Synthesis, structure, and thermolysis of pentacoordinate 1,3,2λ5- oxazaphosphetidines: The intermediates of aza-Wittig reactions

Article abstract of DOI:10.1016/S0040-4039(00)00829-7

1,3,2λ⁵-Oxazaphosphetidines bearing the Martin ligand were synthesized by the reaction of the corresponding iminophosphorane and carbonyl compounds and characterized by X-ray crystallographic analysis. Thermolysis of the oxazaphosphetidine gave

Full text of DOI:10.1016/S0040-4039(00)00829-7

Tetrahedron Letters 41 (2000) 5237±5241
Synthesis, structure, and thermolysis of pentacoordinate
1,3,2l5-oxazaphosphetidines: the intermediates of
aza-Wittig reactions
Naokazu Kano, Xing Jia Hua, Seiji Kawa and Takayuki Kawashima*
Department of Chemistry, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku,
Tokyo 113-0033, Japan
Received 17 April 2000; revised 18 May 2000; accepted 19 May 2000
Abstract
1,3,2l5-Oxazaphosphetidines bearing the Martin ligand were synthesized by the reaction of the corre-
sponding iminophosphorane and carbonyl compounds and characterized by X-ray crystallographic analysis.
Thermolysis of the oxazaphosphetidine gave the cyclic phosphinate and the corresponding imine, indicat-
ing that the oxazaphosphetidine is an intermediate of the aza-Wittig reaction. # 2000 Elsevier Science Ltd.
All rights reserved.
Keywords: oxazaphosphetidine; aza-Wittig reaction; iminophosphorane; X-ray analysis; thermolysis.
There is much interest in the chemistry of small-membered ring compounds with two or more
main group elements in the ring in view of their characteristic structures and unique reactivities.1
In the course of our study on heteracyclobutanes bearing a highly coordinate main group element
at the position adjacent to the heteroatom,2 we have achieved the synthesis of 1,2l5-oxaphos-
phetanes 13 and 1,2l5-azaphosphetidines 2,4 i.e. the intermediates of Wittig reactions and Wittig-
type reactions, respectively.
On the other hand, a nitrogen version of the Wittig reaction, which is called the aza-Wittig
reaction using iminophosphoranes in the place of phosphorus ylides, has also been utilized as an
* Corresponding author. Fax: +81-3-5800-6899; e-mail: takayuki@chem.s.u-tokyo.ac.jp
0040-4039/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00829-7

