Nitrilimines: Evidence for the allenic structure in solution. Experimental and ab initio studies of the barrier to racemization, and first diastereoselective [3 + 2]-cycloaddition

Article abstract of DOI:10.1021/ja9637661

The lithium salts of [bis(diisopropylamino)thioxophosphoranyl]diazomethane (2) and [(diisopropylamino)(dicyclohexylamino)thioxophosphoranyl]diazomethane (5) react with the (diisopropylamino)(dicyclohexylamino)chlorophosphine (3) and bis(diisopropylamino)c

Full text of DOI:10.1021/ja9637661

J. Am. Chem. Soc. 1997, 119, 2819-2824
2819
Nitrilimines: Evidence for the Allenic Structure in Solution,
Experimental and Ab Initio Studies of the Barrier to
Racemization, and First Diastereoselective
[3 + 2]-Cycloaddition
Jean-Luc Faure´,† Re´gis Re´au,† Ming Wah Wong,*,‡ Rainer Koch,‡
Curt Wentrup,*,‡ and Guy Bertrand*,†
Contribution from the Laboratoire de Chimie de Coordination du CNRS, 205, route de Narbonne,
31077 Toulouse Ce´dex 4, France, and Department of Chemistry, The UniVersity of Queensland,
Brisbane, QLD 4072, Australia
ReceiVed October 29, 1996X
Abstract: The lithium salts of [bis(diisopropylamino)thioxophosphoranyl]diazomethane (2) and [(diisopropylamino)-
(dicyclohexylamino)thioxophosphoranyl]diazomethane (5) react with the (diisopropylamino)(dicyclohexylamino)-
chlorophosphine (3) and bis(diisopropylamino)chlorophosphine (6), leading to the nitrilimines 4 (63% yield) and 7
(69% yield), respectively. The lithium salt of 2 also reacts with the bis(dicyclohexylamino)phosphenium ion, affording
nitrilimine 9 in 51% yield. Using the presence of a chiral substituent either at the carbon or at the nitrogen terminus
of the CNN skeleton, variable-temperature solution NMR studies of nitrilimines 4 and 7 demonstrate that they possess
a bent allenic structure. The free energy of activation for racemization is ca. 30 kJ mol-1. Ab initio/DFT studies
performed on nitrilimine with C-P(S)H2 and N-PH2 substituents 10 show that the most likely pathway for the
racemization process is inversion at the carbon atom, followed by rotation of the PSR2 fragment. Bis(trityl)nitrilimine
17 reacts with (R)-R-(acryloxy)-â,â-dimethyl-γ-butyrolactone, leading to diastereomeric pyrazolines 18a,b (3/1 ratio)
in 60% total yield; this is the first example of a diastereoselective [3 + 2]-cycloaddition reaction involving a nitrilimine.
Introduction
Nitrilimines are important building blocks in organic syn-
thesis, particularly in regio- and stereoselective 1,3-dipolar
cycloadditions.1 However, until recently,2 these 1,3-dipoles
were considered reactive intermediates,3 and as a consequence
there has been very little experimental evidence concerning their
actual structures. Ab initio calculations revealed that the lowest
energy conformations of the parent molecule, formonitrilimine
(HCNNH), were the planar propargylic structure A and the bent
allenic form B (Figure 1).4 Depending on the basis set
employed, form A or form B can be the lowest point on the
energy surface. In any case, the energy difference between A
and B was very small, and thus the unsubstituted nitrilimine
was described as a “floppy” molecule.4f More recently,
Figure 1. Lowest energy structures of nitrilimine.
calculations at much higher levels of theory predicted that the
allenic geometry B is favored over the propargylic one A by
14 kJ mol-1,5 and in a very elegant paper, Maier et al. reported
the first matrix-IR spectrum of the parent nitrilimine, which fits
nicely with this prediction.6
We have shown that, using the right set of substituents,
nitrilimines can be obtained as stable compounds.2,7 X-ray
analyses7a-e revealed that, in the solid state, they featured an
allenic structure (form B), and as expected, two enantiomers
were present in the unit cell. However, almost no information
on the structure of nitrilimines in solution is available, even
though most of their 1,3-dipolar reactions are performed in this
phase.
† CNRS.
‡ The University of Queensland.
X Abstract published in AdVance ACS Abstracts, March 1, 1997.
(1) (a) Huisgen, R. Angew. Chem., Int. Ed. Engl. 1963, 2, 565 and 633.
(b) Huisgen, R. J. Org. Chem 1976, 41, 403. (c) Caramella, P.; Gru¨nanger
P. In 1,3-Dipolar Cycloaddition Chemistry; Padwa, A., Ed.; Wiley: New
York, 1984.
Here, using low-temperature NMR studies, we show that
nitrilimines retain the allenic structure in solution, and we
(2) Bertrand, G.; Wentrup, C. Angew. Chem., Int. Ed. Engl. 1994, 33,
527.
(5) (a) Wong, M. W.; Wentrup, C. J. Am. Chem. Soc. 1993, 115, 7743.
(b) Kawauchi, S.; Tachibana, A.; Mori, M.; Shibusa, Y.; Yamabe, T. J.
Mol. Struct. (THEOCHEM) 1994, 310, 255.
(6) Maier, G.; Eckwert , J.; Reisenauer, H. P.; Bothur, A.; Schmidt, C.
Liebigs. Ann. 1996, 1041.
(7) (a) Granier, M.; Baceiredo, A.; Dartiguenave, Y.; Dartiguenave, M.;
Menu, M. J.; Bertrand, G. J. Am. Chem. Soc. 1990, 112, 6277. (b) Granier,
M.; Baceiredo, A.; Bertrand, G.; Huch, V.; Veith, M. Inorg. Chem. 1991,
30, 1161. (c) Re´au, R.; Veneziani, G.; Dahan, F.; Bertrand, G. Angew.
