Nucleohilic addition onto methyl-4H-1,4-oxazzine-3-carboxylate moity: Short access to 1,4-diazine privileged substructures

Full text of DOI:10.1021/jo900291f

SCHEME 1. Preparation of Unsaturated Methyl Ester 2
Nucleophilic Addition onto
Methyl-4H-1,4-oxazine-3-carboxylate Moiety:
Short Access to 1,4-Diazine Privileged
Substructures
Elise Claveau,† Isabelle Gillaizeau,*,†
Justyna Kalinowska-Tluscik,‡ Pascal Bouyssou,† and
Ge´rard Coudert*,†
cally, starting from 1,4-oxazine 1, we outlined the preparation
under anionic conditions of R,ꢀ-unsaturated methyl ester 2
(Scheme 1).
ICOA, UMR CNRS 6005, UniVersite´ d’Orle´ans, 45067
Orle´ans Cedex 2, France, and Faculty of Chemistry,
Jagiellonian UniVersity, ul. R. Ingardena 3,
30-060 Krakow, Poland
The regioselectivity of this functionalization R to the ring
nitrogen was verified by NMR spectra and also by crystal X-ray
analysis. The ORTEP drawing of 2 confirms the flat boat
conformation of this original antiaromatic system (see Support-
ing Information).3
To determine the synthetic potential of the 1,4-oxazine ring,
which appears as a valuable building block for the synthesis of
more complex derivatives, we engaged in a study of its chemical
properties. We first examined the behavior of R,ꢀ-unsaturated
methyl ester 2, an unusual Michael acceptor, in the presence of
a range of nucleophiles. Thus compound 2 was treated, in a
basic medium (K2CO3 6 equiv, CH3CN, rt) with the following
nucleophiles: 1,2,4-triazole, 4-methoxyphenol, and thiophenol.4
The requisite adducts 3a-c, resulting from a classical Michael-
type addition reaction, were thus isolated in fair to good yields
as a single diastereomer (Table 1). The expected 2,3-trans
stereochemistry of 3 was confirmed by the small coupling
isabelle.gillaizeau@uniV-orleans.fr;
gerard.coudert@uniV-orleans.fr
ReceiVed February 10, 2009
constant observed between the H-2 and H-3 protons (3J2-3
)
1,6 Hz).5 It is worth pointing out that, in these cases, the
Michael-type addition reactions allowed an easy access to 2,3-
disubstituted oxazinic systems; moreover, the presence of the
remaining double bond must also be noted, as the use of its
reactivity might lead to many substituted morpholine deriva-
tives.6
To determine the synthetic potential of the original 1,4-
oxazine ring, which appears as a valuable building block
for the synthesis of more complex derivatives, Michael-type
nucleophilic additions were studied. According to the nature
of the nucleophile, either acyclic or cyclic derivatives were
isolated. In the presence of primary amines, a short and
efficient access to diazinic hemiaminals was described.
(2) (a) Nicolaou, K. C.; Shi, G. Q.; Namoto, K.; Bernal, F. Chem. Commun.
1998, 1757. (b) Nicolaou, K. C.; Shi, G. Q.; Gunzner, J. L.; Ga¨rtner, P.; Yang,
Z. J. Am. Chem. Soc. 1997, 119, 5467. (c) Huffman, M. A.; Yasuda, N. Synlett
1999, 471. (d) Jiang, J. L.; Devita, R. J.; Doss, G. A.; Goulet, M. T.; Wyvratt,
M. J. J. Am. Chem. Soc. 1999, 121, 593. (e) Moraes, D. N.; Barrientos-
Astigarraga, R. E.; Castelani, P.; Comasseto, J. V. Tetrahedron 2000, 56, 3327.
(f) Coe, J. W. Org. Lett. 2000, 2, 4205. (g) Wu, J.; Yang, Z. J. Org. Chem.
2001, 66, 7875. (h) Takakura, H.; Sasaki, M.; Honda, S.; Tachibana, K. Org.
Lett. 2002, 2771. (i) Lo Galbo, F.; Occhiato, E. G.; Guarna, A.; Faggi, C. J.
Org. Chem. 2003, 68, 6360. (j) Campbell, I. B.; Guo, J.; Jones, E.; Steel, P. G.
Org. Biomol. Chem. 2004, 2, 2725. (k) Larsen, U. S.; Martiny, L.; Begtrup, M.
