Benzylic Newman-Kwart rearrangement of O-azidobenzyl thiocarbamates triggered by phosphines: pseudopericyclic [1,3] shifts via uncoupled concerted mechanisms

Article abstract of DOI:10.1016/j.tet.2009.01.064

A series of O-(o- and p-azido)benzyl thiocarbamates smoothly rearranged in the course of Staudinger imination reactions with tertiary phosphines, giving rise to the respective S-(o- and p-phosphinimino)benzyl thiocarbamates as a result of an oxygen to sul

Full text of DOI:10.1016/j.tet.2009.01.064

Tetrahedron 65 (2009) 2579–2590
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Benzylic Newman–Kwart rearrangement of O-azidobenzyl thiocarbamates
triggered by phosphines: pseudopericyclic [1,3] shifts via uncoupled concerted
mechanisms
*
*
*
Mateo Alajarin , Marta Marin-Luna, Maria-Mar Ortin, Pilar Sanchez-Andrada , Angel Vidal
´
´
Departamento de Qu´ımica Organica, Facultad de Quımica, Universidad de Murcia, Campus de Espinardo, 30100 Murcia, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
A series of O-(o- and p-azido)benzyl thiocarbamates smoothly rearranged in the course of Staudinger
imination reactions with tertiary phosphines, giving rise to the respective S-(o- and p-phosphinimi-
no)benzyl thiocarbamates as a result of an oxygen to sulfur migration of the functionalized benzyl group.
By contrary, their m-azido isomers did not rearrange under similar conditions. Computational in-
vestigations using DFT methods revealed the uncoupled concerted mechanisms of these 1,3-benzyl shifts
via polar transition states with pseudopericyclic orbital topologies, with the benzyl group migrating in
the plane of the thiocarbamate fragment.
Received 28 November 2008
Received in revised form 29 December 2008
Accepted 5 January 2009
Available online 20 January 2009
Dedicated to Professor Josep Font on the
occasion of his 70th birthday
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Thiocarboxylates
Thione–thiol rearrangement
Pseudosigmatropic shift
Iminophosphoranes
1. Introduction
This rearrangement is proposed to proceed via a zwitterionic
four-center transition state, in accordance with the observation
The Newman–Kwart rearrangement (NKR), reported for the first
time in the sixties,1 is a first-order unimolecular rearrangement
converting O-aryl thiocarbamates into their S-aryl isomers under
heating at 200–300 ꢀC (Scheme 1). It is considered as a general and
efficient method for converting phenols into thiophenols.1c
of the activating role played by electron-withdrawing sub-
stituents at the aromatic nucleus. Kinetic and linear free energy
relationships are also in agreement with this mechanistic
model.2 The NKR is thermodynamically driven by the change
from a weak C]S to a strong C]O double bond. Recent interest
in the NKR focused on using microwaves as a mean for facili-
tating the conversion of electronically and sterically disfavored
substituents.3 As far as the benzylic variant of the NKR is con-
cerned, the main theme of this article, it has been only briefly
mentioned that O-benzyl N-phenylthiocarbamate rearranged
smoothly to the S-benzyl analog under photochemical activation,
in the context of a study on the rearrangement of a series of
O-allylic partners.4
O
NR2
S
NR2
heating
S
O
200-300 °C
subst
subst
NR2
O
S
Whereas a variety of 1,3-allyl shifts between two hetero-
atoms, via [3,3] sigmatropic rearrangements are now well
established,5 similar 1,3-benzylic migrations have been scarcely
reported. The oxygen to oxygen degenerate rearrangement of O-
benzyl carboxylic esters is known to occur slowly at 260 ꢀC with
subst
Scheme 1. Mechanism of the Newman–Kwart rearrangement.
an activation energy over 190 kJ molꢁ1 6
. The nitrogen to sulfur
* Corresponding authors. Tel.: þ34 968 367497; fax: þ34 968 364149 (M.A.); tel.:
þ34 968 367418; fax: þ34 968 364149 (A.V.); tel.: þ34 968 367425; fax: þ34 968
364149 (P.S.A.).
E-mail addresses: alajarin@um.es (M. Alajarin), andrada@um.es (P. Sanche-
z-Andrada), vidal@um.es (A. Vidal).
rearrangement of N-benzylpyridin-2-thiones producing 2-benzyl-
thiopyridines also requires harsh thermal conditions.7 The
thermal O- to S-rearrangement of O-benzyl xanthate, a particular
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.01.064

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M. Alajarin et al. / Tetrahedron 65 (2009) 2579–2590
case of the Scho¨nberg rearrangement,8 occurs at 150 ꢀC yielding
complex mixture of products in which the expected
S
NaH,
a
R1
R1
R2-N=C=S
OH
O
NH-R2
PhCH2SC(O)SCH3 is the major component.9 Similar thermal
rearrangements occur at lower temperatures (100 ꢀC) when
catalyzed by tricaprylmethylammonium chloride10 or pyridine-
N-oxides.11 The doubly benzylic O-benzhydryl xanthate was
reported to rearrange at room temperature.12
THF, r.t., 16 h
N3
N3
2
1
PR3
Et2O, r.t., 6 h
Within the frame of our recent investigations on radical
reactions of ketenimines,13 we discovered an unexpected [1,3]
shift of an o-functionalized benzylic fragment. When several
O-benzyl thionoderivatives bearing an azide function at ortho
position of the aromatic nucleus were submitted to the
Staudinger imination reaction14 of triphenylphosphine, the
reaction products resulted to be the respective imino-
phosphoranes in which the benzylic fragment moved from O
to S (Scheme 2).13b
O
R1
R1 = Cl
S
PR3
NH-R2
PR3
Et2O, r.t., 6 h
N
3
S
O
S
Cl
Cl
+
O
NH-R2
NH-R2
N
PR3
N
PR3
S
O
4d,e
3d,e
PPh3
O
X
S
X
40 °C, 10 h
+ N2
N3
N
PPh3
Scheme 3. Staudinger imination of O-(o-azidobenzyl) thiocarbamates 2.
X = SCH3
X = NHPh
X = OPh
The determination of the structure of compounds 3 was es-
sentially based on their 1H and 13C NMR spectroscopic data. Of
particular relevance are the chemical shifts of the benzylic
methylene protons in their 1H NMR spectra, and the chemical
shifts of the carbon atom of that group in their 13C NMR spectra.
In all cases, a notable upfield shift was observed for the above-
mentioned nuclei when compared with the chemical shifts of
the same nuclei in the corresponding azides 2. Whereas the
Scheme 2. Benzylic O to S rearrangements.
These transformations captured our attention due to the
smooth reaction conditions (Et2O, 25 ꢀC) under which they occur
and their high reaction rates (less than 1 h for completion). Here
we comment on the results obtained from a detailed study of
this peculiar rearrangement. Such study has been carried out
with a series of O-(azido)benzyl thiocarbamates in which the
position of the azide function at the benzene ring varied from
ortho to meta and para. The experimental data collected from the
reaction of these species with tertiary phosphines, along with
the conclusions drawn from an ad-hoc computational study,
allow us to offer a rational explanation for the mechanistic
course of such rearrangement, which accounts for the observed
differences in reactivity between the diverse azido-substituted
thiocarbamates.
benzylic methylene protons appear at
d
¼5.43–5.48 ppm in the
azides 2 the same protons in the iminophosphoranes 3 resonate
at
d
¼4.36–4.54 ppm. The 13C NMR spectra of azides 2 show the
signals due to the benzylic carbon atom at
d
¼65.4–66.8 ppm,
and those of iminophosphoranes 3 at
the 13C NMR spectra of the iminophosphoranes 3 the signals
that appear at higher values (
¼166.8–167.8 ppm) have un-
dergone an upfield shift with respect to the same signals in the
spectra of the azides 2 (
d
¼32.4–32.9 ppm. Also, in
d
d
d
¼187.0–187.6 ppm), accounting for the
presence of a carbonyl instead of a thiocarbonyl group in com-
pounds 3.
Next, we prepared the O-(m-azidobenzyl)thiocarbamates 6 by
reaction of m-azidobenzyl alcohol 5 with sodium hydride and
arylisothiocyanates. The treatment at room temperature of diethyl
ether solutions of azides 6 with triphenylphosphine gave the imino-
phosporanes 7 (Scheme 4, Table 1), in which the benzyl group
remains linked to the oxygen atom.
2. Results and discussion
2.1. Experimental study
The treatment of o-azidobenzyl alcohols 1 with sodium hy-
dride and arylisothiocyanates, in tetrahydrofuran solution at room
temperature, cleanly provided the N-aryl-O-(o-azidobenzyl)th-
iocarbamates 2. The Staudinger reaction of azides 2a–c with
tertiary phosphines, such as triphenylphosphine and tris(4-
methylphenyl)phosphine, in diethyl ether solution at room tem-
perature afforded the rearranged iminophosphoranes 3 in which
Table 1
Phosphazenes 3, 7, and 10
Compound
R1
R2
R3
R
Yield (%)
3a
3b
3c
3d
3e
3f
7a
7b
10a
10b
10c
10d
10e
10f
H
H
CH3
Cl
Cl
H
4-Cl–C6H4
4-CH3–C6H4
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
4-CH3–C6H4
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
40
66
87
82
49
80
72
55
43
91
92
54
84
64
the benzyl fragment is now linked to the
S atom of the
thiocarbamate function (Scheme 3, Table 1). The treatment of
O-(2-azido-5-chlorobenzyl)thiocarbamates 2d,e (R1¼Cl) with
triphenylphosphine resulted in the formation of mixtures of the
S-benzyl rearranged iminophosphoranes 3d,e and its structural
isomers, non-rearranged O-benzyl partners 4d,e. Thus, the pres-
C6H5
4-CH3–C6H4
4-CH3–C6H4
C6H5
4-CH3–C6H4
CH3–CH2
C6H5–CH2
C6H5
4-CH3–C6H4
C6H5–CH2
C6H5–CH2
ence of
a strong electron-withdrawing substituent, such as
H
H
H
H
CH3
H
a chlorine atom in relative para position to the iminophosphorane
group slightly decreases the rate of the [1,3] oxygen to sulfur
migration. Subsequent heating of the mixtures (3d,eþ4d,e) at
40 ꢀC in the absence of solvent completed the conversion of 4d,e
into 3d,e (Scheme 3).
N(CH3)2