Chem., Int. Ed. Engl. 1992, 31, 439. (d) Arthur, M. P.; Baceiredo, A.; Fisher,
J.; DeCian, A.; Bertrand, G. Synthesis 1992, 43. (e) Leue, C.; Re´au, R.;
Neumann, B.; Stammler, H. G.; Jutzi, P.; Bertrand, G. Organometallics
1994, 13, 436. (f) Arthur, M. P.; Goodwin, H. P.; Baceiredo, A.; Dillon, K.
B.; Bertrand, G. Organometallics 1991, 10, 3205. (g) Re´au, R.; Veneziani,
G.; Bertrand, G. J. Am. Chem. Soc. 1992, 114, 6059. (h) Castan, F.;
Baceiredo, A.; Bigg, D.; Bertrand, G. J. Org. Chem. 1991, 56, 1801.
(3) (a) Bock, H.; Dammel, R.; Fischer, S.; Wentrup, C. Tetrahedron Lett.
1987, 28, 617. (b) Wentrup, C.; Fischer, S.; Maquestiau, A.; Flammang, R.
Angew. Chem., Int. Ed. Engl. 1985, 24, 56. (c) Fischer, S.; Wentrup, C. J.
Chem. Soc., Chem. Commun. 1980, 502. (d) Meier, H.; Heinzelmann, W.;
Heimgartner, H. Chimia 1980, 34, 504 and 506. (e) Toubro, H.; Holm, A.
J. Am. Chem. Soc. 1980, 102, 2093.
(4) (a) Guimon, C.; Khayar, S.; Gracian, F.; Begtrup, M.; Pfister-
Guillouzo, G. Chem. Phys. 1989, 138, 157. (b) Kahn, S. D.; Hehre, W. J.;
Pople, J. A. J. Am. Chem. Soc. 1987, 109, 1871. (c) Thomson, C.; Glidewell,
C. J. Comput. Chem. 1983, 4, 1. (d) Moffat, J. B. J. Mol. Struct. 1979, 52,
275. (e) Caramella, P.; Gandour, R. W.; Hall, J. A.; Deville, C. G.; Houk,
K. N. J. Am. Chem. Soc. 1977, 99, 385. (f) Caramella, P.; Houk, K. N. J.
Am. Chem. Soc. 1976, 98, 6397. (g) Houk, K. N.; Sims, J.; Duke, R. E.,
Jr.; Strozier, R. W.; George, J. K. J. Am. Chem. Soc. 1973, 95, 7287. (h)
Hart, B. T. Aust. J. Chem. 1973, 26, 461.
S0002-7863(96)03766-3 CCC: $14.00 © 1997 American Chemical Society

2820 J. Am. Chem. Soc., Vol. 119, No. 12, 1997
Faure´ et al.
Scheme 1
estimate the barrier to racemization and perform an ab initio/
DFT study in order to understand the mechanism of this process.
Lastly, we report the first diastereoselective [3 + 2]-cycload-
dition reaction involving a nitrilimine.
Results and Discussion
Figure 2. 31P NMR spectra of nitrilimine 4 at various temperatures in
a 95/5 solution of 2-methylpentane and CD2Cl2.
In order to reveal the chiral axis which is only present in the
allenic form B, our strategy was based on the preparation of
nitrilimines possessing a chiral substituent either at the carbon
or at the nitrogen terminus. For this purpose, C-(thioxophos-
phoranyl)-N-phosphinonitrilimines offer several advantages.
These derivatives are easily accessible, and they are stable at
room temperature.7a Moreover, the X-ray data for the nitrilimine
17a (Scheme 1) are in excellent agreement with the calculated
MP2/6-311G(2df,2p) geometry of HCNNH,5a showing that for
these phosphorus-substituted nitrilimines, no major electronic
or steric effects are operating. Last but not least, the presence
of the phosphorus nuclei is crucial since 31P NMR spectroscopy
allows a rapid and convenient observation of nitrilimines.8a
The lithium salt of [bis(diisopropylamino)thioxophosphoranyl]-
diazomethane7a (2) reacted in THF, at -80 °C, with the chiral
chlorophosphine 3, leading to the nitrilimine 4 as a yellow oil
in 63% yield. In the same way, nitrilimine 7 was obtained as
a yellow oil in 69% yield, by reacting the lithium salt of the
chiral (thioxophosphoranyl)diazomethane 5 with the bis(diiso-
propylamino)chlorophosphine 6.
Figure 3. 31P NMR spectra of nitrilimine 7 at various temperatures in
a 95/5 solution of 2-methylpentane and CD2Cl2.
Nitrilimines 4 and 7 were characterized by spectroscopy in
solution. At room temperature, in THF, the 31P NMR spectrum
of 4 and 7 consisted of two doublets typical of (thioxo-
phosphoranyl)(phosphino)nitrilimines7a,8a [4, +35.3 and +103.0,
JPP ) 5 Hz; 7, +35.8 and +100.2, JPP ) 5.1 Hz]. Since at 25
°C no evidence for the presence of diastereomers was apparent,
low-temperature 31P NMR spectra of nitrilimines 4 and 7 were
recorded in a 95/5 solution of 2-methylpentane and CD2Cl2
(Figures 2 and 3). For both compounds, below 220 K the JPP
coupling constant was no longer observable, and a shielding of
the two signals occurred on decreasing the temperature. The
temperature-dependent chemical shift is a well-known phe-
nomenon;8b furthermore, the initial chemical shifts were restored
when the solutions were allowed to warm to room temperature.
For nitrilimine 4, at 150 K, the signal corresponding to the chiral
(low-field) σ3-phosphorus atom split into two signals with a
chemical shift difference of 200 Hz; this phenomenon was less
pronounced for the σ4-phosphorus atom, where two broad,
overlapping signals about 50 Hz apart were observed. The
coalescence temperature can be estimated to be 160 K (Figure
2).
The same trend was found for nitrilimine 7, featuring the
chiral substituent at the carbon terminus. At 150 K, two sets
of two doublets were observed, and the splitting was again more
pronounced for the chiral phosphorus atom, which is now the
high-field σ4-one. Here too, the coalescence temperature was
ca. 160-165 K (Figure 3).