5238
e€ective method for the synthesis of nitrogen-containing heterocycles.5 Pentacoordinate 1,3,2-
oxazaphosphetidines, which are considered as the intermediates of aza-Wittig reactions,6 are
anticipated to show the reactivities of both oxaphosphetanes and azaphosphetidines on their
thermolysis. But there have been only few examples on the crystallographically characterized
1,3,2l5-oxazaphosphetidines.7,8 Although an iminophosphorane that is synthesized from the
corresponding phosphine and azide is used for the general aza-Wittig reaction, these previously
reported oxazaphosphetidines were not derived from the corresponding phosphines. For the
elucidation of the mechanism of aza-Wittig reactions, it is important to isolate their intermediates,
although these isolations are ordinarily dicult because of their instability. Here, we describe the
synthesis, crystal structure, and thermolysis of 1,3,2l5-oxazaphosphetidines 3 bearing the Martin
ligand9 and a bulky 2,4,6-triisopropylphenyl (denoted as Tip hereafter) group, which are the ®rst
examples of dioxyazaphosphorane [10-P-5(C2O2N)] with an oxazaphosphetidine framework.
Sequential treatment of PCl3 with TipLi and dilithio derivative 4 of hexa¯uorocumyl alcohol
gave cyclic phosphinite 5 (ꢀP=146.1), which was allowed to react with phenyl azide at ^78ꢀC in
THF to a€ord the corresponding iminophosphorane 6 (ꢀP=25.6) (Scheme 1).9 As compounds 5
and 6 are an air and/or moisture-sensitive oil, they were used without isolation and puri®cation.10
The reactions of iminophosphorane 6 with carbonyl compounds such as benzaldehyde and tri-
¯uoroacetophenone at 60 and 70ꢀC, respectively, gave a diastereomeric mixture of the corre-
sponding 1,3,2l5-oxazaphosphetidines 3a and 3b which were hydrolyzed on silica gel. Treatment
of 6 with hexa¯uoroacetone (denoted as HFA hereafter) at room temperature also gave 3c in a
pure form after chromatographic separation.11 But no reaction took place upon heating a C6D6
solution of 6 and benzophenone in a sealed tube even at 120ꢀC due to its low reactivity and steric
congestion.
Scheme 1.
The structures of 3a±c were strongly supported by their NMR spectra.11 Data for 3c are shown
1
below as a typical example. In the H NMR spectrum of 3c, the ortho proton of the Martin
ligand resonated at low ®eld (ꢀ=8.52), which is a typical feature of compounds with a trigonal-
bipyramidal (TBP) structure bearing a polar apical bond.12 In the 19F NMR spectrum of 3c, four
quartets for the tri¯uoromethyl groups of HFA and the Martin ligand units were observed due to
their nonequivalence emerging from the ring formation. An up®eld shift (from ꢀ=25.6 for 6 to
ꢀ=^18.6 for 3c) observed in the 31P NMR spectra indicates that 3c has a pentacoordinate phos-
phorane structure.3 Oxazaphosphetidine 3c did not dissociate into iminophosphorane 6 and HFA
in CDCl3 solution at room temperature in contrast to Schmidpeter's oxazaphosphetidines.7 The
N-apical pseudorotamer of 3c was not detected by variable temperature NMR spectra between
27ꢀC and 107ꢀC, although N-apical pseudorotamers were observed at room temperature for
azaphosphetidines 2.4

5239
The X-ray crystallographic analysis of 3c13 (Fig. 1) indicated its distorted trigonal±bipyramidal
structure at the phosphorus atom with two oxygen atoms at the apical positions and two carbon
and nitrogen atoms at the equatorial positions (TBP!SP14 22.2%). The structural feature of 3c is
very similar to those of 1 and 2.3,4 While the O1±C1 bond length [1.379(2) A] is somewhat shorter
than those of previously reported oxazaphosphetidines [between 1.406(5) and 1.426(7) A],7,8 the
other bond lengths of the four-membered ring are similar to those of other 1,3,2-oxazaphos-
phetidines and those of the theoretically optimized intermediate of the aza-Wittig reaction.6b The
bond angle between two apical bonds deviates from 180ꢀ by 12.71(7)ꢀ probably due to the ring
strain. The phosphorus atom is placed on the equatorial plane and the torsion angle P1±N1±C1±
O1 is 1.1(1)ꢀ, indicating that the four-membered ring is almost planar. The nitrogen atom has
almost trigonal-planar coordination and the plane of the benzene ring on the nitrogen atom lies
perpendicular to the plane of the four-membered ring, probably emerging from steric repulsion.
Figure 1. ORTEP drawing of 3c with thermal ellipsoid plot (30% probability). Selected bond lengths (A), angles (deg),
and torsion angles (deg): P1±O1, 1.786(1); P1±O2, 1.719(1); P1±C2, 1.815(2); P1±C3, 1.844(2); P1±N1, 1.688(2); N1±
C1, 1.443(2); O1±C1, 1.379(2); O1±P1±O2, 167.29(7); O1±P1±N1, 74.84(7); N1±P1±C2, 121.50(9); N1±P1±C3,
122.31(9); C2±P1±C3, 115.87(10); N1±C1±O1, 96.9(2); P1±O1±C1, 93.2(1); P1±N1±C1, 95.1(1); P1±N1±C1±O1, 1.1(1)
Thermolysis of 3c at 140ꢀC in toluene-d8 gave the corresponding imine 7 (90%) and cyclic
phosphinate 8 (100%) (Scheme 2).15 Furthermore, the oxazaphosphetidine is anticipated to show
other reactivity on the thermolysis, i.e. the formation of the iminophosphorane as in the cases of
azaphosphetidines 2. This process, however, must be reversible. Therefore, thermolysis in the
presence of water was considered to o€er evidence for its existence, because product 6 can be
irreversibly removed from its system by its hydrolysis. In fact, thermolysis of 3c with an excess
amount (20 equiv.) of water (140ꢀC, 3 h) gave HFA (96%), 8 (100%) and aniline (89%) as main
products with a small amount of imine 7 (4%). Aniline derived not from imine 7 but from
iminophosphorane 6, because 7 does not react with water under the same reaction conditions.
Since aniline and 8 are hydrolysis products of 6, the thermolysis process of 3c giving 6 and HFA
was evidenced by their formation. These results indicate two reaction pathways for the thermo-
lysis of 3c. One path is the aza-Wittig reaction giving imine 7 and cyclic phosphinate 8. Thus,
1,3,2l5-oxazaphosphetidines 3c can be regarded as an intermediate of the aza-Wittig reaction.

