A potential intermediate for the aza-Corey-Chaykovsky reaction: Synthesis, structure, and thermolysis of a pentacoordinate 1,2-thiazetidine 1-oxide

Article abstract of DOI:10.1021/ol0618499

Thermolysis of a pentacoordinate 1λ⁶,2-thiazetidine, which was synthesized for the first time and characterized by X-ray crystallographic analysis, gave the corresponding aziridine and a cyclic sulfinate almost quantitatively. The potential intermediacy of a 1λ⁶,2-thiazetidine was suggested in the aza-Corey-Chaykovsky reaction.

Full text of DOI:10.1021/ol0618499

ORGANIC
LETTERS
2006
Vol. 8, No. 20
4625-4627
A Potential Intermediate for the
Aza-Corey Chaykovsky Reaction:
−
Synthesis, Structure, and Thermolysis
of a Pentacoordinate 1,2-Thiazetidine
1-Oxide
Naokazu Kano, Yuya Daicho, and Takayuki Kawashima*
Department of Chemistry, Graduate School of Science, The UniVersity of Tokyo,
7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
takayuki@chem.s.u-tokyo.ac.jp
Received July 26, 2006
ABSTRACT
Thermolysis of a pentacoordinate 1
analysis, gave the corresponding aziridine and a cyclic sulfinate almost quantitatively. The potential intermediacy of a 1
suggested in the aza-Corey Chaykovsky reaction.
λ
6,2-thiazetidine, which was synthesized for the first time and characterized by X-ray crystallographic
6,2-thiazetidine was
λ
−
The Corey-Chaykovsky reaction, the oxirane formation
reaction from a sulfonium or oxosulfonium ylide and a
carbonyl compound, is one of the most useful methods for
preparation of oxiranes.1 Its nitrogen version, the aza-Corey-
Chaykovsky reaction, has been used for the synthesis of
aziridines from a sulfonium2 or oxosulfonium ylide3 and an
imine. Since the appearance this decade of highly stereose-
lective4 and enantioselective5 aza-Corey-Chaykovsky reac-
tions, studies on the reaction mechanism are important to
improve the selