Chemoselective reactions of N1-methyl-2-hydroxy-3-methylamino-3-phenylpropanamide with electrophiles. Synthesis of chiral hexahydro-4-pyrimidinones and oxazolidines

Article abstract of DOI:10.1016/S0040-4020(02)00235-1

The reactivity of (2S,3S)-N1-methyl-2-hydroxy-3-methylamino-3-phenylpropanamide 1, containing three nucleophilic centres has been studied against dihaloalkanes and aldehydes. Hexahydro-4-pyrimidinones or oxazolidines were obtained chemoselectively. Experimental results were explained by 'ab initio' calculations.

Full text of DOI:10.1016/S0040-4020(02)00235-1

TETRAHEDRON
Pergamon
Tetrahedron 58 (2002) 3281±3285
Chemoselective reactions of N1-methyl-2-hydroxy-3-
methylamino-3-phenylpropanamide with electrophiles. Synthesis
of chiral hexahydro-4-pyrimidinones and oxazolidines
a
Chakib Hajji, Mã Luisa Testa, Elena Zaballos-Garcõa, Ramon J. Zaragoza,
a
a
b,p
Â
Â
Â
Å
Âc
Juan Server-Carrio and Jose Sepulveda-Arques
Â
a,p
Â
a
 Â
Departamento de Quõmica Organica, Facultad de Farmacia, Universidad de Valencia, E-46100 Burjassot, Valencia, Spain
 Â
Departamento de Quõmica Organica, Instituto de Ciencia Molecular, Universidad de Valencia, E-46100 Burjassot, Valencia, Spain
b
c
 Â
Departamento de Quõmica Inorganica, Universidad de Valencia, E-46100 Burjassot, Valencia, Spain
Received 31 July 2001; revised 25 February 2002; accepted 26 February 2002
AbstractÐThe reactivity of (2S,3S)-N1-methyl-2-hydroxy-3-methylamino-3-phenylpropanamide 1, containing three nucleophilic centres
has been studied against dihaloalkanes and aldehydes. Hexahydro-4-pyrimidinones or oxazolidines were obtained chemoselectively.
Experimental results were explained by `ab initio' calculations. q 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
phenylpropanamide 1, containing three nucleophilic centres
with dihaloalkanes and aldehydes.
Reactions of nitrogen and/or oxygen dinucleophiles with
dihalomethanes or aldehydes leading to cyclic compounds
have been extensively reported.1 Although amino and
hydroxy groups are the most frequent nucleophiles, carbox-
amides also participate in this type of reactions. In this
context, we can mention the reaction of prolinamide with
dichloromethane2a or the reaction of 2-piperidinecarbox-
amide with glutaraldehyde2b to produce ®ve membered
ring aminals and also the reaction of asparagine with pival-
dehyde3 affording a pyrimidinone which has been used as a
reagent and as a chiral auxiliary in asymmetric synthesis.4
There are a few examples of reactions of compounds with
three nucleophilic groups in vicinal positions with the
mentioned electrophiles and the regioselectivity observed
in the formation of the corresponding cyclic compounds
in these cases is highly emphasized.5
2. Results and discussion
The aminohydroxypropanamide 1, was prepared by oxida-
tion of 3-phenyloxiran-2-ylmethanol8 further esteri®ed9 and
®nally reacted with aqueous methylamine.
There are different possibilities of reaction of compound 1,
containing three nucleophilic centres in 1,2,3 positions with
C-1 electrophiles, and in principle, complex mixtures could
be expected in these reactions. However, when the amide 1
reacted with dichloromethane, dibromomethane, or para-
formaldehyde, the hexahydro-4-pyrimidinone 2a was the
only product that could be isolated from the crude reaction
mixture. On the other hand, the reaction with 2,2-
dimethoxypropane afforded the oxazolidine 3b and in the
same way as the reaction with acetaldehyde or benzalde-
hyde the oxazolidines 3c and e were obtained (Scheme 1).
The reaction with the aldehydes exhibits a high degree of
stereocontrol10 and just in the case of the reaction with
acetaldehyde minor amounts (,5%) of the diastereoisomer
3d were observed in the 1H NMR spectrum. In the reaction
with benzaldehyde, the diastereoisomer 3f was not detected.