Tetrahedron Lett. 2005, 46, 4261. (l) Occhiato, E. G.; Lo Galbo, F.; Guarna, A.
J. Org. Chem. 2005, 70, 7324. (m) Tsukano, C.; Ebine, M.; Sasaki, M. J. Am.
Chem. Soc. 2005, 127, 4326. (n) Fuwa, H.; Ebine, M.; Sasaki, M. J. Am. Chem.
Soc. 2006, 128, 9648. (o) Fuwa, H.; Ebine, M.; Bourdelais, A. J.; Baden, D. G.;
Sasaki, M. J. Am. Chem. Soc. 2006, 128, 16989. (p) Ebine, M.; Fuwa, H.; Sasaki,
M. Org. Lett. 2008, 10, 2275. (q) Fuwa, H.; Sasaki, M. J. Org. Chem. 2009, 74,
212. (r) Ebran, J.-P.; Hansen, A. L.; Gøgsig, T. M.; Skrydstrup, T. J. Am. Chem.
Soc. 2007, 129, 6931. (s) Hansen, A. L.; Ebran, J.-P.; Gøgsig, T. M.; Skrydstrup,
T. J. Org. Chem. 2007, 72, 6464. (t) Lindhart, A. T.; Skrydstrup, T. Chem. Eur.
J. 2008, 14, 8756.
Heterocycles display an intrinsic reactivity that enables rich,
versatile, and productive transformations. Taking into account
their ubiquitous presence in natural products and drugs, the
development of new, fast, and efficient preparative protocols
for these structures remains a fundamental task in organic
synthesis. As part of our interest in using readily available enol
phosphates for the synthesis of new heterocyclic compounds,1,2
we have recently described an original and efficient access to
1,4-oxazine and substituted 1,4-oxazine derivatives.1c Specifi-
(3) (a) Borbulevych, O. Y.; Shishkin, O. V. J. Mol. Struct. 1998, 446, 11.
(b) Trinajstic, N. J. Mol. Struct. 1971, 8, 236.
(4) For 1,4-dihydropyrazine derivatives, see: Rodrigues, A.; Ferreira, P. M.;
Monteiro, L. S. Tetrahedron 2004, 60, 8489.
† University of Orle´ans.
‡ Jagiellonian University.
(1) (a) Mousset, D.; Gillaizeau, I.; Sabatie´, A.; Bouyssou, P.; Coudert, G. J.
Org. Chem. 2006, 71, 5993. (b) Mousset, D.; Gillaizeau, I.; Hassan, J.; Lepifre,
F.; Bouyssou, P.; Coudert, G. Tetrahedron Lett. 2005, 46, 3703. (c) Claveau,
E.; Gillaizeau, I.; Blu, J.; Bruel, A.; Coudert, G. J. Org. Chem. 2007, 72, 4832.
(d) Cottineau, B.; Gillaizeau, I.; Farard, J.; Auclair, M.-L.; Coudert, G. Synlett
2007, 1925. (e) Chaignaud, M.; Gillaizeau, I.; Ouhamou, N.; Coudert, G.
Tetrahedron 2008, 64, 8059.
(5) Two NMR signals were observed for each oxazinic protons that
corresponded to the two conformers (transdiaxial and transdiequatorial structures)
of 3. This was confirmed by performing NMR studies in DMSO-d6 at 80°C;
splitting of the signals was not observed anymore.
(6) Reviews: (a) Wijtmans, R.; Vink, M. K. S.; Schoemaker, H. E; van Delft,
F. L; Blaauw, R. H; Rutjes, F. P. J. T. Synthesis 2004, 641. (b) Sladojevich, F.;
Trabocchi, A.; Guarna, A. Org. Biomol. Chem. 2008, 6, 3328.
10.1021/jo900291f CCC: $40.75
Published on Web 03/11/2009
2009 American Chemical Society
J. Org. Chem. 2009, 74, 2911–2914 2911

TABLE 1. Michael Addition Reaction onto r,ꢀ-Unsaturated
Methyl Ester 2
TABLE 2. Nucleophilic Addition of Secondary Amines onto
r,ꢀ-Unsaturated Methyl Ester 2
a
Z/E ratio of 66:33 as determined by H NMR. b Isolated yield.
