Facile, mild, and highly enantioselective alkynylzinc addition to aromatic aldehydes by BINOL/N-methylimidazole dual catalysis

Article abstract of DOI:10.1021/jo0707535

(Chemical Equation Presented) The dual Lewis acid/base catalytic system, generated from N-methylimidazole (NMI), (R)-1,1′-bi-2-naphthol [(R)-BINOL], and Ti(OiPr)₄, effectively catalyzes the enantioselective alkynylation of aldehydes in the pres

Full text of DOI:10.1021/jo0707535

presence of amine base.3,4 Another system involves the use of
Et2Zn or Me2Zn to prepare in situ the alkynylzincs.5-8 In this
respect, direct use of the readily available and inexpensive
unmodified 1,1′-bi-2-naphthol (BINOL) in combination with Ti-
(OiPr)4 and Et2Zn or Me2Zn has resulted in a series of exciting
findings.9,10
Facile, Mild, and Highly Enantioselective
Alkynylzinc Addition to Aromatic Aldehydes by
BINOL/N-Methylimidazole Dual Catalysis
Fei Yang, Peihua Xi, Li Yang, Jingbo Lan, Rugang Xie, and
Jingsong You*
BINOL-Ti complex can catalyze alkyne addition to alkyl,
aryl, and R,â-unsaturated aldehydes with high ee values and
good yields in the presence of Et2Zn.9a,b However, in these
systems, higher reaction temperatures are generally required in
the first step to prepare the corresponding alkynylzinc from the
terminal alkyne and alkylzinc reagent.9a-c The high temperature
for the preparation of the alkynylzinc reagents may cause the
decomposition of certain functional alkynes. Although the use
of Me2Zn instead of Et2Zn can lower the reaction temperature
in the formation of alkynylzinc, these BINOL-Ti(OiPr)4-Me2-
Zn systems generally require a separate step to synthesize
alkynylzinc.9d,10
Key Laboratory of Green Chemistry and Technology of Ministry
of Education, College of Chemistry, and State Key Laboratory
of Biotherapy, West China Hospital, West China Medical
School, Sichuan UniVersity, 29 Wangjiang Road,
Chengdu 610064, People’s Republic of China
jsyou@scu.edu.cn
ReceiVed April 17, 2007
Quite recently, Pu et al. discovered that the addition of
hexamethylphosphoramide (HMPA) greatly accelerates the
reaction of Et2Zn with terminal alkynes at room temperature
while maintaining the high enantioselectivity for the addition
to aldehydes.11 The mild condition for the formation of
alkynylzinc reagents avoids the reflux of the toluene solutions
of the alkynes and Et2Zn as previously reported9a-c and enables
the use of functional alkynes in this asymmetric reaction with
high enantioselectivity. However, the protocol requires subs-
toichiometric quantities of chiral BINOL (40 mol %), 2 equiv
The dual Lewis acid/base catalytic system, generated from
N-methylimidazole (NMI), (R)-1,1′-bi-2-naphthol [(R)-
BINOL], and Ti(OiPr)4, effectively catalyzes the enantiose-
lective alkynylation of aldehydes in the presence of Et2Zn
in good yields and excellent enantioselectivities of up to 94%
ee at room temperature. The mild reaction conditions make
it possible to use functional alkynes in this asymmetric
addition.
(3) (a) Frantz, D. E.; Fassler, R.; Carreira, E. M. J. Am. Chem. Soc. 2000,
122, 1806. (b) Anand, N. K.; Carreira, E. M. J. Am. Chem. Soc. 2001, 123,
9687. (c) Fa´ssler, R.; Tomooka, C. S.; Frantz, D. E.; Carreira, E. M. Proc.
Natl. Acad. Sci. U.S.A. 2004, 101, 5843.
(4) The use of stoichiometric amounts of chiral amino alcohol-based
ligands: (a) Jiang, B.; Chen, Z. L.; Xiong, W. N. Chem. Commun. 2002,
1524. (b) Chen, Z. L.; Xiong, W. N.; Jiang, B. Chem. Commun. 2002, 2098.
(c) Jiang, B.; Si, Y. G. AdV. Synth. Catal. 2004, 346, 669.
(5) Bisoxazolidine-catalyzed enantioselective alkynylation of aromatic
aldehydes at low temperature (-4 to -15 °C): Wolf, C.; Liu, S. J. Am.
