Synthesis, structural studies and desilylation reactions of some N-2-(trimethylsilyl)ethyl-N-nitrosocarbamates

Article abstract of DOI:10.1016/j.tet.2005.03.044

The present report describes the preparation and characterization of several N-2-(trimethylsilyl)ethyl-N-nitrosocarbamates, designed as precursors to thermally unstable secondary N-nitrosocarbamate anions via fluoride-assisted cleavage. X-ray structural studies demonstrate that the core N-nitrosocarbamate moiety has a nearly planar geometry, with an s-E orientation at the N-N bond. DFT calculations (B3LYP/6-31+G(d)) reproduce accurately the structural features of the title compounds and detailed conformational analysis at the same level of theory addresses the long-standing issue of preferred geometries for three classes of related structures: N-nitrosocarbamates, N-nitrosoureas and N-nitrosoamides. Desilylation studies demonstrate that both the solvent and the fluoride concentration influence the rate of the process.

Full text of DOI:10.1016/j.tet.2005.03.044

Tetrahedron 61 (2005) 4939–4948
Synthesis, structural studies and desilylation reactions of some
N-2-(trimethylsilyl)ethyl-N-nitrosocarbamates
*
Arpitha Thakkalapally and Vladimir Benin
Department of Chemistry, University of Dayton, 300 College Park, Dayton, OH 45469-2357, USA
Received 20 January 2005; revised 9 March 2005; accepted 10 March 2005
Available online 2 April 2005
Abstract—The present report describes the preparation and characterization of several N-2-(trimethylsilyl)ethyl-N-nitrosocarbamates,
designed as precursors to thermally unstable secondary N-nitrosocarbamate anions via fluoride-assisted cleavage. X-ray structural studies
demonstrate that the core N-nitrosocarbamate moiety has a nearly planar geometry, with an s-E orientation at the N–N bond. DFT
calculations (B3LYP/6-31CG(d)) reproduce accurately the structural features of the title compounds and detailed conformational analysis at
the same level of theory addresses the long-standing issue of preferred geometries for three classes of related structures: N-nitrosocarbamates,
N-nitrosoureas and N-nitrosoamides. Desilylation studies demonstrate that both the solvent and the fluoride concentration influence the rate
of the process.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
product depends, as expected, on the steric demand of the
alkyl halide. Smaller and less branched alkyl groups lead
primarily to N-alkylation, while the O-alkylated product
becomes predominant with the use of more sterically
hindered substrates. In addition, the theoretical analysis
and kinetic measurements demonstrated that the N-nitroso-
urethane anion and its O-alkylated derivatives undergo
thermal decomposition in a concerted fashion, through a
four-membered cyclic TS.
The work reported in this article is a reflection of our
continuing efforts to generate and study secondary
N-nitrosocarbamates, a class of thermally unstable and
chemically labile structures.1 The only known example of a
secondary N-nitrosocarbamate, N-nitrosourethane, was pre-
pared more than a 100 years ago from urethane, in a
sequence of nitration followed by partial reduction, and
conversion to the silver salt.2 Its chemistry was recently
revisited, the authors using primarily the organic-soluble
tetrabutylammonium salt (Scheme 1).1
Certain questions, however, were not addressed, such as the
potential influence of the size of the carbamate alkyl (or
aryl) group on the thermal stability of the resultant
N-nitrosocarbamate anions and their O-alkylated deriva-
tives. In addition, varying the size of the carbamate alkyl
(aryl) group would be expected to influence the regio-
selectivity in their alkylation reactions. Hence, our goal has
The experimental studies and gas-phase calculations led to
the conclusion that the N-nitrosourethane anion is a typical
ambident nucleophile, yielding products of both N-alkyl-
ation and O-alkylation, and the ratio of N- to O-alkylated
Scheme 1.
Keywords: N-Nitrosocarbamates; X-ray structures; 2-(Trimethylsilyl)ethyl group; Desilylation; DFT calculations.
*
Corresponding author. E-mail: vladimir.benin@notes.udayton.edu
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.03.044

4940
A. Thakkalapally, V. Benin / Tetrahedron 61 (2005) 4939–4948
leading to the preparation of four N-2-(trimethylsilyl)ethyl-
N-nitrosocarbamates (1a–d, Fig. 1) and the current results
from desilylation experiments. This article also reports the
first crystal structures of N-nitrosocarbamates, compounds
1c and 1d, and compares those with results from gas-phase
DFT calculations (B3LYP/6-31CG(d)).
2. Results and discussion
2.1. Synthesis
The preparation of carbamates 1a–d is outlined in Scheme 2.
The corresponding alcohol (for compounds 1a–c) or 2,4,6-
tris(t-butyl)phenol (for compound 1d) is converted to an
N-2-(trimethylsilyl)ethylcarbamate (2a–d), by means of one
of two general methods (A and B). Method A utilizes a
Hoffmann-type rearrangement reaction of 3-(trimethyl-
silyl)propanamide (4)8 with the corresponding alcohol, in
the presence of NBS and Hg(OAc)2.9 The reaction works
very well for preparation of the ethyl carbamate (2a), but the
yields drop significantly for the t-butyl (2b) and 1-adamantyl
(2c) carbamates, and no reaction is observed in an attempt to
generate the 2,4,6-tris(t-butyl)phenyl carbamate (2d). The
latter was prepared using an alternative approach (Method
B) that includes deprotonation of the starting phenol
followed by reaction with triphosgene, leading to the
generation of 2,4,6-tris(t-butyl)phenyl chloroformate.10
Reaction of the chloroformate with 2-(trimethylsilyl)-
ethanamine (5) affords the carbamate 2d. Compound 5
was prepared according to a patented procedure utilizing
2-(trimethylsilyl)ethanol, which is converted, in a
Mitsunobu reaction, to N-2-(trimethylsilyl)ethylphthali-
mide.11 The phthalimide, upon reaction with hydrazine
Figure 1. Four N-2-(trimethylsilyl)ethyl-N-nitrosocarbamates with a
gradually increasing size of the carbamate ester group.
been to prepare and study other secondary N-nitrosocarba-
mates, with varying size of the carbamate alkyl (aryl) group,
in an attempt to prepare exceptionally stable structures,
suitable for isolation and solid-state studies. The initial
efforts were focused on adaptation of the synthetic strategy
used in the preparation of N-nitrosourethane salts. Such
attempts have proved futile, prompting us to design and
implement a new methodology, based on the fluoride-
assisted cleavage of a 2-(trimethylsilyl)ethyl group (TMSE)
incorporated into thermally and chemically stable N-2-
(trimethylsilyl)ethyl-N-nitrosocarbamates. The TMSE
group has been used in the past as a protecting group for
alcohols and carboxylic acids,3 thiols4,5 and phosphates.6 In
a recent article, Bottaro et al. described its use as a
removable moiety at a nitrogen center, in the generation of
the dinitroamide anion.7
The present report outlines the details of our synthetic work
Scheme 2.

