The MPEG effect: Improving asymmetric processes by simple additives

Article abstract of DOI:10.1021/jo0495079

Small amounts of simple methoxy poly(ethylene glycol)s (MPEGs) have a beneficial effect on catalyzed asymmetric aryl and alkyl transfer reactions onto aldehydes. The enantiomeric excesses of the products are improved, and this MPEG effect allows a reduction of the catalyst loading by a factor of 10.

Full text of DOI:10.1021/jo0495079

SCHEME 1. Ar yl Tr a n sfer to Ald eh yd es Usin g
Bor on ic Acid s
Th e MP EG Effect: Im p r ovin g Asym m etr ic
P r ocesses by Sim p le Ad d itives
J ens Rudolph, Nina Hermanns,† and Carsten Bolm*
Institut fu¨r Organische Chemie der RWTH Aachen,
Professor Pirlet Strasse 1, D-52056 Aachen, Germany
carsten.bolm@oc.rwth-aachen.de
Received March 25, 2004
Abstr a ct: Small amounts of simple methoxy poly(ethylene
glycol)s (MPEGs) have a beneficial effect on catalyzed
asymmetric aryl and alkyl transfer reactions onto aldehydes.
The enantiomeric excesses of the products are improved, and
this “MPEG effect” allows a reduction of the catalyst loading
by a factor of 10.
substituted diaryl methanols with >90% ee. Second, to
our surprise, we found that the ee values increased when
the reactions were performed in the presence of small
amounts of DiMPEG (dimethoxy poly(ethylene glycol);
Scheme 1).7-9
We now wondered about the generality of this “MPEG
effect” and hoped that other catalyzed processes could
also be improved by the presence of this simple additive.
A reduction of the original catalyst loading of 10 mol %
to significantly less was considered as the most desirable
goal of this study.
Efficient catalysts for asymmetric C-C bond forma-
tions are difficult to find.1 Although major progress has
recently been made, catalysts yielding products with high
enantiomeric excesses at low catalyst loadings (e.g., 1 mol
%) are still rare.2 For the transfer of alkyl, alkenyl, and
aryl groups onto aldehydes and imines, organozinc-based
systems proved to be most suitable, and since the initial
discoveries, many catalysts have been developed that lead
to products with excellent enantiomeric excesses in high
yields.3-6 Often, however, 10-20 mol % of the catalyst
are required to achieve synthetically useful results. Thus,
in terms of catalyst loading, major progress is still most
desirable.
Since the increase of enantioselectivity upon DiMPEG
addition had so far only been demonstrated in aryl
transfer reactions from aryl boronic acids catalyzed by
4, it was essential to ensure that the effect also occurred
in reactions with both other aryl sources and different
catalysts. With regard to the first aspect, two systems
were studied. One was purely zinc-based and involved
the use of mixtures of diphenyl- and diethylzinc.4 The
second utilized triphenylborane as the aryl source and
represented a new, previously undescribed aryl transfer
method. By applying commercially available DBNE (N,N-
dibutyl norephedrine) as a catalyst, we confirmed that
the MPEG effect also occurred with other catalyst
systems. The most significant results are summarized in
Table 1.
As demonstrated in our previous studies,4a the applica-
tion of ferrocene 4 in the catalyzed phenyl transfer from
mixtures of ZnPh2 and ZnEt2 onto aldehyde 5 proceeds
well (93% yield) to give the resulting alcohol with
excellent enantioselectivity (98% ee). The data in Table
1 (entry 1) reveal that in this system, the addition of 10
mol % DiMPEG does not affect the ee. Although the yield
Recently, we described catalyzed enantioselective aryl
transfer reactions to aldehydes using ferrocene 4 as the
catalyst and aryl boronic acids as the aryl source.5 Two
aspects were particularly interesting: First, in most
reactions, the enantioselectivies were high, leading to
* To whom correspondence should be addressed.
† Current address: BASF AG, Ludwigshafen, Germany.
(1) (a) Noyori, R. Asymmetric Catalysis in Organic Synthesis;
Wiley: New York, 1994. (b) Comprehensive Asymmetric Catalysis;
J acobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer: Berlin, 1999.
(c) Catalytic Asymmetric Synthesis, 2nd ed.; Ojima, I., Ed.; Wiley-
VCH: New York, 2000.
