Mechanism of anionic dearomatizing reactions of diphenylphosphinamide derivatives: A theoretical and experimental study

Article abstract of DOI:10.1002/chem.200400987

The mechanism of the anionic dearomatisation of phosphinamide derivatives has been investigated both theoretically and experimentally. The potential-energy surface of model reactions was studied at the Becke3LYP/6-31 + G* level of theory, and according to

Full text of DOI:10.1002/chem.200400987

Mechanism of Anionic Dearomatizing Reactions of Diphenylphosphinamide
Derivatives: A Theoretical and Experimental Study
[
b]
[a]
[a]
Antonio Morꢀn Ramallal, Ignacio Fernꢀndez, Fernando Lꢁpez Ortiz,* and
[
b]
Javier Gonzꢀlez*
Abstract: The mechanism of the anion-
ic dearomatisation of phosphinamide
derivatives has been investigated both
theoretically and experimentally. The
potential-energy surface of model reac-
tions was studied at the Becke3LYP/6-
intramolecular nucleophilic addition of
the carbanion to the ortho position of
the aromatic ring leads to the dearoma-
tised products, in a reaction that has
been shown to be under thermodynam-
ic control. Coordinating co-solvents,
such as hexamethyl phosphoramide
(HMPA) or N,N’-dimethyl-N,N’-propyl-
ene urea (DMPU), appear to influence
the reaction by favouring the formation
of solvent-separated ion pairs. The cyc-
lisation reaction of allylphosphinamide
derivatives was also studied. It was
found that both the a- and g-attack of
the allyl anion can take place, however
the formation of the seven-membered
ring products derived from the g-attack
are clearly favoured.
31+G* level of theory, and according
to this study, a pre-reactive complex is
formed between the alkyllithium and
the phosphinamide. This complex
evolves preferentially through NCa-
metalation of the phosphinamide. The
Keywords: anions
· dearomatiza-
tion · density functional calcula-
tions · lithiation · phosphinamides ·
solvent effects
Introduction
other hand, conjugate addition to aromatic hydrocarbons
bearing electron-withdrawing groups (e.g., aldehyde and
ketone, imines, carboxylic acid, carboxylic ester, car-
[3]
[4]
[5]
[6]
The addition of main-group organometallic reagents to aro-
matic compounds is an efficient method for breaking down
the conjugate p system of an aromatic ring and has been ex-
tensively used for the preparation of functionalised alicyclic
[
7]
[8]
[9]
[10]
boxamides, acyl halide, nitriles, oxazolidines, oxazo-
[11]
[12]
lines, triazenes ) has much wider scope as revealed by
the application of this methodology to the synthesis of sev-
eral natural products and non-natural analogues. In N-
[1]
[13]
[14]
and acyclic compounds. In arenes these dearomatising re-
[2]
[15]
[16]
actions are generally limited to polycyclic systems. On the
benzylcarboxamides,
phenyl sulfones,
N-benzylsulfon-
[17]
[18]
amides and N-benzyldiphenylphosphinamides, the dear-
omatisation may take place intramolecularly through an
anionic cyclisation reaction.
[
a] Dr. I. Fernꢀndez, Prof. Dr. F. Lꢁpez Ortiz
ꢂrea de Quꢃmica Orgꢀnica
[19]
[20]
We have recently shown in a synthetic
and NMR
study that upon treatment of N-benzyl-N-methyldiphenyl-
phosphinamide 1a (Scheme 1) with sec-butyllithium in tetra-
hydrofuran (THF) at À908C the mechanism of the cyclo-
dearomatising reaction involves the formation of a dimeric
precomplex I between the starting phosphinamide and the
base, which evolves by ortho-directed and benzylic lithiation
to give the lithium intermediates II and III, respectively.
The benzylic anion III undergoes a cyclisation through intra-
molecular attack at the ortho position of a P-substituted
phenyl ring leading to the four possible dearomatised dia-
stereoisomers IV–VII. The reaction progresses to yield an
equilibrium mixture of derivatives IV and V, plus the ortho-
lithiated intermediate II. Compounds III to VII have been
identified as monomeric, whereas II has been assigned as di-
Universidad de Almerꢃa
Carretera de Sacramento s/n, 04120 Almerꢃa (Spain)
Fax : (+34)950-015-481
E-mail: flortiz@ual.es
[
b] A. M. Ramallal, Prof. Dr. J. Gonzꢀlez
Departamento de Quꢃmica Orgꢀnica e Inorgꢀnica
Universidad de Oviedo
c/Juliꢀn Claverꢃa 8, 33006 Oviedo (Spain)
Fax : (+34)985-103-446
E-mail: fjgf@uniovi.es
Supporting information for this article is available on the WWW
under http://www.chemeurj.org/ or from the author. It contains Carte-
sian coordinates and energies of the stationary points located, P{ H}
NMR spectra showing the product distribution in the dearomatisa-
tion–protonation reaction of 1b and 1D gTOCSY NMR spectra of
compounds 3a and 3b.
3
1
1
3022
ꢄ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/chem.200400987
Chem. Eur. J. 2005, 11, 3022 – 3031

FULL PAPER
meric. In the presence of hexamethyl phosphoramide
(HMPA) or N,N’-dimethyl-N,N’-propylene urea (DMPU),
translocation of the ortho anion II to the benzylic anion III
takes place and the only lithium compounds observed in so-
lution are the dearomatised anions IV and V.
In sharp contrast, the lithiation of 1a with tert-butyllithi-
um in diethyl ether at À908C leads exclusively to the forma-
tion of benzylic anions as a mixture of monomeric and di-
[21]
meric species.
Although the solution NMR study allowed us to identify
the reaction intermediates involved in the transformation of
phosphinamide 1a into the tetrahydrobenzophosphole de-
rivatives VIII, some aspects of the mechanism still require
clarification. Calculation of the energy profile of the process
would be of great interest for understanding some details of
the reaction pathway given in Scheme 1, such as the distri-
bution of ortho and benzylic anions obtained when the met-
alation is carried out in the absence of coordinating solvents,
the translocation mechanism and the stereochemical prefer-
ences of the anionic cyclisation reaction. In addition, the ac-
celerating effect of HMPA and DMPU is poorly under-
stood.
[22]
Ortho-directed metalation of an aromatic ring and ben-
[22g,23]
zylic lithiation
reactions have been the subject of sever-
al theoretical studies. Bailey et al. also investigated theoreti-
cally the anionic cyclisation involving an isolated carbon–
[24]
carbon double bond on 2-(2-vinylphenyl)propyllithium. In
a recent communication we have shown that the anionic cy-
clodearomatisation of phosphinamides can be described as a
Scheme 1. Metalation and cyclisation reactions of phosphinamide 1a (L=
THF or HMPA).
[25]
Michael-type ionic process in contrast to the electrocyclic
ring closure suggested for the analogous reaction of lithiated
[26]
N-benzylarylamides. However, to the best of our knowl-
edge, the theoretical grounds of the dearomatising anionic
cyclisation have not been previously explored.
