Highly selective one-pot synthesis of spirophosphoranes exhibiting reversed apicophilicity by oxidation of dianions generated from P-H spirophosphorane

Article abstract of DOI:10.1021/ol015927y

(formula presented) Mild and highly selective one-pot procedures for obtaining phosphoranes that exhibit reversed (O-cis) apicophilicity are described. On the basis of the procedures, O-cis phosphorane bearing an aryl group (R = 2,4,6-tri-i-propylphenyl)

Full text of DOI:10.1021/ol015927y

ORGANIC
LETTERS
2001
Vol. 3, No. 12
1873-1875
Highly Selective One-Pot Synthesis of
Spirophosphoranes Exhibiting Reversed
Apicophilicity by Oxidation of Dianions
Generated from P−H Spirophosphorane
Kazumasa Kajiyama,† Miki Yoshimune, Masaaki Nakamoto, Shiro Matsukawa,
Satoshi Kojima, and Kin-ya Akiba*
Department of Chemistry, Graduate School of Science, Hiroshima UniVersity,
1-3-1Kagamiyama, Higashi-Hiroshima 739-8526, Japan
akiba@sci.hiroshima-u.ac.jp
Received April 3, 2001
ABSTRACT
Mild and highly selective one-pot procedures for obtaining phosphoranes that exhibit reversed (O-cis) apicophilicity are described. On the
basis of the procedures, O-cis phosphorane bearing an aryl group (R ) 2,4,6-tri-i-propylphenyl) could be isolated for the first time; the
procedure is also applicable for alkyl derivatives. Particularly effective was the use of I2 as an oxidizing reagent.
It is well established that trigonal bipyramidal 10-P-51
phosphoranes prefer to have the more electron-withdrawing
groups of the five substituents at the apical positions on the
basis of the concept of apicophilicity.2 The only exceptions
to this generality had been the case where some sort of steric
constraints disallowed such configurations.3 However, we
have recently succeeded in the first isolation and full
characterization of an phosphorane that exhibits reversed
apicophilicity (O-cis 2b) in which an oxygen atom occupies
an equatorial position and a carbon atom an apical position
in a five-membered ring without applying restrictions that
would not permit the formation of the stereoisomer (O-trans
3b).4 In the presence of pyridine, O-cis 2b was formed as a
major product via a unique thermal cyclization reaction of
* Present address: Advanced Research Center for Science and Engineer-
ing, Waseda University, 3-4-1 Ohkubo, Shinjuku-ku, Tokyo 169-8555,
Japan. E-mail: akibaky@mn.waseda.ac.jp.
† Research Fellow of the Japan Society for the Promotion of Science.
Address: Department of Chemistry, School of Science, Kitasato University,
Kitasato, Sagamihara, Kanagawa 228-8555, Japan.
(1) For N-X-L designation: Perkins, C. W.; Martin, J. C.; Arduengo, A.
J., III; Lau, W.; Alegria, A.; Kochi, J. K. J. Am. Chem. Soc. 1980, 102,
7753-7759.
Zhang, Y.; Glaser, R.; Reed, A. E.; Schleyer, P. v. R.; Streitwieser, A. J.
Am. Chem. Soc. 1991, 113, 55-64. Wasada, H.; Hirao, K. J. Am. Chem.
Soc. 1992, 114, 16-27. Thatcher, G. R. J.; Campbell, A. S. J. Org. Chem.
1993, 58, 2272-2281.
(3) Timosheva, N. V.; Prakasha, T. K.; Chandrasekaran, A.; Day, R.
O.; Holmes, R. R. Inorg. Chem. 1995, 34, 4525-4526. Timosheva, N. V.;
Chandrasekaran, A.; Prakasha, T. K.; Day, R. O.; Holmes, R. R. Inorg.
Chem. 1996, 35, 6552-6560. Vollbrecht, S.; Vollbrecht, A.; Jeske, J.; Jones,
P. G.; Schmutzler, R.; du Mont, W.-W. Chem. Ber./Recl. 1997, 130, 819-
822.
(2) Holmes, R. R. Pentacoordinated PhosphorussStructure and Spec-
troscopy; ACS Monograph 175, 176; American Chemical Society: Wash-
ington, DC, 1980; Vol. I, II. Trippett, S. Phosphorus Sulfur 1976, 1, 89-
98. Holmes, R. R. J. Am. Chem. Soc. 1978, 100, 433-446. Eisenhut, M.;
Mitchell, H. L.; Traficante, D. D.; Kaufman, R. J.; Deutsch, J. M.;
Whitesides, G. M. J. Am. Chem. Soc. 1974, 96, 5385-5397. Moreland, C.
G.; Doak, G. O.; Littlefield, L. B.; Walker, N. S.; Gilje, J. W.; Braun, R.
W.; Cowley, A. H. J. Am. Chem. Soc. 1976, 98, 2161-2165. Buono, G.;
Llinas, J. R. J. Am. Chem. Soc. 1981, 103, 4532-4540. Griend, L. V.;
Cavell, R. G. Inorg. Chem. 1983, 22, 1817-1820. McDowell, R. S.;
Streitwieser, A., Jr. J. Am. Chem. Soc. 1985, 107, 5849-5855. Wang, P.;
(4) Kojima, S.; Kajiyama, K.; Nakamoto, M.; Akiba, K.-y. J. Am. Chem.
Soc. 1996, 118, 12866-12867.
10.1021/ol015927y CCC: $20.00 © 2001 American Chemical Society
Published on Web 05/18/2001