M. Alajarin et al. / Tetrahedron 65 (2009) 2579–2590
2581
reaction conditions, in contrast with the lack of rearrangement in
the meta isomers under similar conditions.
S
NaH, R2-N=C=S
THF, r.t., 16 h
OH
O
NH-R2
The activating effect of the electron-releasing R3P]N sub-
stituents via resonance effects can be rationalized by assuming that
the present O- to S-benzyl shift is basically cationotropic, its rate-
determining step involving the heterolytic cleavage of the original
C–O bond in a sense such that a cationic benzyl group is moving
from the oxygen atom to the more nucleophilic sulfur of an anionic
thiocarbamate fragment (Scheme 6).
N3
N3
6
5
Et2O, r.t., 6 h PPh3
S
O
NH-R2
NHR2
NHR2
S
NHR2
O
N
PPh3
S
O
O
S
7
δ-
CH2
CH2
Scheme 4. Staudinger imination of O-(m-azidobenzyl) thiocarbamates 6.
CH2
δ+
In the 1H NMR spectra of compounds 7 the benzylic protons
appear at
d
¼5.31–5.41 ppm. Their 13C NMR spectra show the sig-
R3P=N
R3P=N
R3P=N
nals due to the benzylic carbon atom at
of the C]S group at
d
¼73.9–74.0 ppm, and that
Scheme 6. Postulated mechanism for the 1,3-benzyl shift from O to S.
d
¼188.7–188.8 ppm.
As azidothiocarbamates 2 and 6 did not rearrange when kept in
CDCl3 solution for weeks, and given that the azide-lacking thio-
carbamate 4-CH3–C6H4CH2OC(S)NHPh remained intact when
treated with PPh3 (1 equiv) in diethyl ether,15 it was clear that the
rearrangement of O-(o-azidobenzyl)thiocarbamates 2 into 3 when
converting the N3 group into R3P]N should be attributed to the
intervention of the iminophosphorane function. Moreover, the
absence of rearrangement in the transformation of the meta ana-
logs 6/7 proved that such intervention is feasible when the
R3P]N is placed at ortho position but not at meta. In order to
elucidate if this ortho activation is either due to some kind of
intramolecular catalysis by virtue of the proximity between the
iminophosphorane and thiocarbamate functions, or electronic in
nature via resonance effects, we obviously assayed the Staudinger
imination of phosphines with the p-azido-substituted thio-
carbamates 9.
In contrast with the classic NKR of aryl groups, activated by
electron-withdrawing substituents at the aromatic nucleus, the
present benzylic version shows an inverse electronic situation as
a result of the methylene group inserted between the oxygen and
sulfur atoms. The activating effect of the ortho and para-R3P]N
electron-releasing substituents is reminiscent of the similar role
played by o- and p-amino groups in 1,4- and 1,6-elimination re-
actions across benzylic fragments, which are on the basis of the
very efficient use of aminobenzyloxycarbonyl self-elimination
linkers for drug delivery applications, first introduced by Katze-
nellenbogen16 and now widely used.17 An example is represented
in Scheme 7. With the amino group acylated the benzyloxycarbonyl
linkers are stable under physiologic conditions, whereas deacyla-
tion to the free amino group promoted a rapid 1,6-elimination
following which the formed cationic iminoquinone methide (in
other words, an stabilized benzyl cation) is trapped by nucleo-
philes, e.g., H2O, and the unstable carbamic or carbonic acid un-
dergoes decarboxylation to release the active amine or alcohol
drug. The triggering amino group has been also originated from
inactive azido groups by chemical reduction18 and quite recently by
a Staudinger reaction with concurrent hydrolysis.19
O-(p-Azidobenzyl)thiocarbamates 9, prepared from benzylic
alcohols 8 by the standard methodology, reacted with triphenyl-
phosphine to yield the rearranged S-[p-(phosphinimino)-
benzyl]thiocarbamates 10 (Scheme 5, Table 1).
R3
R3
S
NaH,
R2-N=C=S
OH
O
NH-R2
O
O
THF, r.t., 16 h
N3
N3
O
X-R
+
8
9
O
X-R
H2N
H2N
Et2O, r.t., 6 h PPh3
H2O
X = NH, O
OH
R3
O
CO2
+
+ HX-R
H2N
S
NH-R2
Scheme 7. Representative 1,6-elimination of unstable carbamic and carbonic acids.
Ph3P
N
10
In our hands, attempts to trap the putative migrating ‘benzyl
cation’ in the O to S rearrangements 2,9/3,10 by externally added
nucleophiles (H2O, alcohols, amines) finished without success, thus
pointing to the concerted nature of the rearrangement, as repre-
sented in Scheme 6. Most probably, there is not a real dissociation
of the substrates into an ion pair, but a rapid [1,3] shift via a tran-
sition state, which should be zwitterionic in some extent, thus ac-
counting for the observed rate acceleration by electronic effects.
A cross-over experiment was designed to distinguish if the title
1,3-benzyl migration is occurring via an intramolecular or in-
termolecular pathway. Thus we treated a 1:1 mixture of two
Scheme 5. Staudinger imination of O-(p-azidobenzyl) thiocarbamates 9.
Compounds 10 were characterized by their analytical and
spectral data, which were essentially similar to those of the anal-
ogous iminophosphoranes 3 (1H NMR: benzylic CH2
d
¼3.90–
4.10 ppm; 13C NMR: benzylic CH2
d¼33.9–34.6 ppm).
The benzylic rearrangement occurring in the transformation of 9
into 10 demonstrated that the mesomeric effect of the electron-
donating [R3P]N–4R3Pþ–Nꢁ–] group should be responsible for
the rate increase allowing the occurrence of the 1,3-benzylic shift in
the ortho and para-substituted thiocarbamates under very mild

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M. Alajarin et al. / Tetrahedron 65 (2009) 2579–2590
different O-(o-azidobenzyl)thiocarbamates, 2b and 2c, with tri-
phenylphosphine under the standard conditions, affording a 1:1
mixture of the iminophosphoranes 3b and 3c in quantitative con-
version (Scheme 8). No cross-over products could be detected in
the 1H NMR spectrum of the crude reaction mixture. The result of
this experiment supports the intramolecularity of the
rearrangements.
demonstrated that the most common iminophosphorane fragment,
Ph3P]N, served as an electron-donating substituent on a phenyl
ring, slightly poorer than a Me2N group when both are placed in
para position (sꢀ¼ꢁ0.40 vs ꢁ0.44).21
2.2. Computational study
To gain insight into the mechanism of the formation of S-ben-
zylthiocarbamates from the corresponding O-benzylthio-
carbamates presented in the experimental part of this work we
have explored the potential energy surface associated to the rear-
rangement of the structurally simpler O-benzylthioesters 12a–c
leading to the S-benzylthioesters 13a–c at the B3LYP/6-31þG**
level of theory (Scheme 10). Additionally, the thiocarbamate 12d
was also investigated. These transformations were selected in order
to compare the simplest unsubstituted case 12a with one con-
taining an electron-releasing NH2 group (as representative of the
experimentally used N]PR3 functions) at a resonance active para
(12b) or inactive meta (12c) position, as well with the simplest
thiocarbamate 12d.
S
S
Me
O
NH
Me
O
NH
+
+
N3
N3
2b
2c
PPh3
Et2O, r.t., 6 h
Me
S
S
O
NH
Me
O
NH
N
PPh3
3b
N
PPh3
3c
Scheme 8. Cross-over experiment of the benzylic NKR.
Phosphazides R3P]N–N]N–R0 are known unstable in-
termediates in the Staudinger reaction. Nevertheless, some phos-
phazides, with the appropriate steric bulkiness and electronic
properties of the substituents in the starting azide and phosphine,
resist the thermal denitrogenation and are stable compounds at
room temperature.20 Particularly, the reaction of azides with elec-
tron-donating tris(dialkylamino)phosphines usually allows the
isolation of stable phosphazides.
O
S
9
6
3
7
1
5
10
S
X
O
8
X
4
2
R
R
13a-d
12a, R = H, X = H
12b, R = p-NH2, X = H
12c, R = m-NH2, X = H
12d, R = H, X = NH2
Scheme 10. 1,3-Benzyl shifts analyzed in the computational study.
We carried out the reaction of azide 9b (R2¼Ph-CH2; R3¼H) with
tris(dimethylamino)phosphine, with the aim of investigating the
feasibility of the [1,3] O- to S-benzylic rearrangement in the
resulting phosphazide. Thus, mixing azide 9b and tris(dimethyla-
mino)phosphine in diethyl ether at room temperature provided
phosphazide 11, in which the benzyl fragment has not experienced
oxygen to sulfur migration (Scheme 9). When heated at 80 ꢀC for
16 h in toluene solution compound 11 was transformed into the
rearranged iminophosphorane 10f.
We have successfully located the transition states TSa–d cor-
responding to the concerted, intramolecular [1,3]-benzyl shifts of
the O-benzylthiocarboxylates 12 for converting into the corre-
sponding S-benzyl isomers 13. Figure 1 shows the geometries of
TSa–d, including significant bond distances, and Figure 2 the
optimized geometry of TSa showing the planes containing the
interacting fragments. In Figure 3 a plot of the molecular elec-
trostatic potential of TSb is shown. Figure 4 displays two quali-
tative reaction profiles at the B3LYP/6-31þG** theoretical level
and the location of the stationary points for the 1,3-benzyl shift in
the O-benzylthioester 12b. In Tables 2 and 3 several relevant
geometric and electronic parameters of the transition structures
Ph
Ph
S
S
P(NMe2)3
Et2O, r.t., 6 h
O
N
H
O
N
H
TSa–d are collected. Table 4 includes pertinent properties of r(r)
N3
N
N
computed at the relevant BCPs of the transition states TSa–d,
whereas Table 5 contains the energy barriers for the trans-
formations 12a–d/13a–d computed at the B3LYP/6-31þG** and
PCM–B3LYP/6-31þG** theoretical levels.
9b
11
N
P(NMe2)3
Transition structures TSa–d show interesting features that we
will comment next. The benzylic carbon atom is almost planar,
the sum of C1–C7–H12, C1–C7–H13, and H12–C7–H13 angles range
from 353ꢀ to 359ꢀ, the highest value is found in TSb (see Table 2).
Thus, the hydrogen atoms attached to the benzylic carbon are
placed almost in the mean plane that includes the phenyl ring
and the benzylic carbon atom, denoted in Figure 2 as s1, which in
turn forms an angle with the plane containing the thiocarboxylate
moiety (s2) close to 100ꢀ (see Fig. 2). More importantly, the
benzylic carbon atom is also found approximately in the plane
defined by the thiocarboxylate fragment (s2). Consequently, the
developing p orbital at the benzylic carbon is nearly perpendic-
Toluene, 80 °C, 16 h
- N2
O
Ph
S
N
H
(Me2N)3P
N
10f
Scheme 9. Phosphazide isolation.
This result indicates that the O- to S-benzyl migration in the
rearrangements discussed above seems to occur once the imino-
phosphorane function formed, and not at the stage of the in-
termediate phosphazides. It is reasonable that phosphazides are
not better electron donors than iminophosphoranes, due to its
extended conjugation. Whereas the instability in solution of
phosphazides seems to have precluded detailed studies of their
electronic effects as substituents on aromatic nuclei, it has been
ular to the
p-system of the O–C]S fragment. This geometry
suggests that the main interactions between the benzylic and O–
C]S fragments are those involving the lone pairs at the oxygen
and sulfur heteroatoms with the p orbital at the benzylic carbon
atom, which are nearly coplanar. This hypothesis has been

