Unexpected cyclization reaction of an overcrowded 2-phosphinophenylmethanimine derivative leading to the formation of the first stable 2-phospha-2h-isoindole derivative

Article abstract of DOI:10.3987/COM-08-S(N)36

The reaction of overcrowded 2-phosphinophenylmethanimine derivative 1 bearing a 2,4,6-tri-t-butylphenyl (Mes*) group on the phosphorus atom and a 2,6-diisopropylphenyl (Dip) group on the nitrogen atom with potassium hydride afforded 2-phospha-2H-isoindole 2 along with Mes*H.

Full text of DOI:10.3987/COM-08-S(N)36

HETEROCYCLES, Vol. 76, No. 2, 2008
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HETEROCYCLES, Vol. 76, No. 2, 2008, pp. 981 - 987. © The Japan Institute of Heterocyclic Chemistry
Received, 13th March, 2008, Accepted, 13th May, 2008, Published online, 15th May, 2008. COM-08-S(N)36
UNEXPECTED CYCLIZATION REACTION OF AN OVERCROWDED
2-PHOSPHINOPHENYLMETHANIMINE DERIVATIVE LEADING TO
THE FORMATION OF THE FIRST STABLE 2-PHOSPHA-2H-ISO-
INDOLE DERIVATIVE#
Norihiro Tokitoh,* Teruyuki Matsumoto, and Takahiro Sasamori
Institute for Chemical Research, Kyoto University, Gokasho, Uji, Kyoto
611-0011, Japan
tokitoh@boc.kuicr.kyoto-u.ac.jp
Abstract – The reaction of overcrowded 2-phosphinophenylmethanimine
derivative 1 bearing a 2,4,6-tri-t-butylphenyl (Mes*) group on the phosphorus
atom and a 2,6-diisopropylphenyl (Dip) group on the nitrogen atom with
potassium hydride afforded 2-phospha-2H-isoindole 2 along with Mes*H.
# Dedicated to Prof. Dr. Ryoji Noyori on the occasion of his 70th birthday.
Recently, β-diketiminato ligands bearing resonance structures with amido and imino moieties have
attracted much attention from the viewpoint of unique monovalent bidentate ligands toward transition
metals and main group elements.1 On the other hand, the coordination chemistry of sp2-hybridized
phosphorus compounds has drawn a great deal of recent attention due to their unique electronic properties
of π-electron systems containing a phosphorus atom,2 whose characteristic low-lying atomic orbital make
it possible to work as a good π-accepter toward the metal center.3 Although there have been much
interest in the chemistry of phosphorus analogues of a β-diketiminato ligand, which should exhibit unique
properties reflecting characteristic features of an sp2-hybridized phosphorus atom,4,5 it is difficult to
isolate and handle such a low-coordinated phosphorus compound. It is well known that a double bond
containing a heavier atom such as a P=C double bond is highly reactive to undergo facile oxidation,
hydrolysis, and self-oligomerization.2 Since the first isolation of stable phosphaalkene (Bickelhaupt et
al.)6 and diphosphene (Yoshifuji et al.)7 around 1980’s, the idea of kinetic stabilization afforded by bulky
substituents has been proven to be very effective for the construction of doubly bonded systems