Abstract in Spanish: Se ha investigado, teꢀrica y experimen-
talmente, el mecanismo de la reacciꢀn de desaromatizaciꢀn
aniꢀnica de derivados de fosfinamidas. La superficie de ener-
gꢁa potencial de reacciones modelo se estudiꢀ al nivel de
teorꢁa Becke3LYP/6-31+G*. De acuerdo con este estudio, se
encontrꢀ que el proceso se inicia con la formaciꢀn de un
complejo pre-reactivo entre el alquil litio y la fosfinamida, a
partir del cual se produce la metalaciꢀn en la posiciꢀn NCa-
preferentemente respecto a la litiaciꢀn en posiciꢀn orto. La
adiciꢀn intramolecular del carbaniꢀn a la posiciꢀn orto del
anillo aromꢂtico conduce a los productos de desaromatiza-
ciꢀn, en una reacciꢀn que estꢂ regida por control termodinꢂ-
mico. Los disolventes coordinantes como la HMPA o la
DMPU parecen influir en la reacciꢀn favoreciendo la forma-
ciꢀn de pares iꢀnicos separados por el disolvente. Se estudiꢀ
tambiꢃn la reacciꢀn de ciclaciꢀn de derivados de allilfosfina-
mida, encontrꢂndose que la ciclaciꢀn aniꢀnica puede tener
lugar tanto por el ataque a travꢃs depor las posiciꢀones a
como de la g del aniꢀn alilo. No obstante, la formaciꢀn de
los productos con estructura cꢁclica de siete eslabones, proce-
dentes del ataque por la posiciꢀn g estꢂ claramente favoreci-
da.
In order to get a deeper insight into the mechanism of the
anionic dearomatisation of phosphinamides, we performed a
study of the potential-energy surface of several model sys-
tems based on the four steps experimentally observed:
1) precomplexation, 2) competing ortho-directed aromatic
metalation and NC -metalation, 3) anion translocation and
a
4) intramolecular cyclisation. The influence of solvents on
the reaction course was also analysed. In addition, the differ-
ent cyclisation modes of N-alkyl-N-allyldiphenylphosphin-
amide (1b) to give the five- or seven-membered systems, 2
and 3 (see Figure 1), respectively, were investigated both
theoretically and experimentally.
Figure 1. N-Allylphosphinamide 1b and five- and seven-membered ring
cyclisation products 2 and 3.
Chem. Eur. J. 2005, 11, 3022 – 3031
www.chemeurj.org
ꢄ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3023

F. Lꢁpez Ortiz, J. Gonzꢀlez et al.
À1
Results and Discussion
Table 1. Relative energies [kcalmol ] of the stationary points located
for the metalation and translocation reactions.
[
a]
Reaction
Stationary point
Relative energy
Computational methods: As a result of the size of the sys-
tems being studied, density functional theory (DFT) meth-
ods were employed because they offer a reasonable balance
between the reliability of the calculation and the computa-
a-directed
lithiation of 1c
6
7
À28.3
À1.3
4
+CH
4
4
À28.2
[27]
tional cost.
ortho-directed
lithiation of 1c
8
9
À27.9
À8.1
The geometry of each stationary point was fully optimised
at the Becke3LYP/6-31+G* or Becke3LYP/3-21+G* level
of theory, and the nature of all the stationary points located
was verified by frequency calculations. All calculations were
5+CH
À37.6
ortho-directed
lithiation of 10
12
14
27.9
À8.2
[28]
carried out with the Gaussian 98 suite of programs.
1
6a+CH
4
À37.7
a-directed
lithiation of 10
13
15
1
À28.2
À9.9
Potential-energy surface for the lithiation step: To use the
simplest model for studying the two possible competing re-
action pathways for the metalation, we considered the reac-
tion of model phosphinamide 1c with methyllithium (as a
model of the lithiation reagent) to give the metalated inter-
mediates 4 or 5 (see Figure 2). The organolithium com-
pounds were considered to be monomers.
6b+CH
4
À41.7
a-directed
lithiation of 11
17
18
À28.6
À10.4
À40.6
1
9+CH
4
[b]
anion translocation of 5
5
2
4
0.0
+41.2
+9.3
0
[
a] The relative energies refer to the sum of the energies of neutral phos-
phinamides and methyllithium. [b] In this reaction, the energies are cal-
culated with respect to the ortho-lithiated intermediate.
Figure 2. Model phosphinamide 1c and C
mediates 4 and 5, respectively.
a
- and ortho-metalated inter-
spect to the reagents. The formation of very stable com-
plexes between organolithium reagents and substituted ben-
zenes has been widely documented, and its role on the aro-
The stationary points located for the ortho- and a-direct-
ed lithiation reactions of 1c are shown in Figure 3, and their
relative energies are listed in Table 1.
According to our results, both reactions start with the bar-
rierless formation of complexes 6 and 8, between the phos-
phinamide and MeLi, which are strongly stabilised with re-
[29,30]
matic lithiation reaction has been studied.
directed deprotonations have alternatively been described
Ortho-
[22b–e]
as kinetically controlled transformations.
In the pre-re-
active complexes 6 and 8, the methyllithium reagent is coor-
dinated to the P=O bond of the phosphinamide moiety, as
indicated by the increase of the
P=O bond length from 1.502 ꢅ
in phosphinamide 1c to 1.522 ꢅ
or 1.517 ꢅ in structures 6 and 8,
respectively. The two pre-reac-
tive complexes show a similar
stability and differ only in the
relative orientation of the MeLi
fragment with respect to the ar-
omatic ring: In complex 6,
which leads to the a-lithiated
intermediate, the Me and NMe2
fragments show a relative syn
orientation, while in 8, the
methyl fragment is close to the
ortho hydrogen in the phenyl
ring.
Next in the reaction coordi-
nate two transition structures, 7
and 9, were located. In 7, the
Figure 3. Stationary points found for the lithiation reaction of model phosphinamide 1c. Bond lengths in ꢅ
and angles in degrees. Colour code of spheres: light blue=hydrogen, small grey=carbon, large grey=lithium,
red=oxygen, dark blue=nitrogen, pink=phosphorus.
C ÀLi bond is being formed as
a
3024
ꢄ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2005, 11, 3022 – 3031

Diphenylphosphinamide Derivatives
FULL PAPER
the C ÀH bond elongates, lead-
a
ing to the formation of a meth-
ane molecule and the a-lithiat-
ed intermediate 4. Similarly, in
the transition structure 9, the si-
multaneous abstraction of the
ortho hydrogen and the forma-
tion of the CorthoÀLi bond takes
place. The bond between the
hydrogen being abstracted and
the carbon atom is almost com-
pletely broken in the transition
structures, as can be seen from
the values of the corresponding
bond lengths: 1.438 (C ÀH in 7)
a
and 1.395 ꢅ (C ÀH in 9).
ortho
Also, in both transition struc-
tures the lithium atom remains
Figure 5. Pre-reactive complexes 12, 13 and 17, and transition structures 14, 15 and 18 located for the lithiation
bonded to the oxygen atom, so of model N-allyl- and N-benzyl phosphinamides 10 and 11, respectively. Bond lengths in ꢅ and angles in de-
in intermediates 4 and 5 lithium grees. For the colour code see the legend of Figure 3.
is di-coordinated.