(2) Recent advances have been summarized in a focused edition on
Enantioselective Catalysis: Bolm, C.; Gladysz, J ., Eds. Chem. Rev.
2003, 103, 2761-3400.
(3) For recent reviews, see: (a) Soai, K.; Shibata, T. In Comprehen-
sive Asymmetric Catalysis; J acobsen, E. N., Pfaltz, A., Yamamoto, H.,
Eds.; Springer: Berlin, 1999; pp 911-922. (b) Pu, L.; Yu, H.-B. Chem.
Rev. 2001, 101, 757-824.
(7) For example, in the absence of DiMPEG, the addition of
2-bromophenyl boronic acid onto benzaldehyde catalyzed by 4 afforded
a product with 73% ee (54% yield). When 10 mol % DiMPEG was
added, the ee of the resulting alcohol increased to 88% (58% yield).
(8) For the influence of achiral additives on reactions with organo-
metallic reagents, see: (a) H2O: Ribe, S.; Wipf, P. Chem. Commun.
2001, 299-307. (b) MeOH: Dosa, P. I.; Ruble, J . C.; Fu, G. C. J . Org.
Chem. 1997, 62, 444-445. (c) Review on additive effects in catalyses:
Vogl, E. M.; Gro¨ger, H.; Shibasaki, M. Angew. Chem. 1999, 111, 1672-
1680; Angew. Chem., Int. Ed. 1999, 38, 1570-1577.
(9) (a) Mun˜oz-Mun˜iz, O.; J uaristi, E. J . Org. Chem. 2003, 68, 3781-
3785. (b) For a review on the use of achiral ligands in asymmetric
catalyses, see: Walsh, P. J .; Lurain, A. E.; Balsells, J . Chem. Rev. 2003,
103, 3297-3344. (c) For effects of chiral additives in enantioselective
reactions with racemic catalysts, see: Mikami, K.; Yamanaka, M.
Chem. Rev. 2003, 103, 3369-3400. (d) For chiral poisoning and
asymmetric activations, see: Faller, J . W.; Lavoie, A. R.; Parr, J . Chem.
Rev. 2003, 103, 3345-3367.
(4) For selected recent examples, see: (a) Bolm, C.; Hermanns, N.;
Hildebrand, J . P.; Mun˜iz, K. Angew. Chem. 2000, 112, 3607-3609;
Angew. Chem., Int Ed. 2000, 39, 3465-3467. (b) Bolm, C.; Kesselgru-
ber, M.; Hermanns, N.; Hildebrand, J . P. Angew. Chem. 2001, 113,
1536-1538; Angew. Chem., Int Ed. 2001, 40, 1488-1490. (c) For an
initial study on the use of ferrocene 4 in aryl transfer reactions using
pure ZnPh2 as an aryl source, see: Bolm, C.; Mun˜iz, K. Chem.
Commun. 1999, 1295-1296. (d) Review: Bolm, C.; Hildebrand, J . P.;
Mun˜iz, K.; Hermanns, N. Angew. Chem. 2001, 113, 3382-3407; Angew.
Chem., Int. Ed. 2001, 40, 3284-3308.
(5) Bolm, C.; Rudolph, J . J . Am. Chem. Soc. 2002, 124, 14850-
14851.
(6) (a) Catalyzed asymmetric aryl-to-imine transfers: Hermanns,
N.; Dahmen, S.; Bolm, C.; Bra¨se, S. Angew. Chem. 2002, 114, 3844-
3846; Angew. Chem., Int. Ed. 2002, 41, 3692-3694. (b) Enantioselective
alkyl-to-imine transfer: Dahmen, S.; Bra¨se, S. J . Am. Chem. Soc. 2002,
124, 5940-5941 and references therein.
10.1021/jo0495079 CCC: $27.50 © 2004 American Chemical Society
Published on Web 05/06/2004
J . Org. Chem. 2004, 69, 3997-4000
3997

as ZnPhEt) is formed,4a and the aryl transfer rate is
reduced.11 Recent DFT calculations revealed that the
equilibrium between ZnEt2 and ZnPh2 on one hand and
2 ZnPhEt on the other is virtually thermoneutral (∆E )
0.2 kJ mol-1).12
TABLE 1. Asym m etr ic P h en yl Tr a n sfer on to Ald eh yd e
5 to Give Alcoh ol 6a
Thus, under Curtin-Hammet conditions,13 all three
organozinc species are present in solution, with ZnPh2
being the most reactive one.11,12 As a consequence, in the
asymmetric catalysis the aldehyde addition product is
formed via two independent routes. The first is catalyzed
(by ferrocene 4 or DBNE) and leads to enantiomerically
enriched diarylmethanols. The second gives a racemate
on an uncatalyzed parallel pathway. The ee of the product
will therefore be determined not only by the stereocontrol
of the catalyst but also by the ratio of these two reactions.