Chem. Soc. 2006, 128, 10996.
(6) Catalytic procedures based on amino alcohol ligands focus on the
addition of phenylacetylene to aromatic aldehydes, while few address the
need to utilize functional alkynes: (a) Xu, Z.; Wang, R.; Xu, J.; Da, C.;
Yan, W.; Chen, C. Angew. Chem., Int. Ed. 2003, 42, 5747. (b) Xu, Z.;
Chen, C.; Xu, J.; Miao, M.; Yan, W.; Wang, R. Org. Lett. 2004, 6, 1193.
(c) Dahmen, S. Org. Lett. 2004, 6, 2113. (d) Fang, T.; Du, D. M.; Lu, S.
F.; Xu, J. Org. Lett. 2005, 7, 2081.
(7) Dinuclear Zn-catalyzed asymmetric alkynylation of R,â-unsaturated
aldehydes at 4 °C: Trost, B. M.; Weiss, A. H.; von Wangelin, A. J. J. Am.
Chem. Soc. 2006, 128, 8.
(8) Selected examples for modified BINOLs as ligands: (a) Moore, D.;
Huang, W. S.; Xu, M. H.; Pu, L. Tetrahedron Lett. 2002, 43, 8831. (b) Xu,
M. H.; Pu, L. Org. Lett. 2002, 4, 4555. (c) Liu, Q. Z.; Xie, N. S.; Luo, Z.
B.; Cui, X.; Cun, L. F.; Gong, L. Z.; Mi, A. Q.; Jiang, Y. Z. J. Org. Chem.
2003, 68, 7921. (d) Liu, L.; Pu, L. Tetrahedron 2004, 60, 7427. (e) Li, Z.
B.; Pu, L. Org. Lett. 2004, 6, 1065.
(9) (a) Moore, D.; Pu, L. Org. Lett. 2002, 4, 1855. (b) Gao, G.; Moore,
D.; Xie, R. G.; Pu, L. Org. Lett. 2002, 4, 4143. (c) Marshall, J. A.; Bourbeau,
M. P. Org. Lett. 2003, 5, 3197. (d) Lu, G.; Li, X.; Chan, W. L.; Chan, A.
S. C. Chem. Commun. 2002, 172.
(10) The method also required 1 equiv of an additional chiral sulfonamide
ligand and was only applied in the addition of phenylacetylene to aromatic
aldehydes below 0 °C for 1-2 days: Li, X. S.; Lu, G.; Kwok, W. H.;
Chan, A. S. C. J. Am. Chem. Soc. 2002, 124, 12636.
(11) (a) Gao, G.; Xie, R. G.; Pu, L. Proc. Natl. Acad. Sci. U.S.A. 2004,
101, 5417. (b) Gao, G.; Wang, Q.; Yu, X. Q.; Xie, R. G.; Pu, L. Angew.
Chem., Int. Ed. 2006, 45, 122. (c) Rajaram, A. R.; Pu, L. Org. Lett. 2006,
8, 2019.
The catalytic asymmetric alkynylzinc addition to aldehydes
can provide a very convenient route to the corresponding chiral
secondary propargylic alcohols,1 which have been identified as
versatile building blocks for fine chemicals, pharmaceuticals,
and natural products.2 It is therefore not surprising that great
efforts have recently been directed toward the development of
this important asymmetric reaction, and two general catalytic
systems are currently considered to be the most practical. One
has recently been discovered by Carreira and co-workers, using
stoichiometric or catalytic quantities of Zn(OTf)2, N-methyl-
ephedrine, and Et3N to afford the desired products in high yields
and enantioselectivities in the addition of terminal acetylenes
to aldehydes.3 In this approach, the zinc alkynylides are
generated in situ from terminal alkynes and Zn(OTf)2 in the
(1) For reviews, see: (a) Frantz, D. E.; Fassler, R.; Tomooka, C. S.;
Carreira, E. M. Acc. Chem. Res. 2000, 33, 373. (b) Pu, L.; Yu, H. B. Chem.
ReV. 2001, 101, 757. (c) Pu, L. Tetrahedron 2003, 59, 9873-9886. (d)
Cozzi, P. G.; Hilgraf, R.; Zimmermann, N. Eur. J. Org. Chem. 2004, 4095.