In order to address possible interpretations of these low-
temperature measurements in terms of restricted rotation due
to the bulky substituents at the phosphorus atoms, we recorded
the 31P NMR spectra of the nitrilimine 17a and of the C-[bis-
(diisopropylamino)thioxophosphoranyl]-N-[bis(dicyclohexylami-
no)phosphino]nitrilimine 9 at low temperature. Note that
nitrilimine 9 is not accessible through the addition of the lithium
salt of 2 to the bis(dicyclohexylamino)chlorophosphine (8),
probably because of the considerable steric hindrance; the
corresponding bis(dicyclohexylamino)phosphenium ion has to
be used and in this way nitrilimine 9 was isolated as yellow
crystals (mp 92 °C) in 51% yield (Scheme 2).
(8) (a) Reed, R.; Bertrand, G. In Phosphorus-31 NMR Spectral Properties
in Compound Characterization and Structural Analysis; Quin, L. D.,
Verkade, J. G., Eds.; VCH Publishers: New York, 1994; p 189. (b)
Handbook of Phosphorus-31 Nuclear Magnetic Resonance Data; Tebby,
J. C., Eds.; CRC Press, Inc.: Boca Raton, 1991.

Nitrilimines
J. Am. Chem. Soc., Vol. 119, No. 12, 1997 2821
Table 1. Calculated Structural Parametersa of Nitrilimine
H2P(S)CNNPH2 (10)
B3-LYP/6-31G*
MP2/
parameter 6-31G*
B3-LYP/
ꢀ ) 1c
ꢀ ) 40d 6-311+G**
exptb
r(P-C)
r(C-N)
r(N-N)
r(N-P)
PCN
CNN
NNP
1.771
1.199
1.246
1.769
1.796
1.200
1.230
1.787
135.6
173.0
117.0
133.3
132.4
1.790
1.199
1.231
1.793
1.796
1.196
1.224
1.783
1.771
1.177
1.236
1.777
138.2
173.6
115.0
145.9
136.4
135.4
173.2
116.4
128.9
130.5
173.0
116.6
135.3
131.2
173.5
118.2
132.1
132.0
τPCNN
τCNNP
a Bond lengths in angstroms and bond angles in degrees. b Crystal
structure of C-[bis(diisopropylamino)thioxophosphoranyl]-N-[bis(di-
isopropylamino)phosphanyl]nitrilimine (1).7a c ꢀ )1 corresponds to the
gas phase. d SCIPCM calculations.
(Vide infra), which predict a lower energy pathway for nitril-
imines than for ketenimine (54 kJ mol-1 9b
and carbodiimide
)
(33-44 kJ mol-1).10c
Several mechanisms of isomerization of nitrilimines can be
envisaged: inversion at the carbon, nitrogen, or phosphorus atom
and rotation about the C-P or N-P bonds. In order to model
the nitrilimines 4 and 7, we have examined the structure of
nitrilimine with C-P(S)H2 and N-PH2 substituents, i.e. H2P(S)-
CNN-PH2 (10). A previous study has shown that inclusion of
electron correlation is essential for the proper description of the
structure of formonitrilimine.5a Here, we have optimized
compound 10 with three correlated levels of theory: MP2/6-
31G*, B3-LYP/6-31G*, and B3-LYP/6-311+G** (Table 1).
The MP2/6-31G* and B3-LYP/6-31G* methods lead to similar
results. Expanding the basis set from 6-31G* to 6-311+G**
has little effect on the optimized geometry. As with the parent
molecule, formonitrilimine (HCNNH), 10 is calculated to have
an allenic structure. The rather short NN bond length (1.230
Å) and long CN bond length (1.199 Å) reflect the -C-dN+dN-
cumulenic skeleton in 10. This is confirmed by the value of
the PCN angle which is close to the value calculated for the
optimized structure of the allenic form of formonitrilimine
(144.6°; for the propargylic form the value is 181.4°).5a Note
that the C-P bond in 10 is almost perpendicular to the N-P
moiety (dihedral angle ) 98.5°, B3-LYP/6-31G*). 10 is a chiral
molecule, and 10′ (Figure 5) represents its enantiomer (mirror
image), with identical energy (Table 2). In fact, the propargylic
structure 11 (Figure 5) corresponds to the transition structure
for inversion at the carbon atom. The calculated structural
parameters of 10 at the B3-LYP/6-31G* level are in very good
accord with those obtained from the X-ray crystal structure7a
of C-[bis(diisopropylamino)thioxophosphoranyl]-N-[bis(diiso-
propylamino)phosphanyl]nitrilimine (1). The calculated bond
lengths are within 0.02 Å and bond angles within 3° of the
experimental values, reiterating that the diisopropylamino
substitutions have no major electronic or steric effects on the
structure. We have also investigated the effects of solvent on
the structure of 10 using the SCIPCM solvation theory.11 As
seen in Table 1, the introduction of a reaction field, in a polar
dielectric medium of ꢀ ) 40, has only a small influence on the
structure of 10 (Table 1). This result is in accord with the fact
that 10 has a modest dipole moment of 2.55 Debye (B3-LYP/
6-31G*).
Figure 4. 31P NMR spectra of nitrilimines 1 (top) and 9 (bottom) at
various temperatures in a 95/5 solution of 2-methylpentane and CD2-
Cl2.
Scheme 2
In analogy with nitrilimines 4 and 7, a temperature-dependent
shielding of the two signals was also observed for derivatives
1 and 9. However, of primary importance, no broadening or
separation of the lines occurred, even at 150 K (Figure 4).
Therefore, the signal separation occurring for nitrilimines 4
and 7 (Figures 1 and 2), featuring a chiral substituent, is due to
the presence of two diastereoisomers which rapidly interconvert
at temperatures above 160 K. This implies that these nitril-
imines possess a bent allenic structure in solution. The free
energy of activation for racemization as estimated at the
coalescence temperature is ca. 30 kJ mol-1. This value is at
the lower limit of the range found for cumulenes such as
ketenimines9 (60-80 kJ mol-1) and carbodiimides10 (28-73
kJ mol-1). The trend is confirmed by theoretical calculations
(9) (a) Jochims, J. C.; Anet, F. A. L. J. Am. Chem. Soc. 1970, 92, 5525.