M. Alajarin et al. / Tetrahedron 65 (2009) 2579–2590
2583
1.698
10
11
9
1.694
9
11
TSa
TSc
14
1.394
1.397
10
2.944
1.244
8
1.388
2.935
13
1.402
14
1.245
1.411
5
1.414
1.425
1.417
5
6
13
6
4
8
4
2.367
1.426
1
3
1
3
2
1.401
2
2.344
1.397
1.415
7
1.416
7
12
1.703
1.390
1.735
1.390
11
12
11
9
9
10
1.245
8
TSd
TSb
1.367
10
2.888
3.048
1.260
1.376
5
1.389
5
1.402
14
1.420
1.416
1.427
8
1.424
14
13
2.439
6
6
13
1.403
4
4
2.298
12
1
3
1
3
1.365
2
2
1.419
1.424
7
1.401
1.416
7
12
1.390
1.377
Figure 1. B3LYP/6-31þG** optimized geometries, showing relevant bond distances, of the transition structures TSa–d located for the [1,3]-benzyl shift transforming O-benzyl
derivatives 12a–d into their S-benzyl isomers 13a–d.
confirmed by the results of the second-order perturbation theory
analysis, which shows strong interactions from the donor lone
pair orbitals at the oxygen and sulfur atoms with the transient p
orbital at the benzylic carbon atom (see Supporting Information).
Also it is worth to note that the sulfur and the oxygen atoms
interact with the benzylic carbon on the same face of s1, and
therefore we are dealing with a [1,3] shift where the benzyl group
acts as the suprafacial component.
where n is the number of bonds directly involved in the reaction,
affords a measure of the degree of advancement of a TS along the
reaction path. One can also obtain information of the absolute
asynchronicity, A, of a chemical reaction, using the expression de-
veloped by Moyano et al.23
Thus, to follow the nature of these [1,3] shifts, we have com-
puted the Wiberg bond indices by using the Natural Bond Orbital
analysis at the
s
C7–O8 and
pC10–S9 bonds, which are breaking,
Among all the located transition states, TSb shows the longest
C7–O and C7–S bonds as well as the shortest C1–C7 bond length (see
Table 2). This latter finding indicates the effective delocalization of
the lone pair at the N14 atom of the para-amino group into the
and at the C7–S9 and p
s
C10–O8 bonds, which are forming along
the chemical reaction. These values are summarized in Table 3.
The C7–O8 bond-breaking process is the most advanced motion
among all the bond-breaking/making processes (%Ev¼75–81%),
showing that this bond is almost broken at the TS. TSb displays
the highest calculated value (81%). By contrast, the C7–S9 bond
formation process is the reaction coordinate that shows less
progress for all these shifts, displaying a small evolution per-
centage (23–31%, the lowest value shown by TSb). Accordingly, by
considering the high degree of evolution found for the C7–O8
benzylic fragment, and it is in agreement with the calculated
P
LN14 value, which is higher in TSb than in TSc (see Table 2), thus
showing that the amino group in TSb is almost flat. Note that when
the NH2 group is placed in meta (TSc) the C1–C7 bond distance is
similar to that found in TSa and TSd.
Bond index analysis can afford a deeper insight into the course
of the chemical reactions than the simple study of the geometrical
characteristics of the transition states. As demonstrated by Moyano
et al.,23 if the evolution of the bond indices corresponding to the
bonds being made or broken in a chemical reaction is analyzed
along the reaction path, a very precise image of the timing and the
extent of the bond-breaking and the bond-forming processes at
every point can be achieved. In order to perform the bond index
analysis is convenient to define a relative variation of the bond
index at the transition states,
chemical reaction as:
dBi, for every bond, i, involved in the
BTi S ꢁ BRi
;
d
Bi ¼
BPi ꢁ BRi
where the superscripts TS, R, and P refer to the TS, reactant, and
product, respectively. It is also possible to calculate the percentage
of evolution24 of the bond order of each one along the rearrange-
ment by using the following expression:
%Ev
¼ Bi ꢂ 100:
d
Besides, the average value, dBav, calculated as:
n
X
1
d
Bav
¼
d
Bi;
n i ¼ 1
**
Figure 2. B3LYP/6-31þG optimized geometry of transition structure TSa showing the
planes containing the interacting benzylic and O–C]S fragments.22

2584
M. Alajarin et al. / Tetrahedron 65 (2009) 2579–2590
Table 2
P
Angle between the s1 and s2 planesa
(
Ls1
–
s2), sum of angles at C7
(
LC7) and N14
P
(
LN14), and bond distances for the C7–O, C7–S, and C1–C7 bonds computed for the
transition structures TSa–d at the B3LYP/6-31þG** theoretical level
P
P
b
b
Ls1
–
s2
LC7
LN14
d
c (C7–O)
dc (C7–S)
d
c (C1–C7)
b
TSa
TSb
TSc
TSd
103.8
101.2
103.3
102.9
353.4
358.6
356.7
356.2
2.33
2.44
2.37
2.30
2.93
3.05
2.94
2.89
1.43
1.40
1.42
1.43
358.1
345.1
a
b
c
See Figures 1 and 2 for notation.
In degrees.
In Angstroms.
suggests a noteworthy assistance of Coulomb interaction between
both charged fragments stabilizing the TS. The charge separation
can also be visualized by computing the molecular electrostatic
potential (MESP) values. In Figure 3 the MESP values for TSb,
reflecting the electron-rich and electron-deficient regions of the
molecule, are shown.
Note that TSb is the structure among the four transition states
that shows the highest value of the dipolar moment, the highest
value of %Ev of the C7–O8 bond-breaking process and the lowest of
the C7–S9 bond formation ones, the highest value of charge sepa-
ration between the O–C]S and benzyl fragments, the highest
asynchronicity value, and also the most favorable transition state
(see below in Table 5).
Figure 3. MESP of TSb plotted onto the electron density surface with an isovalue of
0.01 a.u. showing the highly polar character of the system. The color coding is shown at
the top.
breaking bond and the little evolution found for the C7–S9
forming bond, the migration of the benzyl fragment from the
oxygen to the sulfur atom can be classified as a concerted asyn-
chronic process, accounting for the development of electron
charge separation between the benzyl and O–C]S fragments at
these transition states (see below). The O8–C10 and S9–C10 bonds,
that evolve from single to double bond and from double to single
bond, respectively, are almost simultaneous processes, although
the evolution is higher for the O8–C10 (63–66%) than for the S9–
C10 bond (57–58%). Thus, the elongation of the C7–O8 bond and, in
lower extension, the O8–C10 double bond formation can be seen
as the driving forces of these rearrangements.
The contribution of the NH2 group at the para position of the
phenyl ring for stabilizing the positive charge at the benzylic carbon
atom of TSb is apparent by comparing the sum of natural charges at
P
the benzylic fragment ( qb) with the natural charge calculated at
the benzyl carbon atom (qC7). Thus, in spite of the highest value of
qb shown by TSb ( qb¼þ0.58), the lowest positive charge at that
P
P
carbon is also found in TSb (qC7¼þ0.33).
According to all these data, an important bond deficiency exists
in the transition states, i.e., the bond-breaking C7–O8 process is
more advanced that the C7–S9 bond-forming one, and this is
translated into the important polar character reflected in the sum of
natural charges at the interacting fragments. In the four transition
states TSa–d the electronic deficiency created at the benzylic car-
bon atom by the breaking of the C7–O8 bond is compensated by
The dBav values summarized in Table 3 show that transition
structures TSa–d have somewhat more product-like character than
reactant-like one, being the C7–S9 bond formation, as inferred from
the %Ev values, the only motion in which these TSs have a reactant-
like character.
An analysis of the NBO charges proves the zwitterionic character
of these transition states, more notorious in TSb. Thus, the mi-
formation of a partial
phenyl ring (C1) rather than by the incipient formation of the
p
bond with the adjacent carbon atom at the
C7–
s
grating benzyl group carries a positive charge ranging from þ0.47
S9 bond. The contraction of the C1–C7 bond in going either from
reactants or from products to the transition states supports this
hypothesis. Thus, the bond indices corresponding to the C1–C7
bonds in TSa–d range from 1.26 to 1.37, the highest value shown by
TSb, whereas a notorious decrease of these values can be observed
in reactants and products (see Table 3). Once again, the contribu-
tion of the NH2 group at the para position of the phenyl ring for
stabilizing the positive charge at the benzylic carbon atom of TSb is
evident.
P
to þ0.58 (see qb in Table 3). The sum of natural charges at the O–
C]S moiety is obviously of opposite sign. Therefore, this analysis
30
TSb
With the aim to gain further insight into the nature of these 1,3-
benzyl shifts we have used the AIM25 methodology to calculate
several properties of the electron density at pertinent bond critical
points (BCPs) of the TSs (Table 4).
20
ΔE
10
0
ΔEPCM
The sign of the Laplacian of the electron density, V2[
r(r)], at
12b
a BCP is determined by which energy is in excess over the viral
2:1 average of kinetics to potential energy. A negative value of
V2[
r(r)] is related with the excess of the potential energy at the
ΔEPCM-rxn
ΔErxn
13b
BCP, which means that the electronic charge is concentrated in
the inter-nuclear region and therefore shared by two nuclei, as
occurs in shared electron (covalent) interactions. By contrary,
-10
Reaction Coordinate
positive values of V2[
r(r)] at a BCP reveal an excess in kinetic
Figure 4. Qualitative reaction profiles at the B3LYP/6-31þG** and PCM–B3LYP/6-
31þG** theoretical levels and the location of the stationary points for the 1,3-benzyl
shift 12b/13b.
energy and indicates depletion of electronic charge along the
bond path, as is the case of closed shell interactions (ionic