From the values of the rela-
tive energies (Table 1), the metalation of model phosphin-
amide 1c is predicted to take place at the ortho position of
the phenyl ring, as could be expected from the correspond-
ing pKa values of the aromatic and aliphatic hydrogen
atoms. However, the experimental results indicate that the
cyclodearomatising reaction of phosphinamides requires
always the presence of one benzyl or allyl group (see below)
on the phosphinamide nitrogen (see Figure 1). In order to
test the influence of these substituents on the metalation
site, we investigated the ortho- and a-directed metalation
pathways of the model phosphinamides 10 and 11, shown in
Figure 4. In the case of the benzylic metalation, the small
model phosphinamide 11 was used, due to computational
limitations.
and 18, respectively). However, while the barrier for the
ortho-directed lithiation is almost the same for 1c and 10
(see data in Table 1), the barrier for the a-directed lithiation
is drastically reduced in the case of the N-allylphosphina-
mide 10 and now the metalation takes place at the allylic
position, the C -lithiated intermediate 16b being predicted
a
to be both the kinetic and thermodynamic product. The re-
sults of 11 are similar to the allylic derivative 10 (Figure 5
and Table 1): a small barrier was found for the metalation of
the C -position.
a
Anion translocation step: According to the previous results,
the metalation of the phosphinamides bearing carbanion-
stabilizing groups (e.g., benzyl or allyl) at the nitrogen is ex-
pected to take place at the a-carbon atom. In work closely
related to this, Clayden and co-workers proposed that upon
treatment of N-alkyl-N-benzylarylcarboxamides with a lithi-
um base the metalation could initially occur to some extent
at the ortho position of the aromatic ring, and then a trans-
location of the negative charge would lead to the NC -lithi-
a
[31]
ated anion.
The translocation reaction was studied for the case of
phosphinamide 3, and the transition structure 20 (Figure 6),
corresponding to the transformation of the ortho-lithiated
phosphinamide 5 into the a-anion 4, was located.
Figure 4. N-Allyl- (10) and N-benzyl- (11) model phosphinamides and
lithiated derivatives 16a, b and 19.
In transition structure 20, one of the hydrogen atoms of
the methyl group is being transferred to the ortho position
in the aromatic ring, while the lithium atom remains simul-
taneously bonded to the oxygen and to the aromatic and ali-
phatic carbon atoms. However, this translocation step has a
high activation barrier (see Table 1), so this reaction path-
way can be excluded as being responsible for the formation
of the a-lithiated intermediates in the cyclodearomatisation
of phosphinamides. This result is in agreement with the ex-
perimental observation that ortho-lithiated compound 1a
The potential-energy surface for the lithiation reaction of
phosphinamides 10 and 11 is qualitatively similar to the one
found for the phosphinamide 1c (see Figure 5 and Table 1).
The pre-reactive complexes initially formed (12, 13 and
17) are followed by the transition structures corresponding
to the ortho, allylic and benzylic metalation reactions (14, 15
Chem. Eur. J. 2005, 11, 3022 – 3031
www.chemeurj.org
ꢄ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3025

F. Lꢁpez Ortiz, J. Gonzꢀlez et al.
Figure 6. Transition structure 20 for the anion translocation. Bond lengths
in ꢅ. For the colour code see the legend of Figure 3.
does not evolve into dearomatised products in the absence
[19,20]
of HMPA or DMPU at À908C.
Potential-energy surface for the cyclisation step: According
to the previously described results, the lithiation of benzyl
or allyl phosphinamides will lead to a benzylic or allylic or-
ganolithium, which will undergo intramolecular cyclisation
by nucleophilic attack of the carbanionic centre at the ortho
position of the aromatic ring. As can be seen in Scheme 2,
Figure 7. Transition structures, activation barriers and reaction energies
for the cyclisation reaction of anion 4. Bond lengths in ꢅ. For the colour
code see the legend of Figure 3.
sponding products, 27 and 25, is quite different in that 25 is
À1
predicted to be the most stable by 11.5 kcalmol . Following
these data, 27 and 25 can be considered as the products of
kinetic and thermodynamic control, respectively. As the bar-
rier for the reversion of the kinetic control isomer 27 is
À1
1
2.3 kcalmol lower than the reversion barrier for the ther-
modynamic control isomer 25, it could be proposed that
under thermodynamic-control conditions in the cyclodearo-
matising reactions of phosphinamides the major product will
be that corresponding to the si cyclisation mode, 25, in good
Scheme 2. Stereoisomeric products in the cyclisation reaction of 4.
[19]
four different stereoisomers could be formed in the cyclisa-
tion reaction of the a-metalated intermediate 4, depending
on the face (re or si) of the aromatic ring undergoing the ad-
dition and the relative orientation of the lithium atom with
respect to the phosphorous–oxygen bond.
agreement with the experimental results.
Despite this
agreement, it is important to note that the predicted activa-
tion-barrier results are quite high for reactions that take
place at very low temperatures. This could be an indication
of the limitations of the previous model, as the solvent ef-
fects were not taken into account.
The geometries and activation and reaction energies of
the transition structures (21–24) are shown in Figure 7. In
the transition structures, the lithium atom is bonded either
to the oxygen and nitrogen atoms, as in 23, or to the aromat-
Solvent effects: According to the experimental evidence, co-
ordinating solvents such as HMPA and DMPU strongly in-
fluence the course of the cyclodearomatising reactions, be-
cause in the absence of a co-solvent, the reaction takes
6
ic ring in a h fashion, as in 21, 22 and 24, and the vibration-
al normal mode associated with the imaginary frequency
[19,21]
corresponds to the stretching of the CÀC forming bond.
place very slowly.
The effect of these co-solvents can be
According to the characteristics of these transition struc-
tures, the cyclisation reaction of lithium phosphinamide 4
can be considered as a Michael-type ionic nucleophilic addi-
attributed to their ability for coordinating the lithium
cation. In order to evaluate the solvent effect we studied the
potential-energy surface for the model reaction shown in
Scheme 3, corresponding to the cyclisation of the DMPU-
solvated anion 29. In this case, the lithium atom in each sta-
tionary point is coordinated to one molecule of DMPU. Due
to the size of the system, the stationary points were opti-
mised at the Becke3LYP/3-21+G* level of theory; for com-
[25]
tion and not an electrocyclic reaction.
From the energetic data shown in Figure 7, it can be seen
that transition structures 23 and 21, for the cyclisation in-
volving the re and si faces of the aromatic ring, respectively,
À1
differ only in 0.8 kcalmol , while the stability of the corre-
3026
ꢄ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2005, 11, 3022 – 3031

Diphenylphosphinamide Derivatives
FULL PAPER
nating ligands will change from a contact ion pair to a sol-
vent-separated ion pair thus making the interaction between
the lithium atom and the organic fragment of the organo-
lithium compound weaker and increasing the anionic reac-
tivity of the counterion.
In order to test this hypothesis in the case of the anionic
cyclodearomatisation of lithium phosphinamides, additional
calculations were carried out by using an anionic system to
model the conditions corresponding to a solvent-separated
ion pair. Thus, the potential-energy surface for the cyclisa-
tion reaction of anion 32 was studied and two transition
structures, 33 and 34, were located (Scheme 4).
Scheme 3. Model reaction for the cyclisation of DMPU-coordinated
anion 29.
parison with the results obtained on the unsolvated model,
the corresponding stationary points (4, 21 and 25) were also
re-optimised at the same level of theory.
