Alkyl, unsaturated, (hetero)aryl, and N-protected α-amino ketones by acylation of organometallic reagents

Article abstract of DOI:10.1021/jo0614801

Stable and easily accessible N-acylbenzotriazoles, derived from a variety of aliphatic, unsaturated, (hetero)aromatic, and N-protected α-amino carboxylic acids, were reacted with Grignard and heteroaryllithium reagents to afford corresponding ketones in good to excellent yields.

Full text of DOI:10.1021/jo0614801

effective replacement for the corresponding acid chlorides,
which are usually unstable and sometimes difficult to prepare;11
thus N-acylbenzotriazoles provide a simple and efficient method
to prepare peptides.12
Alkyl, Unsaturated, (Hetero)aryl, and
N-Protected r-Amino Ketones by Acylation of
Organometallic Reagents
Ketones have been prepared by a wide variety of methods.
Among them, the reaction of Grignard or organometallic
reagents with a carboxylic acid is not a practical approach
because of the low yield of ketones and the formation of tertiary
alcohols.13 Previous solutions to this problem have involved the
addition of Grignard or organozinc reagents to acid fluorides,
chlorides, anhydrides, esters, thioesters, and acyl pyrrazolides,14
Weinreb amides,15 or acyl hemiacetals.16 Rapoport and co-
workers also used lithium carboxylate together with Grignard
reagents to form ketones directly from specific N-protected
substituted amino acids in yields which varied from 25 to 87%.17
Acyl isoxazolidides, prepared through three steps from serine,18
have been also used to prepare ketones.19 Limitations associated
with these literature methods have included low yields of
ketones, many side reactions,20 and additional requirements of
either organic ligands or transition metal catalysts.21 The
undesired side reactions were due to reduction of acid chloride
by the Grignard reagent followed by several other reactions.20
Moreover, acylations with acid chlorides suffered from their
sensitivity to moisture and handling difficulties.22 Reactions with
R,â-unsaturated acid chlorides, such as acryloyl chloride, do
not work well because of the accompanying polymerization.23
Furthermore, N-protected R-amino acid chlorides are often
unstable and prone to racemization.24 N-Methoxy-N-methyl
amides (Weinreb amides) cleanly react with Grignard and
organometallic reagents to produce ketones with high selectivity
Alan R. Katritzky,* Khanh N. B. Le, Levan Khelashvili, and
Prabhu P. Mohapatra
Center for Heterocyclic Compounds, Department of Chemistry,
UniVersity of Florida, GainesVille, Florida 32611-7200
katritzky@chem.ufl.edu
ReceiVed July 17, 2006
Stable and easily accessible N-acylbenzotriazoles, derived
from a variety of aliphatic, unsaturated, (hetero)aromatic, and
N-protected R-amino carboxylic acids, were reacted with
Grignard and heteroaryllithium reagents to afford corre-
sponding ketones in good to excellent yields.
(11) Caprio, V. In ComprehensiVe Organic Functional Group Trans-
formations II; Katritzky, A. R., Taylor, R. J. K., Eds.; Elsevier: New York,
2005; p 135.
Great advances have been made in the application of
N-acylbenzotriazoles in organic synthesis as activated derivatives
of carboxylic acids.1 Efficient N-acylbenzotriazole reagents have
been easily prepared from carboxylic acids by (i) thionyl
chloride and 1H-benzotriazole2 (BtH) or (ii) BtSO2Me in the
presence of Et3N for the N-acylation of amines3 and amides,3,4
the O-acylation of aldehydes,5 and the C-acylation of ketones
and heteroaromatics,6 alkylsulfones,7 alkylcyanides,8 alkyla-
zines,9 and R-nitro alkanes.10 Acylations with stable, crystalline
N-acylbenzotriazoles have attracted interest since they offer an
(12) (a) Katritzky, A. R.; Suzuki, K.; Singh, S. K. Synthesis 2004, 2645.
(b) Katritzky, A. R.; Angrish, P.; Hu¨r, D.; Suzuki, K. Synthesis 2005, 398.
(c) Katritzky, A. R.; Angrish, P.; Suzuki, K. Synthesis 2006, 411.
(13) (a) Jorgenson, M. J. Org. React. 1970, 18, 1. (b) Suga, K.; Watanabe,
S.; Yamaguchi, Y.; Tohyama, M. Synthesis 1970, 189. (c) Watanabe, S.;
Suga, K.; Fujita, T.; Saito, N. Aust. J. Chem. 1977, 30, 427.