Since the latter is influenced by the concentrations of the
aryl zinc species, beneficial effects on the enantioselec-
tivity of the asymmetric aryl transfer reaction could be
expected from a shift of the forementioned equilibrium
toward the less reactive mixed zinc organyl (by addition
of ZnEt2) or a deactivation of a major fraction of the most
reactive aryl transfer agent (ZnPh2) by coordination to a
another agent (e.g., MPEG in this case). The previous
results4 and the data shown in entries 1-4 of Table 1
support this interpretation. Both the presence of ZnEt2
and the addition of DiMPEG lead to a lower reaction rate
(by reducing the quantity of ZnPh2) and give a product
with higher ee (by minimizing the uncatalyzed nonasym-
metric parallel reaction). The results with pure ZnPh2
(Table 1, entries 5 and 6) are more difficult to interpret.
The lower yields in the reactions with DiMPEG follow
the proposed scenario and can be regarded as evidence
of a reduced availability of the aryl transfer reagent. The
decreased ee with DBNE as a catalyst precursor, how-
ever, must then be explained by a negative interference
of the catalyzed pathway by DiMPEG.14
DiMPEG (10 mol %)
no additive
as an additivee
catalyst aryl source yield
ee
yield
[%]c
ee
entry precursor (method)b
[%]c [%]d
[%]d
1
2
3
4
5
6
4
ZnPh2/ZnEt2 93 98 (R) 75
98 (R)
(A)
DBNEf ZnPh2/ZnEt2 81 90 (S) 87
95 (S)
96 (R)
93 (S)
(A)
BPh3/ZnEt2
(B)
4
95 93 (R) 96
85 87 (S) 85
DBNEf BPh3/ZnEt2
(B)
4
ZnPh2
(C)
44 77 (R) 30-39 78-87 (R)
73 62 (S) 27-40 20-46 (S)
DBNEf ZnPh2
(C)
a
All experiments were performed multiple times to ensure
reproducibility. In entries 1-4, the yields and the ee values varied
by (5 and (1%, respectively. The reactions performed with ZnPh2
and DiMPEG (entries 5 and 6, right columns) were less reproduc-
b
ible, and the yield and ee ranges of six runs are given. Method
A: 0.65 equiv of ZnPh2 + 1.3 equiv of ZnEt2. Method B: 1 equiv
of BPh3 + 4.3 equiv of ZnEt2. Method C: 1.5 equiv of ZnPh2. c After
d
column chromatography. Enantiomeric ratios were determined
by chiral HPLC using a Chiralcel OD column. e DiMPEG with Mw
) 2500 was used. f (1S,2R)-Enantiomer of DBNE was used. Its
antipode gave the enantiomer of 6 and analogous results.
decreases, the ee remains 98%.10 With DBNE as a
catalyst precusor, however, the situation is different.
Here, DiMPEG has a mostly positive influence, and both
the ee and the yield increase when the reaction is
performed in the presence of the additive (Table 1, entry
2). Analogous observations were made with the new aryl
transfer system based on the use of mixtures of BPh3 and
ZnEt2. In this case, both the catalysis with ferrocene 4
and the one with DBNE were positively affected by the
addition of DiMPEG (Table 1, entries 3 and 4, respec-
tively). Thus, the yield and the ee in the formation of 6
increased when the reactions were performed in the
presence of the additive. The results of aryl transfer
reactions from pure ZnPh2 in the presence of DiMPEG
(Table 1, entries 5 and 6, right columns) were more
complex. Compared to reactions performed without the
additive, the yields were reduced. However, whereas use
of ferrocene 4 as a catalyst precursor gave about equal
or better enantioselectivities, application of DBNE af-
forded alcohol 6 with lower ee. Even though these
reactions proved to be difficult in terms of reproducibility,
the results were particularly important for the mecha-
nistic interpretation of the DiMPEG effect.
