Scope of enantioselective Palladium(II)-catalyzed aerobic alcohol oxidations with (-)-sparteine

Article abstract of DOI:10.1021/jo0269161

Evaluation of the substrate scope for Pd(II)/ (-)-sparteine catalyzed aerobic oxidative kinetic resolution of secondary alcohols is disclosed. An improved system is found with use of tert-butyl alcohol solvent in which benzylic and aliphatic alcohols as well as alcohols containing olefins are effectively oxidatively resolved. For substrates that successfully undergo oxidative kinetic resolution, k_rel values are generally between 10 and 20. Successful scale-up of various substrates to 10-mmol scale is described. Extension to oxidative desymmetrization of 1,3-meso-diols is successful with enantiomeric excesses ranging from 78 to 85%.

Full text of DOI:10.1021/jo0269161

existing kinetic resolutions of alcohols, we discovered the
combination of a Pd(II) salt and (-)-sparteine effectively
catalyzes the oxidative kinetic resolution of secondary
benzylic alcohols with molecular oxygen as the terminal
oxidant.6-10 Aerobic oxidative kinetic resolution has
recently been applied to the synthesis of various phar-
maceuticals.11 A noteworthy limitation of this methodol-
ogy is the low selectivity (krel values <8) for the oxidation
of saturated aliphatic alcohols and allylic alcohols.12
Herein we wish to disclose an improved Pd(II)-catalyzed
aerobic oxidative kinetic resolution of secondary alcohols,
which circumvents this limitation, as well as the sub-
strate scope and application of the Pd(II)/(-)-sparteine
catalyst system in the oxidative desymmetrization of
meso-diols.
Scop e of En a n tioselective
P a lla d iu m (II)-Ca ta lyzed Aer obic Alcoh ol
Oxid a tion s w ith (-)-Sp a r tein e
Sunil K. Mandal, David R. J ensen,
J acob S. Pugsley, and Matthew S. Sigman*
Department of Chemistry, University of Utah,
315 South 1400 East, Salt Lake City, Utah 84112
sigman@chem.utah.edu
Received December 28, 2002
Ab st r a ct : Evaluation of the substrate scope for Pd(II)/
(-)-sparteine catalyzed aerobic oxidative kinetic resolution
of secondary alcohols is disclosed. An improved system is
found with use of tert-butyl alcohol solvent in which benzylic
and aliphatic alcohols as well as alcohols containing olefins
are effectively oxidatively resolved. For substrates that
successfully undergo oxidative kinetic resolution, krel values
are generally between 10 and 20. Successful scale-up of
various substrates to 10-mmol scale is described. Extension
to oxidative desymmetrization of 1,3-meso-diols is successful
with enantiomeric excesses ranging from 78 to 85%.
With the selection of sec-phenethyl alcohol as the
substrate to standardize the initial reaction conditions,
it is possible that optimal conditions for other substrate
classes may have been overlooked. Accordingly, several
reaction parameters were reevaluated with use of the
aliphatic alcohol, 3,3-dimethyl-2-butanol, as the standard
substrate. As a first step in this process, several solvents
were assessed for the oxidative kinetic resolution, using
5 mol % of Pd(CH3CN)2Cl2 in combination with 20 mol
% of (-)-sparteine at 65 °C. In this evaluation, tert-butyl
alcohol, which was the second best in our original solvent
evaluation for sec-phenethyl alcohol,6 gave the highest
selectivity and conversions followed by 1,2-dichloroethane
(Figure 1). Pd(OAc)2 was also evaluated with several sol-
vents under similar conditions. The use of Pd(OAc)2 in
all solvents, except acetonitrile, gave poorer oxidative
kinetic resolutions than PdCl2 and the best results
were found by using 1,2-dichloroethane to give 70.4%
ee at 60.2% conversion, a krel value of 5.5. From the
initial screens, tert-butyl alcohol in combination with
Pd(CH3CN)2Cl2 and (-)-sparteine is clearly the best
system for oxidative kinetic resolution of this aliphatic
Chiral alcohols are ubiquitous in both natural products
and pharmaceuticals. For this reason, access to enantio-
merically enriched chiral alcohols is an important prob-
lem in organic synthesis. Of the many methods to
synthesize enantiomerically enriched alcohols, kinetic
resolutions are particularly attractive since racemic
alcohols are often readily available and inexpensive.
