Synthesis, structure, and reactivity of N -benzoyl iminophosphoranes ortho lithiated at the benzoyl group

Article abstract of DOI:10.1021/jo101151s

Ortho lithiation of N-benzamido-P,P,P-triaryliminophosphoranes through deprotonation with alkyllithium bases was achieved with ortho-C=O and ortho-P=N chemoselectivity. However, the synthetic scope of these processes was rather limited. Ortho-lithiated N-benzamido-P,P,P-triphenyliminophosphorane 8 was efficiently prepared via lithium/halogen exchange of the corresponding ortho-brominated precursor with s-BuLi in THF at -90 °C. The reaction of 8 with a variety of electrophiles provides an easy and mild method for the regioselective synthesis of ortho-modified iminophosphoranes via C- (alkylation and hydroxyalkylation) and C-X (X = I, Si, P, Sn, and Hg) bond-forming reactions. NMR characterization of 8 in THF solution showed that 8 exists as an equilibrium mixture of one monomer and two dimers. The Li atoms of these species become members of five-membered rings through chelation by the ortho-metalated carbon and the carbonyl oxygen. The dimers differ in the relative orientation of the two chelates with respect to the plane defined by the C₂Li ₂ core. The equilibrium between all species is established by splitting the dimers into monomers and subsequent recombination with formation of a different dimer.

Full text of DOI:10.1021/jo101151s

pubs.acs.org/joc
Synthesis, Structure, and Reactivity of N-Benzoyl Iminophosphoranes
Ortho Lithiated at the Benzoyl Group
†
‡
†
guez,‡
~
David Aguilar, Ignacio Fernandez, Luciano Cuesta, Vıctor Yanez-Rodrı
´ ´
ꢀ
§
†
,†
,‡
ꢀ
Tatiana Soler, Rafael Navarro, Esteban P. Urriolabeitia,* and Fernando Lopez Ortiz*
†
ꢀ
ꢀ
Departamento de Compuestos Organometalicos, Instituto de Ciencia de Materiales de Aragon,
´
‡ ꢀ
CSIC-Universidad de Zaragoza, Pedro Cerbuna 12, 50009 Zaragoza, Spain, Area de Quımica Organica,
ꢀ
§
Universidad de Almerıa, Crta. Sacramento s/n, 04120, Almerıa, Spain, and Servicios Tecnicos de
´
Investigacioꢀn, Facultad de Ciencias Fase II, 03690, San Vicente de Raspeig, Alicante, Spain
´
ꢀ
esteban@unizar.es; flortiz@ual.es
Received June 14, 2010
Ortho lithiation of N-benzamido-P,P,P-triaryliminophosphoranes through deprotonation with
alkyllithium bases was achieved with ortho-CdO and ortho-PdN chemoselectivity. However, the
synthetic scope of these processes was rather limited. Ortho-lithiated N-benzamido-P,P,P-triphenyl-
iminophosphorane 8 was efficiently prepared via lithium/halogen exchange of the corresponding
ortho-brominated precursor with s-BuLi in THF at -90 °C. The reaction of 8 with a variety of
electrophiles provides an easy and mild method for the regioselective synthesis of ortho-modified
iminophosphoranes via C-C (alkylation and hydroxyalkylation) and C-X (X=I, Si, P, Sn, and Hg)
bond-forming reactions. NMR characterization of 8 in THF solution showed that 8 exists as an
equilibrium mixture of one monomer and two dimers. The Li atoms of these species become members
of five-membered rings through chelation by the ortho-metalated carbon and the carbonyl oxygen.
The dimers differ in the relative orientation of the two chelates with respect to the plane defined by the
C2Li2 core. The equilibrium between all species is established by splitting the dimers into monomers
and subsequent recombination with formation of a different dimer.
Introduction
compounds 4).2 On the other hand, the lithiated species may
act as bidentate ligands that can be used in the preparation of
Selective ortho lithiation of aryl rings bearing heteroatom-
containing functional groups is a powerful synthetic strategy
in organic and organometallic synthesis.1 From the organic
chemistry point of view, the method gives access to ortho
derivatives with excellent regiocontrol through reactions of
the carbanions with a great variety of electrophiles (Scheme 1,
(2) (a) Clayden, J. P. In Patai Series: The Chemistry of Functional Groups.
The Chemistry of Organolithium Compounds; Rappoport, Z.; Marek, I., Eds.;
Wiley: Chichester, 2004; Part 1, pp 495-646. (b) He, P.; Dong, C.-G.; Hu,
Q.-S. Tetrahedron Lett. 2008, 49, 1906. (c) Coldham, I.; Patel, J. J.;
Raimbault, S.; Whittaker, D. T. E.; Adams, H.; Fang, G. Y.; Aggarwal,
V. K. Org. Lett. 2008, 10, 141. (d) O’Brien, P. Chem. Commun. 2008, 655.
(e) Lulinski, S.; Zajac, K. J. Org. Chem. 2008, 73, 7785. (f) Slocum, D. W.;
Reece, T. L.; Sandlin, R. D.; Reinscheld, T. K.; Whitley, P. E. Tetrahedron
Lett. 2009, 50, 1593. (g) Lygin, A. V.; de Meijere, A. Org. Lett. 2009, 11, 389.
(h) Cho, I.; Meimetis, L.; Britton, R. Org. Lett. 2009, 11, 1903. (i) Gupta, L.;
Hoepker, A. C.; Singh, K. J.; Collum, D. B. J. Org. Chem. 2009, 74, 2231.
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Chem. 2009, 74, 4094. (k) Narasimhan, S. K.; Kerwood, D. J.; Wu, L.; Li, J.;
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(1) (a) Clayden, J. Organolithiums: Selectivity for Synthesis; Pergamon:
Oxford, 2002. (b) Mugesh, G.; Singh, H. B. Acc. Chem. Res. 2002, 35, 226.
(c) Wheatley, A. E. Eur. J. Inor. Chem. 2003, 3291. (d) Schlosser, M. Angew.
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Chem., Int. Ed. 2005, 44, 376. (e) Chinchilla, R.; Najera, C.; Yus, M.
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6452 J. Org. Chem. 2010, 75, 6452–6462
Published on Web 09/03/2010
DOI: 10.1021/jo101151s
r
2010 American Chemical Society

Aguilar et al.
JOCArticle
SCHEME 1. General Procedures of Ortho-Lithiation and
Trapping Reactions
FIGURE 1. Different cyclometalation position on iminophos-
phoranes.
SCHEME 2. Possible Intermediates in the Ortho-Directed
Lithiation of N-Benzoyliminophosphoranes 6
a number of metal complexes via transmetalation reactions
(Scheme 1, complexes 5).3 Ortho lithiation is most commonly
achieved through deprotonation reactions with organo-
lithium bases. According to the CIPE (complex induced
proximity effect) model, the polar group linked to the
aromatic ring directs the approach of the base to the depro-
tonation site by coordination to the lithium atom (Scheme 1,
complex 1) and contributes to the stabilization of the ortho-
lithiated species through intramolecular coordination (Scheme 1,
complex 3).4 When the deprotonation method is not appli-
cable due to the lack of reactivity or the required selectivity,
among other factors, halogen-lithium exchange becomes
a valuable alternative provided that the ortho-halogenated
substrate 2 is readily available.5
Some of us are interested in using iminophosphoranes as
C,N-bidentate ligands for the synthesis of new transition
metal complexes, due to their versatility, structural charac-
teristics, and interesting applications.3f,6 Among them, we
have reported the use of Pd(II),6a Au(I), and Au(III)3f,6i
complexes with ortho-metalated iminophosphoranes as
catalysts, we have studied the orientation of the ortho-
metalation on iminophosphoranes and phosphorus ylides,6b,e
and we have prepared complexes with different nuclear-
ities,6f,g or characterized unusual bonding modes.6c More
interestingly, we have determined that the ortho-palladation
of imino-tri(aryl)phosphoranes contaning N-benzyl substit-
uents can be oriented toward the benzyl ring (exo metalation)
or toward the P-aryl rings (endo metalation) as a function of
the reaction temperature,6d while palladation of N-benzoyl
derivatives affords exclusively the exo derivatives.6h We have
also studied the mechanism of the ortho-palladation by DFT
methods, which showed that the exo metalation (Figure 1) is
under kinetic control, while the product derived from endo
metalation is thermodynamically more stable.6d,h Similar
observations have been perfomed on N-naphthyliminophos-
phoranes.6j This control has deeper implications, and, for
instance, it has allowed the selective functionalization of
different substrates. In a recent example we have been able to
functionalize regioselectively N-naphthyltri(aryl)phosphor-
anes, either at the P-aryl ring or at the N-naphthyl ring.6k
We are interested in the synthesis of new derivatives of
transition metals containing N-benzoyliminophosphoranes
6 metalated at the benzoyl ring, that is, in exo position
(Figure 1 and Scheme 2). While ortho-palladated complexes
derived from this ligand can be easily obtained by C-H bond
activation, this preparative strategy is not successful in other
metals (for instance, in gold derivatives). Therefore, other
synthetic procedures have to be considered. In order to
expand the synthetic applications of iminophosphoranes,
we thought that ortho-lithiated N-benzoyliminophosphor-
anes 6 would be valuable synthons for the preparation of new
(3) Selected references: (a) Kronenburg, C. M. P.; Amijs, C. H. M.;
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2002, 21, 4662. (b) Baier, F.; Fei, Z.; Gornitzka, H.; Murso, A.; Neufeld, S.;
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C. J.; Lee, S. H.; Yu, S. T.; Na, S. J.; Yun, H.; Lee, B. Y. Organometallics
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K. B.; Sklenak, S.; Bailey, W. F. J. Org. Chem. 2000, 65, 2014, and references
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2008, 1787. (h) Aguilar, D.; Bielsa, R.; Contel, M.; Lledos, A.; Navarro, R.;
Soler, T.; Urriolabeitia, E. P. Organometallics 2008, 27, 2929. (i) Aguilar, D.;
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J. Org. Chem. Vol. 75, No. 19, 2010 6453

Aguilar et al.