5240
Scheme 2.
The other path is regeneration of iminophosphorane 6 and HFA. The formation of the imino-
phosphorane is considered as a characteristic reaction of not only azaphosphetidines but also
oxazaphosphetidines.
In summary, we have succeeded in the synthesis and X-ray structural analysis of 1,3,2l5-oxaza-
phosphetidine bearing the Martin ligand. It was found by its thermolysis that oxazaphosphetidine
has two reactivities, respectively, as an oxaphosphetane and an azaphosphetidine.
Acknowledgements
This work was partially supported by Grants-in-Aid for Scienti®c Research from the Ministry of
Education, Science, Sports and Culture of Japan. We thank Professor T. Asano, Oita University,
for his generous gift of an authentic sample of hexa¯uoroisopropylideneaniline. We also thank
Central Glass and Tosoh Akzo Co. Ltd., for the gifts of organo¯uorine compounds and alkyl-
lithiums, respectively.
References
1. (a) Lukevics, E.; Pudova, O. In Comprehensive Heterocyclic Chemistry II; Katritzky, A. R.; Rees, C. W.; Scriven,
E. F. V., Eds.; Pergamon: Oxford, U.K., 1996; Vol. 1B, pp. 1189±1213. (b) Kawashima, T.; Okazaki, R. In
Advances in Strained and Interesting Organic Molecules; Halton, B., Ed.; JAI Press: Stamford, Connecticut, 1999;
Vol. 7, pp. 1±41.
2. (a) Kawashima, T.; Okazaki, R. Synlett 1996, 600±608, and references cited therein. (b) Ohno, F.; Kawashima, T.;
Okazaki, R. J. Am. Chem. Soc. 1996, 118, 697±698. (c) Ohno, F.; Kawashima, T.; Okazaki, R. Chem. Commun.
1997, 1671±1672.
3. (a) Kawashima, T.; Kato, K.; Okazaki, R. J. Am. Chem. Soc. 1992, 114, 4008±4010. (b) Kawashima, T.; Kato, K.;
Okazaki, R. Angew. Chem., Int. Ed. Engl. 1993, 32, 869±870. (c) Kawashima, T.; Kato, K.; Okazaki, R. Angew.
Chem., Int. Ed. 1998, 37, 1606±1606. (d) Kawashima, T.; Kato, K.; Okazaki, R. J. Am. Chem. Soc. 1998, 120,
6848±6848.
4. Kawashima, T.; Soda, T.; Okazaki, R. Angew. Chem., Int. Ed. Engl. 1996, 35, 1096±1098.
5. For recent reviews on the aza-Wittig reaction, see: (a) Gololobov, Y. G.; Kasukhin, L. F. Tetrahedron 1992, 48,
1353±1406. (b) Molina, P.; Vilaplana, M. J. Synthesis 1994, 1197±1218.
6. (a) Koketsu, J.; Ninomiya, Y.; Suzuki, Y.; Koga, N. Inorg. Chem. 1997, 36, 694±702. (b) Lu, W. C.; Liu, C. B.;
Sun, C. C. J. Phys. Chem. A. 1999, 103, 1078±1083.
7. Sheldrick, W. S.; Schomburg, D.; Schmidpeter, A.; von Criegern, T. Chem. Ber. 1980, 113, 55±69.
8. (a) Storzer, W.; Roschenthaler, G.-V.; Schmutzler, R.; Sheldrick, W. S. Chem. Ber. 1981, 114, 3609±3624. (b)
Francke, R.; Dakternieks, D.; Gable, R. W.; Hoskins, B. F.; Roschenthaler, G.-V. Chem. Ber. 1985, 118, 922±930.
9. LiC6H4C(CF3)2OLi, which can be prepared by directed lithiation of hexa¯uorocumyl alcohol, is usually used for
the introduction of this ligand, see: Perozzi, E. F.; Michalak, R. S.; Figuly, G. D.; Stevenson III, W. H.; Dess,
D. B.; Ross, M. R.; Martin, J. C. J. Org. Chem. 1981, 46, 1049±1053.