M. Alajarin et al. / Tetrahedron 65 (2009) 2579–2590
2585
Table 3
P
Natural charges at the benzylic carbon atom (qC7), sums of natural charges at the benzyl fragment ( qb), dipolar moments (
asynchronicity values (A), Wiberg bond indices (Bi), and percentages of evolution through the chemical process of the bond indexes computed for the transition structures TSa–
d at the B3LYP/6-31þG** theoretical level
m
), degrees of advancement of the TSs (
d
Bav),
P
a,b
b
qC7
qb
mc
C7–O8
C7–S9
O8–C10
S9–C10
C1–C7
TSa
TSb
TSc
TSd
0.34
0.33
0.35
0.39
0.47
5.11
BiR
0.830
0.215
0.008
74.8
0.019
0.317
0.977
31.1
1.127
1.533
1.764
63.7
1.798
1.443
1.171
56.7
1.024
1.267
1.030
BTi S
BiP
%Ev
d
Bav¼0.57; A¼0.15
0.58
0.49
0.52
9.68
5.48
4.07
BiR
0.819
0.164
0.008
80.8
0.018
0.239
0.969
23.2
1.136
1.548
1.759
66.1
1.789
1.432
1.177
58.3
1.033
1.364
1.036
BTi S
BiP
%Ev
d
Bav¼0.57; A¼0.20
BiR
0.829
0.204
0.008
76.1
0.019
0.313
0.977
30.1
1.131
1.544
1.758
65.9
1.793
1.433
1.177
58.4
1.023
1.271
1.029
BTi S
BiP
%Ev
d
Bav¼0.58; A¼0.16
BiR
0.836
0.213
0.007
75.1
0.015
0.309
0.982
30.4
1.046
1.427
1.650
63.1
1.580
1.258
1.027
58.2
1.020
1.258
1.029
BTi S
BiP
%Ev
d
Bav¼0.57; A¼0.15
a
b
c
Natural charge with hydrogens summed into the carbon atom.
In atomic units.
In Debyes.
bonds). For the transition states TSa–d the computed values for
V2[
(r)] at the C7–O8 and C7–S9 BCPs are positive, ranging from
the presence of the amino group attached to the carbon atom of the
thiocarbamate function, which is expected to destabilize the polar
transition structure TSd due to the electron-releasing character of
the amino group. On the contrary, the amino group at the para
position in 12b accounts for the stabilization of the transition state
TSb due to its ability to share the partial positive charge at the
benzylic carbon atom. Obviously, this is not possible when the
amino group is not present or placed in the meta position (TSa and
TSc).
r
þ0.083 to þ0.104 and from þ0.048 to þ0.057 a.u., respectively,
indicating very little sharing between the corresponding two
atomic basins. Additionally, the electronic density energy, H(r)
[H(r)¼G(r)þV(r)] evaluated at a BCP can be used to compare the
kinetics G(r) and potential V(r) energy densities on an equal
footing. For all interactions with significant sharing of electrons
H(r) is negative reflecting the covalent character of the in-
teraction. In the cases of the BCPs at C7–O8 and C7–S9 the kinetic
energy density dominates over the potential energy density and
H(r) is therefore positive, as anticipated for closed shell in-
teractions. These results reveal the ionic character of the C7–O8
and C7–S9 breaking/forming bonds at the transition structures
TSa–d, and are in agreement with the assistance of Coulomb
interaction stabilizing the TSs proposed above.
The calculated energy barriers for these [1,3] shifts are collected
in Table 5. All conversions resulted to be exothermic by 10–
11 kcal molꢁ1. The barrier for the conversion 12b/13b is calculated
to be the lowest (the qualitative reaction profile is represented in
Fig. 4), the barrier computed for the transformations 12a/13a and
12c/13c is comparable, and the highest energy barrier is shown
by the conversion 12d/13d. The latter result can be explained by
To evaluate the solvent influence in these processes we have
optimized all the stationary points considering the solvent effect of
diethyl ether (
3
¼4.335) by the PCM method. The results are in-
cluded in Table 5. With the inclusion of diethyl ether the transition
states are stabilized relative to reactants, whereas reactants and
products are similarly stabilized. Thus, whereas the exothermicities
do not vary significantly, the energy barriers decrease around
3 kcal molꢁ1 in all the cases except for the conversion 12b/13b,
where the lowering of the energy barrier is calculated to be of
8.6 kcal molꢁ1 (see Table 5). This result is in accordance with the
higher dipolar moment of TSb when compared with the rest of the
transition structures (see Table 3).
Table 5
Energy barriers (kcal molꢁ1) computed for the transformations 12a–d into 13a–
d through the transition states TSa–da at the B3LYP31þG** and PCM–B3LYP/6-
31þG** theoretical levels
Table 4
Relevant properties of r(r) computed at the BCPs for the breaking C7–O8 and the
B3LYPb
PCM–B3LYPc
forming C7–S9 in the transition states TSa–d at the B3LYP/6-31þG** level of theorya
D
E
DErxn
DEPCM DEPCM-rxn
BCP
TSa
TSb
TSc
TSd
12a/13a (R¼H, X¼H)
32.41
26.69
32.07
35.97
ꢁ11.09
ꢁ10.58
ꢁ11.27
ꢁ11.70
29.19
18.09
28.54
33.03
ꢁ11.12
ꢁ10.51
ꢁ11.14
ꢁ11.38
C7–O8
r
(r)
r
0.0353
0.0941
0.0231
0.0004
0.0292
0.0831
0.0197
0.0011
0.0336
0.0911
0.0221
0.0007
0.0376
0.1036
0.0257
0.0002
12b/13b (R¼p-NH2, X¼H)
12c/13c (R¼m-NH2, X¼H)
12d/13d (R¼H, X¼NH2)
V2[
(r)]
(r)]
G(r)
H(r)
a
See Figure 4 for the notation of the energy barriers.
Energies computed on the fully optimized B3LYP/6-31þG** geometries. The
C7–S9
r
V2[
G(r)
H(r)
(r)
r
0.0205
0.0501
0.0107
0.0018
0.0171
0.0478
0.0097
0.0023
0.0203
0.0503
0.0107
0.0019
0.0222
0.0565
0.0122
0.0019
b
ZPVE corrections, which were not scaled, were computed at the same level and have
been included.
c
Energies computed on the fully optimized PCM–B3LYP/6-31þG** geometries
a
r
(r) is the electron density (e/au3); V2[
r
(r)] is the Laplacian (e/au5); G(r) is the
using diethyl ether as solvent. The ZPVE corrections, which were not scaled, were
computed at the same level and have been included.
kinetic energy density, and H(r) is the energy density.

2586
M. Alajarin et al. / Tetrahedron 65 (2009) 2579–2590
2.3. Summary and conclusions
disconnections in the cyclic array of overlapping orbitals.28,29 The
orbital topologies of the present rearrangements are not those
expected for classic pericyclic 1,3-benzyl shifts as the breaking and
In summary, this theoretical study predicts that the 1,3-benzyl
shift in O-benzylthioesters leading to S-benzylthioesters takes
place by a concerted mechanism involving polar transition struc-
tures where the planes containing the benzylic and the thio-
carboxylate interacting fragments form an angle close to 100ꢀ. The
examination of its geometry along with the NBO analysis unveil
that the main interactions involve the lone pairs at the sulfur and
oxygen atoms with the transient p orbital at the benzylic carbon
atom, pointing to a transition state of pseudopericyclic topology.
That is, the interacting orbitals are not in a closed loop as expected
for a pericyclic transition state (see below).
The cleavage of the bond between the oxygen atom and the
benzylic carbon and the formation of the bond between the sulfur
atom and the same carbon atom take place very asynchronously.
The first occurs in going from the reactant to the transition state,
where that bond is almost broken, whereas the formation of the
latter occurs on going downhill from the TS to the product. There is
a substantial charge separation between the benzylic and thio-
carboxylate fragments involving a noteworthy Coulomb interaction
assistance stabilizing the TSs. The substitution at the para position
of the phenyl ring by electron-releasing substituents (an amino
group in the conversion 12b/13b) results in a substantial lowering
of the energy barrier for the 1,3-benzyl shift by stabilizing the
positive charge at the benzylic carbon atom, the asynchronicity of
the reaction being simultaneously enhanced.
forming sigma bonds do not overlap with the
p system of the thi-
ocarboxylate fragment, but instead they are nearly orthogonal. It is
worth to emphasize that the first pseudosigmatropic shift of
a methylene group has been very recently reported by de Lera and
co-workers.30
A notorious consequence of the geometric characteristics of
these transition states is that chiral benzyl fragments should retain
the absolute configuration of its benzylic carbon atom at the end of
the rearrangement (note that the sulfur and oxygen atoms interact
with the benzylic carbon atom by the same face of the plane con-
taining the benzyl fragment, and therefore, in a classical pericyclic
[1,3] shift the benzyl fragment would be labeled as the suprafacial
component, thus resulting in the retention of its configuration). We
believe that many other heteroatom to heteroatom 1,3-benzyl
shifts can also involve pseudopericyclic transition states and occur
with retention of configuration. This latter proposal has been re-
cently demonstrated by the elegant experiments carried out by
Tsuji and Richard with an enantiomerically enriched phenylethyl
thiobenzoate.31
3. Experimental
3.1. General
It is worth to remark that we are dealing with a strongly asyn-
chronous rearrangement, of the type Jenks qualified as ‘uncoupled
concerted’,26 with a TS where the C–O bond breaking is much more
advanced than the C–S bond formation. In such uncoupled con-
certed process there is no reaction intermediate (i.e., an ion pair in
the present case) but there is no coupling between bond formation
and bond cleavage, both occurring in the same kinetic step but not
simultaneously. This particular mechanism, at the concerted/step-
wise boundary, has been also termed as a ‘two-phase process’ by
other authors.27
In the course of our computational study all attempts to locate
a transition structure for the formation of an intermediate ion pair
failed, the saddle-point searches invariably converging on the
concerted transition states. Such concerted TSs and the hypothet-
ical transition structures for ion pair formation would involve
nearly complete breaking of the C–O bonds and the difference
between the two types of saddle points is that the concerted TSs
also involve C–S formation in some extent. However, as we have
stated above, the degree to which C–S bonds have progressed in the
located TSs is very minor. As a result, such structures are very close
to those expected for the transition states forming ion pairs. Rather
than involving two separate transition structures with extremely
similar geometries it seems that the stepwise and concerted
pathways have merged in the located TSs corresponding to the
uncoupled concerted one.
All melting points are uncorrected. Infrared (IR) spectra were
recorded as Nujol emulsions. 1H NMR spectra were recorded in
CDCl3 at 300 or 400 MHz. 13C NMR spectra were recorded in CDCl3
at 75 or 100 MHz. The chemical shifts are expressed in parts per
million, relative to Me4Si at
d
¼0.00 ppm for 1H, while the chemical
shifts for 13C are reported relative to the resonance of CDCl3
d
¼77.10 ppm or DMSO-d6 d¼35.35 ppm.
2-Azidobenzyl alcohol 1a,32 2-azido-5-methylbenzyl alcohol
1b,33 2-azido-5-chlorobenzyl alcohol 1c,34 3-azidobenzyl alcohol
5,35 and 4-azidobenzyl alcohol 8a18b were prepared following lit-
erature procedures.
3.2. General procedure for the preparation of 4-azido-a-
methylbenzyl alcohol 8b (R3[CH3)
To
a solution of 4-amino-a-methylbenzyl alcohol (1.18 g,
7.25 mmol) in a mixture of water (30 mL) and concentrated sulfuric
acid (5 mL), cooled at ꢁ5 ꢀC, was added dropwise a solution of
sodium nitrite (0.86 g, 12.5 mmol) in 10 mL of water. After 30 min
of stirring, a solution of sodium azide (0.81 g, 12.5 mmol) in 10 mL
of water was added dropwise, and stirring was continued for 16 h.
The mixture was extracted with dichloromethane (2ꢂ30 mL). The
combined organic layers were washed with water (2ꢂ100 mL) and
dried over anhydrous magnesium sulfate. The solvent was removed
under reduced pressure and the resulting oil was purified by col-
umn chromatography [silica gel, hexanes/diethyl ether (1:4, v/v)].
Yield 70%; oil; IR (Neat) 3363, 2099, 1606, 1582, 1507, 1449, 1418,
1294, 1204, 1180, 1129, 1088, 1009, 898, 834 cmꢁ1; 1H NMR (DMSO-
As far as the activating role of electron-donor substituents (o-
and p-R3P]N in the experimental work, o- and p-NH2 in the cal-
culations) is concerned, it is important to note that stepwise and
uncoupled concerted processes should show similar structure–re-
activity relationships, because the unsymmetrical transition state
of the uncoupled concerted one closely resembles one or the other
transition structure of the stepwise reaction. Moreover, the build
up of positive charge at the benzylic carbon atom, especially in TSb,
has been clearly shown by the calculations.
d6, 400 MHz)
5.20 (d, 1H, J¼4.4 Hz), 7.04 (d, 2H, J¼8.4 Hz), 7.36 (d, 2H, J¼8.4 Hz);
13C NMR (DMSO-d6, 100 MHz)
25.9, 67.5, 118.7, 126.9, 137.4 (s),
d
1.29 (d, 3H, J¼6.4 Hz), 4.70 (qd, 1H, J¼6.4, 4.4 Hz),
d
144.5 (s); HRMS (EI): m/z: calcd for C8H9N3O: 163.0746; found:
163.0750.
On the basis of the orbital topologies of the transition states,
these O to S rearrangements here discussed can be qualified as
pseudosigmatropic shifts of benzyl groups by virtue of their pseu-
dopericyclic characteristics. Pseudopericyclic reactions are a subset
of pericyclic reactions, which contain one or more orbital
3.3. General procedure for the preparation of the O-
(azidobenzyl)thiocarbamates 2, 6, and 9
To a solution of the azidobenzyl alcohol 1, 5 or 8 (5 mmol) and
the isothiocyanate (5 mmol) in anhydrous tetrahydrofuran (25 mL)