JOCArticle
stable functionalized derivatives via carbon-carbon and
carbon-heteroatom bond-forming reactions (Scheme 2).
Iminophosphoranes 6 are bifunctional compounds con-
taining a PdN linkage and a carboxamide moiety (CON)
that might promote lithiation at their respective ortho posi-
tions. Examples of ortho lithiations directed by the CON2a,7
and PN8 groups are well known in the literature. Ortho-
lithiated iminophosphoranes behave as bidentate ligands
and have been used in the preparation of a wide number of
metal complexes through Li-metal exchange reactions.3b,c,f,9
We describe here the regioselective deprotonation of
N-benzoyliminophosphoranes at the ortho position of the
phosphorus and carbonyl group as evidenced from trapp-
ing reactions with methyl iodide, an improved method for
generating ortho-lithiated species I (Scheme 2) via halogen-
lithium exchange, the structural characterization of the
intermediate anion formed based on multinuclear magnetic
resonance studies, and the application of this anion in the
synthesis of new derivatives through electrophilic quench
with alkyl, phosphorus, silyl, tin, and mercury halides,
aldehydes, and iodinating reagents.
SCHEME 3. Ortho-PN Deprotonation of 6a and
Intramolecular Quench
SCHEME 4. Ortho-CO Deprotonation of 6b and Subsequent
Methylation
Results and Discussion
peak at δ 196.68 ppm, assignable to the carbonyl carbon of
the benzophenone-like fragment. On the other hand, the 31
P
Deprotonation of CH Bonds As Synthetic Strategy. Imino-
phosphoranes 6a (R1=R2=H), 6b (R1=3-OMe, R2=H),
and 6c (R1 = H, R2 = 2-Br) have been prepared through
methods described in the literature.10 To ascertain the rela-
tive strength of the functional groups presents in 6 as direc-
tors of ortho metalations (DoM), compound 6a was lithiated
under standard deprotonation conditions previously applied
to similar iminophosphoranes.8c,e However, the reaction of
6a with an organolithium base (n-BuLi, s-BuLi, t-BuLi; 1:1.1
molar ratio) in THF or toluene at -90 °C did not promote
observable deprotonation since, after quenching with methyl
iodide and usual aqueous workup, the crude reaction mix-
ture did not show the incorporation of methyl groups into
the aryl rings. When the mixture of 6a and t-BuLi (1:1.1
molar ratio) was allowed to react at -30 °C, the compound 7
was isolated in 30% yield (Scheme 3), together with the
starting iminophosphorane 6a.
NMR spectrum shows a signal at δ 31.32 ppm, charac-
teristic of tri(aryl)phosphine oxides. It is reasonable to
assume that the synthesis of 7 from 6a occurs through ortho
deprotonation of one P-C6H5 ring by the lithium reagent.
The resulting carbanion may undergo intramolecular
attack to the carbonyl carbon, generating a heterocyclic
alkoxide. This intermediate would be hydrolyzed during the
workup leading to 7.
Deprotonation of 6 occurred at the unwanted ortho posi-
tion with respect to the PN linkage, suggesting that the
acidity and/or directing strength of the PN is higher than
that of the CO group. Moreover, intermolecular electro-
philic trapping of the anion failed due to the favored anionic
cyclization reaction with the nearby carbonyl group. We
reasoned that ortho-CO deprotonation could be promoted
by using iminophosphorane derivatives of 6 containing an
additional DoM group in the benzamide ring that could
cooperate with the CO in directing the lithiation reaction.
A good candidate is iminophosphorane 6b, bearing a methoxy
substituent at the meta position of the CO group. In fact, the
treatment of 6b with s-BuLi (1:1.1 molar ratio) in THF at
-90 °C for 30 min results in the synthesis of 6d in 46%
isolated yield (Scheme 4). The variation of the reaction
conditions (alkyllithium reagents, temperature, and reaction
times) did not improve the yield.
Compound 7 was characterized through spectroscopic
methods. The 13C NMR spectrum shows a very deshielded
(7) (a) Clayden, J.; Stimson, C. C.; Helliwell, M.; Keeman, M. Synlett
2006, 873. (b) Laufer, R.; Veith, U.; Taylor, N. J.; Snieckus, V. Can. J. Chem.
2006, 84, 356. (c) Stavrakov, G.; Simova, S.; Dimitrov, V. Tetrahedron:
Asymmetry 2008, 19, 2110. (d) Tilly, D.; Fu, J.-M.; Zhao, B.-P.; Alessi, M.;
Castenet, A.-S.; Snieckus, V.; Mortier, J. Org. Lett. 2010, 12, 68.
(8) (a) Stuckwisch, C. G. J. Org. Chem. 1976, 41, 1173. (b) Steiner, A.;
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Stalke, D. Angew. Chem., Int. Ed. Engl. 1995, 34, 1752. (c) Lopez-Ortiz, F.
Curr. Org. Synth. 2006, 3, 187. (d) Boubekeur, L.; Ricard, L.; Mezailles, N.;
ꢀ
The results aforementioned show that although regio-
selective ortho deprotonation of iminophosphoranes 6 at either
side of the PNCO moiety is feasible, the synthetic usefulness
of these anions is rather limited due to the intramolecular
quench observed for the ortho-PN anion of the parent com-
pound 6a and the poor performance in the case of the ortho-
CO anion arising from the methoxy derivative 6b. Owing
to these drawbacks, we turned our attention to halogen-
lithium exchange reactions11 as a method for accessing ortho-
lithiated iminophosphoranes 6 in high yield. Compound 6c,
Demange, M.; Auffrant, A.; Le Floch, P. Organometallics 2006, 25, 3091.
ꢀ ꢀ ꢀ
´
(e) Garcıa-Lopez, J.; Fernandez, I.; Serrano-Ruiz, M.; Lopez-Ortiz, F.
Chem. Commun. 2007, 4674.
(9) (a) Wingerter, S.; Gornitzka, H.; Bertrand, G.; Stalke, D. Eur. J.
Inorg. Chem. 1999, 173. (b) Wingerter, S.; Gornitzka, H.; Bertermann, R.;
Pandey, S. K.; Rocha, J.; Stalke, D. Organometallics 2000, 19, 3890.
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(c) Wingerter, S.; Pfeiffer, M.; Stey, T.; Bolboaca, M.; Kiefer, W.; Vadapalli
Chandrasekhar, V.; Stalke, D. Organometallics 2001, 20, 2730. (d) Chan,
K. T. K.; Spencer, L. P.; Masuda, J. D.; McCahill, J. S. J.; Wei, P.; Stephan,
D. W. Organometallics 2004, 23, 381. (e) Brown, S. D. J.; Henderson, W.;
Kilpin, K. J.; Nicholson, B. K. Inorg. Chim. Acta 2007, 360, 1310. (f) Kilpin,
K. J.; Henderson, W.; Nicholson, B. K. Inorg. Chim. Acta 2009, 362, 3669.
(10) (a) Bittner, S.; Assaf, Y.; Krief, P.; Pomerantz, M.; Ziemmnicka,
B. T.; Smith, C. G. J. Org. Chem. 1985, 50, 1712. (b) Bittner, S.; Pomerantz,
M; Assaf, Y.; Krief, P.; Xi, S.; Witczak, M. K. J. Org. Chem. 1988, 53, 1.
(c) Chou, W.-N.; Pomerantz, M.; Witzcak, M. K. J. Org. Chem. 1990, 55,
716, and references therein.
(11) Brandsma, L.; Verkruijsse, H. Preparative Polar Organometallic
Chemistry 1; Springer-Verlag: Berlin, 1987.
6454 J. Org. Chem. Vol. 75, No. 19, 2010

Aguilar et al.
JOCArticle
TABLE 1. Transmetalation-Methylation of Stabilized
SCHEME 5. Synthesis and Suggested Reaction Mechanism for
the Formation of 12
Iminophosphorane 6ca
entry
RLi
ratio 6c:RLi:MeI
6a (%)
6e (%)
1
2
3
4
5
6
7
8
n-BuLi
s-BuLi
t-BuLi
t-BuLi
t-BuLi
s-BuLi
s-BuLi
s-BuLi
1:1.1:2.0b
1:1.1:2.0
1:1.1:2.0
1:1.1:2.0b
1:1.5:2.5
1:1.2:5.0c
1:1.5:2.5
1:2.2:3.0
32
22
36
40
13
86
8
68
78
64
60
87
0
92
94
6
aIn all cases 0.11 M solutions of 6c were employed. Conversions were
established on the basis of 31P{1H} NMR spectra. A 2-8% yield of
Ph3P(O) was always observed. b3 h 30 min of contact time between the Li
base and 6c. cH2O as electrophile, time of contact 0.5 h.
polar PN linkage, leading to the hypervalent phosphorus
intermediate 9.13 This species evolves through elimination
of PhLi to give the cyclic iminophosphorane 10,14 which is
N-methylated by the MeI present in the reaction medium.
