Understanding the behavior of N-tosyl and N-2-pyridylsulfonyl imines in CuII-catalyzed aza-Friedel - Crafts reactions

Article abstract of DOI:10.1021/jo800986g

(Chemical Equation Presented) The different behavior of N-tosyl imines and N-(2-pyridyl)-sulfonyl imines in Cu^II-catalyzed AFCR is described. DFT theoretical calculations on the mode of coordination of the copper atom to both types of substrate

Full text of DOI:10.1021/jo800986g

SCHEME 1
Understanding the Behavior of N-Tosyl and
N-2-Pyridylsulfonyl Imines in CuII-Catalyzed
Aza-Friedel-Crafts Reactions
Ine´s Alonso, Jorge Esquivias, Ramo´n Go´mez-Arraya´s, and
Juan C. Carretero*
Departamento de Qu´ımica Orga´nica, Facultad de Ciencias,
UniVersidad Auto´noma de Madrid, Cantoblanco,
28049 Madrid, Spain
formation of side products, especially triarylmethane products.5
This type of product is the result of a facile further Friedel-Crafts
alkylation of the diaryl methyl amine intermediate via a highly
stabilized diaryl methyl carbocation (Scheme 1).
juancarlos.carretero@uam.es
In recent years, we have reported that heterosubstituted metal-
coordinating N-sulfonyl imines, such as 2-pyridylsulfonyl imi-
nes, represent a very appealing novel type of imines, usually
displaying a very different reactivity to that observed with
typical phenylsulfonyl or tosyl imines.6 Within the context of
the AFCR, we have found that the CuII-catalyzed AFCR of
N-methyl indole with the tosyl imine of benzaldehyde provided
the triarylmethane derivative 3, while the same process using
the 2-pyridylsulfonyl imine led selectively to the aza-
Friedel-Crafts adduct 2b.6b We describe herein a more detailed
comparative study on the different behavior of tosyl and
2-pyridylsulfonyl imines in AFCR and a theoretical study
providing some clues to the key role exerted by the 2-pyridyl
unit.
The model N-sulfonyl imines 1a and 1b were readily prepared
by condensation of benzaldehyde with p-tolyl sulfonamide and
2-pyridylsulfonamide, respectively, catalyzed by Amberlist/4 Å
molecular sieves in refluxing toluene7 (93 and 87% yield,
respectively). In Table 1 are shown the results obtained in the
reaction of both sulfonyl imines with N-methyl indole catalyzed
by Cu(OTf)2/(()-BINAP (10 mol %) at different temperatures
and reaction times.
Two main conclusions can be drawn from this study: (a) At
room temperature, the AFCR of the tosyl imine 1a was very
fast (e5 min), giving rise selectively to the triarylmethane 3,
even with only 1 equiv of N-methyl indole (entry 4). The
intermediate sulfonamide 2a could be detected and isolated at
lower temperatures (entries 1 and 2), although mixtures of 2a
+ 3 were always formed. This result shows the easy conversion
of 2a into 3 under the reaction conditions. (b) The 2-pyridyl-
sulfonyl imine 1b displayed a different reactivity profile: the
AFCR was also very fast but completely selective in favor of
the product 2b between -40 °C and room temperature (entries
ReceiVed May 7, 2008
The different behavior of N-tosyl imines and N-(2-pyridyl)-
sulfonyl imines in CuII-catalyzed AFCR is described. DFT
theoretical calculations on the mode of coordination of the
copper atom to both types of substrates allow understanding
this different reactivity.
The Lewis acid promoted aza-Friedel-Crafts reaction (AFCR)
between electron-rich aromatic compounds and imines consti-
tutes a powerful tool for the preparation of benzylic amines and
derivatives.1 This reaction is particularly useful in the case of
highly electrophilic imines, such as those derived from glyox-
alates,2 and trifluoroacetaldehyde.3 In contrast, the AFCR of
less activated substrates, such as imines of aromatic aldehydes,
is more limited,4 mainly due to the lower reactivity and/or the
(1) For recent reviews, see: (a) Nair, V.; Thomas, S.; Mathew, S. C.; Abhilash,
K. G. Tetrahedron 2006, 62, 6731. (b) Bandini, M.; Melloni, A.; Umani-Ronchi,
A. Angew. Chem., Int. Ed. 2004, 43, 550.
(2) (a) Johannsen, M. Chem. Commun. 1999, 2233. (b) Saaby, S.; Fang, X.;
Gathergood, N.; Jørgensen, K. A. Angew. Chem., Int. Ed. 2000, 39, 4114. (c)
Hao, J.; Taktak, S.; Aikawa, K.; Yusa, Y.; Hatano, M.; Mikami, K. Synlett 2001,
1443. (d) Janczuk, A.; Zhang, W.; Xie, W.; Lou, S.; Cheng, J.; Wang, P. G.
