3.5
CO2Et
OH
140 3.0 2.5
120
100
80
60 0.5
40
20 0.837
1.0
13.796 13.770
1.5
38.447
2.0
56.343
HO
61.753 61.616
EtO2C
0.018 0.006
1.212 1.199 1.188 1.176 1.165 1.153
2.360 2.338 2.320
3.480
4.175 4.152 4.144 4.128 4.122 4.104 4.097 4.073 4.065 4.052 4.037
(3S,4R)-diethyl 3,4-dihydroxycyclopentane-1,1-dicarboxylate
CO2Et
OH
0.0 PPM
PPM
S16
140
HO
7 6
HO
120 5 4
100 3
80 37.690 37.606
77.066 76.811 76.398 76.173 75.965 72.435 71.822 70.272 70.191
127.776 127.705 127.121 127.106 126.986 126.903
137.584 137.010
2
60
-0.000
2.011 1.987 1.968 1.927 1.909 1.890 1.870 1.820
2.919
3.255 3.210
4.123 4.107 4.094 4.078 4.059 3.928 3.916 3.904 3.895 3.885
4.389 4.337
7.277 7.249 7.241 7.232 7.210 7.200 7.181 7.178 7.171
(1S,2R)-4-phenythylcyclopentane-1,2-diol
OBn
OH
1 0 PPM
OBn
OH
40
PPM
S17
130 6
120 5 4
110 3
100 2
90
80
77.580 77.167 76.739
7
79.263
127.064
128.272 128.085
-0.000
2.863 2.860 2.855
4.711
7.244 7.238 7.232 7.227 7.223 7.142 7.137 7.129 7.123 7.118 7.108
(1S,2S)-Diphenylethane-1,2-diol
OH
OH
1 0 PPM
OH
OH
PPM
S18
140
120 5
100 4
80 3 2
60
40 1.171
6
21.299
7
78.949 77.581 77.154 76.735
129.385 128.981 126.970 126.148
137.664 137.101
0.007
2.304 2.293
2.810
4.683
7.059 7.049
7.264
(1S,2S)-di-p-tolylethane-1,2-diol
OH
OH
1 PPM
OH
OH
20
PPM
S19
MeO
160
140
MeO
5 4
OH
120
3
100
2
80 55.175
OH
78.767 77.428 77.006 76.582
6
113.467
128.143
7
132.051
159.127
0.009
2.792
3.775
4.643
6.785 6.778 6.754
7.065 7.044 7.036
7.270
(1S,2S)-1,2-bis(4-methoxyphenyl) ethane-1,2-diol
OMe
OH
1 0 PPM
OMe
OH
60
PPM
S20
OH
160 5
140
120 4
100
80 14.228
OH
62.357
6
77.597 77.171 76.751 74.802 74.678
7
128.585 128.212 126.407
140.086
172.867
3 2
60
40
0.000
1.290 1.266 1.257 1.243
4.359 4.349 4.296 4.274 4.249 4.224
5.002 4.994
7.422 7.394 7.371 7.365 7.351 7.345 7.338 7.330 7.308 7.261
(2S,3R)-Ethyl 2,3-dihydroxy-3-phenylpropanoate
O
OH OEt
1 PPM
O
OH OEt
20
PPM
(2S,3R)-Butyl 2,3-dihydroxy-3-phenylpropanoate
S21
180 6
OH
160
140 77.427 77.000 76.578 74.805 74.600
7
128.271 127.901 127.870 126.256
139.902
172.744
5
O
OH OBu
120 4 3
100
80
60
1
40
20
13.530
2
18.853
30.335
65.773
OH O
OH OBu
PPM
PPM
S22
0.000
1.643 1.622 1.612 1.595 1.562 1.381 1.356 1.331 1.307 0.952 0.928 0.904
2.721 2.697
3.109 3.089
4.391 4.380 4.372 4.362 4.241 4.219 4.196
5.019 5.010 4.995 4.984
7.430 7.409 7.403 7.381 7.374 7.355 7.345 7.337 7.315 7.263
HO
5.0
200 4.5
O
HO
180 4.0
160
140 3.5
120 3.0
100 2.5
80
60 29.986 29.730 29.468 29.215 28.960
O
57.638
70.864
205.881 205.863
2.072 2.065 2.057 2.049 2.043
3.331 3.327 3.310 3.287 3.271 3.267 3.260 3.239 3.215 3.195
4.558 4.553 4.549 4.533 4.517 4.512 4.508
4.750 4.743
1,1-Dioxido-(3R,4S)-Tetrahydrothiophene-3,4-diol
S O
OH
2.0 PPM
S O
OH
40
PPM
S23
65
HO
HO 39.973 39.700 39.428 39.145 38.869
61.091
64.819
60
3.5
55
50
3.0
45
40
1.999 1.994 1.989 1.953
2.269
2.306
2.550
2.920 2.908 2.882 2.871 2.844 2.832
3.104 3.096
3.136
3.572 3.567 3.534 3.528
3.611 3.605
(3S, 4R)–Pyrrolidine-3,4-diol
H N
OH
2.5 2.0
35 PPM
H N
OH
PPM
S24