Hydrolysis of the resulting phosphonium salt 11 during
aqueous workup furnishes 12,15 characterized on the basis
of the NMR spectra as a mixture of two rotamers due
to restricted rotation around the C-N bond (Supporting
Information).
brominated at the ortho position of the benzoyl fragment, is
readily available.10a
Halogen-Lithium Exchange as Synthetic Strategy. First,
optimized reaction conditions for Br/Li exchange in 6c were
investigated by analyzing the effect of the alkyllithium base
used, stoichiometry, temperature, and time of contact of the
anion with the reference electrophile, MeI. The results are
summarized in Table 1. Of the three bases assayed, s-BuLi
afforded the best results (entries 1-3) in 30 min at -90 °C.
n-BuLi needs a longer reaction time (3 h 30 min) with
substrate 6c to afford similar conversions (entry 1). In the
case of t-BuLi the increase of the lithiation time produces a
decrease in the yield of the methylated species 6e (entry 4).
Better yields were obtained only at the expense of the
increase of the amounts of t-BuLi and methylating reagent
(1:1.5:2.5; entry 5). Gratifyingly, the use of the same or
slightly higher molar ratios of s-BuLi and MeI (with respect
to entry 5: entries 7, 8) produced the highest conversions of
6e, allowing the use of the less hazardous s-BuLi instead of
t-BuLi. Thus, 6e was almost quantitatively obtained when
the Br/Li exchange was performed with 2.2 equivalents of
s-BuLi at -90 °C in THF during 30 min, and the anion
formed (8) was quenched with MeI.12 In most studied cases
significant amounts of the debrominated compound 6a were
formed, which suggests that the trapping reaction with MeI
proceeds slowly and the anion 8 remaining in solution is
protonated during aqueous workup to give 6a. This hypothe-
sis was demonstrated by using water as electrophile (entry 6).
In this case the anion was instantaneously quenched, afford-
ing 6a in 86% yield. It must be pointed out that this experi-
ment does not exclude that a small amount of 8 undergoes
quenching through proton abstraction from the solvent.
Increasing the temperature of the lithiation-methylation
process to -30 °C lead to a mixture of compounds. Col-
umn chromatography allowed isolating the major product
N-methylated carboxamide 12, bearing a diphenylphos-
phinoyl group at the ortho position, in 41% yield (Scheme 5).
The formation of 12 may be explained by assuming that the
ortho anion arising from the Br/Li exchange reaction under-
goes intramolecular attack to the phosphorus atom of the
31P NMR monitoring of the reaction showed the presence
of a signal at δ -60 ppm appropriate for pentacoordinated
phosphorane 9.16 Ortho functionalization of aromatic rings
with P-containing groups involving DoM reactions and
P-X-Ar (X = N, O, S) to P-CAr migration rearrangement
has been described in a number of cases.17 To the best of our
knowledge, there is no precedent of the participation of
iminophosphoranes in this type of transformations.
Reactivity of the Lithiated Species 8. Once optimized
reaction conditions for the Br-Li exchange and methylation
of 6c were available (entry 8, Table 1), we sought to extend
the process to other electrophiles. To evaluate the scope of
the method, the quench reagents selected involve C-C and
(13) Formation of pentacoordinated phosphoranes through intramole-
cular addition of XH groups (X = O, NH, NHPh) to iminophosphoranes
ꢀ
has been described. (a) Sanchez, M.; Brazier, J.-F.; Houalla, D.; Munoz, A.;
Wolf, R. J. Chem. Soc., Chem. Commun. 1976, 730. (b) Cadogan, J. I. G.;
Gosney, I.; Henry, E.; Naisby, T.; Nay, B.; Stewart, N. J.; Tweddle, N. J.
J. Chem. Soc., Chem. Commun. 1979, 189.
(14) This PhLi elimination is analogous to the displacement of PhLi by
organolithium bases observed in Ph3PdO. (a) Seyferth, D.; Welch, D. E.;
Heeren, J. K. J. Am. Chem. Soc. 1963, 85, 642. (b) Seyferth, D.; Welch, D. E.;
Heeren, J. K. J. Am. Chem. Soc. 1964, 86, 1100. (c) Wittig, G.; Cristau, H. J.
Bull. Soc. Chim. Fr. 1969, 1293.
(15) Briggs, E. M.; Brown, G. W.; Jiricny, J.; Meidine, M. F. Synthesis
1980, 295.
(16) Pentacoordinated phosphoranes are characterized by large negative
31P chemical shifts. (a) Chesnut, D. B.; Quin, L. D. Tetrahedron 2005, 61,
12343, and references therein. (b) For related phosphoranes see also: Garcıa-
´
ꢀ
´
a-Granda, S.; Lopez-
ꢀ
ꢀ
ꢀ
Lopez, J.; Peralta-Perez, E.; Forcen-Acebal, A.; Garcı
Ortiz, F. Chem. Commun. 2003, 856.
(17) Selected references: (a) Melvin, N. S. Tetrahedron Lett. 1981, 22,
3375. (b) Heinicke, J.; Nietzschmann, E.; Tzschach, A. J. Organomet. Chem.
1983, 243, 1. (c) Dhawan, B.; Redmore, D. J. Org. Chem. 1984, 49, 4018.
(d) Jardine, A. M.; Vather, S. M.; Modro, T. A. J. Org. Chem. 1988, 53, 3983.
(e) Masson, S.; Saint-Clair, J.-F.; Saquet, M. Tetrahedron Lett. 1994, 35,
3083. (f) Heinicke, J.; Kadyrov, R. J. Organomet. Chem. 1996, 520, 131.
(g) He, Z.; Modro, T. A. Synthesis 2000, 565. (h) Legrand, O.; Brunel, J. M.;
Buono, G. Tetrahedron 2000, 56, 595. (i) Moulin, D.; Bago, S.; Bauduin, C.;
ꢀ
Darcel, C.; Juge, S. Tetrahedron: Asymmetry 2000, 11, 3939. (j) Mauger, C.;
(12) In all cases, small amounts of Ph3P(O) were observed in the 31P NMR
spectra of the crude reaction mixtures most probably due to hydrolysis of the
PdN linkage of the respective iminophosphoranes during workup.
Vazeux, M.; Masson, S. Tetrahedron Lett. 2004, 45, 3855. (k) Velder, J.;
Robert, T.; Weidner, I.; Neudoerfl, J.-M.; Lex, J.; Schmalz, H.-G. Adv.
Synth. Catal. 2008, 350, 1309.
J. Org. Chem. Vol. 75, No. 19, 2010 6455

Aguilar et al.
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SCHEME 6. Reactivity of Lithiated Species 8 toward Different
Electrophiles
SCHEME 7. Examples of o-Lithiated Dimers Bearing Amide or
Amide-like Functional Groups
via C-C metal-catalyzed cross-coupling reactions.18 Com-
pound 15 can also be viewed as an interesting alternative to
known P,N (or even P,O) chelating ligands.19 Using the same
strategy the novel stannanes 16-18 and silane 19 (Scheme 6)
have been obtained by reaction of 8 with R3SnCl (R=Me,
nBu, Ph) or Me3SiCl, respectively. The organotin derivatives
were isolated as air-stable white solids in high (16) to
moderate (17, 18) yields, while the organosilicon species 19
was isolated as large colorless needles in high yield. Products
16-19 are interesting reagents for participating in, for
instance, Stille (Sn) and/or Hiyama (Si) Pd-catalyzed C-C
couplings processes. This wide prospect of C-heteroatom
couplings (C-Hg, C-I, C-P, C-Sn, and C-Si), which
shows the high synthetic potential of lithiated species 8,
can be complemented with the formation of new carbon-
carbon bonds, other than the methylation reactions previously
described. Thus, addition of benzaldehyde to a solution of 8 led
after the usual workup to the hydroxyalkyl derivative 20. A
brief discussion of the structural characterization of products
13-20 is included in the Supporting Information.
TABLE 2. Regioselective Synthesis of Functionalized
Iminophosphoranes by Br/Li-Exchange-Electrophilic Quench
entry
compd
Eþ
E
yield (%)
1
2
3
4
5
6
7
8
13
14
15
16
17
18
19
20
HgCl2
ICH2CH2I
Ph2PCl
Me3SnCl
Bu3SnCl
Ph3SnCl
Me3SiCl
PhCHO
Hga
I
62
92
41
87
49
44
89
77
PPh2
SnMe3
SnBu3
SnPh3
SiMe3
PhCHOH
aThe bis-aryl derivative was obtained (Scheme 6).
C-heteroatom bond-forming reactions. The obtained
results are shown in Scheme 6 and Table 2.