Tetrahedron Lett. 2002, 43, 4271. (e) Luo, Y.; Li, C.-J. Chem. Commun. 2004,
1930. (f) Jiang, B.; Huang, Z.-G. Synthesis 2005, 2198. (g) Soueidan, M.; Collin,
J.; Gil, R. Tetrahedron Lett. 2006, 47, 5467. (h) Zhao, J.-L.; Liu, L.; Zhang,
H.-B.; Wu, Y.-C.; Wang, D.; Chen, Y.-J. Synlett 2006, 96.
(5) (a) Liu, C.-R.; Li, M.-B.; Yang, C.-F.; Tian, S.-K. Chem. Commun. 2008,
1249. (b) Temelli, B.; Unaleroglu, C. Tetrahedron Lett. 2005, 46, 7941. (c) Ke,
B.; Qin, Y.; He, Q.; Huang, Z.; Wang, F. Tetrahedron Lett. 2005, 46, 1751. (d)
Mi, X.-L.; Luo, S.-Z.; He, J.-Q.; Cheng, J.-P. Tetrahedron Lett. 2004, 45, 4567.
(e) Hao, J.; Taktak, S.; Aikawa, K.; Yusa, Y.; Hatano, M.; Mikami, K. Synlett
2001, 1443.
(3) (a) Gong, Y.; Kato, K.; Kimoto, H. Synlett 2000, 1058. (b) Gong, Y.;
Kato, K. Tetrahedron: Asymmetry 2001, 12, 2121.
(6) (a) Esquivias, J.; Go´mez-Arraya´s, R.; Carretero, J. C. J. Org. Chem. 2005,
70, 7451. (b) Esquivias, J.; Go´mez-Arraya´s, R.; Carretero, J. C. Angew. Chem.,
Int. Ed. 2006, 45, 629. (c) Esquivias, J.; Go´mez-Arraya´s, R.; Carretero, J. C.
J. Am. Chem. Soc. 2007, 129, 1480. (d) Esquivias, J.; Go´mez-Arraya´s, R.;
Carretero, J. C. Angew. Chem., Int. Ed. 2007, 46, 9257. See also: (e) Nakamura,
S.; Nakashima, H.; Sugimoto, H.; Sano, H.; Hattori, M.; Shibata, N.; Toru, T.
Chem.sEur. J. 2008, 14, 2145.
(4) For AFCR of imines derived from aromatic or aliphatic aldehydes, see:
(a) Uraguchi, D.; Sorimachi, K.; Terada, M. J. Am. Chem. Soc. 2004, 126, 11804.
(b) Temelli, B.; Unaleroglu, C. Tetrahedron Lett. 2005, 46, 7941. (c) Ke, B.;
Qin, Y.; He, Q.; Huang, Z.; Wang, F. Tetrahedron Lett. 2005, 46, 1751. (d) Jia,
Y.-X.; Xie, J.-H.; Duan, H.-F.; Wang, L.-X.; Zhou, Q.-L. Org. Lett. 2006, 8,
1621. (e) Wang, Y.-Q.; Song, J.; Hong, R.; Li, H.; Deng, L. J. Am. Chem. Soc.
2006, 128, 8156. (f) Shirakawa, S.; Kobayashi, S. Org. Lett. 2006, 8, 4939. (g)
Kang, Q.; Zhao, Z.-A.; You, S.-L. J. Am. Chem. Soc. 2007, 129, 1484.
(7) Vishwakarma, L. C.; Stringer, O. D.; Davis, F. A. Org. Synth. 1987, 66,
203.