A. Thakkalapally, V. Benin / Tetrahedron 61 (2005) 4939–4948
4941
hydrate followed by acidification, yields 2-(trimethyl-
silyl)ethanamine hydrochloride. In strongly basic conditions
the hydrochloride is converted to the free amine 5.
Nitrosation reactions were carried out utilizing three
different approaches. Nitrosation in a two-phase (water–
ether) system was carried out, with the nitrosating agent
generated in the aqueous layer, upon reaction of NaNO2
with HNO3.12 The method gives satisfactory results for
carbamates 2a–b, but the yield is significantly reduced in the
case of 2c and only traces of nitrosated product are observed
in the reaction of 2d. Better yields for carbamates 2a–c (but
not 2d) were observed when the nitrosation was performed
in anhydrous conditions, with NOBF4 as a nitrosating agent
and the presence of pyridine base.13 The difficulties in
nitrosation of 2d have to be attributed to the steric effect
(hindrance) of the two ortho-positioned t-butyl groups of the
aromatic ring. Successful nitrosation of 2d was eventually
achieved following a modified version of the method of
Overberger and Anselm, which employs NaNO2 in a
mixture of acetic acid and acetic anhydride.14
Figure 3. X-ray structure of 2,4,6-tris(t-butyl)phenyl N-nitroso-N-(2-
trimethylsilyl)ethylcarbamate (1d). The asymmetric unit contains two
unique molecules. The thermal ellipsoids are drawn at 50% probability.
Hydrogen atoms are given arbitrary radii.
2.2. Structural studies
X-ray crystallographic analysis was conducted on com-
pounds 1c and 1d, providing the first reported crystal
structures of N-nitrosocarbamates (Figs. 2 and 3). The
asymmetric unit in the unit cell of 1d contains two unique
molecules and the only major difference between them is the
value of one of the dihedral angles in the TMSE group.
Experimental and theoretical data on selected bond lengths,
angles and torsional angles are shown in Table 1, together
with structural parameters for N-methyl-N-nitroso-p-nitro-
benzamide (MNNB) and N-methyl-N-nitrosourea
(MNU).15 Bond lengths in 1c and 1d are more comparable
to those in the N-nitrosoamide MNNB, particularly the
N]O and C]O bonds. The deviations are slightly greater
between 1c–d and MNU. The C]O bond is longer in
˚
MNU, while the N–N bond is w0.04 A shorter.
The N-nitrosocarbamate sub-structure in 1c and 1d,
O–C(]O)–N–N]O, is very nearly planar, with a slightly
greater twist around the C(1)–N(1) bond in the case of 1c.
The overall distortion from planarity is larger than the
observed in MNU, but less than that of the N-nitrosoamide
MNNB, particularly the N(2)–N(1)–C(1)–O(1) dihedral
angle. The 2-(trimethylsilyl)ethyl group in both 1c and 1d
adopts an anti conformation. The values for the dihedral
angle C(4)–Si–C(3)–C(2) demonstrate that in the case of 1c
and one of the unique molecules in the unit cell of 1d there is
a nearly ideal gauche positioning of the C(2)H2-group
relative to the methyl groups at the silicon center. The
second unique structure for 1d exhibits an almost 188
deviation from the gauche-orientation.
As evident from Table 1, the theoretically derived
structural data are in very close agreement with the
experimental parameters. The reported results are from
gas-phase DFT studies at the B3LYP/6-31CG(d) level of
theory.16–18
All optimized minima structures, except for those of
carbamate 1d, were further validated by frequency calcu-
lations at the same level of theory and they had sets of
only positive second derivatives. Values of Gibbs free
energy differences were obtained after frequency calcu-
lations. The computed values for bond lengths are usually
˚
within G0.01 A of the experimental ones and the
differences between theoretical and experimental values
for angles and dihedral angles are usually within G38. In
general, DFT tends to slightly exaggerate the planarity of
the core structures for both the carbamates 1c–d and MNU.
The global minimum structures for the four N-nitroso-
carbamates 1a–d are shown in Figure 4.
Figure 2. Two orientations of the X-ray structure of 1-adamantyl N-nitroso-
N-(2-trimethylsilyl)ethylcarbamate (1c). The thermal ellipsoids are drawn
at 50% probability. Hydrogen atoms are given arbitrary radii.

4942
A. Thakkalapally, V. Benin / Tetrahedron 61 (2005) 4939–4948
˚
Table 1. Selected experimental (bold characters) and theoretical bond lengths (A) and angles (8) for N-nitrosocarbamates 1a-1d, N-methyl-N-nitroso-p-
nitrobezamide (MNNB) and N-methyl-N-nitrosourea (MNU)
Bond lengths and anglesa
O(1)–C(1)
1a
1b
1c
1db
MNNBc
MNUc
—
1.216
—
1.369
—
1.412
—
1.218
—
1.333
—
1.912
—
118.0
—
114.0
—
—
1.217
—
1.366
—
1.418
—
1.220
—
1.328
—
1.911
—
118.3
—
114.1
—
1.200(4)
1.217
1.360(4)
1.370
1.417(4)
1.419
1.220(3)
1.220
1.323(4)
1.328
1.880(3)
1.912
118.3(2)
118.3
113.2(2)
114.1
1.203(5), 1.197(5)
1.210
1.374(5), 1.359(5)
1.369
1.410(4), 1.405(6)
1.413
1.231(4), 1.222(6)
1.218
1.331(5), 1.342(4)
1.345
1.872(5), 1.886(4)
—
117.1(3), 117.4(3)
118.2
112.6(4), 113.0(4)
114.0
1.204(5)
1.219
1.352(5)
1.369
1.405(6)
1.416
1.218(4)
1.216
—
1.215(2)
1.220
1.326(2)
1.353
1.431(2)
1.431
1.231(2)
1.220
—
N(1)–N(2)
N(1)–C(1)–
O(3)–N(2)–
O(2)–C(1)
—
—
—
—
—
—
Si–C(3)
N(2)–N(1)–C(1)
O(3)–N(2)–N(1)
C(1)–N(1)–N(2)–O(3)
N(2)–N(1)–C(1)–O(1)
C(4)–Si–C(3)–C(2)
116.9(4)
117.8
113.8(4)
113.8
K176.8
K173.3
165.4
162.5
—
116.6(2)
117.1
114.4(2)
116.3
K177.7
180.0
178.5
180.0
—
K177.2(3)
K177.4
173.4(3)
175.8
K56.7(3)
K62.9
K176.6(3), K176.8(5)
K178.4
177.3(3), 176.7(5)
179.2
K76.7(3), K56.3(4)
K59.5
K178.0
—
178.4
—
K59.0
K178.0
—
178.1
—
K60.2
—
—
Theoretical data from global minimum structures optimized at the B3LYP/6-31CG(d) level.
a Atom labels in accordance with the crystallographic designation for compounds 1c–d.
b X-ray data given for each of the two unique molecules in the asymmetric unit of 1d.
c X-ray data from Ref. 15.