Kinetic resolution strategies of alcohols range from
epoxidation of allylic alcohols,1 to oxidative methods,2 to
resolution via acylation either by designed catalysts3 or
enzymes,4 to Mitsunobu strategies.5 As an alternate to
(1) Epoxidation: Martin, V. S.; Woodard, S. S.; Katsuki, T.; Yamada,
Y.; Ikeda, M.; Sharpless, K. B. J . Am. Chem. Soc. 1981, 103, 6237.
(2) Recent oxidative approaches: (a) Sun, W.; Wang, H.; Xia, C.;
Li, J .; Zhao, P. Angew. Chem., Int. Ed. 2003, 42, 1042. (b) Masutani,
K.; Uchida, T.; Irie, R.; Katsuki, T. Tetrahedron Lett. 2000, 41, 5119.
(c) Nishibayashi, I.; Takei, I.; Uemura, S.; Hidai, M. Organometallics
1999, 18, 2291. (d) Gross, Z.; Ini, S. Org. Lett. 1999, 1, 2077 (e)
Hashiguchi, S.; Fujii, A.; Haack, K.-J .; Matsumura, K.; Ikariya, T.;
Noyori, R. Angew. Chem., Int. Ed. Engl. 1997, 36, 288. (f) Rychnovsky,
S. D.; McLernon, T. L.; Rajapakse, H. J . Org. Chem. 1996, 61, 1194.
(3) Kinetic resolutions that have previously been accomplished by
using catalytic acylation: (a) Lin, M.-H.; Rajanbabu, T. V. Org. Lett.
2002, 4, 1607 (b) Vedejs, E.; MacKay, J . A. Org. Lett. 2001, 3, 535. (c)
Copeland, G. T.; Miller, S. J . J . Am. Chem. Soc. 2001, 123, 6496. (d)
Bellemine-Laponnaz, S.; Tweddell, J .; Ruble, J . C.; Breitling, F. M.;
Fu, G. C. Chem. Commun. 2000, 1009. (e) J arvo, E. R.; Copeland, G.
T.; Papaioannou, N.; Bonitatebus, P. J ., J r.; Miller, S. J . J . Am. Chem.
Soc. 1999, 121, 11638. (f) Vedejs, E.; Daugulis, O. J . Am. Chem. Soc.
1999, 121, 5813. (g) Sano, T.; Imai, K.; Ohashi, K.; Oriyama, T. Chem.
Lett. 1999, 265. (h) Miller, S. J .; Copeland, G. T.; Papaioannou, N.;
Horstmann, T. E.; Ruel, E. M. J . Am. Chem. Soc. 1998, 120, 1629. (i)
Ruble, J . C.; Tweddell, J .; Fu, G. C. J . Org. Chem. 1998, 63, 2794. (j)
Ruble, J . C.; Latham, H. A.; Fu, G. C. J . Am. Chem. Soc. 1997, 119,
1492. (k) Kawabata, T.; Nagato, M.; Takasu, K.; Fuji, K. J . Am. Chem.
Soc. 1997, 119, 3169. Using benzoylation: (l) Iwata, T.; Miyake, Y.;
Nishibayashi, Y.; Uemura, S. J . Chem. Soc., Perkin. Trans. 1 2002,
154 and refs 7 and 8 cited therein.
(5) (a) Chandrasekhar, S.; Kulkarni, G. Tetrahedron: Asymmetry
2002, 13, 615. (b) Li, Z.; Zhou, Z.; Wang, L.; Zhou, Q.; Tang, C.
Tetrahedron: Asymmetry 2002, 13, 145. (c) Hulst, R.; Basten, A.;
Fitzpatrick, K.; Kellog, R. M. J . Chem. Soc., Perkin. Trans. 1 1995,
2961.
(6) J ensen, D. R.; Pugsley, J . S.; Sigman, M. S. J . Am. Chem. Soc.
2001, 123, 7475.
(7) For a related oxidative kinetic resolution, see: (a) Ferreira, E.
M.; Stoltz, B. M. J Am. Chem. Soc. 2001, 123, 7725. (b) Bagdanoff, J .
T.; Ferreira, E. M.; Stoltz, B. M. Org. Lett. 2003, 5, 835.