1
a Three equivalents of 1,2,4-triazole used in this case. b Isolated yield.
onto the carbonyl group. In fact, we were pleased to observe
that treatment of R,ꢀ-unsaturated methyl ester 2 with 1 equiv
of benzylamine in acetonitrile at room temperature for 22 h
afforded the original tetrahydropyrazinol 5a in a one-pot process
and in quantitative yield. The structure of 5a was unambiguously
confirmed by crystal X-ray analysis (see Supporting Informa-
tion). This original result paralleled those described by Yao for
the synthesis of a spirocyclic chromophore of chlorofusin.7 Table
3 summarizes the scope of this reaction. A range of primary
amines was allowed to react with R,ꢀ-unsaturated methyl ester
2 and afforded the desired tetrahydropyrazinols 5a-h in good
yields after somewhat prolonged reaction times. In the presence
of 0.5 equiv of 1,4-diaminobutane (Table 3, entry 3), a double
nucleophilic addition was observed to give the original bis-
tetrahydropyrazinol 5c in 87% yield. In the case of propargyl-
amine (Table 3, entry 7), the tetrahydropyrazinol 5g was isolated
in only 26% yield together with 16% of the parent R,ꢀ-
unsaturated methyl ester 2. No improvement of the yield was
observed by warming the reaction. The use of chiral (S)-(-)-
R-methylbenzylamine (Table 3, entry 8) afforded the corre-
sponding tetrahydropyrazinol 5h in 82% yield and as a 47:53
diastereomeric mixture.
With a facile access to benzylic hemiaminal 5a in hand, we
next examined the reactivity of the potential iminium ion
intermediate toward nucleophiles.8 In the presence of BF3 ·Et2O
in dichloromethane at room temperature and by using TMSCN
as a nucleophile, the attempted addition quickly occurred.
However, in this case, simultaneous removal of the Boc group
was also observed to give the unprotected unstable aminonitrile
6, which was quantitatively isolated. It is noteworthy that by
applying the aminonitrile chemistry this versatile intermediate
might afford a broad range of synthetic applications (i.e.,
alkaloids analogues).9
SCHEME 2. Mechanism Hypothesis for the Reaction of
r,ꢀ-Unsaturated Methyl Ester 2 with Secondary or Primary
Amines
We next examined the protocol using primary or secondary
amines as nucleophiles (Scheme 2). Nucleophilic addition of
secondary amines (diethylamine or morpholine) onto R,ꢀ-
unsaturated methyl ester 2 involved the opening of the hetero-
cyclic system via an addition-elimination process. Stable
acyclic enamines 4a and 4b were thus isolated in good yields
as a mixture of Z and E isomers (Table 2).
It is noteworthy that in the previous case (Table 1), given
the nature of the base (K2CO3) and of the nucleophiles, a
Michael-type addition was observed to give adducts 3; no
elimination process could occur. In the second case, in the
presence of secondary amines as nucleophiles (Table 2), the
resulting adduct A (Scheme 2) is envisioned to undergo a
hydrogen transfer to form the oxonium intermediate B. The latter
ultimately goes on to the final acyclic enamine 4 via an
elimination process.
In summary, from 1,4-oxazine moiety, we have developed a
short and efficient method that allowed an easy access to either
morpholine derivatives or diazinic hemiaminals. Ongoing studies
are aimed at expanding the scope of this reaction, in particular
by taking advantage of the reactivity of the potential iminium
These first results incited us to turn this addition-elimination
process to account by using primary amines instead of secondary
ones. By doing so, we expected the formation of a new
heterocyclic diazinic system 51e via the intramolecular nucleo-
philic attack of the intermediate secondary amine (Scheme 2)
(7) (a) Wei, W.-G.; Yao, Z.-J. J. Org. Chem. 2005, 70, 4585. (b) Wei, W.-
G.; Qian, W.-J.; Zhang, Y.-X.; Yao, Z.-J. Tetrahedron Lett. 2006, 47, 4171.
(8) Royer, J.; Bonin, M.; Micouin, L. Chem. ReV. 2004, 104, 2311.
(9) Enders, D.; Shilvock, J. P. Chem. ReV. 2000, 29, 359.