In a previous paper, we presented the regioselective results
concerning the synthesis of chiral 4-substituted 3-methyl-
tetrahydro-1,3-oxazin-5-ols, with excellent yields, by
reaction of 3-methylamino-1,2-diols with dichloro-
methane.6 In this work, in continuation of our interest in
the synthesis of polyfunctionalized molecules,7 we report
the remarkable chemoselective results observed in the
reaction
of
N1-methyl-2-hydroxy-3-methylamino-3-
No traces of the corresponding six membered ring cycliza-
tion products were detected in the reaction with 2,2-
dimethoxypropane or aldehydes.
Keywords: pyrimidinones; oxazolidines; dichloromethane; aminodiols;
regioselectivity.
Corresponding authors. Tel.: 134-96-3864938; fax: 34-96-3864939;
e-mail: ramon.j.zaragoza@uv.es; jose.sepulveda@uv.es
p
The structure of the hexahydro-4-pyrimidinone 2a
0040±4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)00235-1

3282
C. Hajji et al. / Tetrahedron 58 (2002) 3281±3285
Scheme 1.
(R1ˆR2ˆH) was elucidated by spectroscopy. The stereo-
thermodynamic control in these reactions. We have carried
out an `ab initio' theoretical study of the thermodynamic
stability of compounds 2a±d and 3a±d.
chemistry was con®rmed by X-ray analysis (Fig. 1).
1
The structures of compounds 3 were elucidated by H and
13C NMR spectroscopy. NOE experiments carried out with
compound 3b (R1ˆCH3, R2ˆCH3) and 3c (R1ˆH, R2ˆCH3)
con®rmed the cis disposition of hydrogens at C4 and C5 in
3b and C2, C4 and C5 in 3c. The N-methyl group that
All calculations were carried out with the Gaussian 98 suite
of programs.11 The HF/3-21G set parameters were used for
initial energy calculation for all possible conformations and
then, optimisation of geometries and energies were
performed at DFT level using B3LYP/6-31Gp.
1
appears in H NMR as a doublet in compounds 3 because
of the restricted rotation of the amide, was a singlet in the
cyclic hexahydro-4-pyrimidinone 2a.
The hexahydro-4-pyrimidinones 2a±d, can adopt the boat
conformations B1 and B2 and chair conformations C1 and
C2 (Fig. 2), and the oxazolidines 3a±d present two envelope
conformations, E1 with N-atom towards b-face, and E2
with N-atom towards a-face (Fig. 3). The CONHCH3
group in both conformers presents a hydrogen bond between
the NH and the oxygen atom of the oxazolidine. The N-Me
group in hexahydro-4-pyrimidinones 2 and oxazolidines 3
can be up and down and duplicates the number of
possibilities.
The chemoselectivity observed in the reaction of the amide
1 with different C-1 electrophiles could be the result of
The results of this thermodynamic study are shown as
relative energies for each group of compounds. In Table
1, we can ®nd the relative energies of the different confor-
mations of compounds 2a and 3a that could be obtained in
the reaction of amide 1, with dichloromethane, dibromo-
methane or paraformaldehyde. In the same table, we present
the relative energies of compounds 2b and 3b that could be
obtained by the reaction with dimethoxypropane. In the
reaction of amide 1 with acetaldehyde, in addition to regio-
isomers there is the possibility of diastereoisomers. The
relative energies for all the possible conformers of
compounds 2c,d, 3c and d are also presented in the same
table.
Figure 1. A view of the compound 2a showing the labelling scheme. Labels
for carbon atoms only include the number used in the X-ray crystal analysis.
Displacement ellipsoids are drawn at 50% probability level.
R1
Ph
R1
The theoretical study has shown that hexahydro-4-pyrimi-
dinones 2 present greater stability than oxazolidines 3 just in
case of 2a where R1ˆR2ˆH. For example, at DFT level, the
more stable conformation of 2a (C2D) is 1.64 kcal/mol
Ph
R2
R2
C1
B1
R1
R1
R1
R1
R2
Ph
R2
Ph
Ph
R2
R2
Ph
E1
E2
B2
C2
Figure 2. Different conformations for compounds 2.
Figure 3. Different conformations for compounds 3.