(b) Wolf, R.; Wong, M. W.; Kennard, C. H. L.; Wentrup, C. J. Am. Chem.
Soc. 1995, 117, 6789. (c) Firl, J.; Schink, K.; Kosbahn, W. Chem. Lett.
1981, 527. (d) Jochims, J. C.; Lambrecht, J.; Burkert, U.; Zsolnai, L.;
Huttner, G. Tetrahedron 1984, 40, 893. (e) Molina, P.; Alajarin, M.;
Sanchez-Andrala, P.; Cario, J. S.; Martinez-Ripoll, M.; Anderson, J. E.;
Jimeno, J. L.; Elguero, J. J. Org. Chem. 1996, 61, 4289.
(10) (a) Gordon, M. S.; Fischer, H. J. Am. Chem. Soc. 1968, 90, 2471.
(b) Anet, F. A. L.; Jochims, J. C.; Bradley, C. H. J. Am. Chem. Soc. 1970,
92, 2557. (c) Nguyen, M. T.; Riggs, N. V.; Radom, L.; Winnewisser, M.;
Winnewisser, B. P.; Birk, M. Chem. Phys. 1988, 122, 305.
(11) (a) Keith, T. A; Frisch, M. J., to be published. (b) Wiberg, K. B.;
Keith, T. A; Frisch, M. J., Murcko, M. J. Phys. Chem. 1995, 99, 7702.

2822 J. Am. Chem. Soc., Vol. 119, No. 12, 1997
Faure´ et al.
Figure 5. Optimized geometries (B3-LYP/6-31G*) for the equilibrium structures (10 and 10′) and transition structures (11-16) of H2P(S)CNNPH2.
Bond lengths in angstroms and bond angles in degrees.
Table 2. Calculated Total Energiesa (hartrees), Relative Energiesb
of the nitrogen atom, but in mutually perpendicular directions.
(kJ mol-1) and Zero-Point Vibrational Energiesc (ZPVE, kJ mol-1
)
13 lies 55 kJ mol-1 higher in energy than the equilibrium
structures 10. A similar activation barrier (54 kJ mol-1) was
calculated for the nitrogen inversion in ketenimine.9b Nitrilimines
10/10′ have a slightly bent CNN framework (173°). Attempts
to locate the transition structure for inversion on the central
nitrogen atom were not successful. Constraining the CNN
of Nitrilimine H2P(S)CNNPH2 (10) and Transition Structures 11-16
species
total energy
Nid
ZPVE
relative energy
10
10′
11
12
13
14
15
16
-1230.927 61
-1230.927 61
-1230.922 57
-1230.866 41
-1230.906 18
-1230.926 81
-1230.924 31
-1230.925 31
0
0
1
1
2
0
1
1
138.9
138.9
137.5
134.0
137.4
138.9
137.8
137.7
0.0
0.0
11.9
155.8
54.8
2.2
skeleton to be linear (14) increases the energy by just 2 kJ mol-1
.
This result clearly indicates that the CNN bending potential is
extremely flat, and this moiety is best considered to be quasi-
linear. Note that small barriers (Table 2) are calculated for the
rotations about the C-P and N-P bonds via transition structures
15 and 16, respectively.
7.6
4.9
a B3-LYP/6-311+G**//B3-LYP/6-31G* values. b Based on the total
energies together with zero-point vibrational contribution. c B3-LYP/
6-31G* values, scaled by 0.9804.19 d Number of imaginary frequencies
(B3-LYP/6-31G* level).
It is conceivable that the stereoisomerization between 10 and
10′ can occur via a combination of inversion and rotation. The
two most likely pathways for the racemization process are (a)
inversion of the carbon atom followed by rotation of the PSH2
moiety and (b) inversion of the (terminal) nitrogen atom
followed by the rotation of the PH2 fragment. Pathway (b) is
a high-energy process because of the involvement of an
inversion at nitrogen (55 kJ mol-1). Hence, (a) is the preferred
pathway for racemization in 10 and the associated barrier is
predicted to be in the order of 15 kJ mol-1. Inclusion of a
solvent reaction field is predicted to have little effect on the
calculated racemization barrier (change by less than 1 kJ mol-1).
The calculated racemization barrier for 10 is significantly
smaller than the observed value (30 kJ mol-1) for compounds
4 and 7.13 How do we account for this discrepancy between
theory and experiment? Since the racemization of 10 (4 or 7)
has a low activation barrier, the racemization rate will depend
on the rate at which the P(S)R2 group can move through the
solvent cage, and such movement becomes the slowest step for
The calculated barriers for the various isomerization pro-
cesses, at the B3-LYP/6-311+G(3df,2p)//B3-LYP/6-31G* +
ZPVE level, are summarized in Table 2. Inversion at the
phosphorus atom of the PH2 group, via transition structure 12
(Figure 5), is calculated to require a high activation energy of
156 kJ mol-1 (making this process too slow under our
experimental conditions). In contrast, inversion at carbon, via
the propargylic transition structure 11 (Figure 5), requires a
barrier of ca. 12 kJ mol-1 (thus making this process fast, even
at the lowest temperatures accessed in this study). Higher-level
G2(MP2) theory12 predicts a similar barrier height, 15 kJ mol-1
.
The linear NNP structure (13) corresponds to the transition
structure for inversion at the terminal nitrogen atom. However,
13 is a second-order saddle point which has two imaginary
frequencies. Both of the displacement vectors of the normal
modes for the imaginary frequencies correspond to inversion
(12) Curtiss, L. A.; Raghavachari, K.; Pople, J. A. J. Chem. Phys. 1993,
98, 1293.
(13) Semiempirical calculations at the PM3 level give similar racem-
ization barriers for 10 and 7.

Nitrilimines
J. Am. Chem. Soc., Vol. 119, No. 12, 1997 2823
Scheme 3
a diffusion-controlled reaction.14 In other words, the rate of
racemization of 10 (4 or 7) depends on the bulkiness of the
substituents R and the viscosity of the solvent used. For
compounds 4 and 7, one would expect a larger barrier for the
movement of the bulky substituents in solution and hence a
relatively large racemization barrier in a low-temperature
(viscous) solvent.