Structural Characterization of Anionic Species 8. NMR
samples of 8 were prepared in 5 mm tubes, in nondeuterated
THF, under conditions analogous to those used in the bulk
(see Supporting Information for experimental details).20 The
stoichiometry selected corresponded to a ratio of 6c:s-BuLi
of 1:1.2 (Table 1, entry 6). We used an amount of base lower
than the optimum value (entry 8) to avoid possible compli-
cations derived from the formation of mixed aggregates
between the base and 8 when the bromine-lithium exchange
is performed in the presence of a larger excess of s-BuLi. The
samples prepared at -90 °C were transferred to the magnet
precooled at the same temperature. After a short time
interval (2-5 min) for temperature and homogeneity adjust-
ment a series of 7Li, 31P, and 13C NMR spectra were acquired
The reaction of a THF solution of 8 with HgCl2 (2:1 molar
ratio) proceeded under very mild experimental conditions,
affording bis-aryl derivative 13. After the addition of the
mercury salt at -90 °C, stirring was maintained at this
temperature for an additional 30 min, and subsequently it
was allowed to reach room temperature overnight. Then,
simple extraction with CH2Cl2 in order to eliminate the
lithium salts and further evaporation of the organic extracts
gave pure 13 in moderate yield. The ortho-regioselective
introduction of heteroatoms other than bromine in the
benzamide skeleton also occurs under smooth conditions.
The treatment of 8 with di-iodoethane (ICH2CH2I as syn-
thetic equivalent of Iþ) and Ph2PCl (as a source of Ph2Pþ)
afforded excellent yields of 14 and moderate yields of 15,
respectively (entries 2, 3). Compound 14 represents a valu-
able starting material for accessing new iminophosphoranes
(19) (a) Pfeiffer, J.; Kickelbick, G.; Schubert, U. Organometallics 2000,
19, 62. (b) Helmchen, G.; Pfaltz, A. Acc. Chem. Res. 2000, 33, 336. (c) Chen,
H.-P.; Liu, Y.-H.; Peng, S.-M.; Liu, S.-T. Organometallics 2003, 22, 4893.
(d) Speiser, F.; Braunstein, P.; Saussine, L. Acc. Chem. Res. 2005, 38, 784.
(e) Peloso, R.; Pattacini, R.; Cazin, C. S. J.; Braunstein, P. Inorg. Chem. 2009,
48, 11415.
(20) About 5-10 samples were examined. They gave consistent and
reproducible results. Among the variables analyzed we evaluated the effect
of concentration, starting temperature, and time of metalation.
(18) For reviews see: (a) Hartung, C. G.; Snieckus, V. In Modern Arene
Chemistry; Astruc, D., Ed.; Wiley-VCH: Weinheim, FRG, 2002; p 330.
(b) Anctil, E. J. G.; Snieckus, V. J. Organomet. Chem. 2002, 653, 150.
(c) Anctil, E. J. G.; Snieckus, V. In Metal-Catalyzed Cross-Coupling Reac-
tions, 2nd ed.; de Meijere, A.; Diederich, F., Eds.; Wiley-VCH: Weinheim,
FRG, 2004; Chapter 14, p 761.
6456 J. Org. Chem. Vol. 75, No. 19, 2010

Aguilar et al.
JOCArticle
to unravel the solution structure of 8. 1H NMR proved to be
useless due to the appearance of all aromatic protons in a
narrow spectral region.
At -80 °C four singlets located at δP 15.4 (A), 16.1 (B), 17.0
(6c), and 17.5 (6a) ppm in a ratio 1:1:0.6:0.6, respectively,
were observed. The signals of starting material 6c and the
protonated derivative 6a were readily assigned on the basis
of their corresponding 31P chemical shifts.28 Although the
concentration of these compounds is relatively high, they do
not intervene in the structure of 8 (see below). Increasing
the temperature of the sample produced two simultaneous
effects on the 31P NMR spectra: the exchange between the
signals A and B (coalescence temperature Tc ≈ -40 °C) and
the progressive disappearance of these two signals in parallel
with a significant growth of the resonance of 6a (Figure S34).
At -20 °C signals A and B vanished. Quenching the NMR
sample with water and subsequent aqueous workup afforded
a crude mixture, which 31P NMR spectrum showed exclu-
sively the presence of 6a and 6c. Interestingly, the slight
shielding of the phosphorus signals for lithiated species A
and B as compared to the nonlithiated ones 6a and 6c
suggests that the PdN bond is weakly or not coordinated
at all to the lithium cation (see below). All these NMR data
are consistent with the existence in solution of two separated
lithium species differing in the aggregation state. 31P NMR
measurements in the concentration range 0.04-0.150 M
revealed that the variations of the integrals of the high-field
31P signals A and B at -80 °C correlate reasonably well
with an equilibrium monomer-dimer. From the log[dimer]
versus log[monomer] plot (Figure 2), a slope of 1.85 and an
apparent equilibrium constant KMD of 15.6 M-1 at this
temperature was calculated, assuming that the major species
in the most diluted sample (0.04 M) is the monomer A. In the
following, monomeric species A will be also represented as M
and dimers B will be denoted as Dn, where the label n=1, 2,
etc., refers to isomers arising from different arrangements of
the interacting monomers.
To further prove the exchange between phosphorus A and
B, we performed a 2D exchange spectroscopy, 31P{1H}
EXSY, experiment. Using a mixing time τm of 50 ms the
expected correlations indicative of exchange between species
A and B were clearly observed (Figure 3), and, what may be
more significant, the absence of any correlation for the
signals corresponding to 6a and 6c indicates that these
neutral compounds do not participate in a dynamic process
involving lithiated species A and B.
Direct evidence on the aggregation state of aryllithiums
can be derived from 13C NMR data through the well-known
correlation of multiplicity and chemical shift of the ipso
carbon with the degree of aggregation. Increasing aggrega-
tion causes a shielding of the Cipso due to the existence of a
larger number of C-Li contacts.29,30 A recent example
Extensive structural studies of lithiated aromatic species
have provided a general picture about the privileged struc-
tures that ortho-lithiated compounds may adopt.21 In non-
coordinating or ethereal solvents, they tend to form aggregates
by assembling monomeric units through electron-deficient
C-Li-C bridges. In dimers, this binding mode leads to
characteristics Li2C2 cores in which the deprotonated carbon
is bound to two lithium atoms and the lithiums attain the
favorite 4-fold coordination by chelation with the ortho
functional group and/or through bonding to solvent mole-
cules. Ortho-lithiated carboxamides 2122 and 2223 and
oxazolidines 2324 and 2425 are examples structurally related
to ortho lithium species 8, showing this self-aggregation
mode (Scheme 7). Very recently, some of us have reported
the formation of Li-O-Li-O four-membered rings in
the dimerization of ortho-lithiated N,N-diisopropyl-P,P-
diphenylphosphinic amide 25.26 This structural motif in
which dimers show only one Cipso-lithium contact was
unprecedented in aryllithium chemistry.
Phosphorus-31 NMR constitutes a sensitive and easy probe
for monitoring in situ NMR reactions,8e,27 and this nucleus
was our first choice for obtaining structural information of 8.
(21) For recent references see: (a) Reich, H. J.; Goldenberg, W. S.;
Sanders, A. W.; Tzschucke, C. C. Org. Lett. 2001, 3, 33. (b) Reich, H. J.;
€
Goldenberg, W. S.; Gudmundsson, B. O.; Sanders, A. W.; Kulicke, K. J.;
Simon, K.; Guzui, I. A. J. Am. Chem. Soc. 2001, 123, 8067. (c) Reich, H. J.;
Goldenberg, W. S.; Sanders, A. W.; Jantzi, K. L.; Tzschucke, C. C. J. Am.
Chem. Soc. 2003, 125, 3509. (d) Vestergren, M.; Eriksson, J.; Hilmersson, G.;
Hakansson, M. J. Organomet. Chem. 2003, 682, 172. (e) Kronenburg,
C. M. P.; Rijnberg, E.; Jastrzebski, J. T. B. H.; Kooijman, H.; Lutz, M.;
Spek, A. L.; Gossage, R. A.; van Koten, G. Chem. Eur. J. 2004, 11, 253.
;
(f) Reich, H. J.; Goldenberg, W. S.; Sanders, A. W. Arkivok 2004, 97.
(g) Kronenburg, C. M. P.; Rijnberg, E.; Jastrzebski, J. T. B. H.; Kooijman,
H.; Spek, A. L.; van Koten, G. Eur. J. Org. Chem. 2004, 153. (h) Arink,
A. M.; Kronenburg, C. M. P.; Jastrzebski, J. T. B. H.; Lutz, M.; Spek, A. L.;
Gossage, R. A.; van Koten, G. J. Am. Chem. Soc. 2004, 126, 16249.
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(i) Linnert, M.; Bruhn, C.; Ruffer, T.; Schmidt, H.; Steinborn, D. Organo-
metallics 2004, 23, 3668. (j) Jantzi, K. L.; Puckett, C. L.; Guzei, I. A.; Reich,
H. J. J. Org. Chem. 2005, 70, 7520. (k) Jambor, R.; Dostal, L.; Cisarova, I.;
Rouzicka, A.; Holecek, J. Inorg. Chim. Acta 2005, 358, 2422. (l) Singh, K. J.;
Collum, D. B. J. Am. Chem. Soc. 2006, 128, 13753. (m) Kawachi, A.; Tani,
A.; Machida, K.; Yamamoto, Y. Organometallics 2007, 26, 4697. (n) Riggs,
J. C.; Singh, K. J.; Yun, M.; Collum, D. B. J. Am. Chem. Soc. 2008, 130,
13709. (o) Chase, P. A.; Lutz, M.; Spek, A. L.; Gossage, R. A.; van Koten, G.
Dalton Trans. 2008, 5783. (p) Singh, K. J.; Hoepker, A. C.; Collum, D. B.