(14) (a) Zhang, Y.; Rovis, T. J. Am. Chem. Soc. 2004, 126, 15964. (b)
Hansford, K. A.; Dettwiler, J. E.; Lubell, W. D. Org. Lett. 2003, 5, 4887.
(c) Dieter, R. K. Tetrahedron 1999, 55, 4177. (d) Shirley, D. A. In Organic
Reactions; Wiley: New York, 1954; Vol. 8, p 28. (e) Lauer, D.; Staab, H.
A. Chem. Ber. 1969, 102, 1631. (f) Staab, H.; Jost, E. Ann. 1962, 655, 90.
(g) Kuhn, R.; Staab, H. A. Chem. Ber. 1954, 87, 262.
(15) Nahm, S.; Weinreb, S. M. Tetrahedron Lett. 1981, 22, 3815.
(16) Mattson, M. N.; Rapoport, H. J. Org. Chem. 1996, 61, 6071.
(17) (a) Knudsen, C. G.; Rapoport, H. J. Org. Chem. 1983, 48, 2260.
(b) Maurer, P. J.; Takahata, H; Rapoport, H. J. Am. Chem. Soc. 1984, 106,
1095.
(18) Lubell, W. D.; Rapoport, J. Org. Chem. 1989, 54, 3824.
(19) Lubell, W. D.; Jamison, T. F.; Rapoport, H. J. Org. Chem. 1990,
55, 3511.
(1) Katritzky, A. R.; Suzuki, K.; Wang, Z. Synlett 2005, 1656.
(2) (a) Katritzky, A. R.; Zhang, Y.; Singh, S. K. Synthesis 2003, 2795.
(b) Katritzky, A. R.; Meher, N. K.; Cai, C.; Singh, S. K. ReV. Soc. Quim.
Mex. 2004, 48, 275.
(3) Katritzky, A. R.; He, H.-Y.; Suzuki, K. J. Org. Chem. 2000, 65, 8210.
(4) Katritzky, A. R.; Yang, H.; Zhang, S.; Wang, M. ARKIVOC 2002,
XI, 39.
(5) Katritzky, A. R.; Pastor, A.; Voronkov, M. V. J. Heterocycl. Chem.
1999, 36, 777.
(6) (a) Katritzky, A. R.; Pastor, A. J. Org. Chem. 2000, 65, 3679. (b)
Katritzky, A. R.; Jiang, R.; Suzuki, K. J. Org. Chem. 2005, 70, 4993. (c)
Katritzky, A. R.; Meher, N. K.; Singh, S. K. J. Org. Chem. 2005, 70, 7792.
(7) Katritzky, A. R.; Abdel-Fattah, A. A. A.; Wang, M. J. Org. Chem.
2003, 68, 1443.
(8) Katritzky, A. R.; Abdel-Fattah, A. A. A.; Wang, M. J. Org. Chem.
2003, 68, 4932.
(9) Katritzky, A. R.; Abdel-Fattah, A. A. A.; Akhmedova, R. G.
ARKIVOC 2005, 329.
(20) Wang, X.-J.; Zhang, L.; Sun, X.; Xu, Y.; Krishnamurthy, D.;
Senanayake, C. H. Org. Lett. 2005, 7, 5593.
(21) (a) Cardelicchio, C.; Flandanese, V.; Marchese, G.; Ronzini, L.
Tetrahedron Lett. 1987, 28, 2053. (b) Malanga, C.; Aronica, L. A.; Lardicci,
L. Tetrahedron Lett. 1995, 36, 9185.
(22) Aldabbagh, F. ComprehensiVe Organic Functional Group Trans-
formations II; Katritzky, A. R., Taylor, R. J. K., Eds.; Elsevier: New York,
2005; Vol. 5, p 1.
(23) (a) Fristad, W. E.; Dime, D. S.; Bailey, T. R.; Paquette, L. A.
Tetrahedron Lett. 1979, 20, 1999. (b) Paquette, L. A.; Fristad, W. E.; Dime,
D. S.; Bailey, T. R. J. Org. Chem. 1980, 45, 3017.
(10) Katritzky, A. R.; Abdel-Fattah, A. A. A.; Gromova, A. V.; Witek,
R.; Steel, P. J. J. Org. Chem. 2005, 70, 9211.