C. Hajji et al. / Tetrahedron 58 (2002) 3281±3285
3283
Table 1. 3-21G (DE3-21G) and B3LYP/6-31Gp (DEB3LYP) relative energies (kcal/mol) (relative to the most stable conformation of each group of compounds) of
the different conformations for compounds 2a/3a (upper left), 2b/3b (upper right) and 2c/3c/2d/3d (down)
Conformationa
DE3-21G
DEB3LYP
Conformationa
DE3-21G
DEB3LYP
2a
C1A
C2A
B1A
B2A
C1D
C2D
B1D
B2D
6.45
4.22
0.00
7.33
3.25
0.12
0.14
5.25
4.43
0.00
2b
C1A
C2A
B1A
B2A
C1D
C2D
B1D
B2D
B1Ac
13.13
9.11
10.87
9.92
15.46
19.74
8.56
C2Ab
16.19
8.74
9.34
1.79
C2Db
10.55
B1Ab
C2Db
C2Db
1.64
3a
2c
E1A
E2A
E1D
E2D
1.77
E1Ab
2.51
3b
2d
E1A
E2A
E1D
E2D
E2Ab
0.00
1.55
E2Ab
0.00
2.89
2.29
5.19
9.80
C1A
C2A
B1A
B2A
C1D
C2D
B1D
B2D
B1Ab
B1Ab
2.95
C1A
C2A
B1A
B2A
C1D
C2D
B1D
B2D
10.19
7.61
3.20
9.24
6.02
5.11
11.79
12.28
5.44
5.95
11.73
15.26
5.00
9.32
13.83
3.47
C2Ab
11.07
4.35
B1Ab
B1Ab
B1Ab
C2Db
3c
E1A
E2A
E1D
E2D
E2Ab
0.00
3.08
E2Ab
3d
E1A
E2A
E1D
E2D
4.58
1.52
0.10
E2Ab
5.00
2.85
2.02
0.00
5.09
a
The ®nal A or D letter for different conformations of compounds 2 and 3 indicates the position of the methyl group on the nitrogen atom. A (above or b), D
(down or a).
Conformation obtained by evolution of the original conformation.
b
more stable than the more stable conformation of 3a (E1A)
4. Experimental
(Table 1, upper left). In all other cases with substituents at
C-2, the oxazolidines 3b,c are much more stable than the
corresponding hexahydro-4-pyrimidinones. For example,
conformation E2A for 3b is more stable than any conforma-
tion of 2b (Table 1, upper right) and conformation E2A for
3c is more stable than any conformation of 2c,d, and 3d
(Table 1, down).
4.1. General
Unless otherwise speci®ed, materials were purchased from
commercial suppliers and used without further puri®cation.
CH2Cl2 was distilled from calcium hydride under argon.
Analytical thin layer chromatography was performed on
Merck precated silica gel (60 F254) plates and ¯ash column
chromatography was accomplished on Merck Kieselgel 60
(230±240 mesh). Melting points were determined with a
Ko¯er hot-stage apparatus and are uncorrected. 1H and
13C NMR spectra were measured for CDCl3 solutions at
250, 300 and 62.9, 75.4 MHz, respectively, using a Bruker
AC-250, Bruker AC-300 spectrometer and chemical shifts
are recorded relative to Me4Si. High-resolution mass spec-
tral data were obtained on a VG Autospec, TRIO 1000
(Fisons) instrument. The ionisation mode used in mass spec-
tra was electron impact (EI), or chemical ionisation (CI) at
70 eV.
It is worth noting that the predicted conformation C2 (C2A
and C2D have similar energies) for 2a according DFT
calculations is the same as that found in the X-ray spectrum
of this compound. It is also important to stand out that
oxazolidine 3c, with hydrogens at C-2, C-4 and C-5 in cis
position is more stable than its diastereoisomer 3d.
The theoretical study agrees with our experimental results
and supports the idea that the reaction of compound 1 with
dichloromethane or dibromomethane or paraformaldehyde
to give hexahydro-4-pyrimidinone 2a and the reaction with
2,2-dimethoxypropane, acetaldehyde or benzaldehyde to
give oxazolidines 3b,c,e takes place under thermodynamic
control.
4.2. Computing methods
Theoretical HF/3-21G and B3LYP/6-31Gp ab initio calcula-
tions were performed on a Cray-Silicon Graphics Origin
Â
2000 with 64 processors of the Servicio de Informatica de
3. Conclusions
Á
la Universitat de Valencia. All calculations were carried out
with the Gaussian 98 suite of programs.11 The HF/3-21G
level gives reasonable results with just a short time of calcu-
lation, nevertheless the more time-consuming B3LYP/6-
31Gp level gives better results.
