Asymmetric cyclopropanation of styrenes catalyzed by metal complexes of D2-symmetrical chiral porphyrin: Superiority of cobalt over iron

Article abstract of DOI:10.1021/jo070997p

(Chemical Equation Presented) The cobalt(II) complex of D ₂-symmetric chiral porphyrin [Co(1)] is an effective catalyst for highly diastereoselective and enantioselective cyclopropanation of a broad range of styrene derivatives under mild conditions. Dimerization of diazo compounds, a common side reaction in metal-mediated carbene transfer processes, is minimized in a cobalt porphyrin-based system, obviating the need to employ excess substrates and slow addition of diazo compounds. The high catalytic activity and selectivity of [Co(1)] evidently resulted from the appropriate combination of the cobalt ion and the chiral porphyrin 1 as the use of iron(III) complex of the same ligand [Fe(l)Cl] afforded the desired cyclopropane products in low yields and poor enantioselectivity.

Full text of DOI:10.1021/jo070997p

Asymmetric Cyclopropanation of Styrenes
Catalyzed by Metal Complexes of
D2-Symmetrical Chiral Porphyrin: Superiority of
Cobalt over Iron
of diazo reagents while still affording high diastereoselectivity
as well as high enantioselectivity.
2
Inspired by the extraordinary catalytic capabilities of heme-
containing enzymes in nature, metalloporphyrins have been
recognized as an important class of synthetic catalysts for oxo
and related atom/group transfer reactions on account of their
Ying Chen and X. Peter Zhang*
3
unique ligand environment and metal coordination mode. While
porphyrin complexes of several Group 8B metals such as Rh,
Fe, Ru, and Os have been previously known to catalyze
Department of Chemistry, UniVersity of South Florida,
Tampa, Florida 33620-5250, and Department of Chemistry,
UniVersity of Tennessee, KnoxVille, Tennessee 37996-1600
4
-6
7
cyclopropanation,
others revealed the catalytic capability of porphyrin complexes
of Co ([Co(Por)]) for cyclopropanation and related carbene
it was only very recently that we and
8
pzhang@cas.usf.edu
9
,10
transfer processes.
More importantly, we have shown that
ReceiVed May 10, 2007
[Co(Por)]-based asymmetric cyclopropanation could be operated
effectively in a one-pot fashion with alkenes as limiting regents
and did not require the slow addition of diazo reagents,7
e-i
a
practical protocol that is atypical for previously reported catalytic
systems. Furthermore, supported by a new family of D2-
(
2) For selected examples on asymmetric cyclopropanation, see: (a)
Fritschi, H.; Leutenegger, U.; Pfaltz, A. Angew. Chem., Int. Ed. Engl. 1986,
5, 1005. (b) Evans, D. A.; Woerpel, K. A.; Hinman, M. M.; Faul, M. F.
2
J. Am. Chem. Soc. 1991, 113, 726. (c) Doyle, M. P.; Winchester, W. R.;
Hoorn, J. A. A.; Lynch, V.; Simonsen, S. H.; Ghosh, R. J. Am. Chem. Soc.
1
1
993, 115, 9968. (d) Davies, H. M. L.; Hutcheson, D. K. Tetrahedron Lett.
993, 34, 7243. (e) Nishiyama, H.; Itoh, Y.; Matsumoto, H.; Park, S.-B.;
Itoh, K. J. Am. Chem. Soc. 1994, 116, 2223. (f) Nishiyama, H.; Itoh, Y.;
Sugawara, Y.; Matsumoto, H.; Aoki, K.; Itoh, K. Bull. Chem. Soc. Jpn.
The cobalt(II) complex of D
2
-symmetric chiral porphyrin
1
995, 68, 1247. (g) Doyle, M. P.; Zhou, Q. L.; Charnsangavej, C.; Longoria,
M. A.; McKervey, M. A.; Garcia, C. F. Tetrahedron Lett. 1996, 37, 4129.
h) Davies, H. M. L.; Bruzinski, P. R.; Lake, D. H.; Kong, N.; Fall, M. J.