(2) Selected examples: (a) Marshall, J. A.; Wang, X. J. J. Org. Chem.
1992, 57, 1242. (b) Meyers, A. G.; Zhang, B. J. Am. Chem. Soc. 1996,
118, 4492. (c) Tse, B. J. Am. Chem. Soc. 1996, 118, 7094. (d) Fox, M. E.;
Li, C.; Marino, J. P.; Overman, L. E, Jr. J. Am. Chem. Soc. 1999, 121,
5467. (e) Trost, B. M.; Krische, M. J. J. Am. Chem. Soc. 1999, 121, 6131.
(f) Sugiyama, H.; Yokokawa, F.; Shioiri, T. Org. Lett. 2000, 2, 2149. (g)
Aschwanden, P.; Carreira, E. M. In Acetylene Chemistry: Chemistry,
Biology and Material Science; Diederich, F., Stang, P. J., Tykwinski, R.
R., Eds.; Wiley-VCH: Weinheim, Germany, 2005; p 101.
10.1021/jo0707535 CCC: $37.00 © 2007 American Chemical Society
Published on Web 06/08/2007
J. Org. Chem. 2007, 72, 5457-5460
5457

TABLE 1. Some Representative Results from the Screening of
Reaction Conditions for the Additions of Phenylacetylene with
Benzaldehyde in the Presence of (R)-BINOL, Ti(OiPr)4, Et2Zn, and
Ima
of HMPA, 1 equiv of Ti(OiPr)4, and 4 equiv of Et2Zn to achieve
excellent enantioselectivities. Clearly, it is highly desirable to
reduce loadings of chiral BINOL as well as other additives to
make this process practical and economical. This should also
represent a partial solution to a long-standing challenge in
asymmetric catalysis.12
Recently, the concept of dual acid/base catalysis has been
introduced for asymmetric catalytic reactions, in which both
electrophilic and nucleophilic precursors are activated by
catalytic quantities of chiral Lewis acid and base, respectively.13
Imidazole (Im) and its derivatives are ubiquitous in biological
and biochemical structure and function and play the key roles
in the synergistically catalytic mechanisms of many enzymes.
Recently, some examples have demonstrated that imidazoles
can be employed as the base moiety of dual activation or co-
catalysis for the asymmetric catalytic reaction,14 and the basic
nitrogen of the imidazole ring can activate the alkyne.15 Thus
we speculated that application of a double catalytic activation
strategy seems to be one of the most promising solutions, which
should cause the chiral BINOL-Ti complex and Im to activate
electrophiles (carbonyl compounds) and nucleophiles (terminal
alkynes), respectively. Following our continuing interest in the
development of dual catalysis16 as well as imidazole chemistry,17
we therefore focused on dual activation based on imidazole as
well as its derivatives. It is reasonable to assume that imidazoles
1 might meet the requirement as Lewis bases to facilitate the
deprotonation of terminal acetylenes to improve the formation
of alkynylzinc reagents,18 as we had observed that benzaldehyde
was able to react smoothly with phenylacetylene with the
assistance of 5 mol % of N-methylimidazole (NMI) 1a and 2.0
equiv of Et2Zn at room temperature with the formation of the
racemic alkynylation product in 52% yield (Table 1, entry 1).
As expected, we herein report that the truly BINOL-Ti catalytic
version of alkyne addition to aldehyde could be achieved with
high enantioselectivity in the presence of Et2Zn at room
temperature when a catalytic amount of NMI was employed as
Lewis base.11
base
BINOL
yield
ee
entry (mol %)b (mol %) BINOL/Ti(OiPr)4 solvent (%)c (%)d
1
2
3
4
5e
6
7
8
9
1a (5)
1a (10)
1a (5)
1a (2.5)
1a (5)
1a (5)
1a (5)
1a (5)
1a (5)
1a (5)
1a (5)
1a (2.5)
1b (5)
1c (5)
1d (5)
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
THF
52
94
92
72
83
54
92
93
68
ND
10
10
10
10
10
10
10
10
10
10
5
1:2.5
1:2.5
1:2.5
1:2.5
1:2
82
93
91
90
83
89
82
79
60
76
84
87
87
84
1:3
1:5
1:2.5
1:2.5
1:2.5
1:2.5
1:2.5
1:2.5
1:2.5
10
Et2O
11
12
13
14
15
toluene ND
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
68
83
78
71
10
10
10
a Et2Zn/phenylacetylene/aldehyde ) 2:2:1. b NMI (1a), imidazole (1b),
bisglyoxaline (1c), benzimidazole (1d). c Yield of isolated product based
on aldehyde after chromatographic purification. d Enantiomeric excess was
determined by chiral HPLC analysis (Chiralcel OD-H). e The formation time
of zinc phenylacetylide ) 1 h.