2912 J. Org. Chem. Vol. 74, No. 7, 2009

TABLE 3. Nucleophilic Addition of Primary Amines onto
r,ꢀ-Unsaturated Methyl Ester 2
SCHEME 3. Access to 1,4-Diazinic Aminonitrile 6
mmol, 1.1 equiv) was added dropwise. After 5 min of stirring at
-78 °C, a solution of methyl cyanoformate (0.650 mL, 8.19 mmol,
5 equiv) in THF (1 mL), previously dried over molecular sieves (4
Å), was added dropwise. After 1 h at -78 °C, the reaction was
quenched by slow addition of water. The aqueous phase was then
extracted with EtOAc and the organic phase was washed with brine.
The organic phase was dried over anhydrous MgSO4 and concen-
trated. Flash chromatography (petroleum ether/EtOAc, 9:1) afforded
2 (0.370 g, 94%) as a yellow solid: mp 57-58 °C; IR (KBr) 2977,
1
1729, 1705, 1626, 1353, 1136 cm-1; H NMR 250 MHz (CDCl3)
δ 6.81 (s, 1 H), 6.13 (d, J ) 3.9 Hz, 1 H), 5.97 (d, J ) 3.9 Hz, 1
H), 3.78 (s, 3 H), 1.47 (s, 9 H); 13C NMR 62.5 MHz (CDCl3) δ
163.4 (s), 150.3 (s), 143.9 (d), 133.1 (d), 116.6 (s), 112.7 (d), 82.3
(s), 52.0 (q), 28.1 (q); HRMS (EI) m/z [M]+• calcd for C11H15NO5
241.09502, found 241.0954. X-ray crystal data: C11H15NO5, trans-
j
parent, white color crystal, M ) 241.25; triclinic, space group P1,
a ) 6.2233(2) Å, b ) 7.3164(2) Å, c ) 13.5519(4) Å, R )
77.0301(11)°, ꢀ ) 76.9064(10)°, γ ) 81.5540(13)°, V ) 582.67(3)
Å3, Z ) 2, Dcalc ) 1.375 g cm-3; R(int) ) 0.021 and R1 ) 0.043
for reflections with F2 > 2σ(F2). A crystal of 0.25 × 0.22 × 0.14
mm was used.
General Procedure for Preparation of Compounds 3. 4-tert-
Butyl 3-Methyl 2-(4-Methoxyphenoxy)-2,3-dihydro-1,4-oxazine-
3,4-dicarboxylate (3a). To a solution of tert-butyl methyl 4H-1,4-
oxazine-3,4-dicarboxylate 2 (0.050 g, 0.21 mmol, 1 equiv) in MeCN
(2 mL) was added K2CO3 (0.172 g, 1.24 mmol, 6 equiv), followed
by 4-methoxyphenol (0.026 g, 0.21 mmol, 1 equiv), with fast
stirring at room temperature. The reaction was monitored by TLC
(petroleum ether/EtOAc, 8:2), and when no starting material was
detected (44 h), the reaction mixture was filtered through Celite.
The solution was washed with water, the aqueous phase was
extracted with EtOAc, and the organic phases were then washed
with brine. They were dried over anhydrous MgSO4 and concen-
trated. Flash chromatography (petroleum ether/EtOAc/toluene, 7:2:
1) afforded 3a (0.053 g, 70%) as a colorless oil, as an enantiomeric
mixture of the trans diastereomer: IR (NaCl) 2818, 1697, 1436,
1
1236, 1050 cm-1; H NMR 400 MHz (CDCl3) (2 conformers) δ
7.00-7.03 (m, 3.2 H), 6.81-6.84 (m, 3.2 H), 6.56 (dd, J ) 5.2 Hz
and J ) 1.6 Hz, 0.6 H), 6.41 (dd, J ) 5.2 Hz and J ) 1.6 Hz, 1
H), 6.06 (d, J ) 1.6 Hz, 1 H), 6.01 (d, J ) 1.6 Hz, 0.6 H), 5.84 (d,
J ) 5.2 Hz, 0.6 Hz), 5.74 (d, J ) 5.2 Hz, 1 H), 5.17 (s, 1 H), 4.99
(s, 0.6 H), 3.80 (s, 1.8 H), 3.78 (s, 3 H), 3.77 (s, 1.8 H), 3.76 (s, 3
H), 1.55 (s, 9 H), 1.50 (s, 5.4 H); 13C NMR 100 MHz (CDCl3) δ
167.6 (s), 167.3 (s), 155.7 (s), 155.6 (s), 151.9 (s), 151.4 (s), 150.1
(s), 149.7 (s), 124.5 (d), 123.4 (d), 119.0 (d), 118.9 (d), 114.7 (d),
114.6 (d), 107.5 (d), 107.1 (d), 93.7 (d), 93.1 (d), 82.3 (s), 82.1
(s), 57.8 (d), 56.4 (d), 55.7 (q), 53.0 (q), 52.9 (q), 28.3 (q), 28.2
(q); HRMS (EI) m/z [M]+• calcd for C18H23NO7 365.14745, found
365.1504.