In summary, a new highly chemoselective transformation
has been developed for the preparation of chiral hexahydro-
4-pyrimidinones 2, and oxazolidines 3, useful as chiral
templates in asymmetric synthesis. The experimental results
are explained by ab initio calculations.
Therefore, an extensive characterisation for all possible

3284
C. Hajji et al. / Tetrahedron 58 (2002) 3281±3285
conformations was initially carried out at the HF/3-21G
level and then, optimisation of geometries and energies
were performed at DFT level using B3LYP/6-31Gp.
vacuo, dissolved in dichloromethane (10 mL) and washed
with 40% aqueous NaHCO3 solution (15 mL), brine (8 mL),
dried (MgSO4) and concentrated in vacuo to give 3b (94%).
Partial decomposition of 3b into the starting material 1 was
observed after storing for a few days. White solid. Mp 143±
4.2.1. (2S,3S)-N1-Methyl-2-hydroxy-3-methylamino-3-
phenylpropanamide (1). A mixture of (2S,3R)-2,3-epoxy-
3-phenylpropionate methyl ester9 (1 g, 5.2 mmol), methanol
(10 mL) and aqueous methylamine 40% (2.5 mL), was
heated in the pressure reactor at 1008C for 3 h. After cooling
to room temperature, the crude was concentrated in vacuo to
give a white solid which was recrystallised from hexane±
dichloromethane to give 1 (95%). Mp 149±1508C. 1H NMR
spectrum of (2S,3S)-N1-methyl-2-hydroxy-3-methylamino-
3-phenylpropanamide 1 with Mosher acid12 indicated that
20
1448C. [a]D ˆ155 (c 0.07, CHCl3). nmax (CH2Cl2): 3360,
1
1669. H NMR (300 MHz): dˆ1.16 (s, 3H), 1.44 (s, 3H),
2.05 (s, 3H), 2.44 (d, Jˆ5 Hz, 3H), 4.02 (d, Jˆ9.0 Hz, 1H),
4.42 (bs, 1H), 4.51 (d, Jˆ9.2 Hz, 1H), 7.20 (m, 5H). 13C
NMR (75.4 MHz): dˆ17.49 (q), 25.13 (q), 26.7 (q), 33.14
(q), 69.36 (d), 79.14 (d), 95.83 (s), 127.75 (d), 128.10 (d),
128.31 (d), 137.26 (s), 169.93 (s). HRMS (CI): (MH1),
found: 249.1597. C14H21N2O2 requires 249.1603.
20
we had a pure enantiomer ($95%). [a]D ˆ2114 (c 0.033,
4.2.4. (2S,4S,5S)-4-Phenyl-2,3-dimethyloxazolidine-5-N-
methylcarboxamide (3c). The (2S,3S) N1-methyl-2-
hydroxy-3-methylamino-3-phenylpropanamide 1 (0.42 g,
2 mmol) was dissolved in methanol (20 mL), and acetalde-
hyde (2.2 mmol) was added. The mixture was stirred at
room temperature for 2 h. The solvent was evaporated in
vacuo and the residue was puri®ed by chromatography on
silica gel eluting with hexane/ethyl acetate mixtures afford-
CHCl3). nmax (KBr) 3365, 3034, 1659. 1H NMR (250 MHz):
dˆ2.21 (s, 3H), 2.45 (d, Jˆ4.9 Hz, 3H), 3.90 (d, Jˆ4 Hz,
1H), 4.31 (bs, 1H), 4.38 (d, Jˆ4.0 Hz, 1H), 6.73 (d,
Jˆ4.9 Hz, 1H), 7.23 (s, 5H). 13C NMR (62.9 MHz):
dˆ25.31 (q), 33.40 (q), 65.93 (d), 72.76 (d), 127.71 (d),
128.01 (d), 128.12 (d), 136.98 (s), 172.64 (s). HRMS (EI):
(MH1), found: 209.1281. C11H17N2O2 requires 209.1290.
20
ing 3c (92%). Colourless oil. [a]D ˆ147 (c 0.051, CHCl3).