(24) Gross, M.; Meienhofer, J. The Peptides; Academic Press: New York,
1979.
10.1021/jo0614801 CCC: $33.50 © 2006 American Chemical Society
Published on Web 12/01/2006
J. Org. Chem. 2006, 71, 9861-9864
9861

FIGURE 2. Grignard reagents and heteroaryllithium reagents (R2M)
2a-e.
TABLE 1. Addition of Grignard Reagent 2a to
N-Acylbenzotriazoles 1
FIGURE 1. N-Acylbenzotriazoles (R1COBt) 1a-n.
without side reactions.15 However, in certain cases, with
hindered or highly basic reagents, the Weinreb amides show
unusual reactivity.25 Direct acylations using amino acid deriva-
tives required specific protecting groups which were sometimes
difficult to remove.26 Acyl isoxazolidides have concurrent
reductive cleavage of the N-O bond, and ring opening of these
compounds was observed.19
Our approach to develop a general method for the synthesis
of a variety of ketones involved the use of N-acylbenzotriazoles
as the stable alternatives of corresponding acid chlorides or
Weinreb amides. We now report the synthesis of alkyl,
unsaturated, (hetero)aryl, and R-amino ketones in good to
excellent yields from easily accessible N-acylbenzotriazoles with
Grignard reagents or heteroaryllithiums without side reactions.
N-Acylbenzotriazoles 1a-n were readily prepared from
benzotriazole (Bt) and the corresponding carboxylic acid in
excellent yields according to reported procedure (Figure
1).2a,3,6c,12a,27 Grignard and heteroaryllithium reagents 2a-e were
freshly prepared in THF immediately before use (Figure 2).
We found that 1 mmol of 1-benzotriazol-1-ylpropan-1-one
1a on reaction with 1.2 mmol of freshly prepared p-tolylmag-
nesium bromide 2a at 0 °C for 1.5 h gave the corresponding
a Isolated yields after column purification and determined from a single
experiment. b Reaction temperature was varied between 0 and 65 °C and
reaction time between 1.5 and 6.0 h based on TLC profile (diethylether/
hexanes ) 10:1 to 1:1).
in the starting material. We then explored a wide range of
N-acylbenzotriazoles (Figure 1) with Grignard reagents and
organolithium reagents (Figure 2) in the coupling reaction to
test the generality of this method. The results of our efforts are
displayed in Tables 1-3.
A variety of alkyl, aryl, heteroaryl, and unsaturated N-
acylbenzotriazoles, such as 1-benzotriazol-1-ylpropan-1-one2a
1a, benzotriazol-1-ylphenylmethanone3 1b, benzotriazol-1-yl-
naphthalen-1-ylmethanone3 1d, benzotriazol-1-ylfuran-2-yl-
methanone3 1f, 1-benzotriazol-1-ylbut-2-en-1-one2a 1i, and
1-benzotriazol-1-yl-3-phenylpropynone2a 1j, were reacted with
1.2 equiv of p-tolylmagnesium bromide 2a. At the appropriate
temperature and the corresponding reaction time, the desired
alkyl, aryl, heteroaryl, and unsaturated ketones 3a-f were
obtained in 50-89% yields (Table 1). The products were
1
p-tolylpropanone 3a in 89% yield (Table 1). The H NMR
spectra of 3a showed the disappearance of the Bt signals in the
aromatic region, indicating the loss of the benzotriazolyl group
during the reaction. The 13C NMR spectra of 3a showed a signal
at 200.5 ppm corresponding to the carbonyl group of the product
and the disappearance of the signal at 168.8 ppm belonging to
the carbonyl group at the R position of the benzotriazolyl group
(25) (a) Graham, S. L.; Scholz, T. H. Tetrahedron Lett. 1990, 31, 6269.
(b) Graham, S. L.; Scholz, T. H. J. Org. Chem. 1991, 56, 4260.
(26) Roemmele, R. C.; Rapoport, H. J. Org. Chem. 1988, 53, 2367.
(27) Katritzky, A. R.; Singh, S. K.; Cai, C.; Bobrov, S. J. Org. Chem.
2006, 71, 3364.
