Synthesis and characterization of a cyclotriveratrylene-capped azaphosphatrane

Article abstract of DOI:10.1016/j.tetlet.2011.05.127

A cyclotriveratrylene (CTV)-capped azaphosphatrane 4, which contains an endohedral proton within the cavity of the azaphosphatrane, was synthesized in high yield and then characterized. The endohedral proton of 4 was highly sheltered from strongly basic conditions by the CTV-capped structure.

Full text of DOI:10.1016/j.tetlet.2011.05.127

Tetrahedron Letters 52 (2011) 4129–4131
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Tetrahedron Letters
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Synthesis and characterization of a cyclotriveratrylene-capped azaphosphatrane
Yoshimasa Makita a, , Kenta Furuyoshi b, Keisuke Ikeda b, Tomoyuki Fujita b, Shin-ichi Fujiwara a,
⇑
Masahiro Ehara c, Akiya Ogawa b
a Department of Chemistry, Osaka Dental University, 8-1 Kuzuhahanazono-cho, Hirakata, Osaka 573-1121, Japan
b Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Nakaku, Sakai, Osaka 599-8531, Japan
c Institute for Molecular Science, Okazaki 444-8585, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
A cyclotriveratrylene (CTV)-capped azaphosphatrane 4, which contains an endohedral proton within the
cavity of the azaphosphatrane, was synthesized in high yield and then characterized. The endohedral pro-
ton of 4 was highly sheltered from strongly basic conditions by the CTV-capped structure.
Ó 2011 Elsevier Ltd. All rights reserved.
Received 25 April 2011
Revised 24 May 2011
Accepted 27 May 2011
Available online 2 June 2011
The chemistry of atranes that contain five-membered tricyclic
frameworks has attracted considerable interest in recent years.1
Most studies on aza-atranes including tripodal ligands such as
tris(amidoethyl)amine (tren anion) [(RNCH2CH2)3N]3À have
focused on coordination of main group atoms such as phosphorus,
antimony, and bismuth. Azaphosphatranes are precursors of pro-
azaphosphatranes (also known as Verkade’s bases) and are very
amino)chlorophosphine in chloroform solution under a nitrogen
atmosphere produced 4 in 87% yield. Azaphosphatrane 4 can be
safely stored at room temperature as a solid under an inert atmo-
sphere. The structure of 4 was confirmed by HR-MS, and 1H, 13C,
and 31P NMR spectroscopy.7
The 1H NMR profiles of 3 and 4 showed that they possess a
C3-symmetric conformation in DMSO-d6 solution (Scheme 1 and
Fig. 2). The 31P NMR chemical shift at À34.39 ppm for 4 was upfield
compared to that for 1a.8 The large coupling constant of 485 Hz
indicates H–P bond formation. The existence of covalent Neq–P
bonds in 4 was suggested by the observation of P–Neq–CH2 cou-
pling (4.7 Hz) and P–Neq–benzyl-CH2 coupling (6.1 Hz).9 The sig-
nals from the alkyl protons of tren in 4 (i and j) were shifted
downfield compared to those of 3. These results confirm the forma-
tion of an azaphosphatrane structure. Note that the two benzyl
protons (f) split into two average signals at 2.70 and 3.56 ppm
and remained unchanged even at 373 K, indicating that the confor-
mation of the benzyl unit is highly restricted on the NMR
timescale.
useful in
a number of important organic transformations
(Fig. 1).2 Azastibatranes and azabismatranes have been proposed
as potential precursors for metal-organic chemical vapor deposi-
tion of thin films of bismuth- or antimony-containing materials,
respectively.3 Despite kinetically-stabilized aza-atranes being
important to construct a wide variety of these compounds, very
few attempts have been studied to stabilize the central atom of
aza-atranes.
We recently reported novel hemicryptophane 3, which is com-
posed of a cyclotriveratrylene (CTV) moiety and a tren ligand con-
nected by
a
rigid spacer.4 The small covalent molecule
encapsulates the central aza-atrane structure and can be used as
a new kind of protective group for aza-atranes. Recently, Raytchev
et al. reported the first synthesis of an encaged Verkade’s base and
evaluated the thermodynamic and kinetic consequences.5
DFT gas-phase structure optimization and frequency calcula-
tions were performed at the B3LYP/6-31G level of theory.10
A
polarization function (fd = 0.34) was added to the P atom to give
The precursor 2 was slightly longer than hemicryptophane 3
and was neutralized with potassium t-butoxide (t-BuOK) in THF;
the observed pKa was similar to that of deprotonated 1a. In this
Letter, we report the synthesis and characterization of a CTV-
capped azaphosphatrane. The unusual reactivity of the endohedral
proton within the cavity of the molecule is used to clarify the rela-
tionship between the size and reactivity of the hemicryptophane.
Scheme 1 depicts the synthetic route to CTV-capped azaphos-
phatrane 4. Hemicryptophane 3 was synthesized by our previously
OMe
O
O
R
N
H
P
R
R
O
O
N
N
O
N
N
H
P
N
OMe
N
N
reported procedure.6 The reaction of
3 with bis(dimethyl-
OMe
O
1a
: R = Me
1b: R = i-Pr
2
⇑
Corresponding author. Tel./fax: +81 72 864 3162.
E-mail address: makita@cc.osaka-dent.ac.jp (Y. Makita).
Figure 1. Structures of azaphosphatrane 1 and Raytchev’s azaphosphatrane 2.
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.05.127