The DMPU-coordinated transition structure for the cycli-
sation reaction of 31 and the relative energies of the two re-
action pathways are shown in Figure 8. It can be seen that in
Scheme 4. Transition structures and reaction profile for the cyclisation of
the anion 32. For the colour code see the legend of Figure 3. Bond
lengths in ꢅ.
Figure 8. Becke3LYP/3-21+G* optimised DMPU-solvated transition
structure and reaction profiles for the solvated and unsolvated cyclisation
reactions. Bond lengths in ꢅ. For the colour code see the legend of
Figure 3.
The cyclisation of anion 32 takes place through the stereo-
isomeric transition structures 33 and 34, which show a geom-
etry closely resembling one of the transition structures
found in the neutral system (see Figure 7), but with the CÀC
forming bond being less formed than in the case of 21 and
23, indicating an earlier transition structure. However, the
potential-energy surface for the cyclisation of anion 32 is
different from that corresponding to the a-metalated phos-
phinamide 4. It is interesting to note that the activation bar-
rier for the cyclodearomatisation reaction of 32 is predicted
to be notably lower than the values found for 4. This result
seems to indicate that the increase of the anionic character
of the species involved in the reaction, for example, by the
effect of the coordinating additives, will cause a significant
reduction of the reaction barrier, in good agreement with
the experimental findings.
transition structure 31, corresponding to the si-face cyclisa-
tion, the DMPU molecule is coordinated to the lithium
atom, which is still bonded to the organic fragment. The
basic geometric features of this transition structure are very
close to those found for the reaction without a solvent mole-
cule, but the presence of the DMPU molecule significantly
alters the reaction profile: the activation barrier for the cyc-
À1
lisation is reduced by 8.4 kcalmol and the stability of the
reaction product increases, product 30 being predicted to be
À1
3
.8 kcalmol more stable than the starting anion 29.
This result shows that the critical role played by strongly
coordinating co-solvents such as HMPA or DMPU in the cy-
clodearomatising reaction of lithium phosphinamides may
be related to the reduction of the activation barrier upon
complexation of the lithium atom with the strongly coordi-
nating additive. This proposal is in good agreement with the
results reported by Reich and co-workers in the study of the
effect of polar coordinating additives (such as HMPA) on
the structure of different types of organolithium com-
Anionic cyclodearomatisation of N-allylphosphinamide (10):
The model reaction shown in Scheme 2 does not allow for a
detailed discussion of the stereochemistry of the cyclisation
reaction due to the lack of substituents on the carbon atom
at the a-position relative to the nitrogen atom. As a more
suitable model, according to the previous discussion, we
studied the cyclodearomatising reaction of anion 37
(Scheme 5), derived from N-allylphosphinamide 10
(Figure 4).
[32]
pounds. According to these results, the ion-pair structure
of organolithium reagents in the presence of strongly coordi-
Chem. Eur. J. 2005, 11, 3022 – 3031
www.chemeurj.org
ꢄ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3027

F. Lꢁpez Ortiz, J. Gonzꢀlez et al.
the prediction regarding the favoured formation of a seven-
as opposed to a five-membered ring in the anionic cyclisa-
tion of allylphosphinamides, we prepared phosphinamide 1b
(
Figure 1) following the procedure previously reported for
[18b]
the synthesis of 1a and outlined in Scheme 6.
Scheme 5. Cyclisation reaction of allylic anion 37.
In this case, due to the presence of the allyl group, the
cyclisation reaction can occur either at the a-position, to
give the five-membered products, 38 and 39, or at the g-
carbon atom, giving the seven-membered bicyclic systems 40
and 41. In the case of the five-membered products, four pos-
sible stereoisomers may be formed from 38 and 39.
Two transition structures (42 and 43, Figure 9) were locat-
ed for the a-cyclisation of allyl anion 10, leading to the trans
and cis products 38 and 39, respectively. The geometry and
relative energies of the transition structures corresponding
Scheme 6. Synthesis of N-allylphosphinamide 1b and subsequent dearo-
matising reaction: i) MeNHCH CH=CH NEt (2.5 equiv), toluene,
2
2
,
3
À788C; ii) H
6 equiv), THF, À908C, t
À908C, 30 min.
2
O
2
(1 equiv), À308C, THF; iii) RLi (2.5 equiv), DMPU
(
1
; iv) 2,6-di-tert-butyl-4-methylphenol (5 equiv),
The dearomatisation of 1b and
subsequent protonation with 2,6-
di-tert-butyl-4-methylphenol
under the same conditions de-
scribed for the analogous reac-
tion of phosphinamide 1a (met-
alation: sBuLi (2.5 equiv), THF,
À908C in the presence of DMPU
(
6 equiv) for 30 min; protona-
tion: 30 min, À908C) resulted in
the formation of a mixture of
compounds 2, 3a and 3b
Figure 9. Becke3LYP/6-31+G* transition structures and relative energies for the a- and g-cyclisation reactions
of N-allylphosphinamide anion, 10. Bond lengths in ꢅ.
(
Scheme 6) in a ratio of 10:53:37,
respectively, and in a 62% yield
Table 2, entry 1).
(
to the cyclisation at the a-position of the allyl anion are
very similar to those found for anion 32 (Scheme 4). In this
case, the trans product 38 is predicted to be formed prefer-
entially in the a-cyclisation reaction, in good agreement
with the experimental evidence indicating that the CÀC
Table 2. Distribution of products in the dearomatisation–protonation of
1b.
RLi
t1
[h]
Ratio
3b
Yield
[%]
1b
[%]
3a
2
[
a]
sBuLi
sBuLi
tBuLi
0.5
12
24
53
57
60
37
34
32
10
9
8
62
84
98
12
7
–
[
a]
bond formation in the anionic cyclodearomatisation is ster-
eoselective, the trans isomer being the major product.
[
2
a] Recovered Ph P(O)-sBu (9%).
On the other hand, according to the energetic data shown
in Figure 9, the cyclodearomatisation of 37 is predicted to
give the seven-membered ring derivatives 40 and 41 as
major products, corresponding to the g-cyclisation of the
allyl anion via transition structures 44 and 45. In this case,
In agreement with the previous theoretical calculations,
the formation of the seven-membered rings, 3a and 3b, by
g-attack of the allylic anion 46 to one P-substituted phenyl
ring is largely favoured as compared with the anionic cycli-
sation derived from the a-attack (ratio of g-/a-attack of
41 is predicted to be the kinetic product, and 40 the thermo-
dynamic one.
9
0:10). In this case, two stereoisomers were formed as two
Experimental study of the anionic cyclodearomatisation of
phenyl rings can experience the nucleophilic attack of the g-
N-allylphosphinamide (1b): In order to check the validity of
carbanionic centre.
3028
ꢄ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2005, 11, 3022 – 3031

Diphenylphosphinamide Derivatives
FULL PAPER
The recovery of 12% of 1b suggests that the metalation
Experimental Section
time (t ) was too short. This hypothesis was confirmed by
1
the 84% yield obtained when t1 was increased to 12 h
General methods: All reactions and manipulations were carried out in a
dry, N -gas atmosphere using standard procedures. THF was distilled
from sodium/benzophenone immediately prior to use. DMPU was distil-
led from CaH under reduced pressure. Commercial reagents were pur-
chased from Sigma-Aldrich Quꢃmica, S.A., and were all distilled prior to
use except for sBuLi. Thin-layer chromatography (TLC) was performed
on Merck plates with aluminium backing and silica gel 60 F254: For
column chromatography silica gel 60 (40–63 mm) from Scharlau was used.