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HETEROCYCLES, Vol. 76, No. 2, 2008
containing (a) heavier atom(s).2 During the course of our studies on the low-coordinated species of
heavier group 15 elements by taking advantage of kinetic stabilization using bulky substituents,2,8 we
have designed
a
novel phosphorus analogue of
a
benzo-fused β-diketiminato ligand,
2-phosphinophenylmethanimine 1, a possible bidentate ligand toward transition metals and main group
elements.4 In this paper, we describe the synthesis of 2-phosphinophenylmethanimine 1, and the
attempted deprotonation reaction of 1 using potassium hydride leading to the formation of unexpected
heterocyclic compound, 2-phospha-2H-isoindole 2, along with the elimination of Mes* unit. Since no
synthetic work on a 2-phospha-2H-isoindole derivative has been reported so far, the reaction should be of
great importance as a unique synthetic method for the construction of a phosphorus-containing
heterocyclic compound, 2-phospha-2H-isoindole.
R
R
R
Mes*
Mes*
deprotonation
N
N
P
N
P
P
PH
P
N
N
R
R
R
Dip
Dip
1
3
β-diketiminate
phosphorus analogues
of β-diketiminate
P
N
Dip
Mes* =
Dip =
2
2-phospha-2H-isoindole
Scheme 1
2-Phosphinophenylmethanimine 1 was prepared according to Scheme 2.9 Although dichlorophosphines
and phosphines having a P-H bond are generally difficult to handle in the air due to its high reactivity
toward oxygen and moisture, Mes*PCl2 and the related derivatives 5-7 bearing a P-X (X = Cl, H) bond
are stable under ambient conditions owing to the bulky substituent, Mes* group. We have attempted the
deprotonation reaction of 1 in the expectation of the formation of the corresponding phosphide 3 as a
good precursor for the introduction of a transition metal or a main group element between P and N atoms.
While 1 (54 mg, 0.10 mmol) was found to be inert toward potassium hydride (6.0 mg, 0.15 mmol, 1.5
1
eq.) in THF (10 mL) at room temperature as judged by the H NMR spectrum, heating of the reaction
mixture in C6D6 at 60 ºC for 1 h afforded the unexpected products, 2-phospha-2H-isoindole 29 and
Mes*H, quantitatively. 10 Although 2 was found to be decomposed through the purification procedures
using GPLC or column chromatography, a few single crystals of 2 suitable for X-ray crystallographic
analysis were obtained by continual efforts on the recrystallization of the crude mixture. Thus, the

HETEROCYCLES, Vol. 76, No. 2, 2008
983
structural parameters of the first stable 2-phospha-2H-isoindole 2 were revealed by the X-ray
crystallographic analysis (Figure 1).11
Mes*
PCl
Mes*
PH
Br
O
Mes*PCl2
LiAlH4
n-BuLi
THF
–78 ºC
30 min
THF
–78 ºC
3 h
Et2O
0 ºC
30 min
O
O
O
O
O
4
5
6
74%
85%
Mes*
Mes*
DipNH2
colorless cyrstals
mp 181 ºC (decomp)
δP = –62.7
1JPH = 258 Hz
BF3·OEt2
PH
PH
TsOH/H2O
O
N
acetone
reflux
7.5 h
toluene
reflux
13 h
H
H
Dip
7
1
75%
quant.
Scheme 2
Mes*
PH
KH
P
no reaction
+
Mes*H
N
N
Dip
THF
rt
C6D6
60 ºC
H
Dip
1 h
1
2
Scheme 3
Figure 1. (a) Molecular structure of 2 (Major part of disordered molecules). Displacement ellipsoids were
drawn at the 50% probability level) (b) Observed (plane) and calculated (gothic) bond lengths of 2 (Å).
Although the 2-phospha-2H-isoindole skeleton was disordered in the X-ray crystallographic analysis, the
observed structural parameters were supported by the theoretically optimized structure at