Of special interest for heterocyclic synthesis, a diastereose-
lective [3 + 2]-cycloaddition reaction has been observed by
addition at -40 °C of (R)-R-(acryloxy)-â,â-dimethyl-γ-buty-
rolactone to bis(trityl)nitrilimine7c 17. Indeed, diastereomeric
pyrazolines 18a,b were obtained in 60% total yield in a 3/1
ratio according to the integrated AB sections of the pyrazoline
ABX system in the 1H NMR spectra (Scheme 3). Considering
the low energetic barrier between the enantiomerics nitrilimines
in solution, it is quite likely that in this case a Curtin-Hammett
situation prevails.
scaled by 0.9804 to account for the overestimation of ZPVEs at this
level of theory.19 Improved relative energies were obtained through
B3-LYP calculations with the larger 6-311+G** basis set,15 based on
the B3-LYP/6-31G* optimized geometries. Our best relative energies
discussed in the text correspond to the B3-LYP/6-311+G** values
together with zero-point vibrational contributions. The carbon inversion
barrier in 10 was also investigated using the Gaussian-2 [G2(MP2)]
theory.12 The G2(MP2) method, described in detail elsewhere,12 is a
composite procedure based effectively on QCISD(T)/6-311+G(3df,-
2p)//MP2/6-31G* energies (evaluated by making certain additivity
assumptions) together with zero-point vibrational and isogyric correc-
tions. The effects of solvent on the racemization of nitrilimine 10 were
studied using the self-consistent isodensity polarizable continuum model
(SCIPCM)11 of solvation. In this model the solute is taken to occupy
a cavity which is determined self-consistently from an isodensity surface
(0.0004 au), and the solvent is represented by a continuous dielectric,
characterized by a given dielectric constant (ꢀ).
(Dicyclohexylamino)(diisopropylamino)chlorophosphine (3). To
a THF solution (250 mL) of (dicyclohexylamino)dichlorophosphine20
(36.65 g, 0.130 mol), at -78 °C, was added dropwise a THF solution
(30 mL) of freshly prepared LDA (13.91 g, 0.130 mol). The solution
was allowed to warm to room temperature, and the solvent was removed
under vacuum. The residue was treated with pentane and filtered.
Derivative 3 was obtained as an orange solid from an ether solution at
room temperature (34.43 g, 76% yield): mp 240 °C; 1H NMR (200.132
MHz, CDCl3) δ 1.06 (d, JHH ) 6.9 Hz, 6 H, CH3), 1.11 (d, JHH ) 6.9
Hz, 6H, CH3), 1.61 (m, 20 H, CH2), 3.10 (m, 2 H, NCHCH2), 3.55
(sept d, JHH ) 6.9 Hz, JPH ) 12.7 Hz, 2 H, NCHCH3); 13C NMR (62.896
MHz, CDCl3) δ 22.74 (d, JPC ) 11.3 Hz, CH3), 23.93 (d, JPC ) 5.6
Hz, CH3), 25.59 (s, CH2), 26.54 (d, JPC ) 11.5 Hz, CH2), 33.90 (d, JPC
) 12.3 Hz, CH2), 34.44 (d, JPC ) 5.6 Hz, CH2), 47.41 (d, JPC ) 13.8
Hz, NCHCH3), 56.57 (d, JPC) 9.9 Hz, NCHCH2); 31P NMR (32.438
MHz, CDCl3) δ +134.88. Anal. Calcd for C18H36N2ClP: C, 62.32;
H, 10.46; N, 8.07. Found: C, 62.41; H, 10.52; N, 8.01.
Conclusion
We have shown that in solution nitrilimines possess a bent
allenic-type structure B, the energetic barriers between the
enantiomers being experimentally estimated at about 30 kJ
mol-1. Ab initio/DFT studies show that the most likely pathway
for the racemization process is inversion at the carbon atom of
the nitrilimine moiety, followed by rotation of the PSR2
fragment. For the first time, a diastereoselective [3 + 2]-cy-
cloaddition reaction involving a nitrilimine has been performed.
Considering the wide utility of these readily available 1,3-
dipoles, this first example opens new perspectives in heterocyclic
synthesis.
C-[Bis(diisopropylamino)thioxophosphoranyl]-N-[(dicyclohexy-
lamino)(diisopropylamino)phosphino]nitrilimine (4). To a THF
solution (10 mL) of [bis(diisopropylamino)thiophosphoranyl]diazomethane
(2)7a (0.40 g, 1.315 mmol), at -78 °C, was added dropwise a
stoichiometric amount of BuLi in hexanes. After the mixture was
stirred for 30 min at -78 °C, a THF solution (3 mL) of chlorophosphine
3 (0.455 g, 1.315 mmol) was added. The solution was allowed to warm
to room temperature, and the solvent was removed under vacuum. The
residue was treated with pentane and filtered. Nitrilimine 4 was
obtained as a yellow oil (0.484 g, 63%): 1H NMR (200.132 MHz,
CDCl3) δ 1.12 (d, JHH ) 6.8 Hz, 6 H, CH3), 1.23 (d, JHH ) 6.8 Hz, 6
H, CH3), 1.31 (d, JHH ) 6.9 Hz, 12 H, CH3), 1.37 (d, JHH ) 6.8 Hz, 12
H, CH3), 1.66 (m, 20 H, CH2), 2.92 (m, 2 H, NCHCH2), 3.71 (m, 6 H,
Experimental Section
All experiments were performed under an atmosphere of dry argon.
Melting points are uncorrected. 1H, 13C, and 31P NMR spectra were
recorded on Brucker AC80, AC200, WM250, or AMX400 spectrom-
eters. 1H and 13C chemical shifts are reported in ppm relative to Me4-
Si as external standard, and 31P NMR downfield chemical shifts are
expressed with a positive sign, in ppm, relative to external 85% H3-
PO4. Infrared spectra were recorded on a Perkin-Elmer FT-IR
spectrometer 1725 X. Conventional glassware was used. The (R)-R-
(acryloxy)-â,â-dimethyl-γ-butyrolactone was purchased from Aldrich
Chemical Co. and used as received.