[Co(1)] is an effective catalyst for highly diastereoselective
and enantioselective cyclopropanation of a broad range of
styrene derivatives under mild conditions. Dimerization of
diazo compounds, a common side reaction in metal-mediated
carbene transfer processes, is minimized in a cobalt porphy-
rin-based system, obviating the need to employ excess
substrates and slow addition of diazo compounds. The high
catalytic activity and selectivity of [Co(1)] evidently resulted
from the appropriate combination of the cobalt ion and the
chiral porphyrin 1 as the use of iron(III) complex of the same
ligand [Fe(1)Cl] afforded the desired cyclopropane products
in low yields and poor enantioselectivity.
(
J. Am. Chem. Soc. 1996, 118, 6897. (i) Lo, M. M.-C.; Fu, G. J. Am. Chem.
Soc. 1998, 120, 10270.
(
3) Kadish, K. M.; Smith, K. M.; Guilard, R., Eds. The Porphyrin
Handbook; Academic Press: San Diego, CA, 2000-2003; Vols. 1-20.
(4) For the first report, see: Callot, H. J.; Piechocki, C. Tetrahedron
Lett. 1980, 21, 3489.
(5) For a recent review, see: Simonneaux, G.; Le Maux, P. In The
Porphyrin Handbook; Kadish, K. M., Smith, K. M., Guilard, R., Eds.;
Academic Press: San Diego, CA, 2003; Vol. 11, pp 133-159.
(6) For selected examples on metalloporphyrin-based asymmetric cy-
clopropanation, see: (a) Ferrand, Y.; Le Maux, P.; Simonneaux, G. Org.
Lett. 2004, 6, 3211. (b) Berkessel, A.; Kaiser, P.; Lex, J. Chem. Eur. J.
2003, 9, 4746. (c) Teng, P.-F.; Lai, T.-S.; Kwong, H.-L.; Che, C. M.
Tetrahedron: Asymmetry 2003, 14, 837. (d) Che, C. M.; Huang, J.-S.; Lee,
F.-W.; Li, Y.; Lai, T.-S.; Kwong, H.-L.; Teng, P.-F.; Lee, W.-S.; Lo, W.-
C.; Peng, S.-M.; Zhou, Z.-Y. J. Am. Chem. Soc. 2001, 123, 4119. (e) Gross,
Z.; Galili, N.; Simkhovich, L. Tetrahedron Lett. 1999, 40, 1571. (f) Maxwell,
J. L.; O’Malley, S.; Brown, K. C.; Kodadek, T. Organometallics 1992, 11,
645.
Owing to its fundamental and practical importance, transition
metal complex-catalyzed cyclopropanation of alkenes has at-
tracted enormous research interest. A number of chiral metal
complexes have been developed as effective catalysts for
catalyzing asymmetric cyclopropanation, using diazo reagents
as carbene sources, with high to excellent enantioselectivity.
Despite these considerable advances, several important issues
associated with practicality and selectivity of the catalytic
process remain to be fully addressed to further expand practical
applications of asymmetric cyclopropanation. Of the various
1
(
7) (a) Chen, Y.; Huang, L.; Ranade, M. A.; Zhang, X. P. J. Org. Chem.
2
003, 68, 3714. (b) Chen, Y.; Huang, L.; Zhang, X. P. J. Org. Chem. 2003,
68, 5925. (c) Chen, Y.; Huang, L.; Zhang, X. P. Org. Lett. 2003, 5, 2493.
(d) Lee, M.-Y.; Chen, Y.; Zhang, X. P. Organometallics 2003, 22, 4905.
2
(
8
e) Huang, L.; Chen, Y.; Gao, G.-Y.; Zhang, X. P. J. Org. Chem. 2003, 68,
179. (f) Chen, Y.; Zhang, X. P. J. Org. Chem. 2004, 69, 2431. (g) Chen,
Y.; Fields, K. B.; Zhang, X. P. J. Am. Chem. Soc. 2004, 126, 14178. (h)
Chen, Y.; Gao, G.-Y.; Zhang, X. P. Tetrahedron Lett. 2005, 46, 4965. (i)
Chen, Y.; Zhang, X. P. Synthesis 2006, 1679.
(8) Penoni, A.; Wanke, R.; Tollari, S.; Gallo, E.; Musella, D.; Ragaini,
1
combinations of metal ions and supporting ligands, only a
F.; Demartin, F.; Cenini, S. Eur. J. Inorg. Chem. 2003, 1452.
limited number of catalytic systems can effectively cyclopro-
panate alkenes under conditions that are practically desirable:
with alkenes as the limiting reagents and without slow addition
(9) For non-porphyrin Co-based cyclopropanation systems, see: (a)
Niimi, T.; Uchida, T.; Irie, R.; Katsuki, T. AdV. Synth. Catal. 2001, 343,
7
9. (b) Ikeno, T.; Sato, M.; Sekino, H.; Nishizuka, A.; Yamada, T. Bull.