2.3. Conformational analysis
whose case the lowest energy local minimum is the (s-Z,
s-trans) structure. The latter is most likely due to stabilizing
hydrogen bonding realized between the NH2 and NO groups
in MNU, which has been suggested earlier based on NMR
and IR studies.20 In the cases of MNNB and MNU
calculations could not locate a minimum structure corre-
sponding to the (s-Z, s-cis) isomer, which appears to be due
to steric repulsion.
Calculations demonstrate that each of the compounds 1a–d
has a set of rotamers with respect to both the C(1)–N(1)
bond (s-trans and s-cis) and the N(1)–N(2) bond (s-E and
s-Z). Table 2 lists the relative Gibbs free energies and the
Boltzmann statistical contributions for the rotamers of
structures 1a–c, MNU and MNNB. In each case the
corresponding (s-E, s-trans) isomer is the global minimum,
and in the cases of 1c, 1d, MNU and MNNB these are in
agreement with the X-ray crystal structures. Nakayama and
Kikuchi reached similar conclusions in their recent
theoretical studies of several N-nitroso compounds.19 In
almost all of the studied cases the (s-E, s-cis) isomer is the
lowest energy local minimum. One exception is MNU, in
The currently available experimental and theoretical data
provide valuable information towards resolving the issue of
thermal stability of N-nitroso compounds, which in turn
bears relation to the relative stability of the s-E and s-Z
conformations. In the s-Z conformation there is spatial
proximity of the nitroso group oxygen center to the carbonyl
Figure 4. Optimized global minima structures of compounds 1a–d. Data from B3LYP/6-31CG(d) calculations.

A. Thakkalapally, V. Benin / Tetrahedron 61 (2005) 4939–4948
4943
Table 2. Relative Gibbs free energies of conformers of N-2-(trimethylsilyl)ethyl-N-nitrosocarbamates 1a-1c, N-methyl-N-nitroso-p-nitrobezamide (MNNB)
and N-methyl-N-nitrosourea (MNU), with respect to rotation around the N(1)–N(2) bond (s-E and s-Z) and the C(1)–N(1) bond (s-cis and s-trans)a
1a
1b
1c
MNNB
MNU
s-E, s-trans
s-E, s-cis
s-Z, s-trans
s-Z, s-cis
0.0 (89.9)
0.0 (99.5)
0.0 (97.2)
0.0 (100)
0.0 (99.9)
C1.3 (10.1)
C5.5 (w0)
C6.7 (w 0)
C3.2 (0.5)
C6.2 (w0)
C7.7 (w 0)
C2.1 (2.8)
C5.8 (w0)
C6.0 (w 0)
C6.0 (w0)
C6.3 (w0)
—
C9.2 (w0)
C3.9 (0.1)
—
b
b
Data from B3LYP/6-31CG(d) geometry optimizations and frequency calculations. Boltzmann contributions (%) at 298 K given in parentheses.
a Atom labels in accordance with the crystallographic designation for compound 1c.
b Minimum structure was not located.
carbon, and an intramolecular reaction becomes possible,
leading to decomposition (Scheme 3).21,22 No such reaction
is feasible starting with the s-E isomer. Thus, it seems that
greater relative stability of the s-E isomer is a pre-requisite
for thermal stability of the corresponding N-nitroso
compound.
Secondary N-nitrosocarbamate anions are also character-
ized by resonance stabilization and charge delocalization.1
It has been estimated, for example, that N-nitrosourethane is
more acidic than acetic acid.24 Hence, cleavage of the
TMSE group, according to Scheme 4, would be expected to
occur readily. One significant obstacle arises from the fact
that structures 3a–d have been demonstrated (in the case of
3a)1 or are anticipated to be thermally unstable, thus making
it a challenge to find the appropriate conditions for
desilylation that would be sufficiently mild not to trigger
further decomposition of 3a–d to the corresponding
alkoxide (phenoxide) anion 6a–d.
Our current results are based on studies conducted in DMF
or acetonitrile as solvents, with Bu4NF$3H2O as a fluoride
source. Experiments were performed using compounds 1a,
with available independent literature data for comparison,1
and 1d, whose decomposition was particularly easy to
follow by NMR, giving distinct peaks in the aromatic
region. All experiments were performed on an NMR scale,
in deuterated solvents, so that the progress of reaction and
product composition could be monitored directly. Results
from the desilylation experiments are shown in Table 3.
Scheme 3.
Our results and other recent studies are in agreement that the
s-E isomer is indeed the predominant form in the solid state
and in the gas phase.15,19,23 However, it should be noted that
the NMR and IR studies of Snyder and Stock were
interpreted in favor of the s-Z isomers of several N-alkyl-
and N,N0-dialkyl-N-nitrosoureas being exclusively present
in solution.20
(a) Role of the solvent and temperature. The studied
reactions showed clear dependence on the nature of the
solvent, with the rates being consistently higher in DMF.
Thus, in the case of 1a desilylation is complete in 0.5 h even
at K15 8C, while in acetonitrile complete desilylation of 1a
requires 16 h even at C10 8C. The desilylation reaction is
slower in the case of 1d, and the solvent has an even more
pronounced effect. Compound 1d is practically stable in
acetonitrile at C10 8C and only traces of decomposition
products were detected after 24 h and 5-fold excess of
Bu4NF.
2.4. Desilylation studies
The use of the TMSE group as a temporary protecting group
at a nitrogen center was reported recently in the successful
preparation of the dinitroamide anion from N-2-(trimethyl-
silyl)ethyl-N,N-dinitroamine.7 The dinitroamide anion is a
resonance-stabilized species with a delocalized negative
charge and reduced basicity. Thus, not surprisingly,
relatively mild deprotection conditions were employed for
the cleavage reaction.
(b) Amount of Bu4NF$3H2O. As Table 3 indicates, the
Scheme 4.