Mass spectra were determined by atmospheric pressure ionization elec-
trospray (API-ES) on a Hewlett–Packard 5987 A or 1100 apparatus.
(
Table 2, entry 2). However, in both cases 9% of the starting
2
phosphinamide was transformed into the phosphine oxide
2
Ph P(O)-sBu by attack of the base on the phosphorus atom
2
of 1b. This competing reaction was completely inhibited by
using bulky tBuLi as the base. Additionally, the metalation
was allowed to take place for 24 h to assure the complete
conversion of 1b (see Supporting Information). Under these
conditions, 1b gave a mixture of 3a/3b/2 in a ratio of
NMR spectra were recorded on a Bruker Avance DPX300 using CDCl
as solvent. Chemical shifts are referenced to internal tetramethylsilane
3
60:32:8 almost quantitatively (Table 2, entry 3).
1
13
Flash column chromatography of the crude reaction mix-
3 4
for H (300.13 MHz) and C (75.47 MHz), and to external 85% H PO
3
1
for P (121.47 MHz). 2D NMR correlation spectra (gCOSY, gTOCSY,
gNOESY, gHMQC and gHMBC) and selective 1D gTOCSY and
gNOESY were acquired by using standard Bruker software and process-
ing routines.
ture afforded mixtures enriched in 3a and 3b (see Experi-
mental Section) which allowed us to identify each product
based on the analysis of their NMR spectra. The small
amount of azaphosphole 2 present could not be isolated.
The pattern of the signals observed for this compound in
the proton spectrum of the crude reaction mixture and the
selective experiments performed (1D gTOCSY, 1D
gNOESY) allowed the identification of its structure. Focus-
ing on 3a, the [1,4] dienic system of the dearomatised ring is
characterised by the large deshielding and coupling to the
N-Allyl-N-methyldiphenylphosphinamide (1b): N-Allyl-N-benzylamine
(2 mL, 15.03 mmol) was added to a solution of chlorodiphenylphosphine
(
(
(
2.69 mL, 15.03 mmol) and triethylamine (5.21 mL, 37.6 mmol) in toluene
100 mL) at À788C. The mixture was stirred for 30 min and then H
30% v/v; 1.7 mL, 15.03 mmol) was added. Oxidation was completed in
h, and then the reaction was poured into ice water and extracted with
ethyl acetate (3ꢆ15 mL) and washed with 0.1n NaOH (2ꢆ15 mL). The
organic layers were dried over Na SO and concentrated in vacuo afford-
2
O
2
1
2
4
ing 1b as a pale yellow oil. The purity of the phosphinamide was higher
phosphorus nucleus shown by the proton at the b-position
3
than 97% (NMR) and was used without further purification. Yield: 90–
relative to the P–O linkage (d=7.19 ppm,
JPH =
1
9
7
5%; oil; H NMR: d=2.61 (d, JPH =10.8 Hz, 3H; H-6), 3.54 (dd, JPH
=
[18b]
20.6 Hz).
The g-attack of the allylic anion leading to for-
2
.3, J=6.2 Hz, 2H; H-3), 5.21 (dd, J=10.3, JHH =2.9 Hz, 1H; H-5), 5.23
mation of the seven-membered ring is shown in the
(ddd, J=17.2, J=2.9, J=1.4 Hz, 1H; H-5’), 5.80 (ddt, J=17.2, J=10.3,
J=6.2 Hz, 1H; H-4), 7.56–7.41 (m, 6H), 7.88 ppm (m, 4H); C NMR:
13
13
C NMR spectrum by the appearance of a methylene signal
at d=32.97 ppm and two enamine carbons at d=113.15
d=33.54 (d, JPC =3.0 Hz; CH
(H C=), 128.51 (d, JPC =12.6 Hz; CAr), 131.71 (d, JPC =3.0 Hz; CAr),
31.78 (d, JPC =129.2 Hz; Cipso), 132.26 (d, JPC =9.0 Hz; CAr), 134.40 ppm
3 2
), 51.94 (d, JPC =3.0 Hz; CH ), 117.73
3
2
2
(
JPC =3.6 Hz) and 134.521 ppm ( JPC =1.6 Hz) correspond-
1
ing to the CH CH=CHN fragment. The correlations ob-
31
2
(d, JPC =6.6 Hz; HC=); P NMR: d=31.47; MS (API-ES): m/z (%): 295
[M+H+Na] , 294 (100) [M+Na] ; elemental analysis calcd (%) for
+
+
served in the 2D gHMQC and HMBC spectra confirmed
the assignments. The relative configuration of the stereogen-
ic centres was assigned through a 2D gNOESY experiment.
The syn arrangement of the bridgehead proton and the P-
substituted phenyl substituent was deduced from the corre-
lation observed between that methine proton and the ortho
protons of the P-substituted phenyl ring.
C
16
H
18NOP: C 70.84, H 6.69, N 5.16; found: C 70.86, H 6.52, N 5.22.
5
Tetrahydrobenzo[c][1,2]-2l -azaphosphacycloheptenes (3a and 3b): A
solution of tBuLi (1.08 mL of a 1.7m solution in cyclohexane, 1.84ꢆ
À3
1
1
2
0
0
mol) at À908C was added to a solution of phosphinamide 1b (7.38ꢆ
À4
À3
mol) and DMPU (0.53 mL, 4.42ꢆ10 mol) in THF (30 mL). After
À3
4 h, 2,6-di-tert-butyl-4-methylphenol (0.16 g, 3.69ꢆ10 mol) dissolved in
4 mL of THF was added using a cannula. The reaction mixture was stir-
red at À908C for 30 min. Then the mixture was poured into ice water
and extracted with ethyl acetate (3ꢆ15 mL). The organic layers were
1
1
31
31
2 4
dried over Na SO and concentrated in vacuo. H, H{ P} and P NMR
Conclusion
spectra of the crude reaction were measured in order to determine the
stereoselectivity of the process. 3a: Yield=52% (0.114 g) after chroma-
tography (ethyl acetate/hexane 4:1), identified from a mixture 3a/3b
According to the density theory calculations reported, the
anionic cyclodearomatising reaction of phosphinamides is
predicted to occur by a two-step mechanism, involving the
metalation at the benzylic or allylic position and the intra-
molecular, nucleophilic attack of the anionic centre at the
ortho position of the aromatic ring. The formation of the
dearomatised cyclic products is subjected to thermodynamic
control, and the critical role played by the coordinating ad-
ditives seems to be a result of the solvent-separated ion pair
character of the organolithium intermediates involved. The
cyclisation of allylphosphinamide derivatives was shown to
occur preferentially at the g-position of the allyl moiety, in
good agreement with the theoretical calculations.