J. Am. Chem. Soc. 2008, 130, 18008. (q) Konrad, T. M.; Gruenwald, K. R.;
Belaj, F.; Moesch-Zanetti, N. C. Inorg. Chem. 2009, 48, 369. (r) Neshat, A.;
Seambos, C. L.; Beck, J. F.; Schmidt, J. A. R. Dalton Trans. 2009, 4987.
(s) Petrov, A. R.; Rufanov, K. A.; Harms, K.; Sundermeyer, J. J. Organomet.
Chem. 2009, 694, 1212.
(22) Clayden, J.; Davies, R. P.; Hendy, M. A.; Snaith, R.; Wheatley,
A. E. H. Angew. Chem., Int. Ed. 2001, 40, 1238.
(23) Armstrong, D. R.; Boss, S. R.; Clayden, J.; Haigh, R.; Kirmani,
B. A.; Linton, D. J.; Schooler, P.; Wheatley, A. E. H. Angew. Chem., Int. Ed.
2004, 43, 2135.
(24) Stol, M.; Snelders, D. J. M.; Pater, J. J. M.; van Klink, G. P. M.;
Kooijman, H.; Spek, A. L.; van Koten, G. Organometallics 2005, 24, 743.
(25) Jantzi, K. L.; Guzei, I. A.; Reich, H. J. Organometallics 2006, 25, 5390.
(28) In all samples prepared with a ratio of 6c:s-BuLi of 1:1.2 variable
amounts of unreacted 6c and protonated 6a were detected, in agreement with
the reactions performed in laboratory scale. Entry 6 of Table 1 shows that
lithiation is not complete. In addition, the absence of stirring in the NMR
tube, possible difusion of air into the sample, and proton abstraction from
the solvent may contribute to the partial quench of the anion.
ꢀ
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(26) Fernandez, I.; Ona-Burgos, P.; Oliva, J. M.; Lopez-Ortiz, F. J. Am.
Chem. Soc. 2010, 132, 5193.
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(27) (a) Lopez-Ortiz, F.; Pelaez-Arango, E.; Tejerina, B.; Perez-Carreno,
a-Granda, S. J. Am. Chem. Soc. 1995, 117, 9972. (b) Fernandez, I.;
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~
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E.; Garcı
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(29) (a) Bauer, W.; Schleyer, P. V. P. Adv. Carbanion Chem. 1992, 1, 89.
€
ꢀ
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Alvarez-Gutierrez, J. M.; Kocher, N.; Leusser, D.; Stalke, D.; Gonzalez, J.;
Lopez-Ortiz, F. J. Am. Chem. Soc. 2002, 124, 15184. (c) Price, R. D.;
ꢀ
(b) Gunther, H. In Advanced Applications of NMR to Organometallic
Chemistry; Gielen, M.; Willem, R.; Wrackmeyer, B., Eds.; John Wiley:
New York, 1996; Chapter 9, pp 247-290.
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Fernandez, I.; Ruiz-Gomez, G.; Lopez-Ortiz, F.; Davidson, M. G.; Cowan,
J. A.; Howard, J. A. K. Organometallics 2004, 23, 5934. (d) Fernandez, I.;
ꢀ
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(30) (a) Seebach, D.; Hassig, R.; Gabriel, J. Helv. Chim. Acta 1983, 66,
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Lopez-Ortiz, F. Chem. Commun. 2004, 1142. (e) Fernandez, I.; Gonzalez, J.;
Lopez-Ortiz, F. J. Am. Chem. Soc. 2004, 126, 12551. (f) Ruiz-Gomez, G.;
308. (b) Bauer, W.; Winchester, W. R.; Schleyer, P. v. R. Organometallics
1987, 6, 2371. (c) Wehmschulte, R. J.; Power, P. P. J. Am. Chem. Soc. 1997,
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Gudmundsson, B. O.; Dykstra, R. R.; Phillips, N. H. J. Am. Chem. Soc. 1998,
120, 7201.
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FIGURE 2. (a) Log-log monomer-dimer plot based on variable-concentration 31P NMR (202.46 MHz) spectra of 8 at -80 °C,
(b), illustrating the equilibrium between monomer A and dimer B (see Supporting Information for details).
conditions, we use s-BuLi containing 6/7Li isotopes in natural
7
abundance. This implies that Li is the nucleus of choice.29
The 7Li NMR spectrum of a 0.11 M sample of 8 measured at
-80 °C exhibits three major lithium signals, at δLi -1.51 (I),
0.19 (II), and 0.64 (III) ppm, with relative integrals of
1.3:1.1:1, respectively. As in the 31P and 13C NMR spectra,
no coupling of these nuclei to 7Li was observed in the range
from -80 to -115 °C. In order to shed light on the, somehow
7
surprising, counting of lithium signals, a series of 2D Li
EXSY experiments were performed (Figure 4).
At the lowest mixing time of 5 ms used, exchange is
relatively slow and only correlations of I and III with II were
clearly observed (Figure 4a). Increasing the mixing time to
50 ms favors the random exchange among all species in
solution, becoming evident the exchange between I and III
FIGURE 3. 31P{1H} EXSY NMR spectrum (202.46 MHz) of
(see inset boxes in Figure 4b) together with the previously
observed exchange of I/III with II. The results of the NMR
0.15 M 8 at -80 °C in THF with a mixing time of 50 ms.
study are consistent with complex 8 existing in THF solution
closely related to 8 is provided by the solution structure of
as a mixture of one monomer II and two different dimers I
24.31 In 3:2 THF/Et2O at -114 °C exists a mixture of a
monomer (24)1 and a dimer (24)2. The Cipso of (24)1 appears
7
and III. In addition, the 2D Li EXSY map indicates that
dimers I and III exchange preferably through the monomer
as a quartet [1J(7Li,13C) = 29.3 Hz] at δC 206.6 ppm. The
II; that is, they break up into monomers, which subsequently
C-Li carbon of dimer (24)2 is characterized by a heptet
recombine back to dimers. The lack of cross-peaks between I
1
of J(7Li,13C) = 19.0 Hz at δC 194.6 ppm. Similar values
and III for τm=5 ms validates this statement.
are found for other ortho-substituted aryllithiums.30,31
Amine- and ether-chelated ortho aryllithiums have been
shown to exist as an equilibrium mixture of dimeric isomers
Although the multiplicity of the Cipso of 8 could not be
unraveled in the temperature range investigated (down to
-115 °C), the two broad signals located at δC 203.9 and
192.9 ppm are a clear indication of the presence of a monomer
26, 27, and 28 (Chart 1).21a-c,f,h,32
In complex 26 the donating arms are coordinated to
the same lithium atom, while in aggregates 27 and 28, each
and a dimer, respectively (Figure S32, Supporting Information).
lithium atom is coordinated to only one side arm either from
The chemical shift difference of 11 ppm between monomer and
dimer C-Li signals is almost identical to that of related well-
the same face, 27, or from the opposite face, 28, of the C2Li2
plane. The 7Li NMR spectra of dimers 26 are characterized
by two different lithium signals in the same ratio, whereas
the lithium atoms of species 27 and 28 are equivalent and
would show only one signal for each structure. Reich and
co-workers have elegantly shown that the ratio between
characterized ortho-lithiated phenyloxazolines.31
The next relevant source of structural information in
lithiated organophosphorus compounds is the lithium nucleus.
Since we try to reproduce in the NMR tube the bulk reaction
(31) Jantzi, K. L.; Guzei, I. A.; Reich, H. J. Organometallics 2006, 25,
5390.
€
(32) Reich, H. J.; Gudmundsson, B. O. J. Am. Chem. Soc. 1996, 118, 6074.
6458 J. Org. Chem. Vol. 75, No. 19, 2010

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FIGURE 5. Variable-concentration 7Li NMR (194.37 MHz) spec-
tra of 8 in THF at -80 °C. Gaussian multiplication (LB=-20,
GB = 0.04) of the FID prior to FT was applied.
CHART 2. Species 8 Characterized in THF Solution
FIGURE 4. 7Li EXSY NMR spectra (194.37 MHz) of a 0.11 M
sample of 8 at -80 °C in THF with mixing times of (a) 5 ms and
(b) 50 ms.
CHART 1. Structures of Amine- and Ether-Chelated
Aryllithiums (X = NR2, OR)
one may conclude that each signal I/III represents a different
dimeric species. Consequently, lithiums I and III must arise
from dimers of 8 analogous to model systems 27 and 28,
given that their population may be different and they show
only one lithium signal. To summarize, ortho-CO-lithiated
iminophosphorane 8 exists as a mixture of monomer M and
two dimers, D1 and D2 (Chart 2). It is not possible to assign
unequivocally lithiums I and III to the corresponding
aggregate on the basis of their NMR data.21b Significantly,
organolithium 8 can be envisaged as a particular type of
ortho-lithiated carboxamide, and these anions have been
characterized in the solid state as dimers of type D1 (see
compounds 21 and 22, Scheme 7).
aggregates 26, 27, and 28 depends on the nature of the
substituents on NR2 or OR. For instance, in amine-chelating
derivatives, X = NR1R2, in which R1 = R2 = Me, the ratio
26:27:28 in 3:2:1 THF/Me2O/Et2O at -137 °C is 38:15:47,
whereas for R1 = Me, R2 = iPr in 3:2 THF/ether the major
isomer is 27.21b Variable-concentration 7Li NMR spectra of
8 contributed to clarify the solution structure of this organo-
lithium reagent (Figure 5). Lithium II (δLi 0.19 ppm)
showed the lowest integral of all signals at the highest
concentration assayed (150 mM) and became the domi-
nant signal in the most diluted sample. This concentration-
dependent behavior allows assigning lithium II to the mono-
mer species (M). Since the 31P NMR study evidenced the
existence of a monomer-dimer equilibrium, lithium signals I
and III must proceed from dimeric aggregates (Dn). Taking
into account that lithium I is not detected in the 40 mM
sample and that the relative amounts of I (integral 0.74)
and III (integral 1) are similar at a concentration 150 mM,
Conclusions
In summary, we have shown that N-aroyl-P,P,P-triphenyl-
iminophosphoranes 6 can be selectively deprotonated at
the ortho-CO and ortho-PN positions by alkyllithium bases
and subsequently methylated to give new iminophosphor-
anes, albeit in low yields. A more efficient procedure for
accessing ortho-CO-lithiated derivatives of 6 has been devel-
oped making use of Li/Br exchange methodology. The
lithiated species 8 proved to be stable at low temperature.
J. Org. Chem. Vol. 75, No. 19, 2010 6459

Aguilar et al.
JOCArticle
Trapping reactions with a representative series of electro-
philes allowed the transformation of the C-Li bond of 8 into
a wide variety of C-X (X = I, P, Si, Sn, Hg) and C-C bonds,
providing access to new stabilized iminophosphoranes33
not accessible through other synthetic pathways.
(0.644 g, 1.40 mmol) in dry THF (25 mL) at -90 °C was slowly
added 2.0 mL of BuLi (1.4 M, 2.80 mmol) over a period of
s
1 min. The resulting deep red solution was stirred at -90 °C for
30 min. Quenching the anion with MeI indicated that the yield of
[Li{C6H4(C(O)NdPPh3)-2}]n 8 is higher than 95% (see main
text). NMR samples of 8 were prepared in nondeuterated THF.
The solution structure of the key intermediate ortho-CO-
lithiated 8 has been elucidated through multinuclear mag-
netic resonance studies. In THF 8 exists as a mixture of three
species, one monomer, M, and two dimers, D1 and D2, in
which the monomeric units are self-assembled through C2Li2
cores. Each lithium atom is part of a five-membered-ring
chelate due to the coordination with the oxygen atom of the
carbonyl side arm. Dimers differ in the relative orientation
of the two five-membered-ring chelates with respect to the
plane defined by the C2Li2 core, to the same or opposite
sides, leading to a structure with a plane of symmetry, D2, or
a center of inversion, D1, respectively. Further applications
of lithiated species 8 and the ortho-CO-functionalized imino-
phosphoranes in organic and organometallic chemistry are
under investigation.
1
The H NMR (500.13 MHz) spectrum shows broad signals in
the aromatic region arising from species 8 overlapped with 6a
and 6c and is uninformative. The 13C NMR spectrum show
similar features. The relevant signals arise from the C-Li
carbons at δ 203.9 and 192.9 ppm (Figure S35). 7Li NMR
(THF, 194.37 MHz) δ -1.51, 0.19, 0.64; 31P{1H} NMR
(THF, 202.46 MHz) δ 15.4, 16.1.
Synthesis of 2-(Diphenylphosphoryl)-N-methylbenzamide, 12.
To a solution of 6c (0.644 g, 1.40 mmol) in 20 mL of dry THF, at
-30 °C, was slowly added 2.0 mL of sBuLi (1.4 M, 2.8 mmol).
The red solution obtained was stirred for 30 min at this
temperature; then MeI (348.4 μL, 5.60 mmol) was added, and
the stirring was maintained at -30 °C during 2 additional hours.
After the reaction time, the resulting colorless solution was
evaporated to dryness. The treatment of the residue with Et2O
(15 mL) gave impure 12, which was purified by column chroma-
tography (AcOEt/MeOH, 9:1), affording pure 12 as a mixture
of two isomers in 0.4:1 molar ratio. Obtained: 0.193 g (41%
yield). M and m stand for major and minor isomer, respectively.
IR (Nujol) ν 3220 (N-H), 1658 (CdO), 1102 (PdO) cm-1; 1H
NMR (CDCl3, 500.13 MHz) δ 2.27-2.30 (d overlapped, CH3
M þ m), 7.13 (ddd, H6, C6H4 M þ m), 7.49-7.60 (m, H5
(C6H4) þ Hm þ Hp (PPh2), M þ m), 7.66-7.71 (m, Ho, PPh2,
M þ m), 8.01 (t, H4, C6H4, 3JH4H3 = 3JH4H5 = 7.5, m), 8.09 (t,
Experimental Section
For all compounds, C1 is assigned to the carbon linked to the
CO group. Carbon atoms of the P-phenyl rings are labeled as Ci
(ipso), Co (ortho), Cm (meta), and Cp (para).
Synthesis of 2-Bromo-N-(triphenyl-λ5-phosphanylidene)benz-
amide, 6c. Compound 6c has been obtained following the
same experimental method as that reported previously for other
stabilized iminophosphoranes.10a Therefore, PPh3 (2.402 g, 9.15
mmol) was reacted with di-tert-butyl azadicarboxylate (DBAD)
(2.109 g, 9.15 mmol) and 2-bromobenzamide (1.832 g, 3.98
mmol) in THF at 0 °C to give 6c as a white solid in quantitative
yield. 1H NMR (CDCl3, 400.13 MHz) δ 7.18 (m, 1H, C6H4Br),
7.31 (m, 1H, C6H4Br), 7.52 (m, 6H, PPh3), 7.60 (m, 4H, 1H
C6H4Br þ PPh3), 7.88 (m, 7H, 1H C6H4Br þ PPh3); 13C{1H}
NMR (CDCl3, 100.61 MHz) δ 120.6 (s, C6, C6H4Br), 126.8 (s,
C6H4Br), 127.8 (d, Ci, PPh3, 1JPC = 99.3), 128.7 (d, Cm, PPh3,
3JPC = 12.4), 129.8 (s, C6H4Br), 130.7 (s, C6H4Br), 132.4 (d, Cp,
H4, C6H4, 3JH4H3 = 3JH4H5 = 7.5, M), 8.57 (t, H3, C6H4, 4JHP
=
4.8, 3JHH = 7.0, m), 8.60 (t, H3, C6H4, 4JPH = 4.4, 3JHH = 7.0,
m), 8.73 (d, 1H, NH, 3JHH = 4.7, m), 8.88 (d, 1H, NH, 3JHH
=
4.6, M); 13C{1H} NMR (CDCl3, 125.76 MHz) δ 26.1 (s, CH3,
m), 26.1 (s, CH3, M), 116.7 (d, Ci, PPh2, 1JPC = 94.0, m), 121.7
(d, Ci, PPh2, 1JPC = 94.4, M), 129.8 (d, Cm, PPh2, 3JPC = 13.1,
3
M), 129.8 (d, Cm, PPh2, JPC = 13.0, m), 131.7 (d, C3, C6H4,
3
3JPC = 13.6, m), 131.9 (d, C3, C6H4, JPC = 13.4, M), 133.8
2
(d, Co, PPh2, JPC = 9.9, M), 133.7-134.1 (several d over-
lapped, Co þ Cp (PPh2) þ C5 (C6H4), M þ m), 136.0 (d, C4,
C6H4, 4JPC = 2.8, m), 136.1 (d, C4, C6H43, 4JPC = 2.8, M), 137.0
(d, C6, C6H4, M þ m), 166.3 (d, CO, JPC = 2.5, m), 166.4
4
2
PPh3, JPC = 2.9), 133.3 (d, Co, PPh3, JPC = 10.1), 133.4 (s,
3
3
C6H4Br), 142.0 (d, C1, C6H4Br, JPC = 21.2), 177.3 (d, CO,
(d, CO, JPC = 2.8, M); signals corresponding to C1 and C2
2JPC = 6.1); 31P NMR (CDCl3, 161.98 MHz) δ 21.0. Anal.
Calcd for C25H19BrNOP: C, 65.23; H, 4.16; N, 3.04. Found:
C, 65.23; H, 4.17; N, 3.13.
(C6H4) were not observed; 31P{1H} NMR (CDCl3, 202.4 MHz)
δ 27.2 (M), 27.1 (m); MS (MALDI þ) 200 (90%) [OdPPh2]þ.