Chem. Soc. Jpn. 2001, 74, 2139. (c) Nakamura, A.; Konishi, A.; Tatsuno,
Y.; Otsuka, S. J. Am. Chem. Soc. 1978, 100, 3443.
*
Address correspondence to thtis author at the University of South Florida.
Fax: 813-974-1733.
1) (a) Lebel, H.; Marcoux, J.-F.; Molinaro, C.; Charette, A. B. Chem.
ReV. 2003, 103, 977. (b) Davies, H. M. L.; Antoulinakis, E. Org. React.
001, 57, 1. (c) Doyle, M. P.; Forbes, D. C. Chem. ReV. 1998, 98, 911.
(10) For our recent efforts on cobalt porphyrin-catalyzed analogous
nitrene transfer reactions, see: (a) Vyas, R.; Gao, G.-Y.; Harden, J. D.;
Zhang, X. P. Org. Lett. 2004, 6, 1907. (b) Gao, G.-Y.; Harden, J. D.; Zhang,
X. P. Org. Lett. 2005, 7, 3191. (c) Gao, G.-Y.; Jones, J. E.; Vyas, R.; Harden,
J. D.; Zhang, X. P. J. Org. Chem. 2006, 71, 6655.
(
2
1
0.1021/jo070997p CCC: $37.00 © 2007 American Chemical Society
Published on Web 06/23/2007
J. Org. Chem. 2007, 72, 5931-5934
5931

TABLE 1. Diastereo- and Enantioselective Cyclopropanation of
Styrenes Catalyzed by [Co(1)]a
FIGURE 1. Structure of cobalt(II) and Fe(III) complexes of D
symmetric chiral porphyrin 1: [Co(1)] and [Fe(1)Cl].
2
-
SCHEME 1. Cyclopropanation of Styrenes with Diazo
Reagents
symmetric chiral porphyrins,7g which can be straightforwardly
prepared from bromoporphyrin synthons via palladium-catalyzed
11
carbon-heteroatom cross-coupling reactions, it was demon-
strated that the [Co(Por)]-based system can efficiently catalyze
the cyclopropanation reaction in high diastereo- and enantiose-
lectivity. In particular, under the practical one-pot conditions
in the presence of a substoichiometric amount of 4-(dimethy-
lamino)pyridine (DMAP),7i the cobalt complex of chiral por-
phyrin 1 ([Co(1)], Figure 1) could cyclopropanate styrene in
high yields with excellent enantioselectivity (98% ee) as well
7g
as diastereoselectivity (>98% de). In addition to styrene, we
report herein that [Co(1)] is an effective catalyst for highly
diastereo- and enantioselective cyclopropanation of a broad
range of styrene derivatives (Scheme 1). On the basis of
1
2
comparative studies with [Fe(1)Cl] (Figure 1), we wish to
further illustrate the unique attributes of the cobalt center and
its superiority over iron in metalloporphyrin-based asymmetric
cyclopropanation.
To examine the substrate scope of the [Co(1)]-based catalytic
system, cyclopropanation reactions of a series of styrene
derivatives with varied electronic and steric properties were
carried out, along with styrene, using both ethyl diazoacetate
(EDA) and tert-butyl diazoacetate (t-BDA) as carbene sources
(Table 1). Under the one-pot protocol with alkenes as the
limiting reagents, the employment of 1 mol % [Co(1)] in the
presence of 0.5 equiv of DMAP could effectively cyclopropanate
styrene and its various derivatives at room temperature or lower.
For example, cyclopropanation reactions of styrene (Table 1,
entries 1-4) and its neutral derivatives with substituents at
different positions (Table 1, entries 8-20) could be performed
in high yields with excellent diastereoselectivity and enanti-
oselectivity. Similar results were also obtained for a derivative
with an electron-donating substituent (Table 1, entries 5-7).