4944
A. Thakkalapally, V. Benin / Tetrahedron 61 (2005) 4939–4948
Table 3. Experimental conditions and product composition data for desilylation reactions of carbamates 1a and 1d
Carbamate
Solvent
Temperature (8C)
Bu4NF$3H2O
(equiv)
Time
Anion 3 (%)
Anion 6 (%)
1a
DMF
DMF
DMF
DMF
CH3CN
CH3CN
K15
K15
C5
C10
C5
3
5
1
5
5
5
30 min
30 min
24 h
10 min
22 h
16 h
29
31
29b
19
35
41
72c
98e
0f
71a
69
57
81
65
59
C10
1d
DMF
DMF
CH3CN
C10
C5
C10
3
5
5
48 h
23 h
24 h
14d
0
!1
a Structure validated by comparison with authentic sample of 6a–NMe4 in DMF-d7.
b Reaction not complete after 24 h, with 14% residual carbamate 1a present in the mixture.
c Reaction not complete after 48 h, with 13% residual carbamate 1d present in the mixture.
d Structure validated by comparison with a sample of 6d–Li in DMF-d7.
e 2% Residual carbamate 1d.
f
98% Residual carbamate 1d.
process required some excess of the tetrabutylammonium
salt in order to be conducted to completion. In the case of 1a
and 1 equiv of Bu4NF$3H2O, the reaction mixture after 24 h
at 5 8C showed 14% of unreacted carbamate and the
desilylation of 1d with 3 equiv Bu4NF$3H2O at C10 8C
was not complete even after 48 h. Typical runs were
conducted with 3 to 5-fold excess of Bu4NF$3H2O. We
anticipate that the relative amounts of fluoride and rates of
desilylation are influenced by the fact that the used fluoride
source is a trihydrate. It has been shown, both spectro-
scopically and theoretically, that the fluoride anion forms
hydrate clusters with varying number of water molecules.25–27
This is certain to affect the anion’s reactivity and decelerate
the desilylation process.
ambient temperature the sole product is 2,4,6-tris(t-
butyl)phenol, whose signal in the aromatic region is at d
7.20 ppm (Fig. 5f).
The high percentage of ethoxide 6a in the product mixtures
from desilylation of 1a cannot be entirely accounted for by a
process of secondary decomposition of the anion 3a,
particularly at temperatures below 0 8C, since it would
correspond to a much lower thermal stability of 3a than
established in earlier studies. An alternative explanation can
be offered based on the hypothesis that the major portion of
ethoxide is formed via parallel reaction of decomposition of
1a. Previous studies have shown that tetrabutylammonium
(c) Product composition. The immediate product of
desilylation in each case is the corresponding N-nitroso-
carbamate anion 3. However, in most runs, particularly of
carbamate 1a, anion 6 was observed as well, in varying
quantities. In the case of 1a the product structures, 3a and
6a, were validated by comparison with the available in
literature spectral data in acetonitrile solvent.1 In DMF, the
NMR pattern of the product mixtures is similar, and we have
assigned the quartet at d 4.14 and the triplet at d 1.23 to the
anion 3a, while the quartet at d 3.50 and triplet at d 1.06
were assigned to 6a, after comparison with the spectrum of
an independently prepared sample of 6a–NMe4 in DMF-d7.
The maximum amount of 3a in the studied cases,
determined by integration of NMR signals, was about
40%, but in most runs it was lower and not significantly
affected by temperature or the nature of the solvent. The
desilylation of 1d on the other hand occurs with predomi-
nant and in some cases exclusive formation of the desired
product 3d, whose signal for the aromatic H-atoms appears
at d 7.34 ppm in deuterated DMF (Fig. 5a–d).
As Figure 5e demonstrates, subjection of 3d to elevated
temperature leads to its decomposition. The product of
decomposition has a signal for the aromatic protons at d
6.86 ppm, and was identified as the aryloxide anion 6d. For
comparison, we prepared the lithium salt of 2,4,6-tris(t-
butyl)phenol by deprotonation with n-BuLi. The resultant
6d–Li has a signal in the aromatic region at d 6.90 ppm, in
DMF-d7. Anion 6d, in the presence of water in the reaction
mixture, is eventually protonated and after several days at
Figure 5. (a) Carbamate 1d in DMF-d7; (b)–(d) carbamate 1d with 5 equiv
of Bu4NF$3H2O in DMF-d7: (b) 1 h at C5 8C; (c) 3 h at C5 8C; (d) 23 h at
C5 8C; (e) anion 3d after 3 h at C45 8C; (f) anion 3d after 5 days at
ambient temperature. All spectra referenced to the solvent (DMF-d7, d
8.03 ppm).

A. Thakkalapally, V. Benin / Tetrahedron 61 (2005) 4939–4948
4945
Scheme 5.
fluoride solutions are strongly basic and the presence of
water leads to the generation of hydroxide anions.28–30 At
the same time N-nitrosocarbamates are known to be
hydrolytically labile in such conditions.31–33 To verify the
hypothesis, we conducted a trial experiment with ethyl
N-butyl-N-nitrosocarbamate,33–37 which is a close structural
analog of 1a but lacks a silicon center. An NMR sample of it
in DMF-d7 was added to 5 equiv of Bu4NF$3H2O at 5 8C.
The spectrum after 30 min indicated complete decompo-
sition of the starting material with the almost exclusive
formation of 6a, which in this case could occur only via
basic hydrolysis of the starting N-nitrosocarbamate. Hence
we are proposing a two-pathway decomposition for
carbamates 1a–d in the presence of Bu4NF$3H2O, as
reflected in Scheme 5. The significant differences in product
composition between 1a and 1d are due to the presence of
the bulky and branched t-butyl groups in 1d (Figs. 3 and 4),
which render the carbonyl group virtually inaccessible, thus
slowing down considerably the rate of basic hydrolysis.