In the equilibrium situation discussed above (and an
uncatalyzed parallel reaction leading to racemic product),
the catalyst loading is an important factor.15 Usually,
relatively large catalyst quantities are required to guar-
antee that the major amount of the product stems from
the catalyzed pathway. If, however, the uncatalyzed
addition reaction is efficiently suppressed, lower catalyst
loadings should be applicable. This hypothesis was
experimentally confirmed, as revealed by the data pre-
sented in Table 2.16
(11) Kinetic studies by React-IR show a slower aryl transfer from
ZnPh2/ZnEt2 mixtures than from pure ZnPh2. This effect was also found
in a related system. Fontes, M.; Verdaguer, X.; Sola`, L.; Perica`s, M.
A.; Riera, A. J . Org. Chem. 2004, 69, 2532-2543.
(12) Rudolph, J .; Rasmussen, T.; Bolm, C.; Norrby, P.-O. Angew.
Chem. 2003, 115, 3110-3113; Angew. Chem., Int. Ed. 2003, 40, 3002-
3005.
(13) Maskill, H. The Physical Basis of Organic Compounds; Oxford
University Press: Oxford, 1985; pp 293-295.
(14) In principle, the improvement of the catalytic performance upon
addition of MPEG could also be explained by
a dissociation of
ZnPh2 is known to add to aldehydes even in the
absence of a catalyst.4 If ZnPh2 is mixed with ZnEt2, a
new zinc species (most likely a mixed zinc diorganyl such
aggregated catalysts. However, since a linear correlation between the
ee of a ferrocene of type 4 and that of the product was found in a
previous study (Bolm, C.; Mun˜iz, K.; Hildebrand, J . P. Org. Lett. 1999,
1, 491-494), we believe that this explanation is less relevant here.
(15) Interestingly, this uncatalyzed pathway also plays a role in the
diethylzinc addition to aromatic aldehydes. Although it is known that
ZnEt2 does not react with the aldehyde without initial activation, this
situation changes when the reaction started. The formed alkoxide can
then also become a ligand and thus lead to an undirected alternative
pathway.
(10) In some cases, the separation of the polyglycols from the product
alcohols was somewhat problematic, since in the extractive workup
no phase separation of the organic and the aqueous solution was
achieved. This problem could easily be solved by addition of brine (10
mL), affording clean product alcohols without traces of the polyglycols.
3998 J . Org. Chem., Vol. 69, No. 11, 2004

TABLE 2. Dep en d en ce of th e En a n tioselectivity in th e
F or m a tion of Dia r ylm eth a n ol 3 a n d 1-P h en ylp r op a n ol (7)
on th e Ca ta lyst Loa d in ga
TABLE 3. En a n tioselectivities in th e Ca ta lyzed
F or m a tion of (R)-3 in th e P r esen ce of Va r iou s Am ou n ts
a
of Zn Br 2
DiMPEG (25 mol %)
25 mol % DiMPEG
as an additive
10 mol % MonoMPEG
as an additive
no additive
as an additived,e
catalyst
loading
mol %
yield
[%]b
ee
yield
[%]b
ee
ZnBr2
entry [mol %]
yield
[%]b
ee
yield
[%]b
ee
entry
product
[%]c
[%]c
[%]c
[%]c
1
2
3
4
5
6
7
8
10
5
1
0.1
10
5
(R)-3
(R)-3
(R)-3
(R)-3
(R)-7
(R)-7
(R)-7
(R)-7
95
87
84
77
92
81
43
<5
97
95
79
3
93
93
86
nd
61
74
71
72
76
85
79
<10
97
96
93
12
94
94
92
68
1
2
3
4
5
5
10
25
50
100
85
86
80
66
57
97
96
95
94
80
75
89
53
76
55
97
97
95
94
80
a
Ferrocene 4 (10 mol %) was used as a catalyst precursor in
1
0.1
all reactions. DiMPEG: Mw ) 2000 g/mol; MonoMPEG: Mw
)
5000 g/mol. b,c See footnotes of Table 2.
a
Ferrocene 4 was used as a catalyst precursor in all cases.