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HETEROCYCLES, Vol. 76, No. 2, 2008
B3LYP/6-31+G(2d,p) level. The observed bond-alternation in the benzo-moiety suggests the electronic
structure of 2 as a 2-phospha-2H-isoindole derivative. In addition, NBO calculations for the optimized
structure of 2 showed σ- and π-bonds (double bonds) between C1=C2, C3=P, C4=C5, and C6=C7, while
P-N, N-C1, C2-C7, C3-C4, and C5-C6 bonds were computed as single bonds, indicating somewhat
localized π-electrons on the 2-phospha-2H-isoindole skeleton. In the 31P NMR spectrum of 2 (in C6D6),
a signal was observed in the relatively lower field at 182.8 ppm, which is characteristic of an
sp2-hybridized phosphorus atom. Although isoindole derivatives are generally colorless compounds,
2-phospha-2H-isoindole 2 is colored as yellow. Indeed, 2 showed strong absorption around 363 nm
probably corresponding to the π−π* electron transitions in the UV/vis spectrum (in hexane),12 indicating
smaller HOMO-LUMO energy gap of 2 than those of isoindole derivatives, which should reflect the
unique character of a π-electron conjugated system containing low-coordinated phosphorus atom.
The plausible formation mechanism of 2 by the thermal reaction of 1 with potassium hydride was shown
in Scheme 4. Since the P–H proton should be the most acidic among those in 1, the corresponding
phosphide 8 should be a reasonable intermediate in this reaction. In the DFT calculations, the local
minimum structure of model compound 9a, which is a less hindered model compound for 8 bearing
2,6-dimethylphenyl (Dmp) groups on the phosphorus and nitrogen atoms instead of Mes* and Dip groups,
was optimized as shown in Figure 2. Next, the structural optimizations for anion species 9b-d were
performed with the fixed P–N bond lengths as 2.00 (9b), 1.90 (9c), and 1.80 (9d) Å. As a result, it was
found that the P–C(Dmp) bond was elongated as the P and N atoms get closer to each other, indicating
the weakened P–C(Dmp) bond as the P–N bond was shortened. Thus, the generation of 2 and Mes*H in
the reaction of 1 with potassium hydride at 60 ºC is most likely interpreted in terms of the intermediacy of
phosphide 8 giving 2 along with the elimination of Mes* anion species as shown in Scheme 4.
Mes*
PH
Mes*
purification
process
Mes*
+
P
P
N
KH
2 + Mes*H
protonation
N
deprotonation
N
H
Dip
H
Dip
Dip
1
8
2
Scheme 4
In summary, a novel heterocyclic compound, 2-phospha-2H-isoindole 2, was unexpectedly obtained by
heating of overcrowded 2-phosphinophenylmethanimine 1 with potassium hydride at 60 ºC in C6D6
together with Mes*H. Based on the theoretical calculations, the generation of 2 is most likely
interpreted in terms of the intermediacy of the corresponding phosphide 8. This unique reactivity of
2-phosphinophenylmethanimine 1 should be of importance in view of the construction of novel
heterocyclic compounds containing a phosphorus atom.

HETEROCYCLES, Vol. 76, No. 2, 2008
985
Figure 2. Theoretically optimized structures of phosphides 8a-d (B3LYP/6-31+G(2d,p)).
ACKNOWLEDGEMENTS
This work was partially supported by Grants-in-Aid for Creative Scientific Research (No. 17GS0207),
Science Research on Priority Areas (No. 19027024, “Synergy of Elements”), Young Scientist (B) (No.
18750030), and the Global COE Program B09 (International Center for Integrated Research and
Advanced Education in Materials Science) from Ministry of Education, Culture, Sports, Science and
Technology, Japan.
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HETEROCYCLES, Vol. 76, No. 2, 2008
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1
9. Chemical data for 1: yellow crystals, mp 118 °C (decomp.); H NMR (300 MHz, C6D6, 298 K) δ
1.27 (d, 3JHH = 7.2 Hz, 6H), 1.29 (d, 3JHH = 7.2 Hz, 6H), 1.37 (s, 9H), 1.46 (s, 9H), 1.70 (s, 9H), 3.37
(sept, 3JHH = 6.9 Hz, 6H), 6.37 (d, JHH = 3.3 Hz, 1H), 6.51 (d, 1JPH = 258.3 Hz, 1H), 6.79 (pt, JHH
7.5 Hz, 1H), 6.88 (pt, JHH = 7.5 Hz, 1H), 7.17-7.26 (m, 3H), 7.54 (dd, JHH = 2.6, 7.1 Hz, 1H), 7.73 (s,
=
4
13
2H), 8.53 (d, JPH = 1.6 Hz, 1H); C{1H} NMR (75 MHz, C6D6, 298 K) δ 23.8 (CH3), 23.9 (CH3),
28.6 (CH), 31.5 (CH3), 33.5 (CH3), 33.7 (CH3), 33.9 (CH3), 35.3 (C), 38.5 (C), 39.0 (C), 122.3 (CH),
123.2 (CH), 123.5 (CH), 124.7 (CH), 127.0 (CH), 130.3 (CH), 130.4 (C), 130.9 (C), 131.3 (CH),
133.3 (CH), 136.7 (C, d, JPC = 11.8 Hz,), 137.7 (C), 143.7 (C, d, JPC = 30.8 Hz,), 149.9 (C), 151.0
(C), 156.1 (C), 158.2 (C, d, JPC = 21.8 Hz), 162.6 (CH, d, JPC = 5.5 Hz); 31P{1H} NMR (120 MHz,
C6D6, 298 K) δ –62.7. High-resolution MS (ESI) m/z Calcd for C37H53NP 542.3929. Found
542.3910 ([M+H]+). Anal. Calcd for C37H52NP: C, 82.02; H, 9.67; N, 2.59%. Found: C, 82.04; H,
9.72; N, 2.76%. Chemical data for 2: yellow crystals; 1H NMR (300 MHz, C6D6, 298 K) δ 0.98 (d,
3
3JHH = 6.9 Hz, 6H), 1.11 (d, JHH = 6.9 Hz, 6H), 2.38 (sept, 3JHH = 6.9 Hz, 2H), 6.89-7.03 (m, 2H),

