Probing the scope of the asymmetric dihydroxylation of polymer-bound olefins. Monitoring of HRMAS NMR allows for reaction control and on-bead measurement of enantiomeric excess

Article abstract of DOI:10.1021/ja980183d

The aim of this study was (I) to define the scope and limitations of the Sharpless asymmetric dihydroxylation (AD) for polymer-bound olefins of different structural types and (II) to elaborate HRMAS NMR methods for the direct on-bead monitoring of the asymmetric dihydroxylation, including the on-bead determination of enantiomeric excess (ee). (I) 2-Methoxy-4-(2- propenyl)phenol (eugenol, E), 10-undecenoic acid (U), and (E)-4- hydroxystilbene (S) were bound to Wang-resin or TentaGel S-OH. These olefins gave low (E, 32%), intermediate (U, 88%), and very high enantiomeric excesses (S, > 99%) when treated with AD mix β in solution. When bound to the polymers, the trend of the enantioselectivities remained the same [S (97%) > U (20-45%) > E (0-3%)]. However, the absolute ee values demonstrate that only the most selective types of substrates in homogeneous solution have practical potential for enantioselective AD on solid phase. (II) HRMAS NMR was successfully used for on-bead monitoring and for the first time for the ee measurement of the polymer-bound dihydroxylation product. As an example, the full assignment of all resonances of polymer-bound 10-undecenoic acid (U) and its dihydroxylation product is presented. For the ee measurement, the polymer-bound dihydroxylation product was derivatized with Mosher's acid. The integration of seven different pairs of resonances in the ¹³C HRMAS NMR of the diastereomeric Mosher esters gave (in each case) an ee value that agreed within <1% with that determined by chiral HPLC after cleavage of the AD product.

Full text of DOI:10.1021/ja980183d

8994
J. Am. Chem. Soc. 1998, 120, 8994-9000
Probing the Scope of the Asymmetric Dihydroxylation of
Polymer-Bound Olefins. Monitoring by HRMAS NMR Allows for
Reaction Control and On-Bead Measurement of Enantiomeric Excess
Rainer Riedl, Robert Tappe,* and Albrecht Berkessel*
Contribution from the Institut fu¨r Organische Chemie der UniVersita¨t zu Ko¨ln,
Greinstr. 4, D-50939 Ko¨ln, Germany
ReceiVed January 16, 1998
Abstract: The aim of this study was (I) to define the scope and limitations of the Sharpless asymmetric
dihydroxylation (AD) for polymer-bound olefins of different structural types and (II) to elaborate HRMAS
NMR methods for the direct on-bead monitoring of the asymmetric dihydroxylation, including the on-bead
determination of enantiomeric excess (ee). (I) 2-Methoxy-4-(2-propenyl)phenol (eugenol, E), 10-undecenoic
acid (U), and (E)-4-hydroxystilbene (S) were bound to Wang-resin or TentaGel S-OH. These olefins gave
low (E, 32%), intermediate (U, 88%), and very high enantiomeric excesses (S, >99%) when treated with AD
mix â in solution. When bound to the polymers, the trend of the enantioselectivities remained the same [S
(97%) > U (20-45%) > E (0-3%)]. However, the absolute ee values demonstrate that only the most selective
types of substrates in homogeneous solution have practical potential for enantioselective AD on solid phase.
(II) HRMAS NMR was successfully used for on-bead monitoring and for the first time for the ee measurement
of the polymer-bound dihydroxylation product. As an example, the full assignment of all resonances of polymer-
bound 10-undecenoic acid (U) and its dihydroxylation product is presented. For the ee measurement, the
polymer-bound dihydroxylation product was derivatized with Mosher’s acid. The integration of seven different
pairs of resonances in the 13C HRMAS NMR of the diastereomeric Mosher esters gave (in each case) an ee
value that agreed within <1% with that determined by chiral HPLC after cleavage of the AD product.
Introduction
nately, they were not able to determine the enantiomeric excess
of the resulting diol. Han and Janda reported that (E)-cinnamic
acidsbound to various polymersscan be dihydroxylated with
enantiomeric excesses (88-99%) reaching or even surpassing
those of the solution phase AD of ethyl (E)-cinnamate (97%).6b
Obviously, this one data point of the solution-/solid-phase
correlation does not allow for the conclusion that, in the
Sharpless AD, every given olefin will afford the same enan-
tiomeric excess (ee) when polymer supported or when in
homogeneous solution. We selected 2-methoxy-4-(2-propenyl)-
phenol (eugenol, 1a), 10-undecenoic acid (2b), and (E)-4-
hydroxystilbene (1c) as representative olefins: allylbenzene is
known to give intermediate ee values (78%),7 long-chain
R-olefins give quite satisfactory ee values (e.g., 1-decene, 92%),7
and (E)-stilbenes are dihydroxylated with extreme selectivity
[(E)-stilbene, 99.8% ee]5 in the solution-phase Sharpless AD.
Our results suggest that only those olefins that perform best in
solution (e.g., stilbenes) are reasonable substrates for solid-phase
AD. (II) The monitoring of solid-supported transformations is
in most instances carried out post festum, by cleaving the
reaction products off the polymer, followed by standard solution-
phase methods (mostly NMR). Only few publications deal with
nondestructive on-bead analyses by NMR-methods.8 To the best
of our knowledge, no method for the nondestructive on-bead
determination of enantiomeric excess has been reported as yet.
In high-resolution magic angle spinning (HRMAS) NMR, the
combination of reduced but sufficient mobility of the polymer-
bound molecules in the swelling agent and magic angle spinning
In the rapidly developing field of combinatorial chemistry,1-3
libraries of low molecular weight organic compounds are in
most cases synthesized on solid polymeric supports. As a
consequence, the two steps crucial to every synthetic operation,
i.e., (I) the efficient transformation of a given starting material
and (II) the analysis of the resulting product, need to be adapted
from the conditions of the homogeneous solution to those of
the polymer-bound compound. In fact, quite a number of
reactions have already been optimized for solid-phase synthesis.1-3
(I) Interestingly, the potential of the Sharpless asymmetric
dihydroxylation (AD),4,5 which has proven extremely valuable
in “normal” solution-phase organic synthesis, has been inves-
tigated only in two instances: Moberg et al. prepared polymeric
ethyl cinnamate in which the phenyl ring was part of the
polystyrene support and treated it with AD mix R.6a Unfortu-
(1) Combinatorial Chemistry-Synthesis and Application; Wilson, S. R.,
Czarnik, A. W., Eds.; Wiley: New York, 1997.
(2) (a) Acc. Chem. Res. 1996, 29, 111-170 (special issue on combina-
torial chemistry). (b) Chem. ReV. 1997, 97, 347-510 (special issue on
combinatorial chemistry).
