Sequential reactions with Grubbs catalyst and ad-mix-α//βusing pdms thimbles

Article abstract of DOI:10.1021/ol8022215

Incompatible Grubbs catalyst and an osmium dihydroxylation catalyst were site-isolated from each other using polydimethylsiloxane thimbles. The Grubbs catalyst was added to the interior of the thimbles, and AD-mix-α//β was added to the exterior. Organic substrates readily fluxed through the walls of the thimbles and reacted with each catalyst. A series of cascade reactions were developed including those with intermediates possessing low boiling points or that were foul smelling.

Full text of DOI:10.1021/ol8022215

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: ned-bowden@uiowa.edu
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 (4-
methoxystyrene, styrene, 4-methylstyrene, 1-chlorobutane, N-methylimidazole,
hexafluorophosphoric acid, methane sulfonamide, europium tris[3-(heptafluoropropylhydroxy-
methylene)-(+)-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, AD-
mix-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
HO
CO2Et
substrate. Any deviations from this method are given for all subsequent substrates.
In a glove box, Grubbs’ second-generation catalyst (43 mg, 0.05 mmoles) was
OH
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).
13C 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 hepta-
OBn
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
osmium) for 13 h, gave the title compound in 72% yield and 85% ee. The 1H and
13C 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) 13C 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
13C 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-1,2-
diol.
Similarly, the reaction was repeated using AD-mix-β for the dihydroxylation step to give the
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-1,2-
diol.
S6

(1S,2S)-1,2-bis(4-methoxyphenyl) ethane-1,2-diol. Reaction of 4-methoxy styrene (0.34 g,
OMe
2.5 mmoles) with Grubbs’ second generation catalyst (85 mg, 0.1
OH
mmoles) for 6 h, followed by reaction of the subsequent product with
OH
MeO
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 1
H
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(4-
methoxyphenyl) 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

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
catalyst (85 mg, 0.1 mmoles) was allowed to proceed for 9 h followed by
OH
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-dihydroxy-
3-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
catalyst (43 mg, 0.05 mmoles) was allowed to proceed for 8 h followed by
OH
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 7.31-
7.43 (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

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-dihydroxy-
3-phenylpropanoate.
1,1-Dioxido-(3R,4S)-tetrahydrothiophene-3,4-diol. In a glove box, Grubbs’ second
generation catalyst (85 mg, 0.01 mmoles) was placed in a PDMS thimble contained in a
O
O
S
Schlenk flask. The flask was sealed, removed from the glove box and placed under N2.
HO
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).
13C 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
toluenesulfonic acid (0.95 g, 5 mmoles) was allowed to proceed for 6 h. Subsequent
HO
OH
addition of 0.5 mL saturated NaOH in 1/1 MeOH/H2O gave the intermediate 2,5-dihydro-1H-
pyrrole. 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
Isolated yield
(%)
59
78
88
83
91
86
72
1
2
3
4
5
6
7
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’ second-
generation 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’ second-
generation 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 t-
BuOH/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)
(3)
Miller II, A. L.; Bowden, N. B. Chem. Commun. 2007, 25, 2051-2053.
Mwangi, M. T.; Runge, M. B.; Bowden, N. B. J. Am. Chem. Soc. 2006, 128, 14434-
14435.
(4)
(5)
(6)
(7)
Yang, H.; Wang, H.; Zhu, C. J. Org. Chem. 2007, 72, 10029-10034.
Kobayashi, S.; Ishida, T.; Akiyama, R. Org. Lett. 2001, 3, 2649-2652.
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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.
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T. C.; Robina, I.; Vogel, P. Bioorg. Med. Chem. Lett. 2004, 11, 2489-2493.
S15

(3S,4R)-diethyl 3,4-dihydroxycyclopentane-1,1-dicarboxylate
EtO2C
HO
CO2Et
OH
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0
PPM
EtO2C
HO
CO2Et
OH
160
140
120
100
80
60
40
20
PPM
S16

(1S,2R)-4-phenythylcyclopentane-1,2-diol
OBn
HO
OH
7
6
5
4
3
2
1
0PPM
OBn
HO
OH
140
120
100
80
60
40
PPM
S17

(1S,2S)-Diphenylethane-1,2-diol
OH
OH
7
6
5
4
3
2
1
0 PPM
OH
OH
130
120
110
100
90
80
PPM
S18

(1S,2S)-di-p-tolylethane-1,2-diol
OH
OH
7
6
5
4
3
2
1
PPM
OH
OH
140
120
100
80
60
40
20
PPM
S19

(1S,2S)-1,2-bis(4-methoxyphenyl) ethane-1,2-diol
OMe
OH
OH
MeO
7
6
5
4
3
2
1
0 PPM
OMe
OH
OH
MeO
160
140
120
100
80
60
PPM
S20

(2S,3R)-Ethyl 2,3-dihydroxy-3-phenylpropanoate
OH
O
OEt
OH
7
6
5
4
3
2
1
PPM
OH
O
OEt
OH
160
140
120
100
80
60
40
20
PPM
(2S,3R)-Butyl 2,3-dihydroxy-3-phenylpropanoate
S21

OH
O
OBu
OH
7
6
5
4
3
2
1
PPM
OH
O
OBu
OH
180
160
140
120
100
80
60
40
20
PPM
S22

1,1-Dioxido-(3R,4S)-Tetrahydrothiophene-3,4-diol
O
O
S
HO
OH
5.0
4.5
4.0
3.5
3.0
2.5
2.0
PPM
O
O
S
HO
OH
200
180
160
140
120
100
80
60
40
PPM
S23

(3S, 4R)–Pyrrolidine-3,4-diol
H
N
HO
OH
3.5
3.0
2.5
2.0
PPM
H
N
HO
OH
65
60
55
50
45
40
35
PPM
S24