9862 J. Org. Chem., Vol. 71, No. 26, 2006

TABLE 2. Addition of Grignard and Organolithium Reagents
2a-e to N-Acylbenzotriazoles 1
TABLE 3. Addition of Grignard Reagent 2a to
N-Acylbenzotriazoles 1l-n
a Isolated yields after column purification and determined from a single
experiment. b Reaction temperature was varied between -78 to 65 °C and
reaction time between 1.0 and 6.0 h based on TLC profile (diethylether/
hexanes ) 10:1 to 1:1). c 2.2 equiv of Grignard reagents was used.
isolated by column chromatography and were fully characterized
a Isolated yields after column purification (eluent: diethylether/hexanes
) 10:1 to 1:1) and determined from a single experiment. b 2.2 equiv of
Grignard reagents was used.
1
by H/13C NMR spectroscopy and elemental analysis. Com-
pound 3e, where there is a possibility of geometrical isomerism,
is in the E-form as evidenced from the coupling constants (J )
15.6 Hz) between protons attached to the carbon-carbon double
bond.
SCHEME 1
We then attempted to synthesize more complex ketones by
varying both the coupling partners. Coupling reactions were
carried out with one more Grignard reagent as well as some
aryl and (hetero)aryllithium reagents. Thus, p-tolylmagnesium
bromide 2a, allylmagnesium bromide 2b, 2-thienyllithium 2c,
phenylethynyllithium 2d, and 1H-indol-2-yllithium lithium salt28
2e were reacted with N-acylbenzotriazoles, such as benzotriazol-
1-yl-2-hydroxy-3-methylphenylmethanone27 1e (2.2 equiv of
Grignard reagents was used in the presence of a free hydroxyl
group), benzotriazol-1-ylthiophen-2-ylmethanone2a 1g, benzo-
triazol-1-ylphenylmethanone3 1b, (E)-1-benzotriazol-1-yl-3-
thiophen-2-ylpropenone6c 1k, benzotriazol-1-ylpyridin-2-yl-
methanone3 1h, and benzotriazol-1-yl-p-tolylmethanone3 1c, to
give the desired diheteroaryl and unsaturated heteroaryl ketones
3g-l in 32-80% yield (Table 2).
able to isolate any of the side products due to their small
quantity. Also, we found that the pure products 3h, 3i, and 3k
are not stable at room temperature and decomposed considerably
after 2-3 days when stored at room temperature.
We found that tertiary alcohols were not obtained as the side
products in the reaction even after we used excess Grignard
reagent. We therefore propose the tetrahedral intermediate 4 to
explain the preferential formation of ketones over tertiary
alcohols (Scheme 1). The effective chelation of metal ion
between carbonyl oxygen and nitrogen of the benzotriazole
moiety prevents the collapse of the tetrahedral intermediate 4
until the aqueous acidic work up.
When using allyl Grignard reagent 2b, we noticed the
formation of side products on TLC. This may be due to the
formation of products arising from the conjugation of the olefin
to provide the R,â-unsaturated ketones. However, we were not
Our method proved successful with a wide variety of
organometallic reagents and N-acylbenzotriazoles. Ketone 3h
(28) Herbert, J. M.; Maggiani, M. Synth. Commun. 2001, 31, 947.
J. Org. Chem, Vol. 71, No. 26, 2006 9863

has been prepared previously with low yields (16%) by the
Friedel-Crafts reaction of thiophene with 4-chlorobutyryl
chloride.29 The present procedure is obviously higher yielding,
more simple, and convenient. Few examples of unsaturated
heteroaryl ketones are known in the literature. Synthesis of the
unsaturated heteroaryl ketone 3k may be helpful for the access
of complex natural products. Ketone 3m containing the indole
moiety was also conveniently prepared by our method.
acylating agents are used; (ii) additional transition metal catalysts
or organic ligands are avoided; and (iii) useful to excellent yields
of ketones are obtained.
Experimental Section
General Procedure: To a stirred solution of N-acylbenzotriazole
(1 mmol) in dry THF (5 mL) under nitrogen was added dropwise
a freshly prepared solution of Grignard or heteroaryllithium reagent
in THF (c ) 0.5 M, 2.4 mL, 1.2 mmol or 4.8 mL, 2.2 mmol for
N-acylbenzotriazoles containing acidic hydrogens) at the appropriate
temperature. The reaction mixture was stirred until completed
(followed by TLC, solvent system: diethylether/hexanes ) 10:1
to 1:1) and then quenched by saturated ammonium chloride solution.
After extraction by ethyl acetate, the organic layer was washed with
brine and water, dried over anhydrous magnesium sulfate, and
concentrated under reduced pressure. The crude product was then
purified by chromatography over silica gel column (eluent: dieth-
ylether/hexanes ) 10:1 to 1:1).