(3) (a) Hermkens, P. H. H.; Ottenheijm, H. C. J.; Rees, D. C. Tetrahedron
1996, 52, 4527-4554. (b) Hermkens, P. H. H.; Ottenheijm, H. C. J.; Rees,
D. C. Tetrahedron 1997, 53, 5643-5678.
(4) Johnson, R. A.; Sharpless, K. B. Catalytic Asymmetric Dihydroxy-
lation. In Catalytic Asymmetric Synthesis; Ojima, I., Ed.; VCH: Weinheim,
1993; pp 227-272.
(5) Kolb, H. C.; VanNieuwenhze, M. S.; Sharpless, K. B. Chem. ReV.
1994, 94, 2483-2547.
(6) (a) Cernerud, M.; Reina, J. A.; Tegenfeldt, J.; Moberg, C. Tetrahe-
dron: Asymmetry 1996, 7, 2863-2870. (b) Han, H.; Janda, K. D. Angew.
Chem. 1997, 109, 1835-1837; Angew. Chem., Int. Ed. Engl. 1997, 36,
1731-1733.
(7) Becker, H.; Sharpless, K. B. Angew. Chem. 1996, 108, 447-449;
Angew. Chem., Int. Ed. Engl. 1996, 35, 448-451.
S0002-7863(98)00183-8 CCC: $15.00 © 1998 American Chemical Society
Published on Web 08/19/1998

Asymmetric Dihydroxylation of Polymer-Bound Olefins
J. Am. Chem. Soc., Vol. 120, No. 35, 1998 8995
Table 1. Asymmetric Dihydroxylation on Polymeric Supports and
Scheme 2
in Homogeneous Solutiona
yieldd
[%]
ee
[%]
entry substrateb polymerc
ligand
1
2
4a
3a
3a
3a
3a
solution
(DHQD)2AQNe
(DHQD)2AQNe
(DHQD)2PYRf
(DHQD)2PHALg
(DHQD)2PHALg
75
83
62
73
8
32h
0h
W
W
W
W
3
0h
4i
5j
3h
0h
6m
7
4b
3b
3b
3b
3b
3b
solution
(DHQD)2AQNe
(DHQD)2AQNe
(DHQD)2PYRf
(DHQD)2PHALg
(DHQD)2PHALg
(DHQD)2PHALg
78
52
44
96
96
44
88k
32k
34k
41k
20k
45k
W
W
W
W
T
8
9i
10l
11m
12
13
14
4c
3c
3c
solution
W
T
(DHQD)2PHALg
(DHQD)2PHALg
(DHQD)2PHALg
61
41
21
>99n
97n
97n
a If not mentioned otherwise, the reactions were run at room
temperature for 18 h. b See Scheme 2 for the structures of the substrates.
c W: Wang-resin. T: TentaGel S-OH. d Yields refer to the pure, isolated
triols 6a-c/ent-6a-c (see Scheme 2). e Dihydroquinidine 1,4-an-
thraquinonediyl diether.7 f Dihydroquinidine 2,5-diphenyl-4,6-pyrim-
idinediyl diether.5 g Dihydroquinidine 1,4-phthalazinediyl diether.5
h ChiraSpher-type column (Merck; methyl-tert-butyl ether-THF 20:
80). i Reaction run at room temperature for 12 h. j Reaction run at 0
°C for 24 h. k ChiraSpher-type column (Merck; methyl-tert-butyl ether-
THF 70:30). l Reaction run at room temperature for 6 d. m Reaction
run at room temperature for 24 h. n CHIRALCEL OD-H column
(Daicel; hexane-2-propanol 80:20).
Scheme 1
eugenol (1a) and (E)-4-hydroxystilbene (1c) were reacted with
chloroacetic acid, affording the carboxylic acids 2a and 2c. In
the next step, the resins were loaded with the acids 2a and 2c
and with 10-undecenoic acid (2b), using dicyclohexyl carbo-
diimide (DCC) as the coupling agent (Scheme 2). Substrate
loadings were typically in the range of 0.7-1.0 mmol/g (Wang-
resin) and 0.3 mmol/g (TentaGel S-OH).10
The Sharpless AD was carried out with three different ligands
[(DHQD)2AQN,7 (DHQD)2PYR,5 (DHQD)2PHAL4,5] in a 1:1-
mixture of water and THF. In our hands, this solvent system
was the only one affording reasonable conversions of the
polymer-bound substrates 2a-c.11 Under the reaction condi-
tions given in the Experimental Section, the prochiral olefins
3a-c were transformed into the diols 5a-c/ent-5a-c. The
cleavage of the dihydroxylation products 5a-c/ent-5a-c from
the polymeric supports was done in a reductive manner
(DIBAL), affording the corresponding triols 6a-c/ent-6a-c.
The yields and enantiomeric excesses of the isolated triols 6a-
leads to NMR spectra approaching the quality of solution-phase
NMR. We herein describe the application of homo- and
heteronuclear HRMAS NMR for the monitoring of the AD of
polymer-bound 10-undecenoic acid (2b) and for the determi-
nation of the ee of the dihydroxylation product 5b. For the
latter purpose, the product diol 5b was derivatized on the solid
support with Mosher’s acid. As expected, this fast on-bead
method gave ee values that agreed within <1% with those
determined by chiral HPLC after cleavage (Scheme 1).
Results
Wang-resin9 and TentaGel S-OH were selected as polymeric
supports. As a prerequisite for the attachment to the polymers,
(8) (a) Look, G. C.; Holmes, C. P.; Chinn, J. P.; Gallop, M. A. J. Org.
Chem. 1994, 59, 7588-7590. (b) Fitch, W. L.; Detre, G.; Holmes, C. P.;
Shoolery, J. N.; Keifer, P. A. J. Org. Chem. 1994, 59, 7955-7956. (c)
Anderson, R. C.; Jarema, M. A.; Shapiro, M. J.; Stokes, J. P.; Ziliox, M. J.
Org. Chem. 1995, 60, 2650-2651. (d) Anderson, R. C.; Stokes, J. P.;
Shapiro, M. J. Tetrahedron Lett. 1995, 36, 5311-5314. (e) Keifer, P. A. J.
Org. Chem. 1996, 61, 1558-1559. (f) Sarkar, S. K.; Garigipati, R. S.;
Adams, J. L.; Keifer, P. A. J. Am. Chem. Soc. 1996, 118, 2305-2306.
(9) (a) Wang, S. S. J. Am. Chem. Soc., 1973 95, 1328-1333. (b) Lu,
G.; Mojsov, S.; Tam, J.; Merrifield, R. B. J. Org. Chem. 1981, 46, 3433-
3436.
(10) Loadings were determined by cleaving the substrates off the resins
and gravimetry of the chromatographically pure materials.