Synthesis of Bis{2-[(triphenyl-λ5-phosphanylidene)carbamoyl]-
phenyl}mercury(II), 13. To a solution of the iminophosphorane
6c (0.644 g, 1.40 mmol) in dry THF (25 mL) at -90 °C was
slowly added 2.0 mL of sBuLi (1.4 M, 2.80 mmol) over a period
of 1 min. The resulting deep red solution of 8 was stirred at
-90 °C for 30 min. Then HgCl2 (0.190 g, 0.70 mmol) was added
in one portion, and the mixture was further stirred for 15 h,
allowing it to reach room temperature. Then, the solvent was
evaporated to dryness. The white residue was extracted with
CH2Cl2 (3ꢀ15 mL), and the combined extracts were concen-
trated almost to dryness (∼1 mL). The oily residue was treated
with Et2O (15 mL). Further stirring gave 13 as a white solid,
which was filtered, washed with Et2O (15 mL), and dried under
vacuum. Obtained: 0.414 g (62% yield). IR (Nujol) ν 1648
(CdO), 1284 (PdN) cm-1; 1H NMR (CDCl3, 400.13 MHz) δ
7.37-7.39 (m, 2H, H4 þ H5, C6H4), 7.47-7.54 (m, 7H, H6
(C6H4) þ Hm (PPh3)), 7.60 (m, 3H, Hp, PPh3), 7.80 (m, 6H, Ho,
Synthesis of 3-Methoxy-2-methyl-N-(triphenyl-λ5-phosphanyl-
idene)benzamide, 6d. To a suspension of 6b (0.200 g, 0.46 mmol)
s
in dry THF (20 mL) at -90 °C was added 0.36 mL of BuLi
(1.4 M, 0.51 mmol). The red solution was stirred for 30 min at
this temperature. After this time MeI (63.50 μL, 1.02 mmol)
was added, and the mixture was further stirred for 2 h at
-90 °C. Then, the colorless solution was diluted with CH2Cl2
(15 mL) and washed with H2O (3 ꢀ 20 mL). The organic phase
was extracted, dried by stirring with anhydrous MgSO4, and
evaporated to dryness, affording 6d as a white solid. Obtained:
1
0.095 g (46% yield). H NMR (CDCl3, 400.13 MHz) δ 2.23
=
(s, 3H, CH3), 3.85 (s, 3H, OMe), 6.87 (d, 1H, H6, C6H3, 3JH6H5
7.2), 7.17 (t, 1H, H5, C6H3, 3JH5H4 = 7.3), 7.45-7.51 (m, 9H,
Hm þ Hp (PPh3)), 7.69 (m, 6H, Ho, PPh3), 7.78 (d, 1H, H4,
3
C6H3, JH4H3 = 7.7); 31P{1H} NMR (CDCl3, 161.98 MHz)
δ 20.8.
Synthesis of {2-[(Triphenyl-λ5-phosphanylidene)carbamoyl]-
phenyl}lithium, 8. To a solution of the iminophosphorane 6c
3
PPh3), 8.46 (dd, 1H, H3, C6H4, JH3H4 = 7.8, 4JH3H5 = 1.5);
13C{1H} NMR (CDCl3, 100.61 MHz) δ 127.2 (d, Ci, PPh3,
=
3
1JPC = 100.0), 128.1 (s, C6H4), 128.7 (d, Cm, PPh3, JPC
12.5), 130.5 (d, C3, C6H4, 4JPC = 2.6), 131.3 (s, C6, C6H4), 132.5
(33) By analogy with “stabilized phosphorus ylides” (stabilized phos-
phoranes), stabilized iminophosphoranes are those derivatives in which the
negative charge of the nitrogen of the PdN linkage is delocalized through
conjugation with electron-withdrawing groups.
4
2
(d, Cp, PPh3, JPC = 2.6), 133.2 (d, Co, PPh3, JPC = 9.5),
135.9 (s, C6H4), 142.7 (d, C2, C6H4, 3JPC=18.1), 171.6 (s, CO),
6460 J. Org. Chem. Vol. 75, No. 19, 2010

Aguilar et al.
JOCArticle
signals due to C1 (C6H4) were not observed; 31P{1H} NMR
(CDCl3, 161.98 MHz) δ 25.8; MS (MALDIþ) 961 (60%) [M]þ.
Anal. Calcd for [C50H38HgN2O2P2] (961.40): C, 62.5; H, 3.98;
N, 2.91. Found: C, 62.31; H, 3.99; 2.76.
Synthesis of 2-Tri-n-butylstannyl-N-(triphenyl-λ5-phosphanyl-
idene)benzamide, 17. White solid. Obtained: 0.138 g (49% yield).
IR (Nujol) ν 1541 (CdO), 1340 (PdN) cm-1; 1H NMR (CDCl3,
500.13 MHz) δ 0.80-0.97 (m, 15H, CH3CH2, SnBu3), 1.19-
1.25 (m, 6H, CH2, SnBu3), 1.35-1.41 (m, 6H, CH2, SnBu3),
7.43-7.51 (m, 8H, PPh3 þ C6H4), 7.58 (m, 3H, PPh3), 7.67 (m,
1H, C6H4), 7.87 (m, 6H, PPh3), 8.78 (m, 1H, C6H4); 13C{1H}
NMR (CDCl3, 125.76 MHz) δ 11.9 (s, CH2), 12.1 (s, CH3), 27.7
(s, CH2), 29.3 (s, CH2), 127.4 (s, C6H4), 128.4 (d, Ci, PPh3,
1JPC = 91.6), 128.4 (d, Cm, PPh3, 3JPC4 = 12.0), 129.6 (s, C6H4),
129.7 (s, C6H4), 132.0 (d, Cp, PPh3, JPC = 2.7), 133.1 (d, Co,
General Procedure for the Preparation of Compounds 14-20.
To a solution of 6c (0.193 g, 0.42 mmol) in 20 mL of dry THF,
s
at -90 °C, was added 0.60 mL of BuLi (1.4 M, 0.84 mmol).
The resulting red solution of 8 was stirred for 30 min at this
temperature, then reacted with the corresponding electrophile
(0.46 mmol) and allowed to slowly reach room temperature by
stirring for 12 h. The solution obtained was evaporated to
dryness. The excess of base was quenched with MeOH, and
the reaction was poured into water and extracted with CH2Cl2
(3 ꢀ 15 mL). The organic layers were dried over MgSO4 and
concentrated under vacuum. The purification method used is
indicated for each compound (see below).
PPh3, 2JPC = 9.4), 136.1 (s, C6H4), 142.2 (d, C1, C6H4, 3JPC
=
19.1), 146.1 (d, C6, C6H4, 4JPC = 3.1), 176.6 (d, CO, 2JPC = 7.5);
31P{1H} NMR (CDCl3, 202.4 MHz) δ 22.4; 119Sn{1H} NMR
(CDCl3, 186.50 MHz) δ -66.9; MS (ESIþ): 672.1 (M þ 1H).
Anal. Calcd for [C37H46NOPSn] (670.46): C, 66.29; H, 6.92; N,
2.09. Found: C, 66.67; H, 7.24; N, 1.91.
Synthesis of 2-Iodo-N-(triphenyl-λ5-phosphanylidene)benz-
amide, 14. The yellow residue obtained was washed with
Et2O (2 ꢀ10 mL) and recrystallized from a CH2Cl2/pentane
mixture, furnishing pale yellow crystals of 14. Obtained:
0.196 g (92% yield). IR (Nujol) ν 1590 (CdO), 1335 (PdN)
cm-1; 1H NMR (CDCl3, 400.13 MHz) δ 7.02 (m, 1H, C6H4I),
7.33 (m, 1H, C6H4I), 7.54 (m, 6H, Hm, PPh3), 7.63 (m, 3H, Hp,
PPh3), 7.83 (m, 1H, C6H4I), 7.86-7.91 (m, 7H, C6H4I þ Ho
(PPh3)); 13C{1H} NMR (CDCl3, 100.6 MHz) δ 93.9 (d, C6,
Synthesis of 2-Triphenylstannyl-N-(triphenyl-λ5-phosphanyl-
idene)benzamide, 18. Column chromatography (silica gel,
CH2Cl2) afforded a white solid that was recrystallized from
CH2Cl2/pentane. Obtained: 0.135 g (44% yield). IR (Nujol) ν
1530 (CdO), 1358 (PdN) cm-1 1H NMR (CDCl3, 500.13
;
MHz) δ 7.19 (m, 6H, SnPh3), 7.28 (m, 3H, SnPh3), 7.37-7.45
(m, 7H, PPh3 þ C6H4), 7.46 (m, 6H, SnPh3), 7.51 (m, 2H, C6H4),
7.69 (m, 3H, PPh3), 7.71-7.73 (m, 6H, PPh3), 8.83 (m, 1H,
C6H4); 13C{1H} NMR (CDCl3, 125.76 MHz) δ 127.1 (s, C6H4),
127.9 (d, Ci, PPh3, 1JPC = 91.1), 127.3 (s, Cm, SnPh3), 128.3 (d,
Cm, PPh3, 3JPC = 12.2), 129.3 (s, C64H4), 129.4 (s, C6H4), 130.6
(s, Cp, SnPh3), 132.0 (d, Cp, PPh3, JPC = 2.7), 132.9 (d, Co,
PPh3, 2JPC = 10.0), 137.0 (s, C6H4), 137.4 (s, Co, SnPh3), 141.6
C6H4I, 4JPC = 1.1), 127.6 (s, C6H4I), 127.7 (d, Ci, PPh3, 1JPC
=
96.5), 128.7 (d, Cm, PPh3, 3JPC = 12.3), 130.0 (s, C6H4I), 130.1
(s, C6H4I), 132.4 (d, Cp, PPh3, 4JPC = 3.0), 133.3 (d, Co, PPh3,
3
2JPC =10.0), 140.1 (s, C6H4I), 144.90 (d, C1, C6H4I, JPC
=
20.5), 178.3 (d, CO, 2JPC = 7.9); 31P{1H} NMR (CDCl3, 161.98
MHz) δ 21.2; MS (ESIþ) 507.9 (M þ 1H). Anal. Calcd for
[C25H19INOP] (507.41): C, 59.17; H, 3.78; N, 2.76. Found: C,
59.06; H, 3.78; N, 2.41.