Computational Methods. Ab initio15 and density functional16
calculations were carried out using the GAUSSIAN 92/DFT series of
programs.17 The equilibrium and transition structures of nitrilimine
H2P(S)CNNPH2 were optimized with the 6-31G* basis set15 using the
B3-LYP formulation18 of density functional theory, i.e. Becke’s
3-parameter exchange functional18a and the Lee-Yang-Parr cor-
rectional functional.18b Harmonic vibrational frequencies were calcu-
lated at the B3-LYP/6-31G* level in order to characterize the stationary
points as minima and saddle points and to evaluate zero-point
vibrational energies (ZPVEs). The directly calculated ZPVEs were
(15) Hehre, W. J.; Radom, L.; Schleyer, P. v. R.; Pople, J. A. Ab Initio
Molecular Orbital Theory; Wiley: New York, 1986.
(16) (a) Parr, R. G.; Yang, W. Density Functional Theory of Atoms and
Molecules; Oxford University Press: New York, 1989. (b) Density
Functional Methods; Labanowski, J., Andzelm, J., Eds.; Springer: Berlin,
1991.
(17) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Gill, P. M. W.;
Johnson, B. G.; Wong, M. W.; Foresman, J. B.; Robb, M. A.; Head-Gordon,
M.; Replogle, E. S.; Gomperts, R.; Andres, J. L.; Raghavachari, K.; Binkley,
J. S.; Gonzalez, C.; Martin, R. L.; Fox, D. J.; DeFrees, D. J.; Baker, J.;
Stewart, J. J. P.; Pople, J. A. GAUSSIAN 92/DFT; Gaussian Inc.: Pittsburgh,
PA, 1992.
(18) (a) Becke, D. A. J. Chem. Phys. 1993, 98, 5648. (b) Lee, C.; Yang,
W.; Parr, R. G. Phys. ReV. B 1988, 37, 785.
(19) Wong, M. W. Chem. Phys. Lett. 1996, 256, 391.
(20) King, R. B.; Sadanani, N. D. Synth. React. Inorg. Met.-Org. Chem.
1985, 15 (2), 149, 153.
(14) For reviews on diffusion-controlled reactions, see: (a) Noyes, R.
M. In Progress in Chemical Kinetics; Porter, G., Stevens, B., Eds.; Pergamon
Press: Oxford, 1961; Vol. 1, p 129. (b) North, A. M. Q. ReV. 1966, 20,
421. (c) Ingold, K. U. In Free Radicals; Kochi, J. K., Ed.; Wiley-
Interscience: New York, 1973; Vol. 1, Chapter 2. (d) Bamford, C. H.;
Tipper, C. F. H.; Compton, R. G. ComprehensiVe Chemical Kinetics;
Elsevier: Amsterdam, 1985; Vol. 25.

2824 J. Am. Chem. Soc., Vol. 119, No. 12, 1997
Faure´ et al.
NCHCH3); 13C NMR (62.896 MHz, CDCl3) δ 22.50 (d, JPC ) 13.0
Hz, CH3), 22.93 (broad s, CH3), 24.06, 24.15, 24.21, 24.36 (s, CH3),
26.06 (s, CH2), 27.0 (d, JPC ) 5.5 Hz, CH2), 34.99 (d, JPC ) 5.5 Hz,
CH2), 36.14 (d, JPC ) 9.6 Hz, CH2), 46.29 (d, JPC ) 12.4 Hz,
was stirred for 30 min at -78 °C, a THF solution (10 mL) of bis-
(diisopropylamino)chlorophosphine (0.38 g, 1.40 mmol) was added.
The solution was allowed to warm to room temperature, and the solvent
was removed under vacuum. The residue was treated with pentane
and filtered. Nitrilimine 7 was isolated as a yellow oil (0.59 g, 69%):
1H NMR (200.132 MHz, CDCl3) δ 1.13 (d, JHH ) 6.7 Hz, 12 H, CH3),
1.18 (d, JHH ) 6.6 Hz, 12 H, CH3), 1.31 (d, JHH ) 6.7 Hz, 6 H, CH3),
1.37 (d, JHH ) 6.7 Hz, 6 H, CH3), 1.75 (m, 20 H, CH2), 3.26 (m, 2 H,
NCHCH2), 3.51 (sept d, JHH ) 6.7 Hz, JPH ) 11.2 Hz, 2 H, NCHCH3),
3.71 (sept d, JHH ) 6.7 Hz, JPH ) 19.9 Hz, 4 H, NCHCH3); 13C NMR
(62.896 MHz, CDCl3) δ 22.22, 22.27, 22.32, 22.37, 22.61, 22.64, 23.73,
23.85, 24.10, 24.23, 24.29, 24.42 (s, CH3), 25.30, 26.64, 32.42, 33.16
(s, CH2), 45.68 (d, JPC ) 12.3 Hz, PNCHCH3), 45.71 (d, JPC ) 12.3
PNCHCH3), 46.62 (d, JPC ) 5.2 Hz, P(S)NCHCH3), 55.52 (d, JPC
)
9.6 Hz, NCHCH2) the CNN carbon atom is not observed; 31P NMR
(32.438 MHz, C6D6) δ +103.0, +35.3 (d, JPP ) 5.0 Hz); IR (THF)
2039 cm-1 (CNN). Anal. Calcd for C31H64N6P2S: C, 60.55; H, 10.49;
N, 13.67. Found: C, 60.61; H, 10.55; N, 13.71.
[(Dicyclohexylamino)(diisopropylamino)phosphino](trimethylsilyl)-
diazomethane. To a THF solution (10 mL) of (trimethylsilyl)-
diazomethane21 (3.2 g, 28 mmol), at -78 °C, was added the stoichi-
ometric amount of BuLi in hexanes. After the solution was stirred at
this temperature for 30 min, a THF solution (20 mL) of chlorophosphine
3 (9.7 g, 28 mmol) was added dropwise. The solution was allowed to
warm to room temperature, and the solvent was removed under vacuum.