(11) tert-Butyl alcohol-water and acetone-water mixtures proved
inappropriate for the AD of Wang-resin-supported (E)-cinnamic acid, using
K3[Fe(CN)6] as terminal oxidant.

8996 J. Am. Chem. Soc., Vol. 120, No. 35, 1998
Table 2. 13C NMR Data of 3b, 5b/ent-5b, 8/9, and 10/11a
Riedl et al.
ar
1
2/6
3/5
4
R
ar′
1
2/6
3/5
4
R
all
145.5
b
128.1
134.6
70.3
5
159.3
7
115.1
8
130.3
9
129.1
10
66.1
11
1
2
3
4
6
3b
5b/ent-5b
8/9
173.8
174.0
173.8
34.7
34.6
34.6
25.4
25.3
25.3
29.5
30.0
29.4
29.5c
29.5c
29.4
29.6c
29.6c
29.4
29.7c
29.3
25.9
24.9
25.3
25.0d
25.3
34.2
33.5
30.7d
30.6
30.7d
30.5
139.6
114.4
67.1
29.7c
29.4
72.6
74.2d
74.4
74.2d
74.4
66.7d
66.3
10/11f,g
66.7d
66.3
ar′′/ar′′′
1
2
3
4
5
6/10
7/9
8
8/9e
166.7d
166.6
166.4
166.3d
85.0
123.7
55.8
55.6
132.6d
132.4
132.3
132.2d
127.78
127.71
127.59
127.53
128.91
128.83
128.78
128.67
130.19
130.10
130.08
130.06
a Polymer beads were swollen in CD2Cl2 prior to measurement. T ) 298 K. δ: (ppm). b Unambiguous assignment was not possible. c Assignment
of resonances may be opposite. d Resonances of the main diastereomer [R-configuration at the diol’s center of chirality (8, 10)]. e The resolution of
the 2D experiments did not allow for a full assignment to ar′′/ar′′′ of the two diastereomers. f Recorded in homogeneous CD2Cl2 solution. g For the
sake of clarity, atoms are numbered as in the Mosher esters 8 and 9.
Table 3. 1H NMR Data of 3b, 5b/ent-5b, 8/9, and 10/11a
ar
2/6
3/5
R
ar′
2/6
3/5
R
all
6.57b
2
7.05b
4.94
6.94
9
7.27
5.02
3
4
5
6
7
8
10
11a
11b
3b
5b/ent-5b
8/9
2.30
2.30
2.30
1.60
1.60
1.59
1.29
1.29
1.27
1.29
1.29
(1.25
1.29
1.29
/
1.29
1.37
1.39
1.27
1.17
2.04
1.39
1.57
5.81
3.63
5.32d
5.31
5.32d
5.33
4.97
3.36
4.30d
4.27
4.32d
4.30
4.91
3.57
4.62d
4.54
4.64d
4.55
1.29
1.18)c
10/11f,g
ar′′/ar′′′
8/9e
4
6/10
7/9
8
3.47
3.41
3.38
7.48
7.44
7.35
7.37
a Polymer beads were swollen in CD2Cl2 prior to measurement. T ) 298 K. δ: (ppm). b Very broad. c Unambiguous assignment was not possible.
d Resonances of the main diastereomer [R-configuration at the diol’s center of chirality (8, 10)]. e The resolution of the 2D experiments did not
allow for a full assignment to ar′′/ar′′′ of the two diastereomers. f Recorded in homogeneous CD2Cl2 solution. g For the sake of clarity, atoms are
numbered as in the Mosher esters 8 and 9.
c/ent-6a-c are summarized in Table 1. In the cases of 6a/ent-
6a and 6c/ent-6c, the enantiomeric excesses of the triols could
be determined directly by chiral HPLC (see Experimental
Section for conditions). The triol 6b/ent-6b had to be deriva-
tized first: Treatment with carbonyldiimidazole afforded the
cyclic carbonate 7/ent-7, which could again be analyzed by
chiral HPLC (eq 1).
The formulas 5a-c and 6a-c in Scheme 2 represent the
major enantiomers expected according to the Sharpless mne-
monic,5 which in turn is derived from experiments in homo-
geneous solution. In fact, solution-phase asymmetric dihydrox-
ylation and AD on solid support gave the same major enantiomer
in the cases of 5b,c and 6b,c (3a gave the racemic diol rac-5a,
see Table 1, entries 2-5). The assignment of (R,R)-configu-
ration to the triol 6c (obtained enantiomerically pure from
solution-phase AD, see Table 1, entry 12) is further supported
by the fact that both 6c and unsubstituted (R,R)-hydrobenzoin
have the same sense of optical rotation (+).5
HRMAS NMR was used for the characterization of 10-
undecenoic acid supported on Wang-resin (3b), for monitoring
the dihydroxylation of this material (3b f 5b/ent-5b, Scheme
2) and for the characterization of the dihydroxylation product
5b/ent-5b. For the HRMAS NMR characterization of polymer-
bound dihydroxylation product, the material processed according
to entry 10, Table 1, was used (i.e., dihydroxylation for 6 d at
room temperature, affording 20% ee of 5b). We found later
that a higher enantiomeric excess (41%) of the dihydroxylation
product 5b can be achieved by shortening the reaction time (12
h, entry 9, Table 1). The 1H and 13C NMR data of the polymer-
supported compounds 3b, 5b/ent-5b, and 8/9 (see below) are
summarized in Tables 2 and 3. An almost complete assignment
of the resonances was possible by a combination of 1H-DQF-
For comparison, the racemic triols rac-6a-c were also
prepared by conventional solution-phase chemistry (Scheme
2): First, the unsaturated alcohols 4a-c were prepared either
by LAH reduction of the carboxylic acids 2a,b (4a 46%, 4b
77%) or by reacting the phenol 1c with 2-chloroethanol (4c
39%). The subsequent dihydroxylation with K2OsO2(OH)4/
K3[Fe(CN)6] afforded the racemic triols rac-6a-c (6a 75%, 6b
78%, 6c 55%). When the dihydroxylation of the olefins 4a-c
was carried out using AD mix â under standard conditions5 in
tert-butanol/water, the triols 6a-c were obtained in the yields
and enantiomeric excesses stated in Table 1.
1
1
COSY, H-HOHAHA, H,13C-HSQC, and HMBC experi-

Asymmetric Dihydroxylation of Polymer-Bound Olefins
J. Am. Chem. Soc., Vol. 120, No. 35, 1998 8997
Figure 1. 1H,13C-HMBC spectrum of the substrate 3b.
ments. In the case of the HMBC experiments, the use of a
delay of 60 ms for the evolution of the long-range couplings
gave better results than longer evolution delays that fit better
the expected J-couplings. This observation is most likely due
to fast t2-relaxation of the protons. As shown in Figure 1, the
HMBC experiment with 3b even proved the attachment of the
substrate 10-undecenoic acid (2b) to the Wang-resin by a cross-
peak ar′-HR/-C1 and the connection between rings ar and ar′
of the Wang-linker by a cross-peak ar-HR/ar′-C1.