In addition, the catalytic system appeared suitable for styrene
derivatives with electron-withdrawing substituents such as
(
11) (a) Chen, Y.; Zhang, X. P. J. Org. Chem. 2003, 68, 4432. (b) Gao,
a
Performed in toluene for 20 h under N2 with 1.0 equiv of alkene, 1.2
G.-Y.; Chen, Y.; Zhang, X. P. J. Org. Chem. 2003, 68, 6215. (c) Gao,
G.-Y.; Colvin, A. J.; Chen, Y.; Zhang, X. P. Org. Lett. 2003, 5, 3261. (d)
Gao, G.-Y.; Chen, Y.; Zhang, X. P. Org. Lett. 2004, 6, 1837. (e) Gao,
G.-Y.; Colvin, A. J.; Chen, Y.; Zhang, X. P. J. Org. Chem. 2004, 69, 8886.
equiv of EDA or t-BDA, and 1 mol % [Co(1)] in the presence of 0.5 equiv
of DMAP. [alkene]: 0.25 M. b Isolated yields. Determined by GC.
c
d
Determined by chiral GC or chiral HPLC. Carried out for 8 h. f Used 5
e
mol % [Co(1)]. g No diastereomers. h Not resolved.
(12) Wolf, J. R.; Hamaker, C. G.; Djukic, J. P.; Kodadek, T.; Woo, L.
K. J. Am. Chem. Soc. 1995, 117, 9194.
5
932 J. Org. Chem., Vol. 72, No. 15, 2007

SCHEME 2. Possible Mechanism for Cyclopropanation of
Alkenes and Dimerization of Diazo Reagents Catalyzed by
TABLE 2. Diastereo- and Enantioselective Cyclopropanation of
Styrenes Catalyzed by [Fe(1)Cl]a
[M(1)]
halogens and the trifluoromethyl group (Table 1, entries 21-
5). Functional substituents such as the acetoxy group could
be tolerated in the catalytic reaction (Table 1, entries 36 and
7). While 2-vinylnaphthalene was a suitable substrate
Table 1, entries 45-47), higher catalyst loadings were required
3
3
(
to cyclopropanate some of the R-substituted styrenes with good
yields (Table 1, entries 38-44).
It is noteworthy that even the extremely electron-deficient
pentafluorostyrene could be cyclopropanated, albeit in relatively
lower yields (Table 1, entries 33-35). To the best of our
knowledge, these represent the first examples of the catalytic
cyclopropanation of pentafluorostyrene. In most of the above
cases (Table 1), corresponding trans-cyclopropane esters were
produced with excellent diastereo- and enantioselectivity. In
general, better stereoselectivities were observed with t-BDA than
EDA and lowering the reaction temperature could further
improve enantioselectivity. Although the catalytic reactions were
carried out with styrenes as the limiting reagents and without
slow addition of EDA or t-BDA, it is notable that little to no
dimerization side products from the diazo reagents were
observed (Scheme 2).
With the aim of understanding the origin of the practicality
and selectivities associated with [Co(1)]-based cyclopropanation,
comparative catalytic reactions using the iron(III) complex of
the same chiral porphyrin 1 ([Fe(1)Cl], Figure 1) as the catalyst
were carried out (Table 2). Under the same conditions in the
presence of 0.5 equiv of DMAP, the cyclopropanation of styrene
with EDA by [Fe(1)Cl] gave essentially no formation of the
desired product (Table 2, entry 1). The same negative result
was obtained even when a 10-fold excess of styrene was used
a
Performed in toluene for 20 h at rt under N2 with 1 mol % [Fe(1)Cl].
b
Isolated yields. c Determined by GC. d Determined by chiral GC or chiral
HPLC. e Not determined.
entry 5) and for styrene derivatives with different substituents,
including electron-donating (Table 2, entry 6), -neutral (Table
, entry 7), and -withdrawing (Table 2, entries 8-10) groups.
2
Control experiments in the absence of alkene substrate and
DMAP showed that both [Fe(1)Cl] and [Co(1)] could lead to
the dimerization of EDA (data not shown). But [Fe(1)Cl]
catalyzed the dimerization process much more efficiently than
Co(1)]. Additionally, it was found that addition of DMAP
stalled the [Fe(1)Cl]-catalyzed dimerization process as a result
of the formation of white precipitates, which were also
observed in the presence of the alkene substrate (Table 2, entries
and 2). Importantly, the limited catalytic activity of [Co(1)]
toward EDA dimerization was completely inhibited with the
addition of DMAP without formation of other observable
products such as the white precipitates. While significant
amounts of dimerization of diazo reagents occurred in [Fe(1)-
Cl]-catalyzed reactions even with the use of excess amounts of
the alkene substrates (Table 2), no dimer formation was observed
in [Co(1)]-catalyzed cyclopropanation of styrenes regardless of
(Table 2, entry 2). In both cases, however, no dimerization
[
products were detected in the presence of DMAP. Instead,
13
formation of white precipitates was observed in both reactions.