(8) For a review of the use of molecular oxygen as a terminal oxidant
in asymmetric catalysis, see: Sigman, M. S.; J ensen, D. J .; Rajaram,
S. Curr. Opin. Drug Discovery Dev. 2002, 5, 860-869.
(9) For examples of Pd(II)-catalyzed aerobic oxidations, see: (a)
Schultz, M. J .; Park, C.; Sigman, M. S. Chem. Commun. 2002, 3034-
3035. (b) Ten Brink, G.-J .; Arends, I. W. C. E.; Sheldon, R. A. Adv.
Synth. Catal. 2002, 344, 355-369. (c) Kakiuchi, N.; Maeda, Y.;
Nishimura, T.; Uemura S. J . Org. Chem. 2001, 66, 6620. (d) ten Brink,
G.-J .; Arends, I. W. C. E.; Sheldon, R. A. Science 2000, 287, 1636. (e)
Peterson, K. P.; Larock, R. C. J . Org. Chem. 1998, 62, 3185. (f) Kaneda,
K.; Fujii, M.; Morioka, K. J . Org. Chem. 1996, 61, 4502. (g) Gomez-
Bengoa, E.; Noheda, P.; Echavarren, A. M. Tetrahedron Lett. 1994,
35, 7097. (h) Blackburn, T. F.; Schwartz, J . J . Chem. Soc., Chem.
Commun. 1977, 157.
(4) (a) Wong, C.-H.; Whitesides, G. M. Enzymes in Synthetic Organic
Chemistry; Pergamon: Oxford, UK, 1994; Chapter 2. (b) Burgess, K.;
J ennings, L. D. J . Am. Chem. Soc. 1991, 113, 6129. (c) Burgess, K.;
J ennings, L. D. J . Org. Chem. 1990, 55, 1138. (d) Burgess, K.; Cassidy,
J .; Henderson, I. J . Org. Chem. 1991, 56, 2050.
(10) (a) Nishimura, T.; Onoue, T.; Ohe, K.; Uemura, S. J . Org. Chem.
1999, 64, 6750. (b) Nishimura, T.; Onoue, T.; Ohe, K.; Uemura, S.
Tetrahedron Lett. 1998, 39, 6011.
(11) Sudalai, A.; Ali, I. S. Tetrahedron Lett. 2002, 43, 5435.
(12) See Supporting Information for details.
10.1021/jo0269161 CCC: $25.00 © 2003 American Chemical Society
Published on Web 05/07/2003
4600
J . Org. Chem. 2003, 68, 4600-4603

TABLE 1. Scop e of Ben zylic Alcoh ols in th e Oxid a tive
Kin etic Resolu tion
F IGURE 1. Comparison of krel values with use of Pd(OAc)2
and Pd(CH3CN)2Cl2 in different solvents.
substrate giving an enantiomeric excess of 99.9% at
68.5% conversion, a krel value of 17.4.
Of particular interest, the oxidative kinetic resolution
of sec-phenethyl alcohol with Pd(CH3CN)2Cl2 as the metal
source in various solvents showed effective kinetic reso-
lutions can be obtained in both tert-butyl alcohol and 1,2-
dichloroethane solvent. These observations showcase the
need for continued re-optimization throughout the cata-
lyst development process even when subtle changes are
made to the system.
Since both an aliphatic and aromatic substrate suc-
cessfully undergo oxidative kinetic resolutions in tert-
butyl alcohol solvent, this system could lead to a more
general solution for the oxidative kinetic resolution.
However, wide variations in the krel values were observed
when reproducing the initial results for 3,3-dimethyl-2-
butanol. Suspecting that the poor solubility of Pd(II) salts
in tert-butyl alcohol could lead to inconsistent formation
of the active catalyst species, the addition of 20% 1,2-
dichloroethane or toluene as a cosolvent was attempted
to potentially eliminate this issue but led to no improve-
ment. To circumvent the issue of inconsistent formation
of the Pd[(-)-sparteine)]Cl2 complex in situ, isolated
Pd[(-)-sparteine)]Cl2 was used to provide for consistent
results. Additionally, the use of activated 3 Å molec-
ular sieves further improved the reliability of the reac-
tion.13
To ensure the best conditions were selected, several
other reaction variables were evaluated. Reducing the
catalyst loading to 2.5 mol % led to an anticipated slower
oxidation with only 40% conversion after 36 h. Varying
the temperature of the reaction (55 and 70 °C) had little
effect on the krel values. Overall, the optimal conditions
for this oxidative kinetic resolution were 5 mol % of
Pd[(-)-sparteine)]Cl2,12 20 mol % of (-)-sparteine, 0.25
M alcohol in tert-butyl alcohol, and crushed activated
molecular sieves (3 Å) at 65 °C under a balloon pressure
of O2. By re-optimizing for 3,3-dimethyl-2-butanol, a
considerable improvement from a krel of 7.6 (77.8% ee at
58.5% conversion) to a krel of 17.3 (97.2% ee at 60.9%
conversion) in tert-butyl alcohol was observed.
a
b
See Supporting Information for chiral separations.