1
Whereas the lines of the H-spectra were still somewhat
broadened by, e.g., inhomogeneities of the surroundings of the
individual molecules, the 13C-spectra showed line widths of 3-6
Hz for carbon atoms of ar′ and the attached molecules (Figure
2). First of all, the spectra summarized in Figure 2 prove the
complete dihydroxylation of the substrate 3b to the diols 5b/
ent-5b, with basically no byproducts being formed. The very
high quality of the broadband (bb)-decoupled 13C spectra (with
or without heteronuclear NOE transfer) furthermore enabled us
to use HRMAS NMR as a fast method for the determination of
the enantiomeric excess achieved in the reaction 3b f 5b/ent-
5b (Scheme 2): First, the dihydroxylation product 5b/ent-5b
was derivatized with (R)-(+)-Mosher’s acid, affording the
diastereomers 8 and 9. The accumulation of 12 k scans gave a
signal-to-noise ratio sufficient for the reliable determination of
enantiomeric excess. The peak intensities of seven relevant pairs
of resonances (Figure 3) were used to calculate an ee of 20-
21% of the mixture 5b/ent-5b. Comparison with entry 10 of
Table 1 reveals that this is exactly the enantiomeric excess
determined by the more time-consuming three-step procedure
of cleaving the triol 6b/ent-6b off of the resin, derivatization
according to eq 1, and subsequent analysis by chiral HPLC.
For comparison, 1-undecene was dihydroxylated under
standard conditions5 using AD mix â, too. The resulting diols
were derivatized to the bis-Mosher esters 10 and 11, and their
NMR spectra were recorded in homogeneous solution (not
shown). As it turned out, the chemical shifts of the nuclei at
or next to the diol’s center of chirality in the polymer-bound
bis-Mosher esters 8 and 9 are at most slightly affected by the
polymeric matrix (Tables 2 and 3). Most likely, the Wang-
linker plus the substrate’s long alkyl chain account for this
“solution-like” behavior.
Figure 2. Monitoring solid-phase reactions by HRMAS NMR: 13C
NMR spectra of the substrate 3b (trace A), the dihydroxylation product
5b/ent-5b (trace B), and the bis-Mosher esters 8 and 9 (trace C).
Figure 3. Determination of enantiomeric excesses of polymer-bound
products by HRMAS NMR: relevant sections of the 13C NMR spectrum
of the bis-Mosher esters 8 and 9.
(I) HRMAS NMR Spectroscopy. We were able to elaborate
1
experimental conditions that afford H and in particular 13C
NMR spectra of the polymer-supported substrates that are
comparable in quality to the spectra of the low-molecular weight
substrates in homogeneous solution. We believe that HRMAS
NMR allows for the rapid and reliable monitoring of solid-phase
reactions. With this improvement, one of the major drawbacks
of solid-phase synthesis, i.e., the nonapplicability of advanced
NMR techniques for homogeneous solutions, has been re-
moved.12 We are convinced that HRMAS NMR will allow for
the rapid development of further methods of organic synthesis
on solid supports. Due to the high qualitiy of the spectra, we
could even determine enantiomeric excesses of reaction products
on the solid support.12
(II) Scope and Limitations of the Sharpless AD for
Polymer-Bound Substrates. (II.1) Olefinic substrates that give
almost perfect enantioselectivities (> 99% ee) in the Sharpless
Discussion
(12) For a related exo/endo-analysis of norbornane-2-carboxylic acid on
solid support by MAS 13C-NMR, see ref 8c. In this case, the norbornane
derivative analyzed did not result from a solid-phase reaction.
For the sake of clarity, the most important results of our study
are again summarized:

8998 J. Am. Chem. Soc., Vol. 120, No. 35, 1998
Riedl et al.
Recrystallization of the crude product from water furnished the
analytically pure acid as a colorless solid (7.13 g, 53% yield): mp 97
°C (lit.14 96.5-97.5 °C); IR (KBr) 3000-2500 (s), 1754 (s), 1634 (s),
1593 (s), 1518 (s), 1430 (s), 1300 (m), 1262 (s), 1151 (s), 1031 (s),
912 (s), 812 (s) cm-1; 1H NMR (300 MHz, DMSO-d6) δ ) 3.28 (d, J
) 6.6 Hz, 2H), 3.74 (s, 3H), 4.60 (s, 2H), 4.98-5.11 (m, 2H), 5.86-
6.01 (m, 1H), 6.65 (dd, J ) 8.1 Hz, 1.5 Hz, 1H), 6.74-6.82 (m, 2H),
12.98 (s, 1H); 13C NMR (75 MHz, DMSO-d6) δ ) 39.0 (t), 55.5 (q),
65.3 (t), 112.8 (d), 113.6 (d), 115.5 (t), 120.1 (d), 133.1 (s), 137.8 (d),
145.5 (s), 148.8 (s), 170.3 (s); FAB-MS [m/z (% intensity)] 222.0 (100)
[M+], 163.0 (70) [C10H11O2+], 137.1 (54) [C8H9O2+], 91 (46) [C6H3O+].
Anal. Calcd for C12H14O4: C, 64.85; H, 6.35. Found: C, 64.70; H,
6.29.
2-[2-Methoxy-4-(2-propenyl)phenoxy]ethanol (4a). LiAlH4 (0.51
g, 13.5 mmol) was suspended in 50 mL of Et2O and cooled to 0 °C. A
solution of [2-methoxy-4-(2-propenyl)phenoxy]acetic acid (2a) (2.00
g, 9.00 mmol) in 80 mL of Et2O was added dropwise. The mixture
was stirred for 16 h at room temperature. Ice was added, followed by
sufficient 10% H2SO4 to dissolve the white precipitate. The ether phase
was separated, and the aqueous layer was extracted with CH2Cl2 (3 ×
50 mL). The combined organic phases were dried over MgSO4 and
concentrated in vacuo. Purification of the residue by silica gel
chromatography (MeOH-CH2Cl2 1:9, v/v) afforded the pure product
as a colorless oil which solidified upon cooling (870 mg, 46%): mp
31 °C (lit.15 33-34 °C); IR (neat) 3486 (s), 3075 (s), 3001(s), 2935
(m), 2873 (m), 1636 (m), 1591 (m), 1514 (s), 1456 (s), 1420 (s), 1335
Figure 4. Enantiomeric excesses achieved in the asymmetric dihy-
droxylation of olefins: homogeneous solution vs solid-phase reactions.
AD in solution still afford diols that are basically enantiomeri-
cally pure when bound to polymeric supports (ee ) 97%).