10.1021/jo800986g CCC: $40.75
Published on Web 07/09/2008
2008 American Chemical Society
J. Org. Chem. 2008, 73, 6401–6404 6401

TABLE 1. CuII-Catalyzed Reaction of N-Methyl Indole with
N-Tosyl and N-2-Pyridylsulfonyl Imines of Benzaldehyde
SCHEME 3
entrya imine T (°C) t (min) yield of 2 (%)b yield of 3 (%)b
1
2
1a
1a
1a
1a
1b
1b
1b
1b
1b
1b
-40
0
22
22
-40
0
22
22
45
45
120
35
5
2a, 33
2a, 13
2a, -
2a, -
2b, 77
2b, 81
2b, 72
2b, 58
2b, 39
2b, -
35
55
72
38
3
4c
5
5
formation of the highly stabilized carbocation intermediate III,
required for the final Friedel-Crafts alkylation. In contrast, in
the case of the 2-pyridyl analogue, it is reasonable to assume a
preferential coordination of the CuII atom to the pyridyl nitrogen
atom (complex II), instead of the sulfonamide nitrogen, resulting
in a lower leaving group capacity of the sulfonamide moiety
which would make more difficult the cleavage of the C-N bond
and formation of the carbocation intermediate.
180
15
5
5
15
35
6
7
8c
9
50
84
10
a Reaction conditions: 2 equiv of N-methyl indole and 10 mol % of
Cu(OTf)2/(()-BINAP. b In pure product after silica gel chromatography.
c With 1 equiv of N-methyl indole.
To support this hypothesis, and to have an insight of the
coordination mode around the copper atom, the intermediates
and transition states involved in the cleavage of the C-N bond
were theoretically studied at the DFT (B3LYP)8 level by using
the Gaussian03 program.9 The standard 6-31G(d)10 basis set
was used for all atoms except Cu, for which LANL2DZ11 was
employed. Harmonic frequencies were calculated at the same
level of theory to characterize the stationary points and to
determine the zero-point energies (ZPE). Slightly simplified
structures of complexes I and II (with Tol ) Ph, Ar ) Ph, and
1,2-bis(dimethylphosphino)ethane as ligand for the metal) were
used as models.
SCHEME 2
Optimized geometries of complexes and transition states are
depicted in Figure 1. Distances Cu-P and Cu-O are quite
similar in all the structures (in the range 2.37-2.42 and
2.04-2.18 Å, respectively). The copper center in complex I is
assumed to be coordinated with the more electron-rich sulfona-
mide nitrogen and a sulfonyl oxygen. The conformation around
the C-N bond minimizes the steric interaction between one of
the phenyl groups and the methyl groups of the phosphorus
ligand (closest distance: 2.74 Å). In addition, in this conforma-
tion, it is possible a stabilizing π-stacking interaction between
the second phenyl group and the phenylsulfonamide group
(distance between centroids: 4.57 Å). From this complex, TSI
was found in which a clear elongation of the C-N bond is
observed, but the rest of the molecule shows almost the same
conformation as in complex I, although the distance between
centroids increases (5.23 Å). A quite similar arrangement of
the groups is observed in complex IV, resulting upon cleavage
of the C-N bond. In complex II, one of the sulfonyl oxygens
and the pyridyl nitrogen are the atoms coordinated with the
metal. Complexes in which the sulfonamide nitrogen was
involved in the coordination could not be found. However, the
coordination of this atom seems to be essential for the cleavage
step since TSII was the only transition state found in which
i. Cu(OTf)2/(()-BINAP (10 mol %), CH2Cl2, 22 °C, 5-15 min.
5-8). The formation of the triarylmethane 3 was only observed
at higher temperatures (refluxing CH2Cl2), being the only
product after 35 min of reaction (entry 10). This result clearly
indicates that the 2-pyridylsulfonamide 2b is more reluctant to
undergo the second Friedel-Crafts reaction than the parent tosyl
analogue 2a.
This sharp different reactivity between the tosyl imine 1a
and the 2-pyridylsulfonyl imine 1b was also observed in the
AFCR of other electron-rich heteroaromatic compounds, such
as N-methyl pyrrole and 2-methoxy thiophene (Scheme 2). With
both aromatic substrates, the CuII-catalyzed AFCR with the tosyl
imine 1a at room temperature (5-15 min) provided selectively
the corresponding triarylmethane products 4 and 5 (42 and 73%
yield, respectively), while under identical reaction conditions,
the 2-pyridylsulfonyl imine 1b led to the intermediate arylated
sulfonamides 6b and 7b (72 and 65% yield, respectively)
without detecting by 1H NMR the formation of triarylmethane
products.