Scheme 1. Synthesis of Phosphorane with Reversed Apicophilicity O-cis 2
P-H (apical) phosphorane 1b with concomitant H2 elimina-
The dianion 4c was not oxidized by 30% H2O2, and the
starting material 1c was recovered.
It is rationalized that, upon oxidation of the dianion 4,
phosphorane A is formed and then cyclization takes place
to extrude X- by the oxide anion to give 2.
tion,4 whereas 1a-c gave O-trans 3a-c in toluene and
o-dichlorobenzene (Scheme 1).5 One disadvantage of this
procedure is that it is not suitable for the preparation of
phosphoranes that exhibit reversed apicophilicity and may
undergo stereomutation6 around these temperatures. Herein
we report on the mild and highly selective procedures for
preparing phosphoranes that exhibit reversed apicophilicity
O-cis 2 with two Martin ligands and one additional sub-
stituent, which proceeds through the oxidation of in situ
generated dianion 4.
To extend the validity of the oxidation protocol, the
preparation of phosphoranes that exhibit reversed apicophi-
licity, 2d-g, bearing aryl groups was attempted. To prepare
1, aromatic lithium reagents (6 equiv, large excess) were
reacted with P-H (equatorial) spirophosphorane 5 according
to the procedure for alkyl derivatives.5 However, the expected
phosphorane 1 was not obtained at all after usual treatment
of the reaction mixture, giving only the cyclized O-trans 3
along with some decomposition products.
Fortunately, 31P NMR measurements of the reaction
solution showed the formation of the corresponding dianion
4 at room temperature [4d (R)2,4,6-trimethylphenyl): δP
(Et2O) ) -9.8; 4e (R)2,4,6-triethylphenyl): δP (Et2O) )
-10.8; 4f (R)2,4,6-tri-i-propylphenyl): δP (Et2O) ) -10.8].
Thus, oxidative cyclization was attempted as a one-pot
procedure by the addition of iodine (6 equiv) (Scheme 1).
31P NMR observation of the mixtures directly after the
addition of I2 showed the quantitative formation of isomers
that exhibit reversed apicophilicity, O-cis 2d-g. After 30
min at room temperature, the ratio of O-cis 2 to O-trans 3
became 62:38 for 4d, 63:37 for 4e, 99:1 for 4f, and 23:77
for 4g. From the relative stability of 2d-g, it is evident that
steric effect is a major cause for stabilization against
First, for alkyl derivatives, dianions 4a [δP (Et2O) )
-33.5], 4b [δP (Et2O) ) -23.1], and 4c [δP (Et2O) ) -10.1]
were generated in situ by the reaction of 1a [δP (CDCl3) )
-51.9], 1b [δP (CDCl3) ) -33.4], and 1c [δP (CDCl3) )
-14.7, -43.0]5 with 2 equiv of n-BuLi in Et2O at -78 °C,
respectively. Oxidation of the dianion 4 was carried out at
room temperature (or at -78 °C) with 30% H2O2, mCPBA,
and I2. Formation of an isomer that exhibits reversed
apicophilicity, O-cis 2, was observed predominantly or
exclusively by 31P NMR, and the ratio of O-cis 2 and O-trans
3 after 30 min in solution are shown in Table 1.
Table 1. Ratio of O-cis 2 and O-trans 3 in the Reaction
Mixture Determined by 31P NMR (Room Temperature after 30
min) in Et2O
oxidizing reagent
2a :3a
2b:3b
2c:3c
30% H2O2
mCPBA
I2
93:7
92:8
96:4
88:12
>99:<1
>99:<1
88:12
>99:<1
(5) Kajiyama, K.; Kojima, S.; Akiba, K.-y. Tetrahedron Lett. 1996, 37,
8409-8412.
(6) Berry, R. S. J. Chem. Phys. 1960, 32, 933-938.
1874
Org. Lett., Vol. 3, No. 12, 2001