Typical examples are (E)-stilbenes (this work) or (E)-cinnama-
tes.6 (II.2) Less selective olefins such as 10-undecen-1-ol (88%
ee in solution) are dihydroxylated with moderate ees when
bound to polymers (20-45% ee). (II.3) Almost no enantiose-
lectivity is retained when polymer-bound olefins are used that
give moderate selectivities in homogeneous solution, e.g.
2-methoxy-4-(2-propenyl)phenol (eugenol), 32% ee in homo-
geneous solution, 0-3% ee when bound to Wang-resin. The
correlation of ee values found in homogeneous solution and in
solid-phase AD is shown in Figure 4. As a consequence, only
olefins of the first category are reasonable substrates, e.g., for
the construction of combinatorial libraries of polyols by
repetitive olefination/dihydroxylation.13
1
(m), 1261 (s), 1232 (s), 1140 (s), 1034 (s), 914 (s), 806 (m) cm-1; H
NMR (300 MHz, CDCl3) δ ) 2.92 (br s, 1H), 3.32 (d, J ) 6.7 Hz,
2H), 3.83 (s, 3H), 3.88-3.96 (m br, 2H), 4.06-4.09 (m, 2H), 5.05-
5.14 (m, 2H), 5.89-6.04 (m, 1H), 6.71-6.75 (m, 2H), 6.85-6.89 (m,
1H); 13C NMR (75 MHz, CDCl3) δ )39.61 (t), 55.62 (q), 61.09 (t),
71.71 (t), 112.26 (d), 115.43 (d), 115.50 (t), 120.56 (d), 134.00 (s),
137.26 (d), 146.18 (s), 149.79 (s); FAB-MS [m/z (% intensity)] 208.1
(100) [M+], 164.0 (90) [C10H12O2+], 149.1 (50) [C9H9O2+], 131.1 (30)
[C9H7O+], 103.1 (30) [C8H7+], 91.1 (30) [C6H3O+]; HRMS m/z (M+)
calcd 208.10994, obsd 208.11100.
(R,S)-3-[4-(2-Hydroxyethoxy)-3-methoxyphenyl]-1,2-propane-
diol (rac-6a). K3[Fe(CN)6] (1.10 g, 3.30 mmol), K2CO3 (0.46 g, 3.30
mmol) and K2OsO2(OH)4 (0.81 mg, 2.20 µmol) were dissolved in 12.0
mL of a 1:1-mixture of tert-butyl alcohol and water (v/v). 2-[2-
Methoxy-4-(2-propenyl)phenoxy]ethanol (4a, 0.23 g, 1.10 mmol) was
added, and the mixture was stirred at room temperature for 20 h.
Na2SO3 (1.68 g, 13.3 mmol) was added, and stirring was continued
for 1 h. The solution was extracted with EtOAc (5 × 50 mL), and the
combined organic layers were dried over MgSO4. Concentration in
vacuo afforded the crude product. Purification by silica gel chroma-
tography (MeOH-CHCl3 1:9, v/v) afforded the pure triol as a colorless
solid (200 mg, 75% yield): mp 78 °C; IR (KBr) 3530 (s), 3372 (s),
2928 (m), 2879 (m), 2832 (m), 1592 (m), 1515 (s), 1464 (m), 1438
(m), 1420 (m), 1260 (s), 1229 (s), 1156 (m), 1139 (s), 1103 (m), 909
Experimental Section
General Methods. Commercially available chemicals were used
as purchased. Diethyl ether and toluene were distilled from sodium;
CH2Cl2 was distilled from CaCl2. Merrifield resin (chloromethyl
polystyrene, cross-linked with 2% divinylbenzene, 2.1 mmol of Cl/g,
200-400 mesh) was purchased from Fluka, TentaGel S-OH was
purchased from Rapp-Polymere (loading capacity 0.3 mmol/g). Wang
resin was prepared as reported elsewhere.9 All reactions in solution
were monitored by thin-layer chromatography (TLC), using Macherey-
Nagel precoated silica gel plates. Chromatography was performed using
Macherey-Nagel silica gel 60 (particle size 0.04-0.063 mm). Yields
refer to chromatographically and spectroscopically pure compounds.
Melting points were measured on a Bu¨chi apparatus and are uncorrected.
NMR spectra were recorded on a Bruker AC 300 spectrometer using
solvent signals as internal standard. IR spectra were recorded on a
Perkin-Elmer 1600 FTIR spectrometer. Mass spectra were taken on a
Finnigan MAT H-SQ 30 (CI), JEOL JMS-700 (FAB), or VG ZAB-2F
(EI) instrument. Combustion analyses were carried out on an Elementar
Vario EL instrument. Optical rotations were measured on a Perkin-
Elmer 241 polarimeter. HPLC analyses were carried out using a Merck/
Hitachi L-6200A pump and a Merck/Hitachi L-4500 diode array
detector, together with a CHIRALCEL OD-H column (DAICEL
Chemical Industries).
1
(m), 896 (m), 816 (m) cm-1; H NMR (300 MHz, DMSO-d6) δ )
2.45 (dd, J ) 13.8, 7.6 Hz, 1H), 2.67 (dd, J ) 13.8, 5.5 Hz, 1H),
3.24-3.28 (m, 2H), 3.55-3.65 (m, 1H), 3.65-3.70 (m, 2H), 3.72 (s,
3H), 3.89-3.92 (m, 2H), 4.48-4.53 (m, 2H), 4.80 (t, J ) 5.5 Hz, 1H),
6.68 (dd, J ) 8.1 Hz, J ) 1.9 Hz 1H), 6.80-6.84 (m, 2H); 13C NMR
(75 MHz, DMSO-d6) δ )39.3 (t), 55.4 (q), 59.7 (t), 65.3 (t), 70.3 (t),
72.6 (d), 113.2 (d), 113.5 (d), 121.2 (d), 132.3 (s), 146.3 (s), 148.6 (s);
FAB-MS [m/z (% intensity)] 242 (96.7) [M+], 211(2.7) [C11H15O4+],
198 (3.7) [C10H14O4+], 181 (53.4) [C10H13O3+], 167 (3.3) [C9H11O3+],
137 (100.0) [C8H9O2+], 107 (3.5) [C7H7O+], 77 (3.1) [C6H5+], 57 (3.8)
[C3H5O+], 45 (8.8) [C2H5O+], 31 (34.3) [CH3O+]. Anal. Calcd for
C12H18O5: C, 59.49; H, 7.49. Found: C, 59.41; H, 7.50.