M. Alajarin et al. / Tetrahedron 65 (2009) 2579–2590
2587
was added sodium hydride (60% in oil; 0.25 g, 6.25 mmol). The
reaction mixture was stirred at room temperature in an atmo-
sphere of nitrogen for 16 h. Then the tetrahydrofuran was removed
under reduced pressure and the resulting material was partitioned
between dichloromethane (30 mL) and water (30 mL). The organic
layer was separated and dried over anhydrous magnesium sulfate.
After evaporation of the solvent the residue was purified by silica
gel column chromatography using hexanes/diethyl ether (7:3, v/v)
as eluent.
7.42 (t, 1H, J¼7.8 Hz), 7.50 (br s, 2H), 11.02 (s, 1H); 13C NMR (DMSO-
d6, 60 ꢀC, 75 MHz)
d 69.9, 118.0, 118.4, 122.3, 124.2, 124.6, 128.2,
129.7, 137.8 (s), 139.3 (s), 187.1 (s); HRMS (EI): m/z: calcd for
C14H12N2OS: 256.0670; found: 256.0670.
3.4.7. O-(3-Azidobenzyl)-N-(4-methylphenyl)thiocarbamate 6b
Yield 54%; mp 94–97 ꢀC (colorless prisms); IR (Nujol) 3230,
3170, 2111, 1597, 1587, 1551, 1406, 1292, 1223, 1191, 1056, 810, 780,
737, 681 cmꢁ1 1H NMR (DMSO-d6, 60 ꢀC, 400 MHz)
; d 2.26 (s, 3H),
5.55 (s, 2H), 7.06 (d, 1H, J¼6.4 Hz), 7.11–7.16 (m, 3H), 7.22–7.24 (d,
3.4. Characterization data for products 2, 6, and 9
1H, J¼7.2 Hz), 7.32–7.45 (m, 3H), 10.96 (s, 1H); 13C NMR (DMSO-d6,
60 ꢀC, 100 MHz)
d 20.0, 69.8, 118.0, 118.4, 122.3, 124.2, 128.6, 129.7,
3.4.1. O-(2-Azidobenzyl)-N-(4-chlorophenyl)thiocarbamate 2a
Yield 51%; mp 120–122 ꢀC (colorless prisms); IR (Nujol) 3245,
2130, 2120, 1599, 1551, 1492, 1406, 1345, 1301, 1218, 1091, 1021, 824,
134.0 (s), 137.9 (s), 139.3 (s), 187.0 (s); HRMS (EI): m/z: calcd for
C15H14N2OS: 270.0827; found: 270.0827.
753 cmꢁ1; 1H NMR (DMSO-d6, 60 ꢀC, 300 MHz)
d
5.48 (s, 2H), 7.21
3.4.8. O-(4-Azidobenzyl)-N-ethylthiocarbamate 9a
(td,1H, J¼7.5, 1.2 Hz), 7.31–7.37 (m, 3H), 7.43–7.55 (m, 4H); 13C NMR
The 1H and 13C NMR spectra of compound 9a at room temper-
ature (in CDCl3) displayed doubling of the majority of signals,
suggesting the presence of two rotamers in a ratio 1:1.7.
Yield 41%; mp 72–75 ꢀC (colorless prisms); IR (Nujol) 3128, 3071,
2111, 2064,1597,1445,1334,1307,1285,1217,1202,1140,1062,1012,
(DMSO-d6, 60 ꢀC, 75 MHz)
d 66.8, 118.4, 123.6, 124.6, 126.3 (s), 128.1,
128.6 (s), 129.8, 130.0, 136.8 (s), 137.8 (s), 187.0 (s); HRMS (EI): m/z:
calcd for C14H11ClN2OS: 290.0281; found: 290.0283.
3.4.2. O-(2-Azidobenzyl)-N-(4-methylphenyl)thiocarbamate 2b
Yield 71%; mp 104–106 ꢀC (colorless prisms); IR (Nujol) 3213,
2126,1591,1541,1489,1405,1360,1309,1286,1182,1155,1097,1120,
828, 809, 720 cmꢁ1 1H NMR (CDCl3, 300 MHz)
; d 1.07 (t, 3Hminor,
J¼7.5 Hz), 1.15 (t, 3Hmayor, J¼7.5 Hz), 3.20–3.29 (m, 2Hminor), 3.47–
3.56 (m, 2Hmayor), 5.36 (s, 2Hmayor), 5.43 (s, 2Hminor), 6.25 (br s,
1Hmayor), 6.73 (br s, 1Hminor), 6.92–6.97 (m, 4H), 7.28–7.33 (m, 4H);
834, 751 cmꢁ1; 1H NMR (DMSO-d6, 60 ꢀC, 300 MHz)
d
2.26 (s, 3H),
5.47 (s, 2H), 7.11 (d, 2H, J¼8.4 Hz), 7.20 (t, 1H, J¼7.3 Hz), 7.31–7.47
13C NMR (CDCl3, 75 MHz)
d 13.7, 14.2, 38.2, 40.2, 70.8, 72.4, 119.0,
13
(m, 5H), 10.90 (s, 1H); C NMR (DMSO-d6, 60 ꢀC, 75 MHz)
d
19.6,
119.1, 129.8, 129.9, 132.2 (s), 132.5 (s), 140.0 (s), 140.1 (s), 189.4 (s),
189.5 (s); HRMS (EI): m/z: calcd for C10H12N2OS: 208.0670; found:
208.0672.
66.4, 118.2, 122.1, 124.4, 126.6 (s), 128.2, 129.3, 129.5, 133.7 (s), 135.2
(s), 137.5 (s), 187.1 (s); HRMS (EI): m/z: calcd for C15H14N2OS:
270.0827; found: 270.0828.
3.4.9. O-(4-Azidobenzyl)-N-benzylthiocarbamate 9b
3.4.3. O-(2-Azido-5-methylbenzyl)-N-phenylthiocarbamate 2c
Yield 54%; mp 128–130 ꢀC (colorless prisms); IR (Nujol) 3229,
2128, 2087, 1592, 1552, 1494, 1405, 1344, 1288, 1201, 1186, 1079,
The 1H and 13C NMR spectra of compound 9b at room temper-
ature (in CDCl3) displayed doubling of the majority of signals,
suggesting the presence of two rotamers in a ratio 1:2.
1058, 799, 750 cmꢁ1; 1H NMR (DMSO-d6, 60 ꢀC, 400 MHz)
d
2.28 (s,
Yield 73%; mp 90–91 ꢀC (colorless prisms); IR (Nujol) 3222, 2114,
1548, 1507, 1400, 1341, 1285, 1243, 1217, 1201, 1177, 1083, 1061, 960,
3H), 5.43 (s, 2H), 7.13 (t, 1H, J¼7.2 Hz), 7.21 (d, 1H, J¼8.0 Hz), 7.25–
7.33 (m, 4H), 7.51 (br s, 2H), 11.01 (s, 1H); 13C NMR (DMSO-d6, 60 ꢀC,
816, 738 cmꢁ1; 1H NMR (CDCl3, 400 MHz)
d
4.35 (d, 2H, J¼5.6 Hz),
4.67 (d, 2H, J¼5.6 Hz), 5.39 (s, 2H), 5.43 (s, 2H), 6.48 (s, 1H), 6.90 (s,
1H), 6.92–7.31 (m, 18H); 13C NMR (CDCl3, 100 MHz)
47.3, 49.4,
100 MHz)
d 19.9, 66.7, 118.3, 122.2, 124.6, 126.1, 128.1, 130.1, 130.5,
134.1 (s), 134.9 (s), 137.8 (s), 187.0 (s); HRMS (EI): m/z: calcd for
d
C15H14N2OS: 270.0827; found: 270.0830.
71.3, 72.6, 119.0, 127.5, 127.8, 127.9, 128.7, 129.9, 130.0, 132.0 (s),
132.4 (s), 136.3 (s), 136.5 (s), 140.1 (s), 189.4 (s), 190.0 (s); HRMS (EI):
m/z: calcd for C15H14N2OS: 270.0827; found: 270.0827.
3.4.4. O-(2-Azido-5-chlorobenzyl)-N-phenylthiocarbamate 2d
Yield 74%; mp 125–130 ꢀC (colorless prisms); IR (Nujol) 3199,
3045, 2125, 1560, 1449, 1402, 1291, 1220, 1203, 1184, 1057, 888, 805,
3.4.10. O-(4-Azidobenzyl)-N-phenylthiocarbamate 9c
741, 687 cmꢁ1
;
1H NMR (DMSO-d6, 60 ꢀC, 300 MHz)
d
5.45 (s, 2H),
7.15 (t, 1H, J¼8.4 Hz), 7.30–7.36 (m, 3H), 7.45–7.50 (m, 4H), 11.04 (s,
1H); 13C NMR (DMSO-d6, 60 ꢀC, 75 MHz)
66.6, 121.0, 123.0, 125.4,
Yield 78%; mp 114–115 ꢀC (colorless prisms); IR (Nujol) 3238,
2120, 2081, 1597, 1547, 1510, 1494, 1446, 1408, 1336, 1307, 1292,
d
1212, 1172, 1136, 1015, 752, 686 cmꢁ1 1H NMR (DMSO-d6,
;
128.8, 129.2 (s), 129.4 (s), 129.7, 129.8, 137.2 (s), 138.6 (s), 187.6 (s);
HRMS (EI): m/z: calcd for C14H11ClN2OS: 290.0281; found:
290.0284.
300 MHz)
7.46–7.49 (m, 4H), 10.98 (s, 1H); 13C NMR (DMSO-d6, 75 MHz)
70.3, 118.8, 122.2, 124.5, 128.1, 129.5, 132.5 (s), 137.8 (s), 139.0 (s),
d
5.55 (s, 2H), 7.10–7.16 (m, 3H), 7.31 (t, 2H, J¼7.8 Hz),
d
187.1 (s); HRMS (EI): m/z: calcd for C14H12N2OS: 256.0670; found:
3.4.5. O-(2-Azido-5-chlorobenzyl)-N-(4-methylphenyl)-
thiocarbamate 2e
256.0672.
Yield 46%; mp 145–147 ꢀC (colorless prisms); IR (Nujol) 3202,
2125, 2087, 1533, 1396, 1336, 1305, 1185, 1169, 1112, 1038, 866, 812,
3.4.11. O-(4-Azidobenzyl)-N-(4-methylphenyl)thiocarbamate 9d
Yield 55%; mp 92–95 ꢀC (colorless prisms); IR (Nujol) 3193, 2118,
1606, 1587, 1537, 1506, 1395, 1348, 1249, 1175, 1128, 1042, 834, 816,
720 cmꢁ1 1H NMR (DMSO-d6, 60 ꢀC, 300 MHz)
; d 3.10 (s, 3H), 5.43
(s, 2H), 7.12 (d, 2H, J¼8.1 Hz), 7.34–7.48 (m, 5H), 10.95 (s, 1H); 13C
783 cmꢁ1; 1H NMR (DMSO-d6, 300 MHz)
d
2.26 (s, 3H), 5.53 (s, 2H),
7.11 (d, 4H, J¼7.5 Hz), 7.36 (br s, 2H), 7.46 (d, 2H, J¼7.5 Hz), 10.91 (s,
1H); 13C NMR (DMSO-d6, 75 MHz)
20.0, 70.1, 118.8, 122.2, 128.6,
NMR (DMSO-d6, 60 ꢀC, 75 MHz)
d 20.7, 65.4, 121.0, 123.0, 129.3,
129.4 (s), 129.6, 129.8, 134.8 (s), 136.0 (s), 137.2 (s), 187.4 (s); HRMS
d
(EI): m/z: calcd for C15H13ClN2OS: 304.0437; found: 304.0430.
129.5, 132.5 (s), 133.9 (s), 135.3 (s), 139.0 (s), 187.0 (s); HRMS (EI):
m/z: calcd for C15H14N2OS: 270.0827; found: 270.0831.
3.4.6. O-(3-Azidobenzyl)-N-phenylthiocarbamate 6a
Yield 89%; mp 112–114 ꢀC (colorless prisms); IR (Nujol) 3229,
3167, 2121, 1598, 1587, 1556, 1406, 1343, 1294, 1206, 1191, 1044, 865,
3.4.12. O-(4-Azido-a-methylbenzyl)-N-benzylthiocarbamate 9e
The 1H and 13C NMR spectra of compound 9e at room temper-
ature (in CDCl3) displayed doubling of the majority of signals,
suggesting the presence of two rotamers in a ratio 1:1.7.
782, 752, 683 cmꢁ1; 1H NMR (DMSO-d6, 60 ꢀC, 300 MHz)
d
5.57 (s,
2H), 7.06–7.17 (m, 3H), 7.24 (d, 1H, J¼7.5 Hz), 7.32 (t, 2H, J¼7.5 Hz),