As a working hypothesis, we postulated that a different
coordination mode of the electrophilic CuII catalyst to the
sulfonamide intermediates formed after the aza-Friedel-Crafts
reaction could be at the origin of the interesting opposite
selectivity of imines 1a and 1b in this transformation (Scheme
3). We envisaged that the coordination of the CuII catalyst to
the sulfonamide nitrogen of the initial AFCR product resulting
from tosyl imine 1a (complex I) would enhance the ability of
the sulfonamide moiety as a leaving group, facilitating the
(8) (a) Lee, C.; Yang, W.; Parr, R. G. Phys. ReV. B 1988, 37, 785. (b) Becke,
A. D. J. Chem. Phys. 1993, 98, 1372.
(9) Frisch, M. J.; Gaussian 03, revision B.03; Gaussian, Inc.: Pittsburgh PA,
2003.
(10) (a) Ditchfield, R.; Hehre, W. J.; Pople, J. A. J. Chem. Phys. 1971, 54,
724. (b) Hehre, W. J.; Ditchfield, R.; Pople, J. A. J. Chem. Phys. 1972, 56,
2257. (c) Hariharan, P. C.; Pople, J. A. Theor. Chim. Acta 1973, 28, 213.
(11) Hay, P. J.; Wadt, W. R. J. Chem. Phys. 1985, 82, 270.
6402 J. Org. Chem. Vol. 73, No. 16, 2008

FIGURE 1. Optimized structures of model complexes and transition
states most likely involved in the cleavage of the C-N bond of the
AFCR products of tosyl imine (I, TSI, and IV) and 2-pyridylsulfonyl
imine (II, TSII, and V). Distances (Å) and dihedral angles (°) between
selected atoms are also indicated.
FIGURE 2. Energy profile for the cleavage of the C-N bond during
the AFCR from tosyl imine (I, TSI, and IV) and 2-pyridylsulfonyl
imine (II, TSII, and V).
the C-N bond is being broken. According to the distances
around the metal, in TSII, both sulfonamide and pyridyl nitrogen
atoms are involved in the coordination. The conformation around
the C-N bond in complex II locates the diphenylmethyl group
far from the phosphorus ligand and allows a π-stacking
interaction with the pyridine ring (distance between centroids:
4.74 Å). However, in TSII, due to the conformational changes,
the diphenylmethyl group is close to the phosphorus ligand
(closest distance: 2.58 Å) and any stabilizing π-stacking
interaction has been lost. After the cleavage, intermediate V
(X ) N) showing an arrangement of the groups12 similar to
that of IV (X ) CH) was found.
Regarding the relative stabilities of these intermediates, the
energy profile along the reaction coordinate is represented in
Figure 2. The reaction for tosyl imine is both kinetically and
thermodynamically more favored. The opposite situation is
found in the case of the pyridylsulfonyl imine, with an activation
barrier 5.5 kcal ·mol-1 higher than in the case of the tosyl imine.
This clearly higher activation barrier for the 2-pyridylsulfonyl
substrate nicely explains the selectivity found for the pyridyl-
sulfonyl imine 1b in AFCR and is in full agreement with the
experimental fact that the formation of the triarylmethane
product requires a higher temperature from the imine 1b than
from the typical tosyl imine 1a.
showing that, due to the different mode of coordination of the
copper atom to the tosyl and 2-pyridylsulfonyl units, the
activation barrier is significantly higher in the second case.
Experimental Section
N-Sulfonyl imines 1a13 and 1b,6d as well as the triarylmethanes
314 and 415 were previously described in the literature. See
Supporting Information for experimental procedures and charac-
terization data of 1a, 1b, 2a, and 3.
General Procedure for the Aza-Friedel-Crafts Reaction
of N-2-Pyridylsulfonyl imine 1b. A solution of Cu(OTf)2 (3.6 mg,
0.01 mmol) and (()-BINAP (6.8 mg, 0.011 mmol) in CH2Cl2 (0.5
mL) was stirred at rt for 20 min before a solution of imine 1b
(24.6 mg, 0.1 mmol) in CH2Cl2 (0.5 mL) was added. The mixture
was stirred at rt for 5 min, and the electron-rich arene (0.12 mmol)
was added. Upon completion (TLC monitoring), the reaction was
quenched with saturated aq NH4Cl, the organic phase was extracted
with CH2Cl2 (3 × 20 mL), and the combined organic phase was
dried (Na2SO4) and concentrated. The residue was purified by flash
chromatography (n-hexanes-EtOAc 2:1).