3
4
(d, C1, C6H4, JPC = 20.1), 142.2 (d, C6, C6H4, JPC = 4.4),
144.0 (s, Ci, SnPh3), 175.7 (d, CO, 2JPC = 7.1); 31P{1H} NMR
(CDCl3, 202.4 MHz) δ 23.3; 119Sn{1H} NMR (CDCl3, 186.50
MHz) δ -165.1; MS (ESIþ) 654 (M - Ph). Anal. Calcd for
[C43H34NOPSn] (730.43): C, 70.71; H, 4.69; N, 1.92. Found: C,
70.38; H, 4.59; N, 1.98.
Synthesis of 2-Diphenylphosphanyl-N-(triphenyl-λ5-phosphanyl-
idene)benzamide, 15. Purification by column chromatography
over silica gel (CH2Cl2/MeOH, 98:2) yielded 15 as a white
solid. Obtained: 0.197 g (41% yield). IR (Nujol) ν 1590 (CdO),
1329 (PdN) cm-1; 1H NMR (CDCl3, 400.13 MHz) δ 6.81 (m,
1H, C6H4), 7.23-7.27 (m, 7H, PPh3 þ PPh2), 7.30-7.38 (m,
8H, PPh3 þ PPh2), 7.41-7.51 (m, 5H, C6H4 þ PPh2), 7.52-
7.64 (m, 6H, PPh3), 7.69 (m, 1H, C6H4), 8.29 (m, 1H, C6H4);
13C{1H} NMR (CDCl3, 100.61 MHz) δ 126.1 (d, Ci, PPh2,
1JPC = 101.8), 128.1 (d, Ci, PPh3, 1JPC = 97.8), 128.1-129.0
Synthesis of 2-Trimethylsilyl-N-(triphenyl-λ5-phosphanylidene)-
benzamide 19. White solid. Obtained: 0.169 g (89% yield).
Crystals of 19 CH2Cl2 were obtained by slow evaporation of
3
a CH2Cl2 solution of the crude compound. IR (Nujol) ν 1592
1
(CdO), 1331 (PdN) cm-1; H NMR (CDCl3, 400.13 MHz) δ
0.16 (s, 9H, SiMe3), 7.39-7.43 (m, 2H, C6H4), 7.47 (m, 6H,
PPh3), 7.57 (m, 3H, PPh3), 7.63 (m, 1H, C6H4), 7.86 (m, 6H,
PPh3), 8.51 (dd, 1H, C6H4, 3JHH = 7.6, 4JHH = 1.6); 13C{1H}
NMR (CDCl3, 100.61 MHz) δ 0.0 (s, SiMe3), 127.6 (s, C6H4),
(3C, C6H4 þ Cm PPh3 þ Cm PPh2), 131.9 (d, Cp, PPh3, 4JPC
=
4
2.9), 132.0 (s, C6H4), 132.5 (d, Cp, PPh2, JPC = 0.9)
1
3
133.2-133.4 (m, Co, PPh2þPPh3), 133.8 (s, C6H4), 134.1 (s,
127.8 (d, Ci, PPh3, JPC = 98.7), 127.7 (d, Cm, PPh3, JPC
12.2), 128.4 (s, C6H4), 129.2 (s, C6H4), 131.4 (d, Cp, PPh3,
=
3
C6H4), 137.7 (d, C6, C6H4, JPC = 23.1), 140.2 (d, C1, C6H4,
2JPC=14.2), 177.4 (d, CO, 2JPC=9.1); 31P{1H} NMR (CDCl3,
161.98 MHz) δ -6.0 (d, PPh2, 5JPP = 5.1), 22.6 (d, NdPPh3);
MS (ESIþ) 566.1 (M þ 1H). Anal. Calcd for [C37H29NOP2]
(565.6): C, 78.57; H, 5.17; N, 2.48. Found: C, 78.19; H, 5.02;
N, 2.33.
4JPC = 2.8), 132.5 (d, Co, PPh3, JPC = 9.8), 134.1 (d, C6H4,
2
JPC = 1.2), 140.2 (d, C6, C6H4, 4JPC = 3.3), 144.2 (d, C1, C6H4,
3JPC = 19.8), 177.6 (d, CO, 2JPC = 8.1); 31P{1H} NMR (CDCl3,
161.98 MHz) δ 20.8; MS (ESIþ) 454.2 (Mþ1H). Anal. Calcd for
[C28H28NOPSi] CH2Cl2 (538.53): C, 64.68; H, 5.61; N, 2.60.
3
Synthesis of 2-Trimethylstannyl-N-(triphenyl-λ5-phosphanyl-
idene)benzamide, 16. White solid. Obtained: 0.199 g (87% yield).
IR (Nujol) ν 1540 (CdO), 1336 (PdN) cm-1; 1H NMR (CDCl3,
500.13 MHz) δ 0.00 (s, 9H, SnMe3, 2JSnH = 55), 7.43-7.49 (m,
8H, PPh3 þ C6H4), 7.54-7.59 (m, 3H, PPh3), 7.67 (m, 1H,
C6H4), 7.80-7.87 (m, 6H, PPh3), 8.70 (m, 1H, C6H4); 13C{1H}
Found: C, 64.83; H, 5.88; N, 2.61.
Synthesis of 2-[Hydroxy(phenyl)methyl]-N-(triphenyl-λ5-phos-
phanylidene)benzamide, 20. Column chromatography (silica gel,
CH2Cl2) afforded a white solid, which was recrystallized from
CH2Cl2/pentane. Obtained: 0.135 g (77% yield). IR (Nujol) ν
1580 (CdO), 1343 (PdN) cm-1 1H NMR (CDCl3, 400.13
;
1
NMR (CDCl3, 125.76 MHz) δ -6.7 (s, SnMe3, JSnC 378.5),
MHz) δ 4.60 (s, 1H, CH), 5.83 (m, 1H, C6H4), 7.09-7.84 (m,
22H, PPh3 þ Ph þ C6H4), 8.14 (m, 1H, C6H4); 13C{1H} NMR
(CDCl3, 100.61 MHz) δ 76.0 (s, C-OH), 126.1 (s, C6H4), 126.4
(s, Cm, Ph), 127.1 (d, Ci, PPh3, 1JPC = 95.2), 127.3 (s, Cp, Ph),
127.4 (s, C6H4), 128.0 (d, Ci, PPh3, 1JPC = 98.9), 128.1 (d, Cm,
PPh3, 3JPC = 12.2), 129.35 (s, C6H4), 129.63 (s, C6H4), 131.8 (d,
Cp, PPh3, 4JPC = 2.5), 133.0 (d, Co, PPh3, 2JPC = 10.0), 135.3 (s,
3
3
C6H4), 141.9 (d, C1 C6H4, JPC = 20.1), 145.8 (d, C6 C6H4,
127.6 (s, Co, Ph), 128.6 (d, Cm, PPh3, JPC = 12.5), 130.1 (s,
4JPC = 4.1), 178.6 (d, CO, 2JPC = 8.6); 31P{1H} NMR (CDCl3,
202.4 MHz) δ 22.5; 119Sn{1H} NMR (CDCl3, 186.50 MHz)
δ -59.9; MS (ESIþ) 546.0 (M þ 1H). Anal. Calcd for [C28H28-
C6H4), 130.2 (s, C6H4), 132.2 (s, C6H4), 132.3 (d, Cp, PPh3,
4JPC = 2.9), 132.9 (d, Co, PPh3, 2JPC = 10.0), 138.9 (d, C1, C6H4,
3JPC = 19.1), 143.3 (d, C6, C6H4, 4JPC = 1.1), 144.0 (s, Ci, Ph),
2
179.1 (d, CO, JPC = 8.5); 31P{1H} NMR (CDCl3, 161.98
NOPSn] CH2Cl2 (629.16): C, 55.36; H, 4.81; N, 2.23. Found: C,
3
MHz) δ 23.1; MS (ESIþ) 488.1 (M þ 1H). Anal. Calcd for
J. Org. Chem. Vol. 75, No. 19, 2010 6461
55.33; H, 4.97; N, 2.22.

Aguilar et al.
JOCArticle
ꢀ
Juan de la Cierva Program (Ministerio de Ciencia e Innovacion,
Spain) for a research contract.
[C32H26NO2P] (487.54): C, 78.84; H, 5.38; N, 2.87. Found: C,
78.59; H, 5.17; N, 2.49.
Supporting Information Available: Details on general
experimental methods, structural characterization of com-
ꢀ
Acknowledgment. Dedicated to Prof. C. Najera on the
occasion of her 60th birthday. Financial support by the
1
pounds 13-20, copies of H NMR, 13C NMR, and 31P NMR
ꢀ
Ministerio de Educacion y Ciencia (MEC) (projects CTQ2008-
01784 and CTQ2008-117BQU) and the Ramon y Cajal Pro-
spectra of all new compounds, 119Sn{1H} NMR spectra of
16-18, variable-temperature 31P NMR spectra of 8, expansion
of the 13C NMR spectrum of 8, and crystallographic details of
16. This material is available free of charge via the Internet at
http://pubs.acs.org.
ꢀ
gram (I.F.) is gratefully acknowledged. D.A. thanks Gobierno
ꢀ
de Aragon (Spain) and Programa Europa XXI (Caja Ahorros
Inmaculada) for respective research grants. L.C. thanks
6462 J. Org. Chem. Vol. 75, No. 19, 2010