2588
M. Alajarin et al. / Tetrahedron 65 (2009) 2579–2590
Yield 88%; oil; IR (Neat) 3267, 2104, 1659, 1606, 1508, 1454, 1394,
1342, 1294, 1174, 1129,1057, 1029, 1001, 968, 895, 833, 698 cmꢁ1; 1H
NMR (CDCl3, 400 MHz) ,
J¼6.8 Hz), 4.35 (d, 2Hminor, J¼6.0 Hz), 4.56–4.68 (m, 2Hmayor), 5.55
(br s, 1Hminor), 6.37 (q,1Hminor, J¼6.8 Hz), 6.41 (q,1Hmayor, J¼6.8 Hz),
6.49 (br s, 1Hmayor), 6.84–7.28 (m, 18H); 13C NMR (CDCl3, 100 MHz)
3.6.4. Phosphazene 3d (R1¼Cl; R2¼R¼C6H5)
Yield 82%; mp 78–80 ꢀC (colorless prisms); IR (Nujol) 3162,
1592, 1546, 1437, 1282, 1185, 1170, 1109, 1022, 1004, 904, 753, 720,
d
1.48 (d, 3Hminor, J¼6.8 Hz),1.50 (d, 3Hmayor
690 cmꢁ1 1H NMR (CDCl3, 400 MHz)
; d 4.36 (s, 2H), 6.22 (d, 1H,
J¼8.4 Hz), 6.64 (dd, 1H, J¼8.4, 2.8 Hz), 6.95 (t, 1H, J¼7.6 Hz), 7.15 (t,
2H, J¼7.6 Hz), 7.22–7.26 (m, 3H), 7.31 (s, 1H), 7.33–7.37 (m, 6H),
7.41–7.45 (m, 3H), 7.60–7.65 (m, 6H); 13C NMR (CDCl3, 100 MHz)
d
21.8, 21.9, 47.1, 49.2, 77.3, 79.1,118.8,118.9,119.0, 127.4, 127.6, 127.7,
127.79, 127.82, 127.86, 127.89, 128.5, 128.6, 128.69, 128.7, 136.5 (s),
136.6 (s), 137.7 (s), 138.1 (s), 138.7 (s), 139.4 (s), 139.5 (s), 139.9 (s),
188.7 (s), 189.3 (s); HRMS (EI): m/z: calcd for C16H16N2OS:
284.0983; found: 284.0989.
d
32.4, 119.8, 121.3 (d, J¼9.9 Hz), 121.6 (s), 124.0, 127.4, 128.6 (d,
J¼12.0 Hz), 128.9, 129.5, 130.4 (d, J¼100.0 Hz) (s), 131.8 (d,
J¼2.7 Hz), 132.4 (d, J¼9.7 Hz), 133.4 (d, J¼22.7 Hz) (s), 137.9 (s),
148.2 (s), 166.9 (s); 31P NMR (CDCl3, 121.4 MHz, H3PO4)
d 4.06;
HRMS (ESI): m/z: calcd for C32H26ClN2OPS: 552.1192; found:
552.1212.
3.5. General procedure for the preparation of the
phosphazenes 3, 7, and 10
3.6.5. Phosphazene 3e (R1¼Cl; R2¼4-CH3–C6H4; R¼C6H5)
Yield 49%; mp 84–87 ꢀC (colorless prisms); IR (Nujol) 3199,
3175, 1643, 1631, 1589, 1542, 1437, 1400, 1353, 1315, 1186, 1170, 1107,
To a solution of the corresponding azide 2, 6 or 9 (5 mmol) in
anhydrous diethyl ether (15 mL) the tertiary phosphine (5 mmol)
was added. The resulting mixture was stirred at room temperature
in an atmosphere of nitrogen for 3–6 h. Then the precipitated
compounds were isolated by filtration.
1021, 812, 719, 694 cmꢁ1; 1H NMR (CDCl3, 300 MHz)
d 2.20 (s, 3H),
4.36 (s, 2H), 6.23 (d, 1H, J¼8.4 Hz), 6.65 (dd, 1H, J¼8.4, 2.7 Hz), 6.96
(d, 2H, J¼8.4 Hz), 7.13–7.16 (m, 2H), 7.20 (s, 1H), 7.23 (t, 1H,
J¼2.7 Hz), 7.30–7.39 (m, 6H), 7.43–7.47 (m, 3H), 7.61–7.67 (m, 6H);
13C NMR (CDCl3, 75 MHz)
d
20.8, 32.4, 120.1, 121.4 (d, J¼9.8 Hz),
3.6. Characterization data for products 3, 7, and 10
121.8 (s), 127.4, 128.6 (d, J¼12.0 Hz), 129.4, 129.5, 130.4 (d,
J¼100.6 Hz) (s), 131.9 (d, J¼2.1 Hz), 132.4 (d, J¼9.7 Hz), 133.4 (s),
133.7 (d, J¼4.4 Hz) (s), 135.3 (s), 166.8 (s); 31P NMR (CDCl3,
3.6.1. Phosphazene 3a (R1¼H; R2¼4-Cl–C6H4; R¼C6H5)
Yield 40%; mp 90–91 ꢀC (colorless prisms); IR (Nujol) 3289,
1678, 1591, 1481, 1436, 1396, 1342, 1303, 1145, 1111, 1021, 826, 716,
121.4 MHz, H3PO4)
d
4.48; HRMS (ESI): m/z: calcd for
C33H28ClN2OPS: 566.1348; found: 566.1351.
693 cmꢁ1 1H NMR (CDCl3, 400 MHz)
; d 4.51 (s, 2H), 6.45 (d, 1H,
J¼7.6 Hz), 6.64 (t, 1H, J¼7.6 Hz), 6.81 (td, 1H, J¼7.6, 1.2 Hz), 7.16 (d,
2H, J¼8.8 Hz), 7.25–7.27 (m, 2H), 7.33–7.35 (m, 1H), 7.42–7.46 (m,
6H), 7.51–7.55 (m, 3H), 7.70–7.75 (m, 6H), 7.78 (s, 1H); 13C NMR
3.6.6. Phosphazene 3f (R1¼H; R2¼R¼4-CH3–C6H4)
Yield 80%; mp 118–121 ꢀC (colorless prisms); IR (Nujol) 3128,
1584, 1537, 1510, 1483, 1405, 1358, 1332, 1204, 1184, 1106, 1019, 827,
(CDCl3, 100 MHz)
d
32.9, 117.8, 121.1 (d, J¼9.8 Hz), 121.5, 128.0,
808, 753, 662, 649 cmꢁ1 1H NMR (CDCl3, 400 MHz)
; d 2.17 (s, 3H),
128.7 (d, J¼12.0 Hz), 128.9, 130.1 (d, J¼2.1 Hz), 130.9 (d, J¼99.1 Hz)
2.28 (s, 9H), 4.42 (s, 2H), 6.35 (d, 1H, J¼7.6 Hz), 6.51 (t, 1H, J¼7.2 Hz),
6.70 (td, 2H, J¼7.6, 2.0 Hz), 6.91 (d, 2H, J¼8.0 Hz), 7.09–7.14 (m, 8H),