Reactions affording alcohol 3 (entries 1-4) were carried out with
0.25 mmol of p-ClC6H4CHO (2), 0.65 equiv of ZnPh2, and 1.3 equiv
of ZnEt2 in toluene for 12 h at 10 °C. 1-Phenylpropanol (7; entries
5-8) was obtained using the following conditions: 0.25 mmol of
benzaldehyde and 1.5 equiv of ZnEt2 in toluene for 12 h at 0 °C.
tities of the zinc salt were tolerated, and reactions
performed in the presence of even 50 mol % ZnBr2 led to
3 with 94% ee (Table 3, entry 4). Both Di- as well as
MonoMPEG behaved virtually identically. In this context,
it should also be noted that large quantities of ZnBr2 (e.g.,
higher than 50 mol %) do not give a homogeneous
solution in toluene even after long periods of sonication.
Here also the equilibrium between ZnBr2 and ZnPh2 is
important, since ZnBr2 is removed from the reaction
mixture by the formation of ZnBrPh due to large amounts
of ZnPh2 with respect to the bromide. In the absence of
a catalyst, this phenylzinc reagent is expected to react
with the carbonyl compound even faster than ZnPh2.
After column chromatography. c Enantiomeric ratios of 3 were
determined by HPLC using a Chiralcel OB-H column. For the
b
analyses of the enantiomeric ratios of 7, a Chiralcel OD column
was used. DiMPEG with Mw ) 2500 g/mol was used. e Additional
d
experiments showed that the use of 25 or 10 mol % DiMPEG or
10 mol % MonoMPEG (Mw ) 2000 g/mol) leads to virtually
identical results (see also Table 3).
As discussed above, the enantioselective formation of
3 in the presence of 10 mol % ferrocene 4 proceeds well
and affords the product with 97% ee in 95% yield. When
the catalyst loading is reduced to 5 and 1 mol %, the ee
decreases to 95 and 79%, respectively (Table 2, entries 2
and 3). However, this loss of enantioselectivity is signifi-
cantly lower when 25 mol % DiMPEG is added to the
reaction mixture; even with 1 mol % catalyst, 91% ee is
achieved (entry 3). If the catalyst amount is further
reduced to 0.1 mol % (entry 4), the ee of 3 is low with
and without DiMPEG. Interestingly, analogous results
were obtained in diethylzinc additions to benzaldehyde
(Table 2, entries 5-8).17 Again, in the presence of 25 mol
% DiMPEG, a reduction of the catalyst loading to 1 mol
% was possible, and 1-phenylpropanol (7) was obtained
with >90% ee. Without the additive the enantioselectivity
decreases to 86% ee (entry 7). These results demonstrate
that the MPEG effect is not only relevant for phenyl
transfer reactions but also useful for reducing the catalyst
loading (here by a factor of 10) in asymmetric alkylations.
The latter results are relevant for the mechanistic
interpretation of the MPEG effect but also noteworthy,
since diarylzincs are commonly prepared by transmeta-
lation from aryllithium or aryl Grignard reagents by
treatment with zinc dihalides. In this case, various zinc
species together with newly formed (Lewis acidic) metal
salts are present in the reaction mixture, and all of them
can easily interfere with subsequent reactions, thereby
rendering the overall process less enantioselective. On
the basis of the results presented above, we now assumed
that the addition of PEG ethers would suppress these
unwanted nonasymmetric pathways by deactivating the
(achiral) metal catalysts and preventing their nonenan-
tioselective contribution on the overall process. Prelimi-
nary results confirmed this hypothesis. Thus, performing
asymmetric aryl transfer reactions catalyzed by 4 in the
presence of DiMPEG with arylzinc reagents prepared
from ZnBr2 and phenyllithium (followed by filtration
through Celite) afforded diarylmethanol 3 with up to 92%
ee.16a,18 Even though the yields in these first attempts
were rather low (8-31%), the results are promising, and
further optimizations are expected to render this process
synthetically useful.
Assuming that the effect of DiMPEG was related to
its ability to deactivate Lewis acidic species (such as
ZnPh2) by coordination, reactions in the presence of ZnBr2
were performed. Previously, we had found that 10 mol
% of this zinc salt led to racemic 3 in the phenyl transfer
to aldehyde 2 catalyzed by ferrocene 4. As the data in
Table 3 show, the addition of DiMPEG or monomethoxy
poly(ethylene glycol) (MonoMPEG) changed the outcome
of the catalysis significantly. Now, relatively large quan-
In summary, small amounts of simple PEG ethers can
have beneficial effects on catalyzed enantioselective
processes with parallel nonasymmetric pathways pro-
moted by achiral Lewis acids. Particularly noteworthy
is the fact that this MPEG effect allows a reduction of
the catalyst loading and thereby improves the efficiency
of an existing asymmetric catalytic process. Finally, a
new aryl transfer system based on the use of mixtures
of BPh3 and ZnEt2 was introduced.