10-Undecen-1-ol (4b).16 LiAlH4 (3.42 g, 90.0 mmol) was suspended
in 150 mL of absolute Et2O under nitrogen. The suspension was cooled
to 0 °C, and a solution of 10-undecenoic acid (2b, 11.06 g, 60.0 mmol)
in 20.0 mL of absolute Et2O was added in a dropwise manner. The
reaction mixture was allowed to warm to room temperature and stirred
for 16 h. Ice was added, followed by sufficient 10% H2SO4 to dissolve
[2-Methoxy-4-(2-propenyl)phenoxy]acetic Acid (2a). 2-Methoxy-
4-(2-propenyl)phenol (eugenol, 1a, 9.85 g, 60.0 mmol), chloroacetic
acid (5.67 g, 60.0 mmol), and NaOH (5.28 g, 132 mmol) were dissolved
in 30 mL of water and heated to reflux for 6 h. The solution was
allowed to cool to room temperature. It was then acidified to pH ) 1
with concentrated HCl, and the precipitate was separated by filtration.
(13) For the synthesis of the complete series of unnatural L-aldohexoses
by repetitive Sharpless epoxidation/olefination, see: Ko, S. Y.; Lee, A. W.;
Masamune, S.; Reed, L. A., III; Sharpless, K. B.; Walker, F. J. Science
1983, 220, 949-951.
(14) Hickey, M. J. J. Org. Chem. 1948, 13, 443-446.
(15) West, T. F. J. Chem. Soc. 1945, 490.
(16) Bunnell, R. H.; Shirley, D. A. J. Org. Chem. 1952, 17, 1545-1550.

Asymmetric Dihydroxylation of Polymer-Bound Olefins
J. Am. Chem. Soc., Vol. 120, No. 35, 1998 8999
the white precipitate. The ether phase was separated, and the aqueous
layer was extracted with Et2O (3 × 50 mL). The combined organic
layers were dried over Na2SO4 and concentrated in vacuo. The crude
product was purified by distillation (0.35 mbar; 100 °C), affording the
analytically pure product 4b as a colorless liquid (7.80 g, 77% yield):
IR (neat) 3334 (m), 2926 (s), 2855 (s), 1435 (m), 1371 (m), 1056 (m),
[C7H5+], 45 (28) [C2H5O+]. Anal. Calcd for C16H16O2: C, 79.97; H,
6.71. Found: C, 79.71; H, 6.87.
(R,R)-(+)-1-[4-(2-Hydroxyethoxy)phenyl]-2-phenyl-1,2-ethane-
diol (6c). AD-Mix â (252 mg) was dissolved in 4.00 mL of a 1:1-
mixture of tert-butyl alcohol and water (v/v). (E)-2-[4-(2-Phenylethe-
nyl)phenoxy]ethanol (4c, 43.3 mg, 0.18 mmol) was added, and the
mixture was stirred for 18 h at room temperature. The reaction was
quenched by addition of Na2SO3 (270 mg, 2.14 mmol). The resulting
mixture was stirred for 1 h and extracted with CH2Cl2 (5 × 20 mL).
The organic phases were combined, dried over MgSO4, and concen-
trated in vacuo. Silica gel chromatography of the residue (MeOH-
CHCl3 1:9, v/v) furnished the analytically pure triol as a colorless solid
1
994 (m), 909 (m), 722 (w) cm-1; H NMR (300 MHz, CDCl3) δ )
1.10-1.45 (br m, 12H), 1.46-1.52 (m, 2H), 1.72-1.95 (br s, 1H),
1.97-2.09 (m, 2H), 3.63 (t, J ) 6.6 Hz, 2H), 4.87-5.03 (m, 2H), 5.73-
5.88 (m, 1H); 13C NMR (75 MHz, CDCl3) δ )25.73, 28.93, 29.11,
29.40, 29.41, 29.54, 32.79, 33.79, 63.07, 114.10 (all t), 139.21 (d);
FAB-MS [m/z (% intensity)] 151.9 (5.2) [M - H2O+], 123.9 (60), 109.9
(95) [C8H14+], 108.9 (95) [C8H13+], 54.9 (85) [C3H3O+], 40.9 (100)
[C3H5+]. Anal. Calcd for C11H22O: C, 77.58; H, 13.02. Found: C,
77.44; H, 13.01.
(30.0 mg, 61% yield): mp 81 °C; [R]21 +108.5° (c 0.254, CHCl3);
D
IR (KBr) 3416 (s), 3030 (m), 2928 (m), 1613 (m), 1513 (s), 1454 (m),
1388 (m), 1249 (s), 1177 (m), 1080 (s), 1052 (s), 915 (m), 812 (m),
1
726 (m), 698 (s) cm-1; H NMR (300 MHz, CDCl3) 1.57 (br s, 1H),
(R,S)-1,2,11-Undecanetriol (rac-6b). K3[Fe(CN)6] (19.56 g, 60.0
mmol), K2CO3 (8.22 g, 60.0 mmol), and K2OsO2(OH)4 (29.5 mg, 0.4
mol % Os) were dissolved in 200 mL of a 1:1-mixture of tert-butyl
alcohol and water (v/v). 10-Undecen-1-ol (4b, 3.40 g, 20.0 mmol)
was added, and the mixture was stirred at room temperature for 24 h.
The reaction was quenched by the addition of Na2SO3 (30.0 g, 238
mmol), and the mixture was extracted with CH2Cl2 (4 × 200 mL).
The organic layers were combined, dried over MgSO4, and concentrated
in vacuo. Column chromatography of the residue on silica gel
(MeOH-CHCl3 1:9, v/v) furnished the pure triol rac-6b as a colorless
solid (3.19 g, 78%): mp 75 °C (lit.17 74-75 °C); IR (KBr) 3290 (s),
2917 (s), 2850 (s), 1471 (s), 1332 (m), 1086 (s), 1065 (s), 1009 (s);
2.02 (br s, 1H), 2.85 (br s, 1H), 3.90-3.94 (m, 2H), 3.99-4.02 (m,
2H), 4.65 (s, 2H), 6.75 (d, J ) 8.7 Hz, 2H), 7.02 (d, J ) 8.7 Hz, 2H),
7.08-7.11 (m, 2H), 7.18-7.23 (m, 3H); 13C NMR (75 MHz, CDCl3)
δ ) 61.3 (t), 69.0 (t), 78.6 (d), 79.1 (d), 114.1 (d), 127.0 (d), 127.8
(d), 128.1 (d), 128.2 (d), 132.5 (s), 139.9 (s), 158.2 (s); CI-MS [m/z
(% intensity)] 274 (1) [M+], 257 (100) [C16H17O3+], 167 (70)
[C9H11O3+]. Anal. Calcd for C16H18O4: C, 70.06; H, 6.61. Found:
C, 69.80; H, 6.55.