The residue was treated with pentane and filtered. [(Dicyclohexylami-
no)(diisopropylamino)phosphino](trimethylsilyl)diazomethane was ob-
tained as a deep red oil (9.75 g, 82% yield): 1H NMR (200.132 MHz,
CDCl3) δ 0.18 (s, 9 H, SiCH3), 1.12 (d, JHH ) 6.8 Hz, 6 H, CH3), 1.18
(d, JHH ) 6.8 Hz, 6 H, CH3), 1.55 (m, 20 H, CH2), 2.87 (m, 2 H,
NCHCH2), 3.44 (sept d, JHH ) 6.8 Hz, JPH ) 11.7 Hz, 2 H, NCHCH3);
13C NMR (62.896 MHz, CDCl3) δ 1.17 (d, JPC ) 5.1 Hz, SiCH3), 23.45,
23.57, 24.29, 24.45 (s, CH3), 25.64, 26.33, 26.67 (s, CH2), 28.23 (d,
JPC ) 91.2 Hz, PC), 34.19 (d, JPC ) 6.5 Hz, CH2), 35.80 (d, JPC ) 7.6
Hz, CH2), 47.62 (d, JPC ) 12.7 Hz, NCHCH3), 57.53 (d, JPC ) 10.2
Hz, NCHCH2); 31P NMR (32.438 MHz, C6D6) δ +58.6; IR (THF) 2018
cm-1 (CN2). Anal. Calcd for C22H45N4SiP: C, 62.22; H, 10.68; N,
13.19. Found: C, 62.41; H, 10.78; N, 13.11.
Hz, PNCHCH3), 46.22 (d, JPC ) 5.7 Hz, PSNCHCH3), 56.0 (d, JPC
)
7.8 Hz, NCHCH2), 61.25 (d, JPC ) 99.6 Hz, PC); 31P NMR (32.438
MHz, C6D6) δ +100.2, +35.8 (d, JPP ) 5.1 Hz); IR (THF) 2040 cm-1
(CNN). Anal. Calcd for C31H64N6P2S: C, 60.55; H, 10.49; N, 13.67.
Found: C, 60.58; H, 10.52; N, 13.71.
C-[Bis(diisopropylamino)thioxophosphoranyl]-N-[bis(dicyclohex-
ylamino)phosphino]nitrilimine (9). To a THF solution (5 mL) of
[bis(diisopropylamino)thioxophosphoranyl]diazomethane (2) (0.265 g,
0.871 mmol), at -78 °C, was added the stoichiometric amount of BuLi
in hexanes. After the solution was stirred for 30 min at -78 °C, a
THF solution (5 mL) of bis(dicyclohexylamino)phosphenium cation
(0.47 g, 1.20 mmol) was added at -78 °C. The solution was allowed
to warm to room temperature, and the solvent was removed under
vacuum. The residue was treated with pentane and filtered. Nitrilimine
9 was purified by crystallization from acetonitrile at -20 °C as pale
1
yellow crystals (1.12 g, 51%): mp 92 °C; H NMR (200.132 MHz,
CDCl3) δ 1.33 (d, JHH ) 6.5 Hz, 12 H, CH3), 1.38 (d, JHH ) 6.5 Hz,
12 H, CH3), 1.65 (m, 40 H, CH2), 2.97 (m, 4 H, NCHCH2), 3.68 (sept
d, JHH ) 6.5 Hz, JPH ) 19.4 Hz, 4 H, NCHCH3); 13C NMR (62.896
MHz, CDCl3) δ 22.46, 22.97 (s, CH3), 25.80, 26.85, 26.77, 26.94 (s,
CH2), 34.87 (d, JPC ) 5.9 Hz, CH2), 35.80 (d, JPC ) 8.8 Hz, CH2),
46.39 (d, JPC ) 5.9 Hz, NCHCH3), 55.23 (d, JPC ) 9.8 Hz, NCHCH2),
the CNN carbon atom was not observed; 31P NMR (32.438 MHz, C6D6)
δ +101.7, +37.2 (d, JPP) 5.1 Hz); IR (THF) 2040 cm-1 (CNN). Anal.
Calcd for C37H72N6P2S: C, 63.94; H, 10.44; N, 12.09. Found: C, 63.88;
H, 10.42; N, 12.01.
[(Dicyclohexylamino)(diisopropylamino)phosphino]diazo-
methane. To a THF solution (25 mL) of [(dicyclohexylamino)-
(diisopropylamino)phosphino](trimethylsilyl)diazomethane (9.75 g, 23
mmol) was added neat methanol (1.85 mL, 46 mmol). The solution
was stirred for 8 h, the solvent and excess methanol were removed
under vacuum, and the residue treated with pentane. [(Dicyclohexy-
lamino)(diisopropylamino)phosphino]diazomethane was obtained as an
orange liquid and used without further purification (6.69 g, 85%
yield): 1H NMR (200.132 MHz, CDCl3) δ 1.08 (d, JHH ) 6.6 Hz, 6
H, CH3), 1.19 (d, JHH ) 6.6 Hz, 6 H, CH3), 1.65 (m, 20 H, CH2), 2.85
(m, 2 H, NCHCH2), 3.12 (d, JPH ) 20.2 Hz, 1 H, CN2H), 3.46 (sept d,
JHH ) 6.6 Hz, JPH ) 11.1 Hz, 2 H, NCHCH3); 13C NMR (62.896 MHz,
CDCl3) δ 23.77, 23.88, 23.91, 24.04 (s, CH3), 25.12, 25.50 (s, CH2),
31.07 (d, JPC ) 10.5 Hz, PC), 34.61 (d, JPC ) 7.2 Hz, CH2), 35.00 (d,
JPC ) 7.6 Hz, CH2), 46.87 (d, JPC ) 11.6 Hz, NCHCH3), 56.38 (d, JPC
) 9.4 Hz, NCHCH2); 31P NMR (32.438 MHz, C6D6) δ +50.3; IR (THF)
2047 cm-1 (CN2).