7.24 (dt, 1H, J¼7.2, 2.4 Hz), 7.49–7.455 (m, 6H); 13C NMR (CDCl3,
(s), 131.7 (s), 131.9 (d, J¼2.9 Hz), 132.6 (d, J¼9.7 Hz), 136.8 (s),
149.3 (s), 167.8 (s); 31P NMR (CDCl3, 121.4 MHz, H3PO4)
d 3.83;
HRMS (ESI): m/z: calcd for C32H26ClN2OPS: 552.1192; found:
552.1204.
100 MHz)
d
20.7, 21.5, 32.7, 117.2, 120.3, 120.8 (d, J¼9.9 Hz),127.4 (s),
127.6, 129.2 (d, J¼12.3 Hz), 129.3, 129.8, 131.7 (s), 132.1 (s), 132.5 (d,
J¼101. Hz), 133.4 (s), 135.5 (s), 141.9 (s), 149.7 (s), 167.6 (s); 31P NMR
3.6.2. Phosphazene 3b (R1¼H; R2¼4-CH3–C6H4; R¼C6H5)
(CDCl3, 121.4 MHz, H3PO4) d 3.78; HRMS (ESI): m/z: calcd for
Yield 66%; mp 118–121 ꢀC (colorless prisms); IR (Nujol) 3266,
1674, 1643, 1592, 1517, 1481, 1309, 1239, 1152, 1109, 1049, 1021,
C36H35N2OPS: 574.2208; found: 574.2217.
813, 750, 715, 694 cmꢁ1
;
1H NMR (CDCl3, 400 MHz)
d
2.28 (s, 3H),
3.6.7. Phosphazene 7a (R2¼R¼C6H5)
4.54 (s, 2H), 6.45 (d, 1H, J¼7.6 Hz), 6.63 (t, 1H, J¼7.2 Hz), 6.81 (td,
1H, J¼7.6, 1.6 Hz), 7.04 (d, 2H, J¼8.0 Hz), 7.22 (d, 2H, J¼8.4 Hz),
7.36 (dt, 1H, J¼5.2, 2.0 Hz), 7.42–7.47 (m, 6H), 7.50–7.55 (m, 3H),
Yield 72%; mp 124–126 ꢀC (colorless prisms); IR (Nujol) 3057,
1591, 1514, 1483, 1438, 1344, 1331, 1313, 1303, 1194, 1176, 1103, 1035,
1022, 921, 778, 712, 699 cmꢁ1 1H NMR (CDCl3, 60 ꢀC, 400 MHz)
;
7.73–7.79 (m, 6H), 7.80 (s, 1H); 13C NMR (CDCl3, 100 MHz)
d
20.8,
d
5.31 (s, 2H), 6.58 (d, 1H, J¼7.2 Hz), 6.65 (dd, 1H, J¼8.0, 1.2 Hz), 6.77
32.8, 117.4, 120.2, 120.7 (d, J¼9.8 Hz), 127.8, 128.6 (d, J¼10.0 Hz),
129.4, 129.9 (d, J¼2.0 Hz), 131.1 (d, J¼99.6 Hz) (s), 131.7 (d,
J¼2.3 Hz), 132.0 (d, J¼11.9 Hz) (s), 132.5 (d, J¼9.7 Hz), 133.6 (s),
135.6 (s), 149.5 (s), 167.4 (s); 31P NMR (CDCl3, 121.4 MHz, H3PO4)
(s, 1H), 6.89 (t,1H, J¼7.6 Hz), 7.01 (t,1H, J¼7.2 Hz), 7.14–7.18 (m, 2H),
7.23 (br s, 2H), 7.29–7.33 (m, 6H), 7.37–7.41 (m, 3H), 7.62–7.67 (m,
13
6H), 8.09 (s, 1H); C NMR (CDCl3, 60 ꢀC, 100 MHz)
d 74.0, 117.3,
122.1, 123.4, 123.6, 125.3, 128.5 (d, J¼11.8 Hz), 128.7, 128.9, 131.3 (d,
d
2.76; HRMS (ESI): m/z: calcd for C33H29N2OPS: 532.1738; found:
J¼99.2 Hz) (s),131.6 (d, J¼2.6 Hz),132.6 (d, J¼9.3 Hz),135.5 (s),137.6
532.1752.
(s), 151.5 (s), 188.7 (s); 31P NMR (CDCl3, 121.4 MHz, H3PO4)
d 3.82;
HRMS (ESI): m/z: calcd for C32H27N2OPS: 518.1582; found:
518.1592.
3.6.3. Phosphazene 3c (R1¼CH3; R2¼R¼C6H5)
Yield 87%; mp 89–91 ꢀC (colorless prisms); IR (Nujol) 3256,
3178, 1679, 1640, 1600, 1491, 1437, 1346, 1309, 1237, 1186, 1143, 1107,
3.6.8. Phosphazene 7b (R2¼4-CH3–C6H4; R¼C6H5)
1035, 1023, 811, 751, 721, 693 cmꢁ1
;
1H NMR (CDCl3, 400 MHz)
Yield 55%; mp 144–146 ꢀC (colorless prisms); IR (Nujol) 3055,
1594,1522,1483,1437,1334,1317,1304,1264,1196,1178,1106,1036,
999, 836, 780, 744, 719, 694 cmꢁ1; 1H NMR (CDCl3, 60 ꢀC, 400 MHz)
d
2.19 (s, 3H), 4.51 (s, 2H), 6.37 (d, 1H, J¼8.0 Hz), 6.63 (dd, 1H, J¼8.0,
1.6 Hz), 7.04 (t, 1H, J¼7.2 Hz), 7.19–7.26 (m, 3H), 7.34 (d, 2H,
J¼7.6 Hz), 7.42–7.46 (m, 6H), 7.50–7.54 (m, 3H), 7.65 (s, 1H), 7.72–
d
2.31 (s, 3H), 5.41 (s, 2H), 6.68 (d, 1H, J¼7.2 Hz), 6.75 (d, 1H,
7.77 (m, 6H); 13C NMR (CDCl3, 100 MHz)
d
20.4, 32.7, 120.1, 120.5 (d,
J¼7.6 Hz), 6.86 (s, 1H), 6.99 (t, 1H, J¼8.0 Hz), 7.07–7.09 (m, 2H), 7.20
J¼9.6 Hz), 123.9, 126.5 (s), 128.4, 128.5 (d, J¼11.9 Hz), 128.8, 130.5,
(br s, 2H), 7.40–7.44 (m, 6H), 7.48–7.52 (m, 3H), 7.73–7.78 (m, 6H),
130.9 (d, J¼95.6 Hz) (s), 131.6 (d, J¼2.0 Hz), 132.5 (d, J¼9.7 Hz),138.1
8.05 (br s, 1H); 13C NMR (CDCl3, 60 ꢀC, 100 MHz)
d 20.9, 73.9, 117.4,
(s), 146.6 (s), 167.5 (s); 31P NMR (CDCl3, 121.4 MHz, H3PO4)
d
2.77;
122.4 (s), 123.5 (d, J¼4.6 Hz), 123.6 (d, J¼5.6 Hz), 128.6 (d,
J¼12.0 Hz), 128.8, 129.5, 131.5 (d, J¼99.3 Hz) (s), 131.6 (d, J¼2.8 Hz),
132.7 (d, J¼9.5 Hz), 135.1 (s), 135.7 (s), 151.6 (d, J¼2.0 Hz) (s), 188.8
HRMS (ESI): m/z: calcd for C33H29N2OPS: 532.1738; found:
532.1743.