(R,R;S,S)-1-[4-(2-Hydroxyethoxy)phenyl]-2-phenyl-1,2-ethane-
diol (rac-6c). K3[Fe(CN)6] (178 mg, 0.54 mmol), K2CO3 (75.6 mg,
0.54 mmol) and K2OsO2(OH)4 (0.25 mg, 0.40 mol-% Os) were
dissolved in 4.00 mL of a 1:1-mixture of tert-butyl alcohol and water
(v/v). (E)-2-[4-(2-Phenylethenyl)phenoxy]ethanol (4c, 43.3 mg, 0.18
mmol) was added, and the solution was stirred for 18 h at room
temperature. Workup and chromatography as described above for 6c
afforded the racemic triol rac-6c as a colorless solid (27.3 mg, 55%
yield); IR and NMR data were identical to those of 6c.
1
720 (m) cm-1; H NMR (300 MHz, DMSO-d6) δ ) 1.22-1.48 (br s,
16H), 3.16-3.28 (m, 2H), 3.33-3.40 (m, 3H), 4.31-4.34 (m, 2H),
4.41 (t, J ) 5.6 Hz, 1H); 13C NMR (75 MHz, CD3OD) δ ) 26.68,
26.93, 30.57, 30.65, 30.68, 30.82, 33.66, 34.46, 63.02, 67.42 (all t),
73.28 (d); FAB-MS [m/z (% intensity)] 205.1 (0.1) [M + 1+], 173.1
(7) [C10H21O2+], 137.1 (31) [C10H17+], 95.1 (100) [C7H11+], 81.1 (99)
[C6H9+], 55.0 (78) [C4H7+], 41 (62) [C3H5+]. Anal. Calcd for
C11H24O3: C, 64.67; H, 11.84. Found: C, 64.53; H, 11.81.
(E)-[4-(2-Phenylethenyl)phenoxy]acetic Acid (2c). (E)-4-Hydroxy-
stilbene (1c, 1.00 g, 5.00 mmol), chloroacetic acid (945 mg, 10.0 mmol),
and KOH (1.12 g, 20.0 mmol) were dissolved in 100 mL of EtOH and
heated to reflux for 5 h. The colorless precipitate was collected by
filtration and dissolved in 500 mL water with heating. This solution
was acidified to pH ) 1 with concentrated HCl. Upon cooling to 4
°C, the analytically pure acid precipitated as a colorless solid (650 mg,
51%): mp 207 °C (lit.18 208 °C); IR (KBr) 3000-2500 (s), 1706 (s),
1610 (s), 1582 (s), 1433 (s), 1295 (s), 1239 (s), 1180 (s), 1085 (s), 970
(s), 831 (s), 800 (s), 758 (s), 693 (s) cm-1; 1H NMR (300 MHz, DMSO-
d6) δ ) 4.69 (s, 2H), 6.91 (d, J ) 8.8 Hz, 2H), 7.05-7.30 (m, 3H),
7.31-7.40 (m, 2H), 7.50-7.70 (m, 4H), 13.00 (br s, 1H); 13C NMR
(75 MHz, DMSO-d6) δ ) 64.5 (t), 114.7 (d), 126.2 (d), 126.4 (d),
127.3 (d), 127.8 (d), 127.9 (d), 128.7 (d), 130.2 (s), 137.3 (s), 157.5
(s), 170.2 (s); CI-MS [m/z (% intensity)] 255 (100) [M + 1+], 196
(40) [C14H12O+], 165 (15) [C10H13O2+], 107 (20) [C7H7O+]. Anal. Calcd
for C16H14O3: C, 75.58; H, 5.55. Found: C, 75.39; H, 5.55.
Derivatization of 1,2,11-Undecanetriol rac-6b with N,N′-Carbo-
nyldiimidazole for HPLC Analysis. (R,S)-9-(2-Oxo-1,3-dioxolan-
4-yl)nonyl-1H-imidazole-1-carboxylate (rac-7). A solution of (R,S)-
1,2,11-Undecanetriol (rac-6b, 100 mg, 0.49 mmol) and N,N′-
carbonyldiimidazole (160 mg, 0.98 mmol) in 20.0 mL of CH2Cl2 was
stirred for 5 h at room temperature. The solution was washed with
saturated aqueous NaHCO3 solution (2 × 10 mL), and the organic layer
was separated. The organic phase was dried over MgSO4 and
evaporated in vacuo. Purification of the residue by silica gel chroma-
tography (MeOH-CHCl3 1:9, v/v) furnished the cyclic carbonate rac-7
as a colorless oil (156 mg, 98%): IR (neat) 2928 (s), 2856 (s), 1798
(s), 1761 (s), 1471 (m), 1405 (s), 1376 (m), 1318 (m), 1291 (s), 1241
1
(s), 1174 (s), 1061 (s), 1003 (s), 772 (m), 650 (m) cm-1; H NMR
(300 MHz, CDCl3) δ )1.20-1.56 (br s, 12 H), 1.60-1.90 (br s, 4H),
4.02 (dd, J ) 8.3 Hz, 7.2 Hz, 1H), 4.37 (t, J ) 6.7 Hz, 2H), 4.48 (dd,
J ) 8.3 Hz, 7.8 Hz, 1H), 4.62-4.71 (m, 1H), 7.04 (s, 1H), 7.39 (s,
1H), 8.10(s, 1H); 13C NMR (75 MHz, CDCl3) δ ) 24.30 (t), 25.60 (t),
28.37 (t), 28.99 (t), 29.02 (t), 29.16 (t), 29.17 (t), 33.82 (t), 68.22 (t),
69.19 (t), 76.95 (d), 116.87 (d), 130.38 (d), 136.84 (d), 148.53 (s),
154.82 (s); CI-MS [m/z (% intensity)] 325 (100) [M + 1+]. Anal. Calcd
for C16H24N2O5: C, 59.24; H, 7.46; N, 8.64. Found: C, 59.16; H,
7.34; N, 8.57.
Immobilization of Alkenes 2a-c on the Solid Support. The
alkenes 2a-c (2.00 mmol) were dissolved in 50.0 mL of absolute
CH2Cl2 (in the case of (E)-[4-(2-phenylethenyl)phenoxy]acetic acid
2c, absolute DMF was used). DCC (2.00 mmol), a catalytic amount
of DMAP, and Wang-resin or TentaGel S-OH (1.00 mmol OH) were
added, and the resulting suspension was shaken overnight. The resin
was finally filtered off and washed successively with CH2Cl2, DMF,
and MeOH.