4. Experimental
1H and 13C spectra of intermediate and target compounds
were recorded at 300 and 75 MHz, respectively, and
referenced to the solvent (CDCl3: 7.27 ppm and 77.0 ppm;
D2O: 4.76 ppm; acetonitrile-d3: 1.93 ppm; DMF-d7:
8.03 ppm). X-ray structures were obtained using an Oxford
Diffraction Xcalibur3 diffractometer with graphite mono-
chromatic Cu Ka radiation. Structure solution and refine-
ment was preformed using the SHELXTL 6.10 software
package.39 All calculations were performed utilizing the
Gaussian03-Linda/GaussView software package40 on a
Linux-operated cluster (QuantumCube QS4-2400C by
Parallel Quantum Solutions, Fayetteville, AR). Constant
temperature desilylation reactions were conducted using the
Isotemp 1016S circulating bath. Elemental analysis was
provided by Atlantic Microlab, Norcross, GA. HRMS data
was provided by the Mass Spectrometry and Proteomics
facility at the Ohio State University. Nitrosonium tetra-
fluoroborate was purchased from the Lancaster chemical
company. 3-(Trimethylsilyl)propanamide (4)8 and 2,4,6-
tris(t-butyl)phenyl chloroformate10 were synthesized,
following previously reported procedures. 2-(Trimethyl-
siyl)ethanamine (5) was prepared according to a published
3. Conclusions
Our efforts to date have led to the formulation and
implementation of a new synthetic strategy aimed at the
preparation and isolation of secondary N-nitrosocarbamates
via desilylation of chemically and thermally stable tertiary
N-2-(trimethylsilyl)ethyl-N-nitrosocarbamates.
patent work.11 The H NMR data for compounds 4 and 5,
and precursors to them, are reported in this article, as they
were previously unavailable.
1
4.1. X-ray crystallography of 1-adamantyl N-2-
trimethylsilylethyl-N-nitrosocarbamate (1c)
The current article presents the first solid-state structural
studies of N-nitrosocarbamates. X-ray data have demon-
strated that both of the studied target structures exist as s-E
conformers in the solid state, with a nearly planar
N-nitrosocarbamate moiety. Further, DFT calculations
demonstrate that the s-E orientation at the N–N bond is
the preferred arrangement in the gas phase as well, for
N-nitrosocarbamates, N-nitrosoureas and N-nitrosoamides.
A crystal (yellow plate) of 1c (C16H28N2O3Si) having
approximate dimensions 0.324!0.206!0.083 mm was
mounted on a glass fiber. The preliminary set of cell
constants was calculated from reflections harvested from 5
sets of 15 frames, merged to 139 peaks that were used to
derive the initial orientation matrix. Data acquisition was
conducted at 150 K using the phi and omega scans
technique. Final cell constants were determined based on
the full data set, leading to a triclinic cell (P-1) with
Desilylation studies demonstrate that the process depends
on several factors: temperature, solvent and concentration of
fluoride anion. The current methodology, employing Bu4-
NF$3H2O, seems to be most effective in cases of structures
with large and branched carbamate groups, whose steric
hindrance effectively suppresses the competing process of
basic hydrolysis of the N-nitrosocarbamate, the latter
leading directly to the anions 6 rather than 3. Use of
anhydrous fluoride ion sources, such as tetrabutyl-
ammonium triphenyldifluorosilicate (TBAT)28,30 or CsF/
CsOH mixtures38 may prove advantageous in optimizing
the yields of the N-nitrosocarbamate anions 3.
˚
˚
these dimensions: aZ6.6116 (13) A, bZ9.8970 (18) A, cZ
˚
13.958 (2) A, aZ75.660 (14)8, bZ84.856 (14)8, gZ89.407
3
˚
(14)8, VZ881.3 (3) A . For ZZ2 and FWZ324.49, the
calculated density is 1.223 g/cm3. Non-hydrogen atoms
were refined anisotropically; hydrogen atoms were
assigned based on geometry. The final structure has values
for the unweighted agreement factor R1Z0.0459 based on
1300 strong reflections (IO4s) and R1Z0.0489 based on all
data.

4946
A. Thakkalapally, V. Benin / Tetrahedron 61 (2005) 4939–4948
4.2. X-ray crystallography of 2,4,6-tris(t-butyl)phenyl N-
2-trimethylsilylethyl-N-nitrosocarbamate (1d)
(D2O) d 2.94–3.01 (m, 2H), 0.84–0.91 (m, 2H), K0.03 (s,
9H).
A crystal (yellow needle) of 1d (C24H42N2O3Si) having
approximate dimensions 0.358!0.079!0.072 mm was
mounted on a glass fiber. The preliminary set of cell
constants was calculated from reflections harvested from 5
sets of 15 frames, merged to 155 peaks that were used to
derive the initial orientation matrix. Data acquisition was
conducted at 100 K using the phi and omega scans
technique. Final cell constants were determined based on
the full data set, leading to an orthorhombic cell (Pbca) with
(C) 2-(Trimethylsilyl)ethanamine. 1H NMR (CDCl3) d
2.71–2.78 (m, 2H), 2.10 (broad s, 2H), 0.73–0.80 (m,
2H),-0.01 (s, 9H).
4.4. Preparation of N-2-(trimethylsilyl)ethylcarbamates.
General procedure (Method A)
To a stirred solution of 3-(trimethylsilyl)propanamide
(3.40 mmol) and mercuric acetate (4.60 mmol) in
anhydrous N,N-dimethylformamide (10 mL), was added a
solution of the corresponding alcohol (102.50 mmol) in
anhydrous N,N-dimethylformamide (3 mL), at ambient
temperature and under nitrogen. This was followed by
addition of a solution of NBS (4.50 mol) in N,N-dimethyl-
formamide (2 mL). The reaction was stirred for 12 h at room
temperature. The solvents were removed at reduced
pressure and methylene chloride (50 mL) was added to the
residual solid. The organic extract was washed with water
(5!25 mL), dried (MgSO4) and the solvent was removed
under reduced pressure. The resultant residue was passed
through a short silica gel filter (hexane–ethyl acetateZ3:1)
and the solvents were removed under reduced pressure to
give the desired carbamate. Further purification via column
chromatography (hexane: ethyl acetateZ3:1) led to isolated
products that were O95% pure by NMR.
˚
˚
these dimensions: aZ11.3845 (11) A, bZ20.5755 (18) A,
˚
cZ45.454 (4) A, aZ90.008, bZ90.008, gZ90.008, VZ
3
˚
10647.2 (17) A . For ZZ16 and FWZ434.67, the calcu-
lated density is 1.075 g/cm3. Non-hydrogen atoms were
refined anisotropically; hydrogen atoms were assigned
based on geometry. The final structure has values for the
unweighted agreement factor R1Z0.0917 based on 7208
strong reflections (IO4s) and R1Z0.1193 based on all data.
4.3. Fluoride-assisted desilylation of ethyl N-2-(tri-
methylsilyl)ethyl-N-nitrosocarbamate (1a) and 2,4,6-
tris(t-butyl)phenyl N-2-(trimethylsilyl)ethyl-N-
nitrosocarbamate (1d). General procedure
In a typical run 0.020 mol of carbamate 1, dissolved in
0.7 mL of the appropriate deuterated solvent (acetonitrile-d3
or DMF-d7), was added to Bu4NF$3H2O (0.020–0.10 mol,
1–5 equiv) at K15 8C (ice–acetone bath). The resultant
solution was transferred into an NMR tube and kept at the
appropriate temperature until disappearance of the signals
of the starting material. NMR measurements were con-
ducted at regular time intervals. The change in quantity of
reactant/product was monitored via integration of the NMR
signals relative to the multiplet of Bu4NC centered at d
1.76 ppm.