a One-half equivalent of 1,4-diaminobutane used in this case.
b Starting material was recovered in 16% yield. c Isolated yield.
ion. This method might constitute a useful tool to easily prepare
a range of direct precursors of natural products and offers the
potential advantage of directly introducing molecular diversity
onto the molecules as a result of the original choice of the
starting nucleophile.
General Procedure for Preparation of Compounds 4. Methyl
2-(tert-Butoxycarbonyl(2-oxoethyl)amino-3-(diethylamino)acry-
late (4a). To a solution of tert-butyl methyl 4H-1,4-oxazine-3,4-
dicarboxylate 2 (0.050 g, 0.21 mmol, 1 equiv) in MeCN (2 mL)
was added K2CO3 (0.172 g, 1.24 mmol, 6 equiv), followed by
diethylamine (0.021 mL, 0.21 mmol, 1 equiv), with fast stirring at
room temperature. The reaction was monitored by TLC (petroleum
ether/EtOAc, 6:4), and when no starting material was detected (7
h), the reaction mixture was filtered through Celite. The solution
was washed with water, the aqueous phase was extracted with
Experimental Section
Only representative procedures and characterizations of the
products are described here. Full details can be found in Supporting
Information.
tert-Butyl Methyl 4H-1,4-Oxazine-3,4-dicarboxylate (2). A solu-
tion of tert-butyl 4H-1,4-oxazine-4-carboxylate 11c (0.300 g, 1.64
mmol, 1 equiv) in THF (15 mL) was cooled to -78 °C under argon.
Subsequently, n-butyllithium (1.13 mL, 1.6 M in hexane, 1.80
J. Org. Chem. Vol. 74, No. 7, 2009 2913

EtOAc, and the organic phases were then washed with brine. They
were dried over anhydrous MgSO4 and concentrated. Flash chro-
matography (petroleum ether/EtOAc, 6:4) afforded 4a (0.049 g,
75%) as a colorless oil, as a mixture of Z and E isomers: IR (NaCl)
330.15796, found 330.1591. X-ray crystal data: C18H24N2O5 H2O,
transparent, white color crystal, M ) 348.40; monoclinic, space
group P21/c, a ) 14.2955(4) Å, b ) 8.3964(2) Å, c ) 16.8240(5)
Å, ꢀ ) 105.4699(12)°, V ) 1946.24(9) Å3, Z ) 4, Dcalc ) 1.25 g
cm-3; R(int) ) 0.036 and R1 ) 0.064 for reflections with F2 >
2σ(F2). A crystal of 0.35 × 0.25 × 0.10 mm was used.
1
2971, 1730, 1653, 1627, 1425, 1165 cm-1; H NMR 250 MHz
(CDCl3) δ 9.78-9.83 (m, 1.5 H), 7.30 (s, 0.5 H), 7.17 (s, 1 H),
3.65 (s, 3 H), 3.64 (s, 1.5 H), 3.52-3.60 and 3.92-4.06 (m, 3 H),
3.21-3.38 (m, 6 H), 1.43 (s, 4.5 H), 1.40 (s, 9 H), 1.17 (t, J ) 7.3
Hz, 3 H), 1.16 (t, J ) 7.3 Hz, 6 H); 13C NMR 62.5 MHz (CDCl3)
δ 201.2 (d), 201.0 (d), 168.2 (s), 168.1 (s), 156.8 (s), 155.0 (s),
144.6 (d), 143.6 (d), 101.2 (s), 100.7 (s), 81.6 (s), 80.9 (s), 61.4
(t), 60.7 (t), 51.3 (q), 46.8 (t), 28.3 (q), 14.3 (q); HRMS (EI) m/z
[M]+• calcd for C15H26N2O5 314.18417, found 314.1860.