Data
represent a single experiment. c Pd(MeCN)2Cl2 at 70 °C and 0.25
M alcohol. Pd(OAc)2 at 60 °C and 0.25 M alcohol.
d
Su b st r a t e Scop e. The benzylic substrate scope of
the oxidative kinetic resolution with isolated Pd[(-)-
sparteine)]Cl2 and tert-butyl alcohol solvent was first
examined. As was observed with the previous systems,
simple benzylic alcohols (Table 1, entries 1-7) undergo
an effective kinetic resolution with similar krel values
observed with use of both 1,2-dichloroethane and tert-
butyl alcohol as solvents. However, in all cases, the
catalyst system performs better with tert-butyl alcohol
as the solvent. A substrate with two trifluoromethyl
groups gives a relatively low krel value (entry 8). Cyclic
benzylic substrates (entries 9-16) are good substrates
for the kinetic resolutions with krel values ranging from
13.5 to 21.0. Of particular note, both furyl- and ferrocene-
substituted alcohols undergo effective kinetic resolutions
(entries 22 and 26).
Substrates with two large substituents are relatively
poor for oxidation and kinetic resolution (entries 17 and
20). This finding fits with the interpretation that the
differential in size of the substituents plays a significant
role in the overall efficiency of the kinetic resolution.
Additionally, the previous observation of a lower krel value
as the size of R1 increases fits this notion. When R1 is
(13) Molecular sieves have been used by Uemura as a catalyst to
disproportionate H2O2 formed in the reaction, see ref 10a. We also
found that addition of a drop of water to the reaction mixture inhibits
the reaction.
J . Org. Chem, Vol. 68, No. 11, 2003 4601

TABLE 2. Scop e of Non -Ben zylic Alcoh ols in th e
Oxid a tive Kin etic Resolu tion
TABLE 3. Oxid a tive Kin etic Resolu tion on 10 m m ol
Sca le
a
b
Data represent a single experiment. Isolated yield of ketone.
a
b
See Supporting Information for chiral separations.
Data
represent a single experiment. c Pd(MeCN)2Cl2 at 70 °C and 0.25
M alcohol.
oxidative kinetic resolution was performed on a 10-mmol
scale for several substrates. Good overall mass recovery
was observed of both the optically enriched alcohol and
the prochiral ketone byproduct (Table 3). These larger
scale reactions did require slightly increased reaction
times of 24 h, compared to 20 h for smaller scale
reactions, and showed a slight decrease in krel values
(1.2-1.7). Overall, scale-up of the oxidative kinetic
resolution of alcohols was effective for aliphatic, allylic,
and benzylic alcohols.
Exten sion to m eso-Diol Desym m etr iza tion . A re-
lated enantioselective oxidation with significant potential
in organic synthesis is the oxidative desymmetrization
of a meso-diol.15 A variety of diol substrates are poten-
tially useful in such a desymmetrization reaction, includ-
ing 1,2- and 1,3-diols. The enantioselective oxidation of
1,3-diols leads to enantiomerically enriched â-hydroxy-
carbonyl compounds (aldol-type products), and significant
effort has been made to develop methodology for these
reactions.16,17 Therefore, the catalyst system developed
for the oxidative kinetic resolution of alcohols was
evaluated in the oxidative desymmetrization of 1,3-meso-
diols. Generally good yields (69-79%) and good ee values
(78-85%) of â-keto alcohols are obtained from various
meso-1,3-diols (Table 4). Upon scaling up the reaction to
functionalized with either a ketone, ester, alkyne, or
trifluoromethyl group, poor kinetic resolutions result.