Dihydroxylation of Polymer-Bound Alkenes 3a-c. AD mix â
(1.40 g) [contains 0.4 mol % Os, 3.00 mmol K3[Fe(CN)6], 3.00 mmol
K2CO3, and 1.0 mol % (DHQD)2PHAL; same composition when the
ligands (DHDQ)2AQN or (DHDQ)2PYR were used, see Table 1] and
95.0 mg (1.00 mmol) MeSO2NH2 were dissolved in 30.0 mL of a 1:1-
mixture of THF and H2O (v/v). The polymer-bound alkenes 3a-c
(1.00 mmol) were added, and the suspension was stirred for the period
of time stated in Table 1. The resin 5a-c/ent-5a-c was collected by
(E)-2-[4-(2-Phenylethenyl)phenoxy]ethanol (4c). (E)-4-Hydroxy-
stilbene (1c, 580 mg, 2.96 mmol), KOH (253 mg, 4.44 mmol), and
2-chloroethanol (715 mg, 8.88 mmol) were dissoloved in 100 mL of
MeOH and heated to reflux for 8 h. Evaporation of the solvent gave
a colorless residue. Purification by silica gel chromatography (EtOAc)
afforded 275 mg (39%) of the analytically pure product as a colorless
powder: mp 148-149 °C; IR (KBr) 3421 (m), 3297 (m), 1605 (s),
1512 (m), 1255 (m), 1180 (m), 1096 (m), 1052 (m), 966 (m), 924 (m),
1
815 (s), 693 (m) cm-1; H NMR (300 MHz, DMSO-d6) δ ) 3.68-
3.75 (m, 2H), 4.01 (m, 2H), 4.88 (t, J ) 5.5 Hz, 1H), 6.94 (d, J ) 8.8
Hz, 2H), 7.03-7.29 (m, 3H), 7.30-7.41 (m, 2H), 7.47-7.58 (m, 4H);
13C NMR (75 MHz, DMSO-d6) δ ) 59.6 (t), 69.6 (t), 114.7 (d), 126.1
(d), 126.2 (d), 127.2 (d), 127.8 (d), 128.1 (d), 128.7 (d), 129.6 (s),
137.4, (s) 158.4 (s); EI-MS [m/z (% intensity)] 240 (99) [M+], 196
(100) [C14H12O+], 165 (40) [C10H13O2+], 152 (30) [C9H12O2+], 89 (20)
(17) Sisido, K.; Kawanisi, M.; Kondo, K.; Morimoto, T.; Saito, A.;
Hukue, N. J. Org. Chem. 1962, 27, 4073-4076.
(18) Cavallini, G.; Massarani, E.; Nardi, D.; D’Ambrosio, R. J. Am.
Chem. Soc. 1957, 79, 3514-3517.

9000 J. Am. Chem. Soc., Vol. 120, No. 35, 1998
Riedl et al.
filtration and washed successively with a 1:1 mixture of THF and H2O
(v/v) and with CH2Cl2. The resin was dried in vacuo over P2O5.
Release of the Dihydroxylation Products from the Polymer. The
dried resin 5a-c/ent-5a-c was suspended in 50.0 mL of absolute
toluene, and 5.00 mL of 1.00 M DIBAL in n-hexane was added at
room temperature under argon. The suspension was stirred at 0 °C
for 6 h. The reaction was quenched with MeOH. Sufficient 1.00 M
HCl was added to dissolve the white precipitate. The resin was filtered
off and washed successively with a 1:1 mixture of THF and H2O (v/v)
and with MeOH. The filtrate was extracted with CHCl3 until no more
product could be detected by TLC. The combined extracts were dried
over MgSO4 and concentrated in vacuo. Silica gel chromatography
(MeOH-CHCl3 1:9, v/v) furnished the pure dihydroxylation products
6a-c/ent-6a-c (yields and enantiomeric excesses are summarized in
Table 1).
Derivatization of the Polymer-Bound Dihydroxylation Product
5b/ent-5b with (R)-(+)-Mosher’s Acid. The polymer-bound dihy-
droxylation product 5b/ent-5b (80.0 mg, 0.13 mmol) was suspended
in 3.00 mL of absolute CH2Cl2 and 120 mg (0.51 mmol, 4 equiv) of
(R)-(+)-Mosher’s acid and 160 mg (0.78 mmol, 6 equiv) of DCC was
added. The suspension was shaken for 10 h at room temperature. The
polymer (mixture of the diastereomers 8, 9) was collected by filtration
and washed with CH2Cl2.
points in t2; 3 s pre-scan delay, phase sensitive in t1 using TPPI. 1H-
HOHAHA:20 160 t1 experiments with 16 scans each and 2k data points
in t2, 3 s pre-scan delay, 43 ms mixing time, phase sensitive in t1 using
TPPI. Spectral width of both experiments: 5000 Hz. Processing
included the application of squared sinebell window functions shifted
by π/2 in both dimensions and zero-filling to obtain a matrix of 2k ×
512 real data points after Fourier transformation. Nondecoupled
1H,13C-HMBC:21 128 t1 experiments with 96 scans each and 2k data
points in t2, 3 s pre-scan delay, 60 ms delay for the evolution of
longrange couplings (JH,C ) 8.3 Hz). Nonshifted sinebell window
functions and zero-filling were applied to obtain a matrix of 2k × 512
real data points after Fourier transformation. The spectrum was
calculated in the magnitude mode. 1H,13C-HSQC:22 128 t1 experiments
with 40 scans each and 2k data points in t2, 3 ms pre-scan delay, phase
sensitive in t1 using TPPI. In both dimensions, squared sinebell window
functions shifted by π/3 and zero filling were applied to obtain a matrix
of 2k × 512 real data points after Fourier transformation. Spectral
widths were 5000 Hz in F2 and 15 000 Hz (HSQC) or 22 500 Hz
(HMBC) in F1.
Acknowledgment. The authors thank Dr. Ralf M. Devant,
Merck KGaA, Darmstadt, Germany, for the determination of
the enantiomeric excesses of the compounds 6a and 7 by HPLC
on a ChiraSpher-type column. The authors furthermore ac-
knowledge financial support from the Fonds der Chemischen
Industrie and in particular a doctoral fellowship to R.R.
HRMAS NMR Spectroscopy. HRMAS NMR experiments were
carried out on a BRUKER-AVANCE DRX 500 instrument using a 4
1
mm H,13C,15N HRMAS probe with deuterium-lock. Samples of the
Wang-resins 3b, 5b/ent-5b, and 8/9 were swollen in CD2Cl2 and
measured at a sample rotation rate of 5500 Hz, T ) 298 K. 1H,1H
DQF-COSY:19 256 t1 experiments with 16 scans each and 2k data
JA980183D
(19) Rance, M.; Sørensen, O. W.; Bodenhausen, G., Wagner, G.; Ernst,
R. R.; Wu¨thrich, K. Biochem. Biophys. Res. Commun. 1983, 117, 479-
485.
(21) Bax, A.; Summers, M. F. J. Am. Chem. Soc. 1986, 41, 2093-2094.
(22) Bodenhausen, G.; Ruben, D. J. Chem. Phys. Lett. 1980, 69, 185-
189.
(20) Bax, A.; Davis, D. G. J. Magn. Reson. 1985, 65, 355-360.