pseudorotation in the isomers that exhibit reversed apico-
philicity. In the case of 2f, pseudorotation was sufficiently
slow to allow the isolation of pure product.7 The X-ray
structures of 2f and 3f shown in Figure 1 verify their
structure.8
rane 5. The optimum oxidizing reagent in our hands is I2,
since not only were the reaction temperatures mild but also
the reaction conditions could be anhydrous. We believe that
this method is applicable for the preparation of a wide range
of phosphoranes that exhibit reversed apicophilicity, a novel
class of pentacoordinate phosphorus compounds.
Acknowledgment. The authors are grateful to Central
Glass Co. Ltd. for a generous gift of hexafluorocumyl
alcohol. Partial support of this work through Grant-in-Aid
for Scientific Research (09239103, 09440218, 11166248,
11304044) provided by the Ministry of Education, Science,
Culture, and Sports of the Japanese Government is heartily
acknowledged.
Supporting Information Available: Preparation, spectral
details, and elemental analyses for 2a-g and 3a-g. This
material is available free of charge via the Internet at http://
pubs.acs.org.
OL015927Y
(7) Alkylspirophosphorane 2b. To a solution of 5 (3.09 g, 5.99 mmol)
in Et2O (50 mL) was added n-BuLi (1.52 M hexane solution, 11.7 mL,
18.0 mmol) at 0 °C, and then the solution was stirred for 3 h at room
temperature. The solution was allowed to cool to -78 °C, and then I2 (4.60
g, 18.1 mmol) was added. The mixture was stirred for 1 h at -78 °C. The
resulting solution was washed with aqueous Na2S2O3 (50 mL ×2) and brine
(50 mL ×2), and the organic layer was dried over anhydrous MgSO4 and
concentrated in vacuo. Resulting crude product was washed with n-hexane
to afford a white solid of 2b (3.12 g, 5.45 mmol, 91.1%). Preparation by
hydrogen elimination and the spectral data of 2b were already reported.4
The properties of 2a are similar to those of 2b and 2f and will be reported
in due course. Arylspirophosphorane 2f. To a solution of 1-bromo-2,4,6-
tri-i-propylbenzene (0.769 g, 2.72 mmol) in Et2O (5 mL) was added n-BuLi
(1.46 mL, 2.33 mmol, c 1.62 M in hexane) at -78 °C. The mixture was
allowed to warm to room temperature and was stirred for 4 h. To the mixture
was added a solution of P-H (equatorial) spirophosphorane 5 (200 mg,
0.388 mmol) in Et2O (5 mL) at -78 °C, and stirring was continued at room
temperature for 1 h followed by the addition of I2 (591 mg, 2.33 mmol).
After quenching with aqueous Na2S2O3, the mixture was extracted with
Et2O (3 × 30 mL), and the collected organic layer was dried over MgSO4.
The solvent was evaporated in vacuo. Purification was carried out by TLC
(silica gel, hexane/CH2Cl2 3:1) and recrystallization from hexane/CH2Cl2
to give 2f (197 mg, 0.275 mmol, 71%).
(8) Crystallographic data (excluding structure factors) for the structures
reported in this paper have been deposited with the Cambridge Crystal-
lographic Data Centre as supplementary publication nos. CCDC-154409
and 154410. Copies of the data can be obtained free of charge on application
to CCDC, 12 Union Road, Cambridge CB2 1EZ, U.K. (fax: (+44)1223-
336-033; e-mail: deposit@ccdc.cam.ac.uk). Crystals suitable for X-ray
structure determination were mounted on a MacScience MXC3 diffracto-
meter and irradiated with graphite-monochromated Cu KR radiation (λ )
1.54178 Å) for data collection. The structure was solved using the teXsan
(Rigaku) system and refined by full-matrix least-squares. Crystal data for
2f: monoclinic system, space group P21/c (No. 14), a ) 17.918(3) Å, b )
12.896(2) Å, c ) 16.333(3) Å, â ) 117.02(1)°, V ) 3362.2(9) Å3, Z ) 4,
Fcalc ) 1.419 g cm-3. R ) 0.0567 (Rw ) 0.0958) for 4357 observed
reflections (433 parameters) with I > 3σ(I). Goodness of fit ) 1.281. Crystal
data for 3f: monoclinic system, space group C2/c (No. 15), a ) 36.539(4)
Å, b ) 10.590(1) Å, c ) 19.564(3) Å, â ) 117.773(9)°, V ) 6698(1) Å3,
Z ) 8, Fcalc ) 1.425 g cm-3. R ) 0.0669 (Rw ) 0.1009) for 3845 observed
reflections (433 parameters) with I > 3σ(I). Goodness of fit ) 1.011. The
apical bonds of 2f are longer than the corresponding equatorial bonds; O1-
P1(ap) 1.778(2) > O2-P1(eq) 1.677(2) Å, and C2-P1(ap) 1.887(3) > C1-
P1(eq) 1.824(3) Å, whereas the pairs of bonds of 3f are almost equal;
O-P(ap) 1.755(2), 1.763(2) Å, and C-P(eq) 1.824(4), 1.830(4) Å.
(9) It is not clear at present why 6 equiv of aryllithiums and 3 equiv of
alkyllithiums give the best yield of 2.
Figure 1. Crystal structures (30% thermal ellipsoids) of 2f and
3f.
On the basis of the success generating dianion 4 directly
from 5 by excess (6 equiv) aryllithiums, the same procedure
was applied with aliphatic lithiums (3 equiv). Formation of
the dianion 4a-c was observed by 31P NMR, and the same
results were obtained as shown in Table 1 by I2 oxidation.9
In summary, we have developed a mild and one-pot
procedure for preparing phosphoranes that exhibit reversed
apicophilicity, O-cis 2, by using P-H (equatorial) phospho-
Org. Lett., Vol. 3, No. 12, 2001
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