HETEROCYCLES, Vol. 76, No. 2, 2008
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7.07 (d, 3JHH = 7.6 Hz, 2H), 7.21 (dd, 3JHH = 7.6 Hz, 1H), 7.58 (d, 3JPH = 3.9 Hz, 1H), 7.70 (d, JHH
=
8.1 Hz, 1H), 7.98 (dd, JHH = 3.6, 8.4 Hz, 1H); 13C{1H} NMR (75 MHz, C6D6, 298 K) δ 24.8 (CH3),
25.4 (CH3), 28.3 (CH), 122.7 (CH, d, JPC = 18.8 Hz,), 123.2 (CH, d, JPC = 3.8 Hz), 123.6 (CH),
124.3 (CH, d, JPC = 1.9 Hz,), 129.4 (CH), 131.4 (C, d, JPC = 7.5 Hz,), 135.6 (CH, d, JPC = 8.3 Hz,),
138.7 (C, d, JPC = 10.5 Hz,), 145.0 (C, d, JPC = 2.3 Hz), 150.3 (C), 158.3 (C, d, JPC = 41.3 Hz,);
31P{1H} NMR (120 MHz, C6D6, 298 K) δ 182.8; High-resolution MS (ESI-TOF) m/z Calcd for
C19H23NP: 296.1563. Found 296.1560 ([M+H]+).
10. The resulting Mes*H was isolated in 95% yield. When 1 was heated in C6D6 for several hours in
the absence of KH, no change was observed by the 1H NMR spectra.
11. X-Ray crystallographic data for 2 (C19H22NP): M = 295.35, T = 103(2) K, triclinic, P–1 (no.2), a =
5.9609(2) Å, b = 11.1103(3) Å, c = 13.2811(3) Å, α = 72.1129(9)º, β = 86.2549(11)º, γ = 79.382(3)º,
V = 822.69(4) Å3, Z = 2, Dcalc = 1.192 g cm–3, µ = 0.161 mm–1, λ = 0.71070 Å, 2θmax = 51.0, 7063
measured reflections, 3004 independent reflections (Rint = 0.0291), 212 refined parameters, GOF =
1.225, R1 = 0.0868 and wR2 = 0.2219 [I>2σ(I)], R1 = 0.0882 and wR2 = 0.2225 [for all data], largest
diff. peak and hole 0.561 and -0.343 e.Å–3. The central P–N–C moiety was disordered (0.83 : 0.17).
Crystallographic data (excluding structure factors) for the structure reported in this paper have been
deposited with the Cambridge Crystallographic Data Centre as supplementary publication no. CCDC
680783. Copies of the data can be obtained free of charge on application to CCDC, 12 Union Road,
Cambridge CB21EZ, UK (fax: (+44)1223-336-033; E-mail: deposit@ccdc.cam.ac.uk.). The
intensity data were collected on a Rigaku/MSC Mercury CCD diffractometer. The structure was
solved by direct methods (SHELXS-97) and refined by full-matrix least-squares procedures on F2
for all reflections (SHELXL-97).
12. The hexane solution of the mixture of 2 and Mes*H was used in the measurement of UV-vis
spectrum. Since Mes*H exhibits no absorption in the visible light region, the observed absorption
should be assignable to those of 2.