Cycloadducts 18a and 18b. To a THF solution (10 mL) of freshly
prepared bis(triphenylmethyl)nitrilimine 177c (0.282 g, 0.536 mmol),
at -40 °C, was added the stoichiometric amount of (R)-R-(acryloxy)-
â,â-dimethyl-γ-butyrolactone (0.098 g, 0.536 mmol). The solution was
allowed to warm to room temperature, and the solvent was removed
under vacuum. The residue was washed with pentane (2 × 5 mL).
Diastereomers 18a and 18b (in a 3:1 ratio according to 1H NMR
spectroscopy) were obtained as a yellow powder (0.228 g, 60%). 18a
(75%)/18b (25%): 1H NMR (250.133 MHz, CDCl3) δ 1.22, 1.29 (s, 6
H, CH3, 18a and 18b), 2.26 (dd, 0.75 H, JHaHb ) 17.8 Hz, JHHx ) 12.9
Hz, CHaHbCHxCOO, Ha or b, 18a), 2.33 (dd, 0.25 H, JHaHb ) 17.7
Hz, JHHx ) 12.8 Hz, CHaHbCHxCOO, Ha or b, 18b), 2.57 (dd, 0.75 H,
JHaHb ) 17.8 Hz, JHHx ) 7.5 Hz, CHaHbCHxCOO, Ha or b, 18a), 2.61
(dd, 0.25 H, JHaHb ) 17.8 Hz, JHHx ) 7.4 Hz, CHaHbCHxCOO, Ha or
[(Dicyclohexylamino)(diisopropylamino)thioxophosphoranyl]-
diazomethane (5). To a pentane solution (20 mL) of [(dicyclohexy-
lamino)(diisopropylamino)phosphino]diazomethane (6.69 g, 19 mmol)
was added, at 0 °C, an excess of elemental sulfur (0.7 g, 21 mmol).
After the solution was stirred overnight at room temperature, the excess
of sulfur was filtered off and the solvent was removed under vacuum.
Derivative 5 was isolated by column chromatography (pentane/ether,
90/10, Rf ) 0.7) as yellow crystals (5.30 g, 72% yield): mp 103-104
b, 18b), 3.93 (s, 2 H, CH2O), 4.06 (dd, 0.75 H, JHHx ) 7.5 Hz, JHHx
)
1
12.9 Hz, CHaHbCHxCOO, 18a), 4.19 (dd, 0.25H, JHHx) 7.5 Hz, JHHx
) 12.8 Hz, CHaHbCHxCOO, 18b), 5.39 (s, 0.75H, OCH, 18a), 5.44 (s,
°C; H NMR (200.132 MHz, CDCl3) δ 1.26 (d, JHH ) 6.7 Hz, 6 H,
CH3), 1.35 (d, JHH ) 6.7 Hz, 6 H, CH3), 1.77 (m, 20 H, CH2), 3.2 (m,
2 H, NCHCH2), 3.67 (sept d, JHH ) 6.7 Hz, JPH ) 19.4 Hz, 2 H,
NCHCH3), 3.88 (d, JPH ) 10.6 Hz, 1 H, CN2H); 13C NMR (62.896
MHz, CDCl3) δ 22.34, 22.38, 22.89, 22.94 (s, CH3), 25.48, 26.76 (s,
CH2), 33.15 (d, JPC ) 7.3 Hz, CH2), 33.19 (d, JPC ) 7.9 Hz, CH2),
40.47 (d, JPC ) 134.4 Hz, PC), 46.39 (d, JPC ) 5.4 Hz, NCHCH3),
56.51 (d, JPC ) 4.7 Hz, NCHCH2); 31P NMR (32.438 MHz, C6D6) δ
+58.2; IR (THF) 2095 cm-1 (CN2). Anal. Calcd for C19H37N4PS: C,
59.34; H, 9.70; N, 14.57. Found: C, 59.41; H, 9.73; N, 14.61.
C-[(Dicyclohexylamino)(diisopropylamino)thioxophosphoranyl]-
N-[bis(diisopropylamino)phosphino]nitrilimine (7). To a THF solu-
tion (5 mL) of diazo derivative 5 (0.54 g, 1.40 mmol), at -78 °C, was
added the stoichiometric amount of BuLi in hexanes. After the solution
0.25 H, OCH, 18b), 7.20 (m, 30 H, H aromatiques, 18a and 18b); 13
C
NMR (CDCl3) 18a δ 19.97 (s, CH3); 22.98 (s, CH3), 39.95 (s, C(CH3)2),
42.75 (s, CH2 pyrazoline), 60.93 (s, NCH), 61.83 (s, Ph3CC), 75.14 (s,
CH2 lactone), 75.81 (s, OCH), 78.64 (s, NCPh3), 126.05 (s, Carom),
126.83 (s, Carom), 127.08 (s, Carom), 127.54 (s, Carom), 129.34 (s, Carom),
130.15 (s, Carom), 143.42 (s, Carom), 143.83 (s, Carom), 157.29 (s, CNN),
171.34 (s, CO lactone), 172.14 (s, CO ester). 18b δ 19.73 (s, CH3),
22.72 (s, CH3), 39.78 (s, C(CH3)2), 42.96 (s, CH2 pyrazoline), 60.80
(s, NCH), 61.83 (s, Ph3CC), 75.20 (s, CH2 lactone), 75.87 (s, OCH),
78.66 (s, NCPh3), 126.18 (s, Carom), 126.91 (s, Carom), 127.34 (s, Carom),
127.78 (s, Carom), 129.55 (s, Carom), 143.26 (s, Carom), 143.69 (s, Carom),
157.08 (s, CNN), 171.60 (s, CO lactone), 172.93 (s, CO ester).
Acknowledgment. Thanks are due to the CNRS (France)
and the ARC (Australia) for financial support of this work.
(21) (a) Martin, M. Synth. Commun. 1983, 13, 809. (b) Seyferth, D.;
Menzel, H.; Dow, A.; Flood, T. J. Organomet. Chem. 1972, 44, 279. (c)
Barton, T. J.; Hoekman, S. K. Synth. React. Inorg. Met.-Org. Chem. 1979,
9, 297.
JA9637661