4.4.1. Ethyl N-2-trimethylsilylethylcarbamate (2a)
(Method A). Yield: 85%. Colorless liquid: 1H NMR
(CDCl3) d 4.69 (bs, 1H), 4.10 (q, JZ7.0 Hz, 2H), 3.18–
3.24 (m, 2H), 1.24 (t, JZ7.0 Hz, 3H), 0.77–0.83 (m, 2H),
0.01 (s, 9H); 13C NMR (CDCl3) d 156.5, 60.6, 37.4, 18.2,
14.6, K1.7; HRMS (FABC) m/z Calcd for C8H19NO2Si
[MCNa]C 212.1083, found 212.1076.
4.4.2. t-Butyl N-2-trimethylsilylethylcarbamate (2b)
(Method A). Yield: 36%. Colorless liquid: 1H NMR
(CDCl3) d 5.80 (bs, 1H), 3.10–3.19 (m, 2H), 1.41 (s, 9H),
0.81–0.87 (m, 2H), 0.04 (s, 9H); 13C NMR (CDCl3) d 155.7,
79.0, 37.0, 28.4, 18.1, K1.7; HRMS (FABC) m/z Calcd for
C10H24NO2Si [MCNa]C 240.1396, found 240.1396. Anal.
Calcd for C10H23NO2Si: C, 55.25; H, 10.66; N, 6.44. Found:
C, 55.50; H, 10.54; N, 6.14.
4.3.1. Ethyl N-nitrosocarbamate, tetrabutylammonium
1
salt (3a–Bu4N). H NMR (DMF-d7, anion only) d 4.14 (q,
JZ7.1 Hz, 2H), 1.23 (t, JZ7.1 Hz, 3H); 1H NMR
(acetonitrile-d3, anion only) d 4.09 (q, JZ7.1 Hz, 2H),
1.21 (t, JZ7.1 Hz, 3H).1
4.3.2. 2,4,6-Tris(t-butyl)phenyl N-nitrosocarbamate,
tetrabutylammonium salt (3d–Bu4N). H NMR (DMF-
d7, anion only) d 7.34 (s, 2H), 1.43 (s, 18H), 1.31 (s, 9H).
1
4.4.3. 1-Adamantyl N-2-trimethylsilylethylcarbamate
(2c) (Method A). Yield: 50%. White solid: mp 92–94 8C.
1H NMR (CDCl3) d 4.42 (bs, 1H), 3.12–3.20 (m, 2H), 2.17
(m, 3H), 2.10 (m, 6H), 1.65 (m, 6H), 0.75–0.82 (m, 2H),
0.02 (s, 9H); 13C NMR (CDCl3) d 155.4, 41.7, 37.0, 36.2,
30.8, 18.2, 11.2, K1.7; HRMS (FABC) m/z Calcd for
C16H30NO2Si [MCNa]C 318.1865, found 318.1876; Anal.
Calcd for C16H29NO2Si: C, 65.03; H, 9.89; N, 4.74. Found:
C, 65.24; H, 9.93; N, 4.58.
4.3.3. 3-(Trimethylsilyl)propanamide (4).8 (A) 3-(Tri-
methylsilyl)propanoyl chloride. H NMR (CDCl3) d 2.80–
2.87 (m, 2H), 0.91–0.97 (m, 2H), 0.03 (s, 9H).
1
(B) 3-(Trimethylsilyl)propanamide. 1H NMR (CDCl3) d
5.61 (broad s, 2H), 2.17–2.24 (m, 2H), 0.80–0.87 (m, 2H),
0.02 (s, 9H).
4.4.4. 2,4,6-Tris(t-butyl)phenyl N-2-trimethylsilylethyl-
carbamate (2d) (Method B). A solution of 2-(trimethyl-
silyl)ethanamine (0.22 g, 1.85 mmol) and pyridine (0.15 g,
1.85 mmol, 0.15 mL) in dichloromethane (5 mL) was added
dropwise over 15 min period to a solution of 2,4,6-tris(t-
butyl)phenyl chloroformate (0.60 g, 1.85 mmol) in
dichloromethane (5 mL) at 0 8C (ice–water), followed by
4.3.4. 2-(Trimethylsilyl)ethanamine (6).8,11 (A) N-2-(tri-
methylsilyl)ethylphthalimide. 1H NMR (CDCl3) d 7.82–7.85
(m, 2H), 7.68–7.71 (m, 2H), 3.69–3.75 (m, 2H), 0.99–1.05
(m, 2H), 0.07 (s, 9H).
1
(B) 2-(Trimethylsilyl)ethanamine hydrochloride. H NMR

A. Thakkalapally, V. Benin / Tetrahedron 61 (2005) 4939–4948
4947
stirring at ambient temperature for 12 h. The mixture was
washed with water, the organic layer was separated, dried
(MgSO4) and the solvent removed. The resultant residue
was passed through a short silica gel filter and the product
eluted with methylene chloride. The solvent was removed to
yield the product as a white solid (0.34 g, 45%). Further
purification via recrystallization from hexane, to yield white
needles: mp 157–159 8C. 1H NMR (CDCl3) d 7.31 (s, 2H),
4.99 (bs, 1H, NH), 3.28–3.36 (m, 2H), 1.37 (s, 18H), 1.32 (s,
9H), 0.88–0.94 (m, 2H), 0.06 (s, 9H); 13C NMR (CDCl3) d
155.2, 146.7, 145.7, 141.9, 123.1, 37.8, 35.6, 34.8, 31.52,
31.47, 18.4, K1.6; Anal. Calcd for C24H43NO2Si: C, 71.05;
H, 10.68; N, 3.45. Found: C, 71.23; H, 10.90; N, 3.45.
liquid: 1H NMR (CDCl3) d 3.68–3.74 (m, 2H), 1.65 (s, 9H),
0.66–0.72 (m, 2H), 0.04 (s, 9H); 1H NMR (acetonitrile-d3) d
3.65–3.72 (m, 2H), 1.60 (s, 9H), 0.63–0.69 (m, 2H), 0.01 (s,
9H); 13C NMR (CDCl3) d 152.0, 85.0, 37.4, 28.0, 15.5,
K2.0; HRMS (FABC) m/z Calcd for C10H23N2O3Si [MC
Na]C 269.1297, found 269.1301.