1
3
(
92:8); oil; H NMR: d=1.94 (m, J=15.0,
JHH =6.2 Hz, 1H; H-5), 2.67
(
m, J=15.0 Hz, 1H; H-5’), 2.83 (m, 2H; H-8), 2.90 (d, JPH =7.3 Hz, 3H;
H-10), 3.01 (m, 1H; H-5a), 5.02 (ddd, JPH =2.9, J=10.3, J=7.0 Hz, 1H;
H-4), 5.57 (dddt, JPH =5.5, J=9.9, J=3.3, J=1.9 Hz, 1H; H-6), 5.72 (m,
J=9.9 Hz, 1H; H-7), 5.84 (ddd, JPH =9.9, J=10.3, J=1.5 Hz, 1H; H-3),
7.19 (m, JPH =20.6, J=3.7 Hz, 1H; H-9), 7.58–7.41 (m, 3H), 7.80 ppm (m,
1
3
2
J
H); C NMR: d=27.21 (d, JPC =13.8 Hz; CH
PC =2.4 Hz; CH ), 36.39 (d, JPC =7.8 Hz; CH), 113.15 (d, JPC =3.6 Hz;
HC=), 123.21 (d, JPC =1.8 Hz; HC=), 128.59 (d, JPC =12.5 Hz; CAr),
29.30 (d, JPC =9.6 Hz; CAr), 130.63 (d JPC =128.0 Hz; Cipso), 131.20 (d,
JPC =117.7 Hz; C=), 131.52 (d, JPC =10.3 Hz; CAr), 131.57 (d, JPC
.9 Hz; CAr), 134.52 (d, JPC =1.2 Hz; HC=), 141.40 ppm (d, JPC =6.6 Hz;
2 2
), 32.97 (CH ), 35.46 (d,
3
1
=
2
3
1
HC=); P NMR: d=28.08; LC-MS (API-ES): m/z (%): 272 (100)
M+1] , 271 (22) [M] , 256 (12); elemental analysis calcd (%) for
18NOP: C 70.84, H 6.69, N 5.16; found: C 70.79, H 6.77, N 5.15. 3b:
+
+
[
16
C H
Yield=22% (0.059 g) after chromatography (ethyl acetate/hexane 4:1),
1
identified from a mixture 3b/3a (74:26); oil; H NMR: d=2.11 (ddd, J=
Chem. Eur. J. 2005, 11, 3022 – 3031
www.chemeurj.org
ꢄ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3029

F. Lꢁpez Ortiz, J. Gonzꢀlez et al.
3
1
7
3.9,
J
HH =6.6, J=4.3 Hz, 1H; H-5), 2.61 (m, 1H; H-8,8’), 2.67 (d, J=
dujar-Sꢀnchez, M. J. Iglesias, F. Lꢁpez-Ortiz, Tetrahedron Lett. 2002,
43, 9611.
.3 Hz, 3H; H-10), 3.17 (dt, J=13.9, J=6.3 Hz, 1H; H-5’), 3.64 (m, 1H;
H-5a), 5.10 (c, J=8.0 Hz, 1H; H-4), 5.66 (m, 2H; H-6,7), 5.85 (m, 2H;
[10] a) L. N. Pridgen, M. K. Mokhallalati, M. J. Wu, J. Org. Chem. 1992,
57, 1237; b) M. K. Mokhallalati, K. R. Muralidharan, L. N. Pridgen,
Tetrahedron Lett. 1994, 35, 4267.
1
3
H-3,9), 7.51 (m, 3H), 7.79 ppm (m, 2H); C NMR: d=26.96 (d, JPC
=
1
5.0 Hz; CH
2 2 3
), 31.77 (d, JPC =1.2 Hz; CH ), 34.73 (d, JPC =4.2 Hz; CH ),
3
6.26 (d, JPC =6.6 Hz; CH), 113.30 (d, JPC =1.8 Hz; HC=), 123.13 (d,
[11] a) B. A. Barner, A. I. Meyers, J. Am. Chem. Soc. 1984, 106, 1865;
b) A. I. Meyers, D. Hoyer, Tetrahedron Lett. 1984, 25, 3667; c) A. I.
Meyers, B. A. Barner, J. Org. Chem. 1986, 51, 120; d) A. I. Meyers,
G. P. Roth, D. Hoyer, B. A. Barner, J. Am. Chem. Soc. 1988, 110,
J
PC =1.8 Hz; HC=), 128.40 (d, JPC =12.6 Hz; CAr), 129.16 (d, JPC
=
1
28.0 Hz; Cipso), 129.85 (d, JPC =8.4 Hz; HC=), 131.94 (d, JPC =3.0 Hz;
CAr), 133.23 (d, JPC =9.0 Hz; CAr), 133.31 (d, JPC =121.3 Hz; C=),
1
35.03 (d, JPC =3.0 Hz; HC=), 139.01 ppm (d, JPC =12.6 Hz; HC=);
4
611; e) A. I. Meyers, G. Licini, Tetrahedron Lett. 1989, 30, 4049;
3
1
+
P NMR: d=33.25; LC-MS (API-ES): m/z (%): 272 (100) [M+H] , 192
f) D. J. Rawson, A. I. Meyers, J. Org. Chem. 1991, 56, 2292; g) J.
Clayden, M. N. Kenworthy, Org.Lett. 2002, 41, 787.
(
5
8); elemental analysis calcd (%) for C16
.16; found: C 70.69, H 6.80, N 5.19.
H18NOP: C 70.84, H 6.69, N
[
[
12] K. Nishiwaki, T. Ogawa, K. Matsuo, Angew. Chem. 2002, 114, 502;
Angew. Chem. Int. Ed. 2002, 41, 484.
13] a) A. I. Meyers, K. Higashiyama, J. Org. Chem. 1987, 52, 4592;
b) R. C. Andrews, S. J. Teague, A. I. Meyers, J. Am. Chem. Soc.
1
988, 110, 7854; c) A. J. Robichaud, A. I. Meyers, J. Org. Chem.
1991, 56, 2607; d) T. G. Gant, A. I. Meyers, Tetrahedron Lett. 1993,
4, 3707; e) A. N. Hulme, S. S. Henry, A. I. Meyers, J. Org. Chem.
Acknowledgements
3
The authors thank CIEMAT (Ministerio de Ciencia y Tecnologꢃa, Spain)
for allocating computer time. Financial support by the Ministerio de
Ciencia y Tecnologꢃa (Project PPQ2001-3266) is gratefully acknowledged.
I.F. thanks Junta de Andalucꢃa for a doctoral fellowship. A.M.R. ac-
knowledges a doctoral fellowship from FICYT (Gobierno del Principado
de Asturias).
1995, 60, 1265; f) J. Clayden, K. Tchabanenko, Chem. Commun.
2000, 317; g) L. F. Basil, H. Nakano, R. Frutos, M. Kopach, A. I.
Meyers, Synthesis 2002, 2064; h) J. Clayden, C. J. Menet, D. J. Mans-
field, Chem. Commun. 2002, 38; i) J. Clayden, C. J. Menet, K. Tcha-
banenko, Tetrahedron 2002, 58, 4727; j) A. J. Reynolds, A. J. Scott,
C. I. Turner, M. S. Sherburn, J. Am. Chem. Soc. 2003, 125, 12108.
14] a) G. P. Roth, C. D. Rithner, A. I. Meyers, Tetrahedron 1989, 45,
[
6
949; b) A. Dehghani, X. Bai, S. W. Mascarella, W. D. Bowen, F. I.
[
1] For reviews see: a) G. Bartoli, Acc. Chem. Res. 1984, 17, 109;
b) T. G. Gant, A. I. Meyers, Tetrahedron 1994, 50, 2297; c) A. I.