1
3
In the absence of DMAP, the desired cyclopropane was
produced in a low yield with almost no asymmetric induction,
albeit with good diastereoselectivity (Table 2, entry 3). The
observed formation of significant amounts of side dimerization
products was likely responsible for the low yield of the desired
cyclopropanation products (Scheme 2). In the absence of
DMAP, the use of large excess amounts of styrene reduced the
formation of dimerization products, giving an improved yield
of the desired product but still poor enantioselectivity (Table
1
1
3
2, entry 4). Similar results were obtained with t-BDA (Table 2,
7
e-i
the presence or absence of DMAP (Table 1).
Together with
(
13) Preliminary NMR data suggest the white precipitates consisted of
the results from the above catalytic reactions (Tables 1 and 2),
these control experiments illustrate the distinctive capability of
cobalt in discriminating the desired cyclopropanation from the
undesired dimerization, two competitive processes that are
a mixture of two related compounds that contain both DMAP and ethyl
acetate units, presumably resulting from carbene transfer from the iron center
to DMAP. In the absence of either DMAP or EDA, no white precipitates
were observed.
J. Org. Chem, Vol. 72, No. 15, 2007 5933

presumably catalyzed by the same metalloporphyrin carbene
intermediate (Scheme 2).
sealed, and its contents were heated with stirring. The reaction
mixture was heated at 70 °C for 9 h. The resulting mixture was
cooled to room temperature, taken up in ethyl acetate, and
transferred to a separatory funnel. The mixture was washed with
water 3 times and concentrated in vacuo. The pure compound was
obtained after flash column chromatography (silica gel, ethyl
acetate:hexanes (v/v) 1:4) as a red solid (0.099 g, 91%). UV-vis
In summary, we have shown [Co(1)] is an effective catalyst
for highly diastereoselective and enantioselective cyclopropa-
nation of a broad range of styrene derivatives under the one-
pot practical protocol with alkene substrates as the limiting
reagents and without slow addition of diazo reagents. Through
comparative studies, we have demonstrated the unique charac-
teristics of cobalt and its superiority over iron in metallopor-
phyrin-catalyzed asymmetric cyclopropanation. We are currently
working to expand the scope of the [Co(1)]-based catalytic
system to include non-styrene substrates. Continuing efforts are
underway to further understand the origin of the practicality
and selectivity associated with [Co(1)]-catalyzed asymmetric
cyclopropanation.
(
CH
HRMS-EI ([M] ) calcd for C84
339.6909 with an isotope distribution pattern that is the same as
the calculated one.
Synthesis of Chiral Iron Porphyrin [Fe(1)Cl]. Free base chiral
porphyrin (0.043 g) and anhydrous FeCl (0.030 g) were placed in
2 2
Cl ), λmax nm (log ꢀ) 414 (5.37), 529 (4.14), 549 (3.84).
+
8 4
H96CoN O 1339.6887, found
1
2
an oven-dried, resealable Schlenk tube. The tube was capped with
a Teflon screwcap, evacuated, and backfilled with nitrogen. The
screwcap was replaced with a rubber septum, and 2,6-lutidine (0.020
mL) and dry DMF (4 mL) were added via syringe. The tube was
purged with nitrogen for 2 min, and then the septum was replaced
with the Teflon screwcap. The tube was sealed, and its contents
were heated at 160 °C with stirring. The resulting mixture was
Experimental Section
Synthesis of Free-Base Chiral Porphyrin 1.7g 5,15-Bis(2,6-
2 2
cooled to room temperature, taken up in CH Cl , and transferred
dibromophenyl)-10,20-bis[3,5-di(tert-butyl)phenyl]porphyrin (0.231
g, 0.2 mmol), (S)-(+)-2,2-dimethylcyclopropanecarboxamide (0.362
to a separatory funnel. The mixture was washed with 0.1 M HCl,
then washed with water 3 times and concentrated in vacuo. The
pure compound was obtained as a red solid (0.043 g, 93%). UV-
g, 3.2 mmol), Pd(OAc)
2
(0.018 g, 0.08 mmol), Xantphos (0.093 g,
(1.045 g, 3.2 mmol) were placed in an
0
.16 mmol), and Cs CO
2
3
vis (CH
HRMS-EI ([M] ) calcd for C84
371.6650.