4.6.3. 1-Adamantyl N-2-trimethylsilylethyl-N-nitroso-
carbamate (1c). Yield: 30% by the aqueous method, 81%
by the anhydrous method. Yellow solid, recrystallized from
petroleum ether at K25 8C, to yield yellow plates: mp 98–
99 8C. 1H NMR (CDCl3) d 3.67–3.73 (m, 2H), 2.29 (m, 9H),
1.72 (m, 6H), 0.66–0.72 (m, 2H), 0.04 (s, 9H); 13C NMR
(CDCl3) d 151.4, 85.0, 41.3, 37.4, 36.0, 31.0, 15.5, K1.9.
Anal. Calcd for C16H28N2O3Si: C, 59.22; H, 8.70; N, 8.63.
Found: C, 59.03; H, 8.73; N, 8.45.
4.5. Preparation of N-2-trimethylsilylethyl-N-nitroso-
carbamates. General procedure (aqueous method)
To a solution of the corresponding alkyl N-2-(trimethyl-
silyl)ethylcarbamate 2a–c (1.25 mmol) in ether (2 mL) was
added a solution of sodium nitrite (11.21 mmol) in water
(2 mL). Without stirring or cooling, nitric acid (1.5 mL,
35%) was added directly to the lower layer over 1 h. The
organic layer was separated, washed with water, then
washed four times with saturated sodium bicarbonate, dried
(MgSO4) and the solvent removed to afford the correspond-
ing alkyl N-nitroso-N-2-(trimethylsilyl)ethylcarbamate
1a–c. Further purification by column chromatography
(silica gel, hexane: CH2Cl2Z2:1) led to isolated products
that were O95% pure by NMR.
4.6.4. 2,4,6-Tris(t-butyl)phenyl N-2-trimethylsilylethyl-
N-nitrosocarbamate (1d). Carbamate 2d (0.23 g,
0.57 mmol) was dissolved in a mixture of acetic acid
(3.0 mL) and acetic anhydride (4.5 mL). The resultant
solution was cooled to 5 8C (ice–water) and NaNO2 (0.83 g,
12.06 mmol) was added in small portions, over 2-h period,
while keeping the temperature below 10 8C. Upon complete
addition, the resultant mixture was stirred for additional
12 h at ambient temperature. The solvents were removed at
reduced pressure and the residue was portioned between
water and ether. The ether extract was stirred for 10 min
with saturated aq NaHCO3, the organic layer was separated,
dried (MgSO4) and the solvent removed at reduced pressure.
The resultant yellow oil was flash chromatographed on a
short silica gel column (hexane: methylene chlorideZ5:1).
The yellow colored, highly mobile fraction was collected
and the solvent removed, leaving 0.21 g (84%) of the
product as a yellow oil, which slowly solidified. Recrystal-
lized from methanol at K30 8C to yield yellow needles: mp
4.6. Preparation of N-2-trimethylsilylethyl-N-nitroso-
carbamates. General procedure (anhydrous method)
To a stirred solution of the corresponding alkyl N-2-
(trimethylsilyl)ethylcarbamate 2a–c (5.00 mmol) and
anhydrous pyridine (10.00 mmol) in anhydrous acetonitrile
(2.5 mL) at K20 8C, was added in one portion solid NOBF4
(10.00 mmol). The solution was stirred at 0 8C under
nitrogen for a period of 1–2 h and the progress of the
reaction was followed by thin layer chromatography
(hexane–CH2Cl2Z2:1), the product exhibiting a rapidly
moving yellow spot. The solvent was removed and the
resultant mixture was passed through a short silica gel filter
(hexane–CH2Cl2Z2:1). Removal of the solvents at reduced
pressure gave the product 1a–c that were O95% pure by
NMR.
1
62–64 8C. H NMR (CDCl3) d 7.41 (s, 2H), 3.84–3.89 (m,
2H), 1.39 (s, 18H), 1.37 (s, 9H), 0.74–0.78 (m, 2H), 0.07 (s,
9H); 1H NMR (acetonitrile-d3) d 7.43 (s, 2H), 3.79–3.85 (m,
2H), 0.68–0.74 (m, 2H), 0.02 (s, 9H); 1H NMR (DMF-d7) d
7.48 (s, 2H), 3.89–3.95 (m, 2H), 0.72–0.78 (m, 2H), 0.07 (s,
9H); 13C NMR (CDCl3) d 153.5, 148.0, 145.4, 141.4, 123.5,
37.9, 35.6, 34.9, 31.51, 31.48, 15.4, K2.0. Anal. Calcd for
C24H42N2O3Si: C, 66.31; H, 9.74; N, 6.44. Found: C, 66.09;
H, 9.77; N, 6.46.
5. Supporting information available
4.6.1. Ethyl N-2-trimethylsilylethyl-N-nitrosocarbamate
(1a). Yield: 72% by the aqueous method, 78% by the
anhydrous method. Yellow liquid: 1H NMR (CDCl3) d 4.53
(q, JZ7.3 Hz, 2H), 3.70–3.77 (m, 2H), 1.45 (t, JZ7.3 Hz,
3H), 0.65–0.72 (m, 2H), 0.03 (s, 9H); 1H NMR (acetonitrile-
d3) d 4.43 (q, JZ7.0 Hz, 2H), 3.67–3.73 (m, 2H), 1.38 (t,
Crystallographic data (excluding structure factors) for the
structures in this paper have been deposited with the
Cambridge Crystallographic Data Centre as supplementary
publication numbers CCDC 258576 and 258577. Copies of
the data can be obtained, free of charge, on application to
CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax:
C44-(0)1223-336033 or e-mail: deposit@ccdc.cam.ac.uk].
1
JZ7.0 Hz, 3H), 0.63–0.68 (m, 2H),-0.01 (s, 9H); H NMR
(DMF-d7) d 4.54 (q, JZ7.2 Hz, 2H), 3.75–3.81 (m, 2H),
1.42 (t, JZ7.2 Hz, 3H), 0.67–0.73 (m, 2H), 0.05 (s, 9H); 13C
NMR (CDCl3) d 153.7, 64.2, 37.6, 15.4, 14.2, K2.0; HRMS
(FABC) m/z Calcd for C8H19N2O3Si [MCNa]C 241.0984,
found 241.0981. Anal. Calcd for C8H18N2O3Si: C, 44.01; H,
8.31; N, 12.83. Found: C, 44.34; H, 8.38; N, 12.63.