M. Alajarin et al. / Tetrahedron 65 (2009) 2579–2590
2589
(s); 31P NMR (CDCl3, 121.4 MHz, H3PO4)
d
2.26; HRMS (ESI): m/z:
3.7. Preparation of phosphazide 11
calcd for C33H29N2OPS: 532.1738; found: 532.1748.
To a solution of the azide 9b (1.49 g, 5 mmol) in anhydrous
diethyl ether (30 mL) tris(dimethylamino)phosphine (0.82 g,
5 mmol) was added. The resulting mixture was stirred at room
temperature in an atmosphere of nitrogen for 6 h. Then the pre-
cipitated solid was isolated by filtration.
3.6.9. Phosphazene 10a (R2¼CH3CH2; R3¼H; R¼C6H5)
Yield 43%; mp 87–89 ꢀC (colorless prisms); IR (Nujol) 3150,
1658, 1603, 1504, 1437, 1287, 1176, 1145, 1103, 995, 831, 805, 744,
717, 694 cmꢁ1
;
1H NMR (CDCl3, 400 MHz)
d
1.01 (t, 3H, J¼7.2 Hz),
3.18–3.21 (m, 2H), 3.96 (s, 2H), 5.27 (s, 1H), 6.63 (d, 2H, J¼7.6 Hz),
6.87 (d, 2H, J¼7.6 Hz), 7.32–7.36 (m, 6H), 7.40–7.44 (m, 3H), 7.62–
3.7.1. Phosphazide 11 (R2¼C6H5–CH2; R3¼H; R¼N(CH3)2)
7.67 (m, 6H); 13C NMR (CDCl3, 100 MHz)
d
14.5, 33.9, 35.9, 122.8 (d,
The 1H and 13C NMR spectra of compound 11 at room temper-
ature (in CDCl3) displayed doubling of the majority of signals,
suggesting the presence of two rotamers in a ratio 1:2.1.
Yield 78%; mp 150–153 ꢀC (colorless prisms); IR (Nujol) 3133,
1544, 1505, 1345, 1280, 1255, 1163, 1065, 992, 855, 841, 755, 731,
J¼17.8 Hz), 125.6 (s), 128.1 (d, J¼11.9 Hz), 128.8, 130.5 (d, J¼98.9 Hz)
(s),131.2 (d, J¼2.7 Hz),132.1 (d, J¼9.4 Hz),149.9 (s); 31P NMR (CDCl3,
121.4 MHz, H3PO4) d 3.39; HRMS (ESI): m/z: calcd for C28H27N2OPS:
470.1582; found: 470.1584.
703, 658 cmꢁ1 1H NMR (CDCl3, 300 MHz)
; d 2.65 (d, 18Hmayor,
J¼9.2 Hz), 2.67 (d, 18Hminor, J¼9.2 Hz), 4.34 (d, 2Hminor, J¼5.6 Hz),
4.69 (d, 2Hmayor, J¼5.2 Hz), 5.38 (s, 2Hmayor), 5.43 (s, 2Hminor), 6.92
(br s, 1Hmayor), 7.02 (br s, 1Hminor), 7.11–7.38 (m, 18H); 13C NMR
3.6.10. Phosphazene 10b (R2¼C6H5–CH2; R3¼H; R¼C6H5)
Yield 91%; mp 154–155 ꢀC (colorless prisms); IR (Nujol) 3148,
1602, 1541, 1503, 1436, 1317, 1271, 1141, 1108, 1019, 960, 949, 939,
851, 719, 693 cmꢁ1
;
1H NMR (CDCl3, 300 MHz)
d
4.02 (s, 2H), 4.38
(CDCl3, 75 MHz) d 37.2, 47.1, 49.0, 72.2, 73.5, 120.6, 127.5, 127.6,
(d, 2H, J¼5.7 Hz), 5.50 (s, 1H), 6.64 (d, 2H, J¼8.1 Hz), 6.90 (d, 2H,
127.7, 128.5, 128.6, 128.8, 129.0, 131.6 (s), 132.0 (s), 136.4 (s), 136.8
J¼8.1 Hz), 7.16–7.25 (m, 5H), 7.33–7.46 (m, 9H), 7.63–7.69 (m, 6H);
(s), 152.1 (s), 152.5 (s), 189.5 (s), 190.3 (s); 31P NMR (CDCl3,
13C NMR (CDCl3, 75 MHz)
d
34.4, 45.2, 123.2 (d, J¼17.5 Hz), 125.9 (s),
121.4 MHz, H3PO4) d 42.45; HRMS (ESI): m/z: calcd for
C21H32N7OPS: 461.2127; found: 461.2131.
127.5, 127.6, 128.5 (d, J¼11.7 Hz), 129.2, 130.6 (d, J¼106.9 Hz) (s),
131.7 (d, J¼2.6 Hz), 132.5 (d, J¼9.6 Hz), 137.7 (s), 150.1 (s), 167.6 (s);
31P NMR (CDCl3, 121.4 MHz, H3PO4)
d
4.10; HRMS (ESI): m/z: calcd
3.8. Preparation of phosphazene 10f
for C33H29N2OPS: 532.1738; found: 532.1739.
A solution of the phosphazide 11 (1 mmol) in anhydrous toluene
was heated at 80 ꢀC for 16 h. Then the solvent was removed under
reduced pressure to give 10f as viscous oil.
3.6.11. Phosphazene 10c (R2¼C6H5; R3¼H; R¼C6H5)
Yield 92%; mp 160–162 ꢀC (colorless prisms); IR (Nujol) 3165,
1683, 1601, 1551, 1502, 1435, 1308, 1249, 1163, 1150, 1129, 1110, 1017,
999, 853, 720 cmꢁ1
;
1H NMR (CDCl3, 400 MHz)
d
4.04 (s, 2H), 6.64
3.8.1. Phosphazene 10f (R2¼C6H5–CH2; R3¼H; R¼N(CH3)2)
(d, 2H, J¼8.0 Hz), 6.91 (d, 2H, J¼8.0 Hz), 6.98–7.02 (m, 2H), 7.19–
Yield 64%; oil; IR (Neat) 3205, 1667, 1602, 1507, 1454, 1352, 1293,
7.23 (m, 2H), 7.29–7.32 (m, 2H), 7.33–7.38 (m, 6H), 7.41–7.46 (m,
1265, 1193, 1065, 982, 840, 737, 701 cmꢁ1 1H NMR (CDCl3,
;
3H), 7.63–7.68 (m, 6H); 13C NMR (CDCl3, 100 MHz)
d
34.3, 119.3,
400 MHz)
d
2.61 (d, 18H; J¼9.6 Hz), 4.06 (s, 2H), 4.41 (d, 2H,
122.9 (d, J¼17.8 Hz), 123.8 (s), 125.0 (s), 128.1 (d, J¼12.0 Hz), 128.6,
128.9, 130.4 (d, J¼99.3 Hz) (s), 131.3 (d, J¼2.5 Hz), 132.1 (d,
J¼9.6 Hz), 137.4 (s), 150.1 (s); 31P NMR (CDCl3, 121.4 MHz, H3PO4)
J¼5.2 Hz), 5.53 (t, 1H, J¼5.2 Hz), 6.65 (d, 2H, J¼8.0 Hz), 6.97 (d, 2H,
J¼8.0 Hz), 7.08–7.11 (m, 1H), 7.15–7.22 (m, 2H), 7.24–7.28 (m, 2H);
31P NMR (CDCl3, 121.4 MHz, H3PO4)
d 22.32; HRMS (ESI): m/z: calcd
d
3.57; HRMS (ESI): m/z: calcd for C32H27N2OPS: 518.1582; found:
for C21H32N5OPS: 433.2065; found: 433.2068.
518.1587.
3.9. Computational details
3.6.12. Phosphazene 10d (R2¼4-CH3–C6H4; R3¼H; R¼C6H5)
Yield 54%; mp 139–143 ꢀC (colorless prisms); IR (Nujol) 3154,
1685, 1603, 1541, 1503, 1435, 1306, 1238, 1150, 1108, 819, 719,
All structures were optimized using the functional B3LYP36 and
the 6-31þG** basis set37 as implemented in the Gaussian 03 suite of
programs.38 All energy minima and transition structures were
characterized by frequency analysis. The energies reported in this
work include the zero-point vibrational energy corrections (ZPVE)
and are not scaled. The intrinsic reaction coordinates (IRC)39 were
followed to verify the energy profiles connecting each transition
state to the correct local minima, by using the second-order Gon-
zalez–Schlegel integration method.40 Wiberg bond orders41 and
natural atomic charges were calculated within the natural bond
orbital (NBO) analysis.42 The asynchronicity23,43 of the reactions
was determined by using a previously described approach.23 The
solvent effects have been considered by B3LYP/6-31þG** calcula-
tions using a Self-Consistency Reaction Field (SCRF)44 method,
based on the Polarized Continuum Model (PCM)45 of Tomasi and
co-workers, in diethyl ether as solvent. The topological properties
of the electron density at the bond critical points (BCPs) have been
characterized with the AIMPAC package46 in the framework of the
quantum theory of atoms in molecules (QTAIM) developed by
Bader.25,47
692 cmꢁ1; 1H NMR (CDCl3, 400 MHz)
d 2.29 (s, 3H), 4.10 (s, 2H), 6.73
(d, 2H, J¼8.0 Hz), 6.98 (d, 2H, J¼8.0 Hz), 7.07 (d, 2H, J¼8.0 Hz), 7.24–
7.26 (m, 3H), 7.40–7.44 (m, 6H), 7.48–7.52 (m, 3H), 7.71–7.76 (m,
6H); 13C NMR (CDCl3, 100 MHz)
d 20.8, 34.6, 119.9, 123.3 (d,
J¼17.8 Hz), 125.7 (s), 128.6 (d, J¼11.9 Hz), 129.3, 129.5, 130.8 (d,
J¼98.9 Hz) (s), 131.7 (d, J¼2.6 Hz), 132.6 (d, J¼9.7 Hz), 134.0 (s),
135.3 (s), 150.4 (s); 31P NMR (CDCl3, 121.4 MHz, H3PO4)
d 3.83;
HRMS (ESI): m/z: calcd for C33H29N2OPS: 532.1738; found:
532.1746.
3.6.13. Phosphazene 10e (R2¼C6H5–CH2; R3¼CH3; R¼C6H5)
Yield 84%; mp 155–157 ꢀC (colorless prisms); IR (Nujol) 3166,
1656, 1603, 1534, 1506, 1432, 1366, 1325, 1222, 1177, 1106, 1027,
998, 828, 718, 691 cmꢁ1 1H NMR (CDCl3, 400 MHz)
; d 1.66 (d, 3H,
J¼7.2 Hz), 4.43 (d, 2H, J¼5.6 Hz), 4.68 (q, 1H, J¼7.2 Hz), 5.57 (t, 1H,
J¼5.6 Hz), 6.74 (d, 2H, J¼8.0 Hz), 7.01 (d, 2H, J¼7.6 Hz), 7.23–7.28
(m, 3H), 7.29–7.33 (m, 2H), 7.42–7.47 (m, 6H), 7.51–7.55 (m, 3H);
13C NMR (CDCl3, 100 MHz)
d
23.1, 44.2, 44.9, 123.1 (d, J¼17.5 Hz),
127.4, 127.5, 127.6, 128.5 (d, J¼11.6 Hz), 128.6, 130.6 (s), 130.7 (d,
J¼98.6 Hz) (s), 131.6 (d, J¼2.6 Hz), 132.6 (d, J¼9.7 Hz), 137.8 (s),
Acknowledgements
150.1 (s), 167.6 (s); 31P NMR (CDCl3, 121.4 MHz, H3PO4)
d 3.40;
HRMS (ESI): m/z: calcd for C34H31N2OPS: 546.1895; found:
This work was supported by the MCYT and FEDER (Projects
´
CTQ2005-02323/BQU and CTQ2008-05827/BQU), and Fundacion
546.1898.

2590
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´
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Supplementary data
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2009.01.064.
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