Very slow oxidation is observed with the ester and
trifluoromethyl group (entries 18 and 24) while no
apparent oxidation is observed for the propargylic alcohol
(entry 21).14 However, benzoin does undergo a rapid and
clean oxidation but with an inefficient kinetic resolution
(entry 19). These poor oxidation results are consistent
with the observations of Uemura and co-workers in their
related aerobic oxidation system and reflect either the
ability to chelate the metal (ester or alkyne) or an overall
difficult oxidation (trifluoromethyl).10
The assessment of scope continued by evaluation of
several nonbenzylic substrates. Substrates with a large
substituent (i.e. tert-butyl) perform very well (Table 2,
entries 1 and 5). A substrate with a cyclopropyl substitu-
ent undergoes a reasonably effective kinetic resolution
with a krel value of 9.1. Substrates containing olefins are
viable substrates for oxidation. Kinetic resolutions of
these substrates again rely on a significant difference in
size to provide for an effective kinetic resolution. As an
example, cyclohexenol undergoes a rapid oxidation but
with a poor kinetic resolution. Of particular interest,
racemic isopugelol, which contains a terminal homoallylic
olefin, is an excellent substrate for oxidation and kinetic
resolution with no observation of double bond isomer-
ization. While an improved procedure would include the
use of air in place of pure O2, reactions run under an air
atmosphere are not effective due to substantial decom-
position of the catalyst.
(15) For examples of nonenzymatic desymmetrization of meso-diols
see: (a) Trost, B. M.; Mino, T. J . Am. Chem. Soc. 2003, 125, 2410. (b)
Hodgson, R.; Majid, T.; Nelson, A. J . Chem. Soc., Perkin Trans. 1 2002,
14, 1631-1643. (c) J iang, L.; Burke, S. D. Org. Lett. 2002, 4, 3411-
3414. (d) Harada, T.; Sekiguchi, K.; Nakamura, T.; Suzuki, J .; Oku,
A. Org. Lett. 2001, 3, 3309-3312. (e) Harada, T.; Yamanaka, H.; Oku,
A. Synlett 2001, 1, 61-64. (f) Yamada, S.; Katsumata, H. J . Org.
Chem. 1999, 64, 9365. (g) Oriyama, T.; Imai, K.; Hosoya, T.; Sano, T.
Tetrahedron Lett. 1998, 39, 397. (h) Via acetal cleavage, see: Fujioka,
H.; Nagatomi, Y.; Kotoku, N.; Kitagawa, H. Tetrahedron 2000, 56,
10141. (i) Kinugasa, M.; Harada, T.; Oku, A. J . Am. Chem. Soc. 1997,
119, 9067.
Since this reaction involves the use of a reagent in the
gas phase, it is imperative to show the reaction is
amenable to common laboratory scale. For this purpose,
(14) For an example of Vanadium-catalyzed aerobic oxidations of
propargylic alcohols, see: Maeda, Y.; Kakiuchi, N.; Matsumura, S.;
Nishimura, T.; Kawamura, T.; Uemura, S. J . Org. Chem. 2002, 67,
6718-6724.
(16) For a recent review, see: Machajewski, T. D.; Wong, C.-H.;
Lerner, R. A. Angew. Chem., Int. Ed. 2000, 39, 1352.
(17) For a review of catalytic asymmetric Mukaiyama aldol reac-
tions, see: Carreira, E. M. Comput. Asym. Catal. 1999, I-III, 997.
4602 J . Org. Chem., Vol. 68, No. 11, 2003

TABLE 4. Oxid a tive Desym m etr iza tion of
1,3-m eso-Diols
consistent with the prediction, based on acid/base chem-
istry, that tert-butyl alcohol should not replace a chloride
ligand in the resting state of the catalyst.19 Consistent
with these observations, we consider the simplest expla-
nation of the improved kinetic resolutions in tert-butyl
alcohol solvent to be its enhanced ability to support
cationic intermediates due to its higher polarity.
In conclusion, the scope of Pd(II)/(-)-sparteine cata-
lyzed enantioselective oxidations has been evaluated.
Replacement of 1,2-dichloroethane with tert-butyl alcohol
as solvent has provided for an improved catalyst system
that is effective not only for benzylic alcohols but also
for allylic and aliphatic alcohols. Applying this methodol-
ogy to the desymmetrization of 1,3-meso-diols has also
been accomplished to deliver chiral â-keto alcohols in
good yield and enantioselectivity. While higher krel values
have been obtained in other alcohol kinetic resolutions,
the value of this kinetic resolution protocol is the simplic-
ity in which it can be accomplished and the ability to
isolate synthetically viable levels of the optically active
alcohols. All reagents are commercially available and the
consumed reagent is molecular oxygen. Alcohols are
generally used without extensive purification.