Meyers, J. Heterocycl. Chem. 1998, 35, 991; d) H. Yamamoto, S.
Saito, Pure Appl. Chem. 1999, 71, 239; e) M. J. Mealy, W. F. Bailey,
J. Organomet. Chem. 2002, 646, 59; f) J. Clayden, M. N. Kenworthy,
Synthesis 2004, 1721.
Carroll, Tetrahedron Lett. 1994, 35, 8969; c) F. Y. Carroll, X. Bai, A.
Dehghani, S. W. Mascarella, W. Williams, W. D. Bowen, J. Med.
Chem. 1999, 42, 4621; d) A. Ahmed, R. A. Bragg, J. Clayden, K.
Tchabanenko, Tetrahedron Lett. 2001, 42, 3407; e) R. A. Bragg, J.
Clayden, M. Blandon, O. Ichihara, Tetrahedron Lett. 2001, 42, 3411;
f) U. Engelhardt, A. Sarkar, T. Linker, Angew. Chem. 2003, 115,
[
2] a) For a review see: R. C. Fuson, Adv. Organomet. Chem. 1964, 1,
2
591; Angew. Chem. Int. Ed. 2003, 42, 2487.
2
2
21; b) C. W. Jaeger, N. Kornblum, J. Am. Chem. Soc. 1972, 94,
545; c) S. S. Hixson, J. Chem. Soc. Chem. Commun. 1974, 574;
[
15] a) A. Ahmed, J. Clayden, M. Rowley, Chem. Commun. 1998, 297;
b) J. Clayden, C. S. Frampton, C. McCarthy, N. Westlund, Tetrahe-
dron 1999, 55, 14161; c) J. Clayden, C. J. Menet, D. J. Mansfield,
Org. Lett. 2000, 2, 4229; d) J. Clayden, K. Tchabanenko, S. A. Yasin,
M. D. Turnbull, Synlett 2001, 302; e) J. Clayden, Y. J. Y. Foricher,
H. K. Lam, Eur. J. Org. Chem. 2002, 3558; f) J. Clayden, C. J.
Menet, Tetrahedron Lett. 2003, 44, 3059.
16] a) J. K. Crandall, T. A. Ayers, J. Org. Chem. 1992, 57, 2993; b) A.
Padwa, M. A. Filipkowski, D. N. Kline, S. S. Murphree, P. E. Yeske,
J. Org. Chem. 1993, 58, 2061.
d) M. Daney, R. Lapouyade, H. Bouas-Laurent, Tetrahedron Lett.
978, 19, 783; e) M. A. Fox, A. Ranade, I. Madany, J. Organomet.
1
Chem. 1982, 239, 269; f) M. Takagi, M. Nojima, S. Kusabayashi, J.
Am. Chem. Soc. 1982, 104, 1636; g) G. Kaupp, H. W. Grꢇter, E.
Teufel, Chem. Ber. 1982, 115, 3208.
[
[
3] a) K. Maruoka, M. Ito, H. Yamamoto, J. Am. Chem. Soc. 1995, 117,
[
9
091; b) S. Saito, K. Shimada, H. Yamamoto, E. M. Marigorta, I.
Fleming, Chem. Commun. 1997, 1299; c) M. Shindo, K. Koga, K. To-
mioka, J. Org. Chem. 1998, 63, 9351; d) S. Saito, T. Sone, K. Shima-
da, H. Yamamoto, Synlett 1999, 81.
[
17] a) H. J. Breternitz, E. Schaumann, G. Adiwidjaja, Tetrahedron Lett.
1
4
991, 32, 1299; b) V. K. Aggarwal, M. Ferrara, Org. Lett. 2000, 2,
107; c) V. K. Aggarwal, E. Alonso, M. Ferrara, S. E. Spey, J. Org.
4] a) A. I. Meyers, J. D. Brown, D. Laucher, Tetrahedron Lett. 1987, 28,
5
279; b) K. Tomioka, M. Shindo, K. Koga, J. Am. Chem. Soc. 1989,
Chem. 2002, 67, 2335; d) R. Luisi, V. Capriati, S. Florio, R. Ranaldo,
Tetrahedron Lett. 2003, 44, 2677.
1
11, 8266; c) K. Tomioka, T. Okamoto, M. Kanai, H. Yamataka, Tet-
rahedron Lett. 1994, 35, 1891; d) D. W. Brown, M. Lindquist, M. F.
Mahon, B. Malm, G. N. Nilsson, A. Ninan, M. Sainsbury, C. Wester-
lund, J. Chem. Soc. Perkin Trans. 1 1997, 2337; e) M. Shindo, K.
Koga, K. Tomioka, J. Org. Chem. 1998, 63, 9351; f) S. V. Kolotuchin,
A. I. Meyers, J. Org. Chem. 2000, 65, 3018; g) K. Tomioka, Y.
Shioya, Y. Nagaoka, K. I. Yamada, J. Org. Chem. 2001, 66, 7051.
5] B. Plunian, J. Mortier, M. Vaultier, L. Toupet, J. Org. Chem. 1996,
[
18] a) I. Fernꢀndez, F. Lꢁpez-Ortiz, B. Tejerina, S. Garcꢃa-Granda, Org.
Lett. 2001, 3, 1339; b) I. Fernꢀndez, F. Lꢁpez-Ortiz, A. Menꢈndez-
Velꢀzquez, S. Garcꢃa-Granda, J. Org. Chem. 2002, 67, 3852; c) G.
Ruiz-Gꢁmez, F. Lꢁpez Ortiz, Synlett 2002, 781.
19] I. Fernꢀndez, A. Forcꢈn-Acebal, F. Lꢁpez-Ortiz, S. Garcꢃa-Granda,
J. Org. Chem. 2003, 68, 4472.
[
[
[
[
20] I. Fernꢀndez, J. Gonzꢀlez, F. Lꢁpez-Ortiz, J. Am. Chem. Soc. 2004,
6
1, 5206.
1
26, 12551.
6] a) K. Tomioka, M. Shindo, K. Koga, Tetrahedron Lett. 1990, 31,
[
[
21] I. Fernꢀndez, F. Lꢁpez-Ortiz, Chem. Commun. 2004, 1142.
22] a) W. Bauer, P. von Raguꢈ Schleyer, J. Am. Chem. Soc. 1989, 111,
1
3
1
739; b) K. Tomioka, M. Shindo, K. Koga, Tetrahedron Lett. 1993,
4, 681; c) M. Shindo, K. Koga, Y. Asano, K. Tomioka, Tetrahedron
999, 55, 4955.
7
191; b) N. J. R. van Eikema-Hommes, P. von Raguꢈ Schleyer,
Angew. Chem. 1992, 104, 768; Angew. Chem. Int. Ed. Engl. 1992, 31,
755; c) J. M. Saꢀ, P. M. Deyꢀ, G. A. SuÇer, A. Frontera, J. Am.
Chem. Soc. 1992, 114, 9093; d) N. J. R. van Eikema-Hommes, P. von
Raguꢈ Schleyer, Tetrahedron 1994, 50, 5903; e) T. Kremer, M.
Junge, P. von Raguꢈ Schleyer, Organometallics 1996, 15, 3345;
f) S. T. Chadwick, R. A. Rennels, J. L. Rutherford, D. B. Collum, J.