TABLE 2. Scope of Asymmetric Phenylacetylene Addition to
Aromatic Aldehydes
aldehyde
(Ar)
yield
(%)a
ee
entry
product
(%)b
1
2
3
4
5
6
7
8
9
Ph
3a
3b
3c
3d
3e
3f
3g
3h
3i
92
91
92
81
95
80
85
91
87
82
92
85
93
93
94
92
92
92
92
93
93
91
87
93
2-MeC6H4
3-MeC6H4
4-MeC6H4
3-ClC6H4
4-ClC6H4
4-BrC6H4
4-FC6H4
4-MeOC6H4
3-MeOC6H4
2-furyl
Initial studies on the development of the asymmetric reaction
conditions revealed that the quantity of NMI was crucial to the
outcome of the reaction, and the effect of the chiral Lewis acid/
(12) In this regard, one impressive example has been illustrated by the
recent studies of the Carreira group, in which a catalytic version of the
addition procedure could be conducted at elevated temperatures, i.e., 60
°C, to overcome the kinetic barrier inhibiting protonation of the first formed
Zn-alkoxide, avoiding the use of stoichiometric quantities of Zn(OTf)2 and
N-methylephedrine. See ref 3b.
10
11
12
3j
3k
3l
2-naphthyl
(13) For reviews on the concept of dual acid/base catalysis, see: (a)
Gro¨ger, H. Chem.sEur. J. 2001, 7, 5247. (b) Rowlands, G. J. Tetrahedron
2001, 57, 1865. (c) Shibasaki, M.; Yoshikawa, N. Chem. ReV. 2002, 102,
2187. (d) Shibasaki, M.; Kanai, M.; Funabashi, K. Chem. Commun. 2002,
1989. (e) Ma, J. A.; Cahard, D. Angew. Chem., Int. Ed. 2004, 43, 4566.
(14) (a) Imbriglio, J. E.; Vasbinder, M. M.; Miller, S. J. Org. Lett. 2003,
5, 3741. (b) Aroyan, C. E.; Vasbinder, M. M.; Miller, S. J. Org. Lett. 2005,
7, 3849. (c) Utsumi, N.; Zhang, H.; Tanaka, F.; Barbas, C. F., III. Angew.
Chem., Int. Ed. 2007, 46, 1878.
a Yield of isolated product based on aldehyde after chromatographic
purification. b Enantiomeric excess was determined by chiral HPLC analysis
(Chiralcel OD-H). The absolute configurations of adducts were assigned
by comparison with literature data.
base ratio is described in Table 1, which shows a clear maximum
at 5 mol % of NMI in combination with 10 mol % of (R)-
BINOL, 25 mol % of Ti(OiPr)4, and 2 equiv of Et2Zn in CH2-
Cl2 at room temperature (Table 1, entry 3). Further increasing
the quantity of NMI might lead to diminished enantioselectivity,
which should be attribute to the competition between the dual
catalysis path and the Lewis base (only NMI) catalysis path,
although the chemical yield of propargylic alcohol could be
improved slightly (compare entries 1-3 in Table 1). These
results show that our optimized catalytic system significantly
overcomes troubles potentially arising from the chemical
(15) Grotjahn, D. B. Chem.sEur. J. 2005, 11, 7146.
(16) Ma, K. Y.; You, J. S. Chem.sEur. J. 2007, 13, 1863-1871.
(17) (a) You, J. S.; Yu, X. Q.; Zhang, G. L.; Xiang, Q. X.; Lan, J. B.;
Xie, R. G. Chem. Commun. 2001, 1816. (b) Yuan, Y.; Gao, G.; Jiang, Z.