(1-Methyl-1H-indol-3-yl)(phenyl)-N-[(2-pyridyl)sulfonyl]metha-
namine (2b): Yield 72%, yellow solid; mp 202-204 °C; 1H NMR
(300 MHz, CDCL3) δ 8.24 (ddd, J ) 4.6, J ) 1.6, and J ) 0.8 Hz,
1H), 7.65 (m, 1H), 7.58-7.42 (m, 2H), 7.31-7.10 (m, 8H), 7.05
(m, 1H), 6.61 (s, 1H), 6.51 (s, 1H), 6.24 (d, J ) 7.0 Hz, 1H), 6.03
(d, J ) 7.0 Hz, 1H), 3.59 (s, 3H); 13C NMR (75 MHz, CDCL3) δ
157.7, 149.5, 140.0, 137.2, 137.1, 127.5, 128.2, 127.3, 126.0, 125.8,
122.1, 122.0, 119.6, 119.5, 114.4, 109.2, 55.5, 32.6; MS-FAB+ m/z
In conclusion, tosyl aryl imines and 2-(pyridyl)sulfonyl aryl
imines display a very different behavior in CuII-catalyzed AFCR
with electronically rich heteroaromatic compounds: at room
temperature, the former lead to the triarylmethane product
through a double Friedel-Crafts process, while the latter afford
selectively the diarylmethyl sulfonamide intermediate. DFT
theoretical calculations on the second Friedel-Crafts reaction
have provided some clues to this different reactive profile,
(13) Garc´ıa Ruano, J. L.; Alema´n, J.; Cid, M. B.; Parra, A. Org. Lett. 2005,
7, 179.
(14) (a) Nair, V.; Abhilash, V. K.; Vidya, N. Org. Lett. 2005, 7, 5857. (b)
Tabatabaeian, K.; Mamaghani, M.; Mahmoodi, N.; Khorshidi, A. Can. J. Chem.
2006, 84, 1541.
(15) (a) Singh, K.; Behal, S.; Hundal, M. S. Tetrahedron 2005, 61, 6614.
(b) Biaggi, C.; Benaglia, M.; Raimondi, L.; Cozzi, F. Tetrahedron 2006, 62,
12375.
(12) Another complex slightly less stable than V (0.3 kcal · mol-1) with only
N/N-coordination was also found (see Supporting Information).
J. Org. Chem. Vol. 73, No. 16, 2008 6403

337.1 (M+, 53), 235.1 [M+ - SO2(2-Py), 100]; HRMS-FAB+ calcd
for C21H19O2N3S (M+) 377.1198, found 377.1193.
Bis(1-methyl-1H-pyrrol-2-yl)(phenyl)methane (4):.15 Yield 42%,
white solid; mp 81-82 °C (lit15b 85-86 °C); 1H NMR (300 MHz,
CDCL3) δ 7.26-7.15 (m, 3H), 7.08-7.02 (m, 2H), 6.51 (dd, J )
2.2 and J ) 2.0 Hz, 2H), 5.94 (dd, J ) 3.5 and J ) 2.8 Hz, 2H),
5.41 (ddd, J ) 3.3, J ) 1.9, and J ) 0.9 Hz, 2H), 5.19 (s, 1H),
3.31 (s, 6H); 13C NMR (75 MHz, CDCL3) δ 141.3, 133.5, 128.8,
128.6, 128.4, 128.2, 126.6, 122.0, 108.9, 106.4, 42.0, 33.9; MS-
ESI+ m/z 251.1 ((M + H)+, 100), 301.0 (M+ - CH3, 22); HRMS-
ESI+ calcd for C17H18N2 [(M + H)+] 251.1548, found 251.1543.
Bis(5-methoxythiophen-2-yl)(phenyl)methane (5): Yield 73%,
(1-Methyl-1H-pyrrol-2-yl)(phenyl)-N-[(2-pyridyl)sulfonyl]metha-
1
namine (6b): Yield 72%, white solid; mp 165-167 °C; H NMR
(300 MHz, CDCL3) δ 8.35 (ddd, J ) 4.6, J ) 1.6, and J ) 0.8 Hz,
1H), 7.60 (m, 2H), 7.25 (m, 1H), 7.15-7.05 (m, 5H), 6.57 (m,
1H), 6.12 (d, J ) 9.1 Hz, 1H), 5.89 (dd, J ) 3.6 and J ) 2.8 Hz,
1H), 5.82 (d, J ) 9.1 Hz, 1H), 5.58 (m, 1H), 3.69 (s, 3H); 13C
NMR (75 MHz, CDCL3) δ 157.4, 149.7, 138.2, 137.4, 130.2, 128.1,
127.4, 127.3, 126.1, 123.6, 122.0, 110.0, 106.7, 55.2, 34.3; MS-
FAB+ m/z 328.1 (M+, 21), 170.1 (M+ - SO2(2-Py), 100); HRMS-
FAB+ calcd for C17H18N3O2S (M+) 328.1122, found 328.1120.