A key limitation is the use of (-)-sparteine as the chiral
element. While it is a relatively inexpensive reagent,
access to (+)-sparteine is synthetically challenging20 and
the development of useful analogues is ongoing.21 Sig-
nificant effort in our laboratory has focused on the
understanding of this process and the development of
new catalyst systems with antipodal selectivity.22 Future
work will utilize the mechanistic information garnered
to both eliminate the need for exogenous (-)-sparteine
in the kinetic resolution and develop new catalysts that
can utilize air instead of pure O2 as the terminal oxidant.
a
Values after one recrystallization from dichloromethane
b
(0.5 mL)/hexane (2.0 mL) at -20 °C for 24 h. On 10 mmol
scale (3.23 g).
10 mmol, the oxidative desymmetrization performs quite
well (entry 2). Only a small difference in enantioselec-
tivity is observed when a substituent at the 3-position is
incorporated (entry 6). Additionally, activated C-Br
bonds are tolerated in the oxidative desymmetrization.
Very little over oxidation to the dione is observed. The
enantiomeric excess of the products can be enhanced
through recrystallization to 90-95% ee with only a small
decrease of yields (∼15%).
Unfortunately, 1,2-diols are not good substrates for
oxidative desymmetrization. meso-Hydrobenzoin oxidized
to benzoin with a maximum ee of 37%. cis-1,2-Cyclohex-
anediol and cis-1,2-cyclopentanediol oxidized to the cor-
responding R-hydroxy ketone with only 10% ee. In these
cases, the yield of the R-hydroxy ketone was low due to
over oxidation yielding the diketone as the major product.
Mech a n istic Con sid er a tion s. Considering the ki-
netic resolutions are generally better in tert-butyl alcohol
than in DCE as solvent, some mechanistic experiments
were performed.18 In a study of the kinetics of oxidative
kinetic resolutions, it was found the rate dependence on
exogenous (-)-sparteine concentration fits the same
model for both tert-butyl alcohol and DCE solvents. A
possible explanation for the enhanced reactivity in tert-
butyl alcohol is the Pd[(-)-sparteine]Cl2 could react with
tert-butyl alcohol in the presence of base to form a new
species where the chloride ligands are replaced with
alkoxide ligands. To test if this is thermodynamically
favorable, Pd[(-)-sparteine]Cl2 was heated in tert-butyl
alcohol (65 °C, 20 h) in the presence of exogenous (-)-
sparteine. 1H NMR analysis of the resulting isolated
complex showed only Pd[(-)-sparteine]Cl2, with no in-
corporation of tert-butyl alcohol. This observation is
Ack n ow led gm en t. This work was supported by the
National Institutes of Health (NIGMS No. RO1
GM63540) and by a Research Innovation Award spon-
sored by Research Corporation. We would like to thank
the University of Utah Research Foundation, Merck
Research, Rohm and Haas Research, and Invenux Inc.
for partial support of this research. We thank J ohnson
Matthey for palladium salts. S.K.M. would like to thank
the University of Utah for sponsorship of a Faculty
Intern position. D.R.J . is supported by an ACS Division
of Organic Chemistry Graduate Fellowship sponsored
by Schering-Plough Research Institute.
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures, characterization data, NMR spectra, and chiral
chromatographic separation data. This material is available
free of charge via the Internet at http://pubs.acs.org.
J O0269161
(19) These observations do not rule out the possibility that tert-butyl
alcohol transiently interacts with the catalyst.
(20) Smith, B. T.; Wendt, J . A.; Aube, J . Org. Lett. 2002, 4, 2577-
2579.
(18) (a) Mueller, J . A.; J ensen, D. R.; Sigman, M. S. J . Am. Chem.
Soc. 2002, 124, 8202-8203. (b) Mueller, J . A.; Sigman, M. S. J . Am.
Chem. Soc., in press.
(21) Dearden, M. J .; Firkin, C. R.; Hermet, J .-P. R.; O’Brien, P. J .
Am. Chem. Soc. 2002, 124, 11870-11871.
(22) J ensen, D. R.; Sigman, M. S. Org. Lett. 2003, 5, 63-65.
J . Org. Chem, Vol. 68, No. 11, 2003 4603