Acknowledgements
Partial funding for this project was provided by the
University of Dayton Research Council. V. Benin thanks
Prof. Albert Fratini from the Chemistry Department at the
4.6.2. t-Butyl N-2-trimethylsilylethyl-N-nitrosocarba-
mate (1b). Yield: 69% by the aqueous method. Yellow

4948
A. Thakkalapally, V. Benin / Tetrahedron 61 (2005) 4939–4948
20. Snyder, J. K.; Stock, L. M. J. Org. Chem. 1980, 45, 886–891.
21. White, E. H.; Aufedermarsh, C. A. J. J. Am. Chem. Soc. 1961,
83, 1174–1178.
University of Dayton, for his invaluable help in acquiring
and resolving the X-ray structures. V. Benin is also grateful
to Prof. Piotr Kaszynski from the Chemistry Department at
Vanderbilt University, for valuable suggestions and
unbiased opinion in the process of writing and concluding
this article.
22. Darbeau, R. W.; Perez, E. V.; Sobieski, J. I.; Rose, W. A.;
Yates, M. C.; Boese, B. J.; Darbeau, N. R. J. Org. Chem. 2001,
66, 5679–5686.
23. Yamaguchi, K.; Matsumura, G. Acta Crystallogr. 1992, C48,
1051–1054.
24. Hantzsch, A.; Schumann, M.; Egler, A. Chem. Ber. 1899, 32,
1703–1716.
Supplementary data
25. Xantheas, S. S.; Dunning, T. H., Jr J. Phys. Chem. 1994, 98,
13489–13497.
Energies and thermodynamic parameters of optimized
minimum structures of compounds 1a–d, MNU and
26. Xantheas, S. S. J. Phys. Chem. 1996, 100, 9703–9713.
27. Cabarcos, O. M.; Weinheimer, C. J.; Lisy, J. M.; Xantheas,
S. S. J. Chem. Phys. 1999, 110, 5–8.
1
MNNB are summarized in Table S1. Images of H NMR
spectra of compounds 1b and 2a are shown in Figure S1.
28. Pilcher, A. S.; Ammon, H. L.; DeShong, P. J. Am. Chem. Soc.
1995, 117, 5166–5167.
Supplementary data associated with this article can be found
at 10.1016/j.tet.2005.03.044
29. Cox, D. P.; Terpinski, J.; Lawrynowicz, W. J. Org. Chem.
1984, 49, 3216–3219.
30. Pilcher, A. S.; DeShong, P. J. Org. Chem. 1996, 61,
6901–6905.
31. Gold, B.; Linder, W. B. J. Am. Chem. Soc. 1979, 101,
6772–6773.
References and notes
32. Moss, R. A. J. Org. Chem. 1966, 31, 1082–1087.
33. Wilds, A. L.; Meader, A. L. J. J. Org. Chem. 1948, 13,
763–779.
1. Benin, V.; Kaszynski, P.; Radziszewski, G. J. Am. Chem. Soc.
2002, 124, 14115–14126.
2. Thiele, J.; Lachman, A. Justus Liebigs Ann. Chem. 1895, 288,
304–311.
34. Hartman, W. W.; Phillips, R. In Organic Syntheses, Collect.
Vol. II; Wiley: New York, 1943; p 464.
3. Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic
Synthesis; Wiley: New York, 1999; pp 64, 399–400.
4. Yang, W.; Koreeda, M. J. Am. Chem. Soc. 1994, 116,
10793–10794.
35. Hartman, W. W.; Brethen, M. R. In Organic Syntheses,
Collect. Vol. II; Wiley: New York, 1943; p 278.
36. Moss, R. A. Tetrahedron Lett. 1966, 7, 711–718.
37. Yellow liquid: 1H NMR (CDCl3) d 4.55 (q, J.H., 2H), 3.75 (t,
JZ7.1 Hz, 2H), 1.47 (t, JZ7.2 Hz, 3H), 1.33–1.43 (m, 2H),
1.18–1.30 (m, 2H), 0.89 (t, JZ7.2 Hz, 3H); 13C NMR (CDCl3)
d 154.0, 64.3, 40.7, 29.0, 20.0, 14.3, 13.5.
5. Hamm, M. L.; Cholera, R.; Hoey, C. L.; Gill, T. J. Org. Lett.
2004, 6, 3817–3820.
6. Wada, T.; Sekine, M. Tetrahedron Lett. 1994, 35, 757–760.
7. Bottaro, J. C.; Penwell, P. E.; Schmitt, R. J. J. Am. Chem. Soc.
1997, 119, 9405–9410.
38. Busch-Petersen, J.; Bo, Y.; Corey, E. J. Tetrahedron Lett.
1999, 40, 2065–2068.
8. Sommer, L. H.; Rockett, J. J. Am. Chem. Soc. 1951, 73,
5130–5134.
39. SHELXTL, version 6.10; Bruker AXS, Inc.: Madison, WI,
2000.
9. Jew, S.; Park, H. G.; Park, H.; Park, M.; Cho, Y. Tetrahedron
Lett. 1990, 31, 1559–1562.
40. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.;
Robb, M. A.; Cheeseman, J. R.; Montgomery, J. A., Jr.;
Vreven, T.; Kudin, K. N.; Burant, J. C.; Millam, J. M.; Iyengar,
S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.;
Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada,
M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida,
M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.;
Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Bakken, V.;
Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.;
Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski,
J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.;
Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels,
A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.;
Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.;
Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.;
Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R.
L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.;
Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson,
B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A.
Gaussian 03, R.C. Gaussian, Inc.: Wallingford, CT, 2004.
10. Nagel, M.; Hansen, H.-J. Helv. Chim. Acta 2000, 83,
1022–1045.
11. Schirlin, D.; Collard, J.- N.; Danzin, C. (Merrell Dow
Pharmaceuticals Inc.) USA. Eur. Pat. Appl. EP0291787,
1988, p 32.
12. Waddell, S. T.; Santorelli, G. M. Tetrahedron Lett. 1996, 37,
1971–1974.
13. Romea, P.; Urpi, F.; Vilarassa, J. J. Org. Chem. 1989, 54,
3209–3211.
14. Overberger, C. G.; Anselme, J.-P. J. Org. Chem. 1963, 28,
592–593.
15. Prout, K.; Fail, J.; Hernandez-Cassou, S.; Miao, F. M. Acta
Crystallogr.. 1982, B38, 2176–2181.
16. Becke, A. D. Phys. Rev. A 1988, 38, 3098–3100.
17. Lee, C.; Yang, W.; Parr, R. G. Phys. Rev. B 1988, 37, 785–789.
18. Frisch, M. J.; Pople, J. A.; Binkley, J. S. J. Chem. Phys. 1984,
80, 3265–3269.
19. Nakayama, N.; Kikuchi, O. J. Mol. Struct. (Theochem) 2001,
536, 213–218.