(5-Methoxythiophen-2-yl)(phenyl)-N-[(2-pyridyl)sulfonyl]metha-
1
yellow oil; H NMR (300 MHz, CDCL3) δ 7.25-7.15 (m, 5H),
6.32 (dd, J ) 3.8 and J ) 1.1 Hz, 2H), 5.92 (d, J ) 3.8 Hz, 2H),
5.40 (s, 1H), 3.75 (s, 6H); 13C NMR (75 MHz, CDCl3) δ 165.7,
143.2, 133.3, 128.4, 128.3, 127.1, 123.2, 102.8, 60.1, 48.1; MS-
ESI+ m/z 317.1 ((M + H)+, 100); HRMS-ESI+ calcd for
C17H16O2S2 [(M + H)+] 317.0670, found 317.0665.
1
namine (7b): Yield 65%, white solid; mp 153-155 °C; H NMR
(300 MHz, CDCL3) δ 8.43 (ddd, J ) 4.6, J ) 1.6, and J ) 0.8 Hz,
1H), 7.70-7.59 (m, 2H), 7.26 (ddd, J ) 7.3, J ) 4.7, and J ) 1.4
Hz, 1H), 7.14-7.08 (m, 5H), 6.20 (dd, J ) 3.9 and J ) 1.1 Hz,
1H), 5.84 (d, J ) 8.1 Hz, 1H), 5.80 (d, J ) 3.9 Hz, 1H), 5.71 (dd,
J ) 8.1 and J ) 1.1 Hz, 1H), 3.71 (s, 3H); 13C NMR (75 MHz,
CDCL3) δ 166.8, 157.6, 149.8, 139.3, 137.5, 129.9, 128.4, 127.9,
127.2, 126.3, 124.2, 122.0, 103.0, 60.2, 58.3; MS-FAB+ m/z 361.1
(M+, 11); HRMS-FAB+ calcd for C17H18N2O3S2 (M+) 361.0666,
found 361.0661.
Acknowledgment. Financial support of this work by the
Ministerio de Educacio´n y Ciencia (MEC, project CTQ2006-
01121) and Consejer´ıa de Educacio´n de la Comunidad de
Madrid, Universidad Auto´noma de Madrid (UAM/CAM CCG07-
UAM/PPQ-1799) is gratefully acknowledged. J.E. thanks the
MEC for a predoctoral fellowship. A generous allocation of
computer time at the Centro de Computacio´n Cient´ıfica de la
UAM is also acknowledged.
General Procedure for the Synthesis of Triarylmethanes from
N-Tosyl Imine 1a. A solution of Cu(OTf)2 (3.6 mg, 0.01 mmol)
and (()-BINAP (6.8 mg, 0.011 mmol) in CH2Cl2 (0.5 mL) was
stirred at room temperature for 20 min before a solution of sulfonyl
imine 1a (25.9 mg, 0.1 mmol) in CH2Cl2 (0.5 mL) was added. The
mixture was stirred at room temperature for 5 min, and then the
electron-rich arene (0.12 mmol) was added. Upon completion (TLC
monitoring), the reaction was quenched with saturated aq NH4Cl,
the organic phase was extracted with CH2Cl2 (3 × 20 mL), and
the combined organic phase was dried (Na2SO4) and concentrated.
The residue was purified by flash chromatography (n-
hexanes-EtOAc 4:1).
Supporting Information Available: Copies of NMR spectra.
Experimental procedures and characterization data for 1a, 1b,
2a, and 3. Full citation for ref 9, Cartesian coordinates for all
optimized structures and their electronic energies and ZPVEs.
This material is available free of charge via the Internet at
http://pubs.acs.org.
JO800986G
6404 J. Org. Chem. Vol. 73, No. 16, 2008