1
4.2.2.
hydro-4-pyrimidinone (2a). Procedure a. A solution of
(2S,3S) N1-methyl-2-hydroxy-3-methylamino-3-phenyl-
(5S,6S)-6-Phenyl-5-hydroxy-1,3-dimethylhexa-
nmax (®lm) 3380, 1669. H NMR (300 MHz): dˆ1.40 (d,
Jˆ5.1 Hz, 3H), 2.09 (s, 3H), 2.51 (d, Jˆ5.1 Hz, 3H), 3.75
(d, Jˆ9.1 Hz, 1H), 4.02 (q, Jˆ5.1 Hz, 1H), 4.49 (d,
Jˆ9.1 Hz, 1H), 6.48 (bs, 1H), 7.21 (m, 5H). 13C NMR
(75.4 MHz): dˆ18.89 (q), 25.31 (q), 35.59 (q), 72.23 (d),
80.16 (d), 93.36 (d), 127.91 (d), 127.96 (d), 128.01 (d),
136.06 (s), 170.00 (s). HRMS (EI): (MH1), found:
234.1359. C13H18N2O2 requires 234.1368.
propanamide 1 (0.42 g, 2 mmol) in dichloromethane
(20 mL) was heated in a pressure reactor at 1008C for 3
days.
Procedure b. A solution of (2S,3S) N1-methyl-2-hydroxy-3-
methylamino-3-phenylpropanamide 1 (0.42 g, 2 mmol) in
dibromomethane (30 mL) was heated in a pressure reactor
at 508C for 3 days.
4.2.5. (2S,4S,5S)-2,4-Diphenyl-N5,3-dimethyl-1,3-oxazo-
lane-5-carboxamide (3e). The (2S,3S) N1-methyl-2-
hydroxy-3-methylamino-3-phenylpropanamide 1 (0.42 g,
2 mmol) was dissolved in methanol (20 mL), and benzalde-
hyde (2.2 mmol) was added. The mixture was stirred at
room temperature for 5 h. The solvent was evaporated in
vacuo and the residue was puri®ed by chromatography on
silica gel eluting with hexane/ethyl acetate mixtures afford-
Procedure c. A solution of (2S,3S) N1-methyl-2-hydroxy-3-
methylamino-3-phenylpropanamide 1 (0.42 g, 2 mmol) in
benzene (30 mL) or methanol (20 mL) and paraformalde-
hyde (0.08 g) was heated in a pressure reactor at 1008C for
8 h.
20
ing 3e (91%). White solid. Mp 156±1578C. [a]D ˆ269 (c
1
0.6, CHCl3). nmax (KBr) 3320, 1659. H NMR (300 MHz):
The mixtures obtained by the procedures a, b or c were
cooled at room temperature. The solvent was evaporated
in vacuo and the residue was puri®ed by chromatography
on silica gel eluting with hexane/ethyl acetate mixtures
affording 2a. (a) 67%, (b) 85%, (c) 92%. White solid. Mp
dˆ2.04 (s, 3H), 2.52 (d, Jˆ5.1 Hz, 3H), 3.99 (d, Jˆ9.2 Hz,
1H), 4.67 (d, Jˆ9.2 Hz, 1H), 4.84 (s, 1H), 6.44 (bs, 1H),
7.26 (m, 3H), 7.36 (m, 2H), 7.41 (m, 3H), 7.61 (m, 2H). 13C
NMR (75.4 MHz): dˆ25.46 (q), 35.51 (q), 71.74 (d), 80.82
(d), 98.13 (d), 128.16 (d), 128.21 (d), 128.95 (d), 129.94 (d),
136.37 (s), 137.22 (s), 169.64 (s). Calcd For C18H20N2O2: C,
72.95; H 6.80; N 9.45. Found: C, 72.75; H 6.86; N 9.23.
20
130±1318C. [a]D ˆ131 (c 0.05, CHCl3). nmax (KBr) 3405,
1
1654. H NMR (250 MHz): dˆ2.14 (s, 3H), 3.00 (s, 3H),
3.37 (d, Jˆ9.5 Hz, 1H), 3.94 (d, Jˆ9.5 Hz, 1H), 4.19 (d,
Jˆ9.9 Hz, 1H), 4.20 (d, Jˆ9.9 Hz, 1H), 7.37 (m, 5H). 13C
NMR (62.9 MHz): dˆ32.15 (q), 39.36 (q), 69.85 (d), 70.63
(d), 71.65 (t), 128.02 (d), 128.61 (d), 138.69 (s), 170.53 (s).
HRMS (EI): (M1), found: 220.1213. C12H16N2O2 requires
220.1211.