L.; You, J. S.; Zhou, Z. Y.; Yuan, D. Q.; Xie, R. G. Tetrahedron 2002, 58,
8993. (c) Lan, J. B.; Chen, L.; Yu, X. Q.; You, J. S.; Xie, R. G. Chem.
Commun. 2004, 188. (d) Wang, W. H.; Xi, P. H.; Su, X. Y.; Lan, J. B.;
Mao, Z. H.; You, J. S.; Xie, R. G. Cryst. Growth Des. 2007, 7, 741. (e)
Zhu, L. B.; Cheng, L.; Zhang, Y. X.; Xie, R. G.; You, J. S. J. Org. Chem.
2007, 72, 2737.
(18) Takita, R.; Fukuta, Y.; Tsuji, R.; Ohshima, T.; Shibasaki, M. Org.
Lett. 2005, 7, 3849. Also see ref 15.
5458 J. Org. Chem., Vol. 72, No. 14, 2007

TABLE 3. Catalytic, Enantioselective Addition of Functional Alkynes to Aromatic Aldehydesa,b
a The time of alkynylzinc formation ) 24 h. b Yield of isolated product based on aldehyde after chromatographic purification. Enantiomeric excess was
determined by chiral HPLC analysis (Chiralcel OD-H or AD-H). The absolute configurations of adducts were assigned by comparison with literature data.
c 2.1 equiv of RCCH.
incompatibility of Lewis acids and bases and suppresses the
NMI-initiated background reaction. Furthermore, a series of
imidazoles (e.g., imidazole 1b, bisglyoxaline 1c, and benzimi-
dazole 1d) were also tested in the reaction between benzalde-
hyde and phenylacetylene, indicating NMI gave the best result
(Table 1, entries 3, 13-15).
We found that this reaction was strongly influenced by the
solvent: superior results could be obtained with CH2Cl2, while
low enantioselectivities were found in toluene, diethyl ether,
and THF (Table 1, entries 3, 9-11). We then varied the amount
and ratio of both (R)-BINOL and Ti(OiPr)4 and found that the
best ee value was obtained when the (R)-BINOL/Ti(OiPr)4 ratio
is 1/2.5 (Table 1, entries 3, 6-8). It is noteworthy that 10 mol
% of (R)-BINOL proved to be adequate in terms of both
reactivity and selectivity (compare entries 3 and 12 in Table
1). In addition, no significant changes in ee values were observed
when the reaction temperature was decreased from room
temperature to 0 °C, but it slowed down the reaction rate and
reduced the yield of the product.
Having optimized the (R)-BINOL/NMI-catalyzed alkynyla-
tion of benzaldehyde with phenylacetylene, we decided to screen
a series of aromatic aldehydes and acetylenes to evaluate the
scope of this reaction. We were delighted to find that alkyny-
lation of electron-rich and -deficient aromatic aldehydes with
phenylacetylene gave the corresponding propargylic alcohols
in excellent ee values (87-94% ee) and yields (80-95%) at
room temperature (Table 2). It is noteworthy that the enanti-
oselectivity of the reaction seems to be independent of the
substitution of the aromatic aldehyde. Thus this catalytic process
displays relatively wide substrate scope, and the presented results
are comparable to those attained by substoichiometric and/or
stoichiometric amounts of BINOL-Ti(OiPr)4-HMPA-Et2Zn
as previously reported by Pu and co-workers.11a
Furthermore, the optimized conditions were also applicable
to some quite challenging alkynes for existing catalytic systems,
as summarized in Table 3. For example, ethynylcyclohexene
and cyclopropylacetylene instead of phenylacetylene, both good
chemical yields and excellent enantioselectivities, were achieved,
although a longer time of alkynylzinc formation (24 h) was
required, which compared to the results obtained with Wolf’s
bisoxazolidine catalyst system (Table 3, 3n-3o).5 Trimethyl-
silylacetylene is a particularly desirable alkyne due to the
possible use of the desilylated product for alkylation and the
Sonogashira coupling.19 To our delight, our catalytic system
could also be employed in the asymmetric addition of trimeth-
ylsilylacetylene to aldehydes. The corresponding 3-silylprop-
argylic alcohols were obtained in up to 88% yield and 93% ee
(Table 3, 3p-3r).20 γ-Hydroxy-R,â-acetylenic esters are very
useful in the synthesis of highly functionalized organic mol-
ecules.21 Noteworthy, our dual catalytic system could also be
used for this asymmetric addition of methyl propiolate with
benzaldehyde with high enantioselectivity (Table 3, 3m).