Because one of the most important features of biologically
active amino ketones is associated with the presence of an
asymmetric R-carbon in their structures, total control of chirality
represents a major goal during the synthesis of these amino
ketones. Literature synthesis of chiral aryl R-amino ketones via
Friedel-Crafts-type reactions involves N-protected R-amino
acid chlorides.30 Direct acylation using amino acids has been
described by Rapoport.16,17 We reacted the N-acylbenzotriazole
derivatives, such as (2-benzotriazol-1-yl-2-oxoethyl)carbamic
acid benzyl ester12a 1l, (2-benzotriazol-1-yl-1-methyl-2-oxoet-
hyl)carbamic acid benzyl ester12a 1m, and (2-benzotriazol-1-
yl-1-benzyl-2-oxoethyl)carbamic acid benzyl ester12a 1n, with
2.2 equiv of p-tolylmagnesium bromide 2a to give the novel
aryl R-amino ketones 3n-t in 40-67% yield (Table 3). To
demonstrate that racemization does not occur during the reaction,
D, L, and D,L mixtures of ketones 3o-q and 3r-t were
synthesized from D, L, and D,L mixtures of N-acylbenzotriazoles
1m and 1n, respectively. As determined by chiral HPLC analysis
(using Chirobiotic T column, detection at 254 nm, flow rate
0.5 mL/min, solvent MeOH/H2O ) 99:1, solution concentration
0.1 mg/mL), 3r and 3s showed single peaks at 6.2 and 6.5 min,
respectively, where as the D,L mixture 3t showed two peaks at
6.2 and 6.5 min. A doping experiment was carried out by mixing
the solution of 3r with 2 drops of the solution of 3t, and the
HPLC showed an enhanced peak at 6.2 min corresponding to
3r and a small peak at 6.5 min corresponding to 3t. The same
doping experiment was also carried out with 3s and 3t, and the
HPLC traces have been included in the Supporting Information.
Yields for 3b-f, 3h-m, and 3n-t were calculated for the
pure isolated products after the purification by column chro-
matography. In all the cases, 10-20% of the corresponding
starting materials was recovered. Compounds containing un-
saturated bonds such as 3e,f, 3h,i, and 3k were found to be
unstable at room temperature. We were not able to isolate any
side products in all the above reactions. Efforts were made to
optimize the yields of 3c-e and 3h by refluxing the reaction
mixture for several hours in THF.
(2-Hydroxy-3-methylphenyl)-p-tolylmethanone (3g): Yield
1
0.18 g (80%); yellow crystal; mp ) 62 °C; H NMR δ 7.59 (d, J
) 8.0 Hz, 2H), 7.45 (d, J ) 8.0 Hz, 1H), 7.36 (d, J ) 8.0 Hz, 1H),
7.30 (d, J ) 8.0 Hz, 2H), 6.78 (t, J ) 8.0 Hz, 1H), 2.45 (s, 3H),
2.32 (s, 3H); 13C NMR δ 201.5, 161.4, 142.5, 136.8, 135.3, 131.1,
129.4, 128.9, 127.2, 118.4, 117.8, 21.5, 15.5. Anal. Calcd for
C15H14O2: C, 79.62; H, 6.24. Found: C, 78.98; H, 6.48.
D-(1-Benzyl-2-oxo-2-p-tolylethyl)carbamic Acid Benzyl Ester
(3r): Yield 0.21 g (56%), oil; [R]25D ) -10 (CHCl3, c ) 1.2); 1H
NMR δ 7.85 (d, J ) 8.1 Hz, 2H), 7.34-7.30 (m, 5H), 7.26 (d, J
) 8.1 Hz, 2H), 7.20-7.18 (m, 3H), 6.97-6.95 (m, 2H), 5.74 (d, J
) 8.0 Hz, 1H), 5.58 (dd, J ) 11.7, 5.8 Hz, 1H), 5.10 (s, 2H), 3.26
(dd, J ) 13.8, 6.0 Hz, 1H), 2.99 (dd, J ) 13.8, 5.4 Hz, 1H), 2.41
(s, 3H); 13C NMR δ 197.3, 155.6, 144.8, 136.4, 135.5, 132.0, 129.6,
129.5, 128.7, 128.5, 128.3, 128.1, 127.9, 126.9, 66.8, 56.3, 39.1,
21.7. Anal. Calcd for C24H23NO3: C, 77.19; H, 6.21; N, 3.75.
Found: C,76.99; H, 6.33; N, 3.57.