Am. Chem. Soc. 2000, 122, 8640; g) J. M. Saꢀ, Helv. Chim. Acta
2002, 85, 814; h) D. R. Armstrong, S. R. Boss, J. Clayden, R. Haigh,
[
7] a) J. Clayden, Y. J. Y. Foricher, H. K. Lam, Chem. Commun. 2002,
2
2
138; b) J. Clayden, Y. J. Y. Foricher, H. K. Lam, Eur. J. Org. Chem.
002, 3558.
[
[
8] S. Saito, T. Sone, M. Murase, H. Yamamoto, J. Am. Chem. Soc.
000, 122, 10216.
2
9] a) G. Rio, B. Sillion, Bull. Soc. Chim. Fr. 1961, 831; b) M. Martynoff,
Bull. Soc. Chim. Fr. 1962, 272; c) C. M. Andujar-Sꢀnchez, M. J. Igle-
sias, F. Lꢁpez-Ortiz, Tetrahedron Lett. 2002, 43, 2565; d) C. M. An-
3030
ꢄ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2005, 11, 3022 – 3031

Diphenylphosphinamide Derivatives
FULL PAPER
B. A. Kirmani, D. J. Linton, P. Schooler, A. E. H. Wheatley, Angew.
Chem. 2004, 116, 2187; Angew. Chem. Int. Ed. 2004, 43, 2135.
23] a) W. F. Bailey, A. D. Khanolkar, K. Gavaskar, T. V. Ovaska, K.
Rossi, Y. Thiel, K. B. Wiberg, J. Am. Chem. Soc. 1991, 113, 5720;
b) D. R. Armstrong, J. Clayden, R. Haigh, D. J. Linton, P. Schooler,
A. E. H. Wheatley, Chem. Commun. 2004, 1694.
[30] a) M. Al-Aseer, P. Beak, D. Hay, D. J. Kempf, S. Mills, S. G. Smith,
J. Am. Chem. Soc. 1983, 105, 2080; b) A. I. Meyers, L. M. Funetes,
W. F. Reiker, J. Am. Chem. Soc. 1983, 105, 2082; c) A. I. Meyers,
D. A. Dickman, J. Am. Chem. Soc. 1987, 109, 1263; d) D. R. Hay, Z.
Song, S. G. Smith, P. Beak, J. Am. Chem. Soc. 1988, 110, 8145;
e) J. E. Resek, P. Beak, J. Am. Chem. Soc. 1994, 116, 405; f) H.
Luitjes, F. J. J. de Kanter, M. Schakel, R. F. Scmitz, G. W. Klumpp, J.
Am. Chem. Soc. 1995, 117, 4179; g) D. R. Anderson, N. C. Faibish, P.
Beak, J. Am. Chem. Soc. 1999, 121, 7553; h) K. M. B. Gross, P. Beak,
J. Am. Chem. Soc. 2001, 123, 315; i) P. I. Arvidsson, G. Hilmersson,
O. Davidsson, Helv. Chim. Acta 2002, 85, 3814; j) W. F. Bailey, P.
Beak, S. T. Kerrick, S. H. Ma, K. B. Wiberg, J. Am. Chem. Soc. 2002,
124, 1889; k) G. R. Krow, S. B. Herzon, G. Lin, F. Qiu, P. E. Sonnet,
Org. Lett. 2002, 4, 3151; l) F. Gohier, A.-S. Castanet, J. Mortier, Org.
Lett. 2003, 5, 1919.
[31] a) A. Ahmed, J. Clayden, M. Rowley, Tetrahedron Lett. 1998, 39,
6103; b) R. A. Bragg, J. Clayden, Tetrahedron Lett. 1999, 40, 8327.
[32] a) H. J. Reich, J. P. Borst, R. R. Dykstra, D. P. Green, J. Am. Chem.
Soc. 1993, 115, 8728; b) H. J. Reich, K. J. Kulicke, J. Am. Chem. Soc.
1996, 118, 273; c) H. J. Reich, D. P. Green, M. A. Medina, W. S.
Goldenberg, B. O. Gudmundsson, R. R. Dykstra, N. H. Phillips, J.
Am. Chem. Soc. 1998, 120, 7201; d) H. J. Reich, J. E. Holladay, T. G.
Walker, J. L. Thompson, J. Am. Chem. Soc. 1999, 121, 9769;
e) W. H. Sikorski, H. J. Reich, J. Am. Chem. Soc. 2001, 123, 6527;
f) H. J. Reich, W. S. Goldenberg, A. W. Sanders, K. L. Janttzi, C. C.
Tzschucke, J. Am. Chem. Soc. 2003, 125, 3509.
[
[
[
24] W. F. Bailey, M. J. Mealy, K. B. Wiberg, Org. Lett. 2002, 4, 791.
25] A. Morꢀn Ramallal, F. Lꢁpez-Ortiz, J. Gonzꢀlez, Org. Lett. 2004, 6,
2
141.
26] J. Clayden, S. Purewal, M. Helliwell, S. J. Mantell, Angew. Chem.
002, 114, 1091; Angew. Chem. Int. Ed. 2002, 41, 1049.
[
[
[
2
27] For a description of the theoretical methods see: F. Jensen, Introduc-
tion to Computational Chemistry, Wiley, 1999, pp. 177–193.
28] Gaussian 98 (Revision A.3), M. J. Frisch, G. W. Trucks, H. B. Schle-
gel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, V. G. Zakrzewski,
J. A. Montgomery, Jr., R. E. Stratmann, J. C. Burant, S. Dapprich,
J. M. Millam, A. D. Daniels, K. N. Kudin, M. C. Strain, O. Farkas, J.
Tomasi, V. Barone, M. Cossi, R. Cammi, B. Mennucci, C. Pomelli,
C. Adamo, S. Clifford, J. Ochterski, G. A. Petersson, P. Y. Ayala, Q.
Cui, K. Morokuma, D. K. Malick, A. D. Rabuck, K. Raghavachari,
J. B. Foresman, J. Cioslowski, J. V. Ortiz, B. B. Stefanov, G. Liu, A.
Liashenko, P. Piskorz, I. Komaromi, R. Gomperts, R. L. Martin,
D. J. Fox, T. Keith, M. A. Al-Laham, C. Y. Peng, A. Nanayakkara,
C. Gonzalez, M. Challacombe, P. M. W. Gill, B. G. Johnson, W.
Chen, M. W. Wong, J. L. Andres, M. Head-Gordon, E. S. Replogle,
J. A. Pople, Gaussian, Inc., Pittsburgh, PA, 1998.
[
29] For reviews see: a) P. Beak, A. I. Meyers, Acc. Chem. Res. 1986, 19,
3
56; b) P. Beak, A. Basu, D. J. Gallagher, Y. S. Park, S. Thayumana-
van, Acc. Chem. Res. 1996, 29, 552; c) M. C. Whisler, S. MacNeil, V.
Snieckus, P. Beak, Angew. Chem. 2004, 116, 2256; Angew. Chem.
Int. Ed. 2004, 43, 2206.
Received: September 28, 2004
Published online: March 11, 2005
Chem. Eur. J. 2005, 11, 3022 – 3031
www.chemeurj.org
ꢄ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3031