(16) Catalyst loading can also be reduced when a PEG-supported
ferrocene is applied as a catalyst. (a) Hermanns, N. Dissertation,
RWTH Aachen, Aachen, Germany, 2002. (b) For the synthesis and
application of this catalyst, see also: Bolm, C.; Hermanns, N.; Claâen,
A.; Mun˜iz, K. Bioorg. Med. Chem. Lett. 2002, 12, 1795-1798.
(17) Without the additive, this reaction has been studied before. For
details, see: Bolm, C.; Mun˜iz-Fernandez, K.; Seger, A.; Raabe, G.;
Gu¨nther, K. J . Org. Chem. 1998, 63, 7860-7867.
(18) Rudolph, J .; Bolm, C. Unpublished results.
J . Org. Chem, Vol. 69, No. 11, 2004 3999

addition of the precatalyst followed by the aldehyde as decribed
unter method A.
Exp er im en ta l Section
Meth od A. Under an inert atmosphere, in a well-dried
reaction vessel (18 mm, 50 mm high) with a Teflon-coated
stirring bar, diphenyl zinc (36 mg, 0.16 mmol) is dissolved in
toluene (2 mL). After treatment of the mixture with ZnEt2
(33 µL, 0.33 mmol), the solution is stirred for 15-30 min. When
required, dimethoxy poly(ethylene glycol) (63 mg, 0.025 mmol,
Mw ) 2500 g/mol) dissolved in toluene (2 mL) is added. Then,
the precatalyst (ferrocene 4, 12 mg, 0.025 mmol; DBNE, 6.6 mg,
0.025 mmol) is added. After stirring for another 15-30 min at
room temperature, the mixture is cooled to 10 °C. Finally, the
aldehyde (p-Cl-benzaldehyde, 35 mg, 0.25 mmol; p-Me-benzal-
dehyde, 30 mg, 30 µL, 0.25 mmol) is added in one portion. After
stirring for 12 h at 10 °C, the reaction mixture is quenched with
H2O (10 mL) and extracted with dichloromethane (3 × 50 mL).
The organic layers are combined and dried (MgSO4), and the
solvents are removed under reduced pressure. Subsequent
purification by flash chromatography (pentane/diethyl ether
[85:15]) affords diaryl methanols 3 or 6.
Meth od C. Under an inert atmosphere, in a well-dried
reaction vessel (18 mm L, 50 mm high) with a Teflon-coated
stirring bar, diphenyl zinc (82 mg, 0.375 mmol) is dissolved in
toluene (2 mL). When required, dimethoxy poly(ethylene glycol)
(63 mg, 0.025 mmol, Mw ) 2500 g/mol) dissolved in toluene
(2 mL) is added. The protocol continues with the addition of
the precatalyst followed by the aldehyde as decribed unter
method A.
Ack n ow led gm en t. We are grateful to the Fonds der
Chemischen Industrie and to the Deutsche Forschungs-
gemeinschaft (DFG) within the SFB 380 and the GK
440 for financial support. We also thank BAYER AG
for the generous donation of BPh3, Inga Walzel for
preparative contributions, and Prof. Dr. Per-Ola Norrby,
Sandra Saladin, and Dr. Hans Adolfsson for helpful
discussions.
Meth od B. In a well-dried reaction vessel (18 mm L, 50 mm
high) with a Teflon-coated stirring bar, triphenyl borane (60 mg,
0.25 mmol) is dissolved in toluene (2 mL) under an inert
atmosphere. After treatment of the mixture with ZnEt2 (110 µL,
1.075 mmol) in one portion, the solution is stirred at room
temperature for 15-30 min. When required, dimethoxy poly-
(ethylene glycol) (63 mg, 0.025 mmol, Mw ) 2500 g/mol) dissolved
in toluene (2 mL) is added. The protocol continues with the
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
analysis and spectra, as well as HPLC conditions for the
enantiomeric ratio determinations for products 3, 6, and 7.
This material is available free of charge via the Internet at
http://pubs.acs.org.
J O0495079
4000 J . Org. Chem., Vol. 69, No. 11, 2004