X-Ray crystal data. 2a, C12H16N2O2, Mˆ220.27, ortho-
rhombic
Pcab,
aˆ10.031(1),
bˆ10.764(1),
cˆ
22.090(1) A, Uˆ2385.1(3) A , Dcˆ1.23 g cm23
,
Zˆ8,
Ê
Ê 3
Mo Ka (lˆ0.7107 A), mˆ0.85 cm21. Data reduction with
XRAY76 System.13 From the 2335 independent re¯ections,
1243 were considered observed with the I.2s(I) criterion.
The structure was solved by direct methods using the
program SIR92.14 Re®nement by least-squares on F2 with
SHELXL9715 (175 parameters). All non-hydrogen atoms
were anisotropically re®ned. Hydrogen atoms, except
those of methyl groups that were placed at calculated
positions, were found in Fourier difference maps and
their positions were re®ned. Weighting scheme
Ê
4.2.3. (4S,5S)-4-Phenyl-2,2,3-trimethyl-oxazolidin-5-N-
methylcarboxamide (3b). To a solution of (2S,3S) N1-
methyl-2-hydroxy-3-methylamino-3-phenylpropanamide 1
(0.260 g, 1.25 mmol) in acetone (15 mL) was added 2,2-
dimethoxypropane (2 mL, 16.3 mmol) and catalytic amount
of p-toluenesulfonic acid and the mixture was stirred at
room temperature for 3 days or a pressure reactor at
1008C for 3 h. After the solution was concentrated in

C. Hajji et al. / Tetrahedron 58 (2002) 3281±3285
3285
wˆ1/[s2(Fo )1(0.0854P)2] were Pˆ(Fo 12Fc )/3. Final
2
2
2
8. Gao, Y.; Hanson, R.; Klunder, J. M.; Ko, S. Y.; Masamune,
H.; Sharpless, K. J. Am. Chem. Soc. 1987, 109, 5765±5780
values: R1ˆ0.055, wR2ˆ0.129, Sˆ1.001 and Drmax
ˆ
Ê 23
(2R,3R)-(1)-3-Phenyloxiran-2-ylmethanol,
available from Aldrich.
commercially
0.28, Drminˆ20.21 e A . Molecular graphics were done
with ORTEP3 for Windows.16
9. Legters, J.; Thijs, L.; Zwanennburg, T. B. Rec. Trav. Chim.
Pays-Bas 1992, 111, 1±15.
The crystal structure has been deposited at the Cambridge
Crystallographic Data Centre (CCDCC 168109).
10. (a) Agami, C.; Couty, F.; Lequesne, C. Tetrahedron 1995, 51,
4043±4056. (b) Agami, C.; Rizk, T. Tetrahedron 1985, 41,
537±540. (c) Arsenyadis, S.; Huang, P. Q.; Morellet, N.;
Beloeil, J. C.; Husson, H. P. Heterocycles 1990, 31, 1789±
1799.
Acknowledgements
Â
Â
We are indebted to Direccion General de Investigacion
11. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.;
Robb, M. A.; Cheeseman, J. R.; Zakrzewski, V. G.;
Montgomery, J. A.; Stratmann, R. E.; Burant, J. C.; Dapprich,
S.; Millam, J. M.; Daniels, A. D.; Kudin, K. N.; Strain, M. C.;
Farkas, O.; Tomasi, J.; Barone, V.; Cossi, M.; Cammi, R.;
Mennucci, B.; Pomelli, C.; Adamo, C.; Clifford, S.; Ochterski,
J.; Petersson, G. A.; Ayala, P. Y.; Cui, Q.; Morokuma, K.;
Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman,
J. B.; Cioslowski, J.; Ortiz, J. V.; Stefanov, B. B.; Liu, G.;
Liashenko, A.; Piskorz, P.; Komaromi, I.; Gomperts, R.;
Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng,
C. Y.; Nanayakkara, A.; Challacombe, M. W.; Gill, P. M.;
Johnson, B.; Chen, W.; Wong, M. W.; Andres, J. L.; Gonzalez,
C.; Head-Gordon, M.; Replogle, E. S.; Pople, J. A. Gaussian
98 (Revision A.6); Gaussian, Inc.: Pittsburgh, PA, 1998.
12. Jacob, III, P. J. Org. Chem. 1982, 47, 4165±4167. Samples of
optically active 1 and racemic 1 were individually converted
Â
Â
Cientõ®co y Tecnica, for project PB98-1451 and PB98-
1429. Ma Luisa Testa, thanks Generalitat Valenciana for a
PhD Grant.
References
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