L-(1-Benzyl-2-oxo-2-p-tolylethyl)carbamic Acid Benzyl Ester
(3s): Yield 0.14 g (40%), oil; [R]25D ) +10 (CHCl3, c ) 1.0); 1H
NMR δ 7.85 (d, J ) 8.1 Hz, 2H), 7.33-7.31 (m, 5H), 7.26 (d, J
) 8.1 Hz, 2H), 7.19-7.16 (m, 3H), 6.98-6.95 (m, 2H), 5.74 (d, J
) 8.0 Hz, 1H), 5.58 (dd, J ) 11.7, 5.8 Hz, 1H), 5.09 (s, 2H), 3.26
(dd, J ) 13.8, 6.0 Hz, 1H), 2.98 (dd, J ) 13.8, 5.4 Hz, 1H), 2.41
(s, 3H); 13C NMR δ 197.3, 155.6, 144.7, 136.4, 135.5, 132.0, 129.6,
129.5, 128.7, 128.5, 128.3, 128.1, 127.9, 126.9, 66.8, 56.3, 39.1,
21.6. Anal. Calcd for C24H23NO3: C, 77.19; H, 6.21; N, 3.75.
Found: C, 76.87; H, 6.42; N, 3.45.
D,L-(1-Benzyl-2-oxo-2-p-tolylethyl)carbamic Acid Benzyl Es-
ter (3t): Yield 0.18 g (50%), oil; 1H NMR δ 7.85 (d, J ) 8.1 Hz,
2H), 7.33-7.30 (m, 5H), 7.27 (d, J ) 8.1 Hz, 2H), 7.09-7.17 (m,
3H), 6.98-6.94 (m, 2H), 5.72 (d, J ) 8.0 Hz, 1H), 5.58 (dd, J )
11.7, 5.8 Hz, 1H), 5.10 (dd, J ) 20.6, 12.4 Hz, 2H), 3.26 (dd, J )
13.8, 6.0 Hz, 1H), 2.99 (dd, J ) 13.8, 5.4 Hz, 1H), 2.41 (s, 3H);
13C NMR δ 197.3, 155.6, 144.8, 136.4, 135.5, 132.0, 129.5, 129.4,
128.7, 128.4, 128.2, 128.0, 127.9, 126.8, 66.7, 56.2, 39.0, 21.7.
Anal. Calcd for C24H23NO3: C, 77.19; H, 6.21; N, 3.75. Found:
C, 76.96; H, 6.76; N, 3.50.
In summary, a simple, efficient, and broadly applicable
general method for the preparation of alkyl, unsaturated,
(hetero)aryl, and N-protected R-amino ketones by acylation of
the corresponding N-acylbenzotriazoles with Grignard and
heteroaryllithium reagents has been developed. Features of this
method include the following: (i) stable and easily accessible
Acknowledgment. We thank Dr. C. D. Hall for checking
the manuscript for language usage.
(29) El-Khagawa, A. M.; El-Zohry, M. F.; Ismail, M. T. Phosphorous
Sulfur 1987, 33, 25.
(30) (a) Buckley, T. F., III; Rapoport, H. J. Am. Chem. Soc. 1981, 103,
6157. (b) McClure, D. E.; Arison, B. H.; Jones, J. H.; Baldwin, J. J. J.
Org. Chem. 1981, 46, 2431. (c) Nordlander, J. E.; Payne, M. J.; Njoroge,
F. G.; Balk, M. A.; Laikos, G. D.; Vishwanath, V. M. J. Org. Chem. 1984,
49, 4107. (d) Nordlander, J. E.; Njoroge, F. G.; Payne, M. J.; Warman, D.
J. Org. Chem. 1985, 50, 3481. (e) Di Gioia, M. L.; Leggio, A.; Liguori,
A.; Napoli, A.; Siciliano, C.; Sindona, G. J. Org. Chem. 2001, 66, 7002.
Supporting Information Available: Experimental procedures,
spectroscopic data, elemental analysis, and melting points for
compounds 3a-f and 3h-q. This material is available free of
charge via the Internet at http://pubs.acs.org.
JO0614801
9864 J. Org. Chem., Vol. 71, No. 26, 2006