Methyl 4-Benzyl-5-cyano-1,4,5,6-tetrahydropyrazine-2-carboxy-
late (6). To a solution of hemiaminal 5a (70 mg, 0.20 mmol, 1
equiv) in CH2Cl2 (2 mL) was added trimethylsilyl cyanide (38 µL,
0.30 mmol, 1.5 equiv), followed by BF3 ·OEt2 (37 µL, 0.30 mmol,
1.5 equiv). The mixture was stirred at room temperature for 30
min. The reaction was then hydrolyzed by addition of water. The
aqueous phase was extracted with CH2Cl2. The organic phase was
washed with brine, dried over anhydrous MgSO4, and concentrated.
Removal of the solvent afforded 6 (52 mg, 100%) as a yellow oil:
IR (NaCl) 3367, 2952, 2922, 2850, 2234, 1692, 1639, 1455, 1299,
General Procedure for Preparation of Tetrahydropyrazinols
5. 1-tert-Butyl 2-Methyl 4-Benzyl-5,6-dihydro-5-hydroxypyrazine-
1,2(4H)-dicarboxylate (5a). To a solution of tert-butyl methyl 4H-
1,4-oxazine-3,4-dicarboxylate 2 (0.295 g, 1.22 mmol, 1 equiv) in
MeCN (12 mL) was added K2CO3 (1.014 g, 7.34 mmol, 6 equiv),
followed by benzylamine (0.134 mL, 1.22 mmol, 1 equiv), with
fast stirring at room temperature. The reaction was monitored by
TLC (DCM/MeOH, 98:2), and when no starting material was
detected (22 h), the reaction mixture was filtered through Celite.
The solution was washed with water, the aqueous phase was
extracted with EtOAc, and the organic phases were then washed
with brine and dried over anhydrous MgSO4. Removal of the solvent
afforded 5a (0.426 g, 100%) as a white solid: mp 164-165 °C; IR
1
1157 cm-1; H NMR 250 MHz (CDCl3) δ 7.29-7.39 (m, 5 H),
6.75 (s, 1 H), 4.30 (s, 2 H), 4.00 (t, 1 H, J ) 2.3 Hz), 3.76 (s, 3 H),
3.42 (AB syst.: 2 × dd, 2 H, 3.24 ppm and 3.60 ppm, J ) 12.5 Hz
and J ) 2.8 Hz and J ) 2.5 Hz); 13C NMR 62.5 MHz (CDCl3) δ
165.1 (s), 134.9 (s), 129.2 (d), 128.7 (d), 128.5 (d), 125.7 (d), 116.4
(s), 112.5 (s), 57.9 (t), 51.6 (q), 45.6 (d), 44.4 (t); MS (IS) m/z )
258.0 [M + H]+. Slow decomposition of 6 over several hours
precluded satisfactory HRMS analysis.
Acknowledgment. We are grateful to the CNRS and the
Region Centre for financial support.
(KBr) 3471, 3065, 2975, 2951, 1716, 1683, 1602, 1438, 1169 cm-1
;
1H NMR 250 MHz (CDCl3) δ 7.21-7.39 (m, 5 H), 7.04 (s, 1 H),
4.86 (br s, 1 H), 4.44 (AB syst.: 2 × d, 2 H, 4.35 ppm and 4.54
ppm, J ) 15.0 Hz), 3.49 (s, 3 H), 3.53 (AB syst.: 2 × dd, 2 H,
2.75 ppm and 4.30 ppm, J ) 13.3 Hz and J ) 1.5 Hz and J ) 2.0
Hz), 3.49 (br s, 1 H), 1.43 (s, 9 H); 13C NMR 62.5 MHz (CDCl3)
δ 165.1 (s), 154.9 (s), 136.6 (s), 134.2 (d), 129.0 (d), 128.1 (d),
127.9 (d), 105.0 (s), 81.1 (s), 77.3 (d), 56.3 (t), 51.3 (q), 46.8 (t),
28.1 (q); HRMS (EI) m/z [M - H2O]+• calcd for C18H24N2O5
Supporting Information Available: Detailed experimental
procedures, full characterization for all new compounds syn-
thesized, 1H and 13C NMR Spectra for compounds 2-6, X-ray
structures and CIF files of compounds 2 and 5a. This material
is available free of charge via the Internet at http://pubs.acs.org.
JO900291F
2914 J. Org. Chem. Vol. 74, No. 7, 2009