5241
10. Cyclic phosphinite 5 gave the corresponding phosphinate 8 on exposure to air. Iminophosphorane 6 also gave
readily 8 in the presence of water.
11. Selected spectroscopic and analytical data for 3c: colorless crystals; mp 178±181ꢀC (dec.); H NMR (500 MHz,
1
CDCl3) ꢀ 0.27 (d, 3JHH=6.6 Hz, 3H), 1.06 (d, 3JHH=6.6 Hz, 3H), 1.11 (d, 3JHH=6.6 Hz, 3H), 1.13 (d, 3JHH=6.9
3
3
3
Hz, 6H), 1.33 (d, JHH=6.6 Hz, 3H), 2.76 (sept, JHH=6.9 Hz, 1H), 3.54 (sept, JHH=6.6 Hz, 1H), 3.72 (sept,
3JHH=6.6 Hz, 1H), 6.77 (d, 4JPH=7.2 Hz, 1H), 7.03 (d, 4JPH=7.2 Hz, 1H), 7.12 (d, 3JHH=7.6 Hz, 2H), 7.22±7.29
3
3
4
(m, 3H), 7.58 (brs, 1H), 7.67 (t, JHH=7.6 Hz, 1H), 7.73 (dd, JHH=7.6 Hz, JHP=9.4 Hz, 1H), 8.52 (dd,
3JHH=7.6 Hz, 3JHP=11.4 Hz, 1H); 19F NMR (254 MHz, CDCl3) ꢀ ^76.53 (q, 4JFF=9.8 Hz), ^74.99 (q, 4JFF=9.8
Hz), ^72.71 (q, 4JFF=9.8 Hz), ^72.35 (q, 4JFF=9.8 Hz); 31P NMR (109 MHz, CDCl3) ꢀ ^18.6 (s); MS(FAB): m/z
734 ([M+H]+, 8.7%). Anal. calcd for C33H32NF12O2P: C, 53.80; H, 4.46; N, 2.09. Found: C, 54.03; H, 4.40; N,
1.91.
12. Granoth, I.; Martin, J. C. J. Am. Chem. Soc. 1979, 101, 4618±4621.
13. Crystal data for 3c at 296 K with Mo Ka radiation (l=0.71070 A): C33H32F12NO2P; MW=733.58; monoclinic;
space group P21/c; a ˆ 10:437ꢁ2† A, b ˆ 18:668ꢁ3† A, c ˆ 17:753ꢁ3† A; ꢁ ˆ 105:29ꢁ1†ꢀ; V ˆ 3336:5ꢁ9† A3; Z ˆ 4;
Dc ˆ 1:460 g cm^3; m(Mo Ka)=1.81 cm^1; R (Rw)=0.043 (0.023).
14. Holmes, R. R.; Deiters, J. A. J. Am. Chem. Soc. 1977, 99, 3318±3326.
15. The ratio of these products was determined based on the integral of 19F NMR spectra of the reaction solution.