Representative Procedure for Cyclopropanation Reactions.
2 2
Cl ), λmax nm (log ꢀ) 419 (5.34), 508 (4.36), 580 (4.08).
oven-dried, resealable Schlenk tube. The tube was capped with a
Teflon screwcap, evacuated, and backfilled with nitrogen. The
screwcap was replaced with a rubber septum, and THF (4 mL)
was added via syringe. The tube was purged with nitrogen for 2
min, and then the septum was replaced with the Teflon screwcap.
The tube was sealed, and its contents were heated with stirring.
The reaction was conducted at 100 °C for 48 h. The resulting
mixture was cooled to room temperature, taken up in ethyl acetate,
and concentrated in vacuo. The crude product was then purified
+
8 4
H96ClFeN O 1371.6592, found
1
Catalyst (1 mol %) and DMAP (50 mol %) were placed in an oven-
dried, resealable Schlenk tube. The tube was capped with a Teflon
screwcap, evacuated, and backfilled with nitrogen. The screwcap
was replaced with a rubber septum, and toluene (0.5 mL) and 1.0
equiv of styrene (0.25 mmol) were added via syringe, followed by
1.2 equiv of diazo compound and toluene again (0.5 mL). The tube
by flash chromatography (silica gel, ethyl acetate:hexanes (v/v) 1:4)
1
was purged with nitrogen for 1 min and its contents were stirred at
room temperature. After the reaction finished, the resulting mixture
was concentrated and the residue was purified by flash silica gel
chromatography to give the product. See the Supporting Information
for all characterizations.
as purple solids (0.217 g, 85%). H NMR (300 MHz, CDCl
3
) δ
8
8
3
.99 (d, J ) 4.8 Hz, 4H), 8.87 (d, J ) 4.8 Hz, 4H), 8.44 (br, 4H),
.04 (d, J ) 1.5 Hz, 4H), 7.83 (m, 4H), 6.50 (br, 4H), 1.53 (s,
6H), 0.87 (s, 12H), 0.69 (br, 4H), -0.05-0.14 (m, 20H), -2.34
s, 2H). 13C NMR (75 MHz, CDCl
3
) δ 169.6, 149.3, 139.8, 139.2,
(
1
2
5
33.6, 130.3, 129.8, 122.7, 121.8, 117.4, 35.0, 31.7, 29.0, 26.3,
Acknowledgment. We are grateful for financial support of
this work from the University of Tennessee and the University
of South Florida for Startup Funds, the American Chemical
Society for a PRF-AC grant, and the National Science Founda-
tion for a CAREER Award. Funding for the USF Department
of Chemistry Mass Spectrometry Facility has been furnished
in part by the NSF (CRIF:MU-0443611).
2.3, 20.2, 18.3. UV-vis (CH
2
Cl
2
), λmax nm (log ꢀ) 422 (5.46),
+
17 (4.17), 552 (3.77), 591 (3.66), 646 (3.53). HRMS-EI ([M] )
98 8 4
calcd for C84H N O 1282.7711, found 1282.7715 with an isotope
distribution pattern that is the same as the calculated one.
Synthesis of Chiral Cobalt Porphyrin [Co(1)].7g Free base
2
chiral porphyrin 1 (0.100 g) and anhydrous CoCl (0.080 g) were
placed in an oven-dried, resealable Schlenk tube. The tube was
capped with a Teflon screwcap, evacuated, and backfilled with
nitrogen. The screwcap was replaced with a rubber septum, and
Supporting Information Available: Analytical data and NMR
spectra for all products. This material is available free of charge
via the Internet at http://pubs.acs.org.
2,6-lutidine (0.027 mL) and dry THF (5 mL) were added via
syringe. The tube was purged with nitrogen for 2 min, and then
the septum was replaced with the Teflon screwcap. The tube was
JO070997P
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934 J. Org. Chem., Vol. 72, No. 15, 2007