In summary, we report the facile and mild highly enantiose-
lective alkynylation of aldehydes using the dual acid/base
catalysis, in which the BINOL/Ti(OiPr)4 complex would activate
aldehydes while NMI would promote the deprotonation of
terminal alkynes at room temperature. Therefore, the addition
of catalytic quantities of NMI greatly reduced the temperature
for the formation of the alkynylzinc reagents and significantly
improved the previous BINOL/Et2Zn/Ti(OiPr)4 system.11 Thus
the mild reaction conditions make it possible to use some quite
challenging alkynes, such as ethynylcyclohexene, cyclopropy-
lacetylene, trimethylsilylacetylene, and methyl propiolate, in this
asymmetric addition. To the best of our knowledge, our dual
acid/base catalytic system is among the most effective systems
so far reported for the asymmetric alkynylzinc addition to
aromatic aldehydes. The easy availability of the chiral ligand
and NMI as well as the metal reagents and the mild reaction
conditions make this process very practical.
Experimental Section
General Procedure for the Catalytic Enantioselective Addi-
tion of Alkyne to Aldehyde. Under nitrogen, to a flame-dried test
(19) (a) Sonogashira, K. In ComprehensiVe Organic Synthesis; Trost,
B. M., Fleming, I., Eds.; Pergamon Press: New York, 1991; Vol. 3, p 521.
(b) Marshall, J. A.; Schaaf, G. M. J. Org. Chem. 2001, 66, 7825. (c) Burova,
S. A.; McDonald, F. E. J. Am. Chem. Soc. 2002, 124, 8188. (d) Burova, S.
A.; McDonald, F. E. J. Am. Chem. Soc. 2004, 126, 2495. (e) Zhang, Y. D.;
Tang, Y. F.; Luo, T. P.; Shen, J.; Chen, J. H.; Yang, Z. Org. Lett. 2006, 8,
107.
(20) There was not any information describing the asymmetric addition
of trimethylsilylacetylene to aldehydes in the BINOL-Ti(OiPr)4-HMPA-
Et2Zn as previously reported by Pu and co-workers. See ref 11.
(21) (a) Trost, B. M.; Shi, Z. J. Am. Chem. Soc. 1994, 116, 7459. (b)
Trost, B. M.; Crawley, M. L. J. Am. Chem. Soc. 2002, 124, 9328. (c)
Tejedor, D.; Garcia-Tellado, F.; Marrero-Tellado, J. J.; de Armas, P. Chem.s
Eur. J. 2003, 9, 3122. (d) Trost, B. M.; Ball, Z. T. J. Am. Chem. Soc. 2004,
126, 13942. (e) Meta, C. T.; Koide, K. Org. Lett. 2004, 6, 1785.
J. Org. Chem, Vol. 72, No. 14, 2007 5459

tube containing (R)-BINOL (7.2 mg, 0.025 mmol) and 3 mL of
CH2Cl2 were sequentially added NMI (0.0125 mmol, 1 µL), alkyne
(0.5 mmol), and Et2Zn (0.5 mmol, 1.25 M in toluene). The resulting
mixture was stirred at room temperature (20-23 °C) for 2 h,
followed by the addition of Ti(OiPr)4 (0.0625 mmol, 18.5 µL). After
1 h of stirring, an aldehyde (0.25 mmol) was added, and the
resulting mixture was stirred for an additional 12 h. Saturated NH4-
Cl solution (5 mL) was added to quench the reaction, and the
mixture was extracted with ethyl acetate. The combined organic
layers were dried over anhydrous MgSO4, and solvents were
removed under reduced pressure. The residue was purified by flash
column chromatography (silica gel, 10% EtOAc in petroleum ether)
to give the product.
Acknowledgment. This work was supported by grants from
the National Natural Science Foundation of China (No.
20572074), and the Program for New Century Excellent Talents
in University (NCET-04-0881).
Supporting Information Available: Experimental procedures
and full spectroscopic data for all compounds. This material is
available free of charge via the Internet at http://pubs.acs.org.
JO0707535
5460 J. Org. Chem., Vol. 72, No. 14, 2007