4130
Y. Makita et al. / Tetrahedron Letters 52 (2011) 4129–4131
structure is supported experimentally by the upfield shift of the
OMe
O
phenyl protons (d and e) of 4 in its 1H NMR spectrum (Scheme 1
and Fig. 2). The P–Nax bond length (2.18 Å) is slightly elongated
compared to that in the known crystal structure of 1a (1.98 Å).11
However, the theoretically determined 31P chemical shift (d
À33.2 ppm) agrees well with experimental results.
H
N
H
N
O
a
N
OMe
h
OMe
j
c
N
The reaction of 1a with excess t-BuOK (pKa = 32)12 or sodium
hexamethyldisilazide (NaHMDS; pKa = 26)13 in dry DMSO-d6 solu-
tion at ambient temperature simultaneously produced deproto-
nated 1a in 69% yield and deuterated 1a in 31% yield. However, 4
remained unchanged under harsh neutralization conditions in an
excess of t-BuOK, NaHMDS, or deprotonated 1a in dry DMSO-d6
or THF-d8 solutions at 343 K after 24 h.14 Moreover, the base so-
dium methylsulfinylmethylide (NaDMSO; pKa = 35),13 which is
smaller than the 23-membered entrance of the cavity, was also un-
able to neutralize 4 at 343 K after 24 h. Sterically hindered 1b was
neutralized immediately in these harsh conditions. These results
indicate that the CTV-capped structure protects the endohedral
proton of azaphosphatrane significantly and that its reactivity is
closely connected to the size of the CTV-capped structure.
H
i
f
b
e
O
d
3
P(NMe2)2Cl
CHCl3
OMe
O
Cl
N
O
N
P
g
H
a
N
OMe
h
OMe
j
c
N
i
f
b
Novel CTV-capped azaphosphatrane 4 was obtained in high
yield. The reactivity of the endohedral proton of 4 was suppressed
as a result of protection by the CTV-capped structure. This novel
protecting group is applicable to the synthesis of other unstable
aza-atrane structures; research focused on this is in progress.
e
O
d
4
Scheme 1. Synthesis of CTV-capped azaphosphatrane 4.
Acknowledgments
a better description of the penta coordination. The optimized
structure of cation 4 is shown in Figure 3. The CTV-capped struc-
ture forms a folded helical structure because of stabilization
We thank Mr. F. Asanoma from the Nara Institute of Science and
Technology under the Kyoto Advanced Nanotechnology Network
program for measuring NMR spectra. We thank Dr. H. Ijyuin from
caused by CH-p interactions between the phenyl ring spacers. This
Figure 2. 1H NMR spectra (400 MHz, DMSO-d6, 298 K) of: (a) 3, and (b) 4.
Figure 3. (a) Optimized structure of cation 4; hydrogen atoms were omitted for clarity. (b) Space filling model of cation 4.

Y. Makita et al. / Tetrahedron Letters 52 (2011) 4129–4131
4131
7. Mp >280 °C; 1H NMR (DMSO-d6, 400 MHz): d (ppm) 2.70 (dd, 3H, JPH = 32.4 Hz,
JHH = 16.0 Hz), 3.11–3.21 (m, 12H), 3.37 (s, 9H), 3.56 (dd, 3H, JPH = 31.2 Hz,
JHH = 16.0 Hz), 3.48 (d, 3H, JHH = 13.3 Hz), 4.41 (d, 1H, JPH = 485 Hz), 4.84 (d, 3H,
JHH = 12.9 Hz), 5.93 (d, 6H, JHH = 8.7 Hz), 6.17 (d, 6H, JHH = 8.7 Hz), 7.34 (s, 3H),
Kanagawa University for measuring ESI-MS spectra. This work was
supported by a Grant-in-Aid for Young Scientists (B) (21791957).
7.53 (s, 3H); 13C NMR (DMSO-d6, 100 MHz)
d (ppm) 33.8, 42.4, 46.1 (d,
Supplementary data
JPC = 5.7 Hz), 50.1 (d, JPC = 9.5 Hz), 55.2, 114.1, 115.3, 127.8, 129.4, 131.2, 133.0,
138.8, 141.7, 149.6, 158.3; 31P NMR (DMSO-d6, 243 MHz) d À34.39 ppm; IR
(KBr) 3422, 2935, 2733, 2360, 1608, 1504, 1207 cmÀ1; HR-MS (ESI–TOF) Calcd
for C51H52N4O6P1: 847.3624 [M]+. Found: 847.3600 [M]+.
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2011.05.127.
8. Lensink, C.; Xi, S.; Daniels, L.; Verkade, J. J. Am. Chem. Soc. 1989, 111, 3478.
9. See Supplementary data.
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6.
A
solution
of
hemicryptophane
3
(50 mg,
62
l
mol)
and
14. General neutralization procedure for 4. A solution of 4 (4.8 mg, 5.4
base (27 mol) in dry DMSO-d6 (0.60 mL) was allowed to stand at 373 K for
24 h. The progress of the reaction was observed by 1H and 31P NMR analysis.
lmol) and
bis(dimethylamino)chlorophosphine (14
l
L, 96
lmol) in chloroform (2.7 mL)
l
was stirred at 0 °C for 30 min under a nitrogen atmosphere and allowed to
warm to ambient temperature for 48 h. The reaction mixture was added
dropwise to diethyl ether. The precipitate was filtered to give 49.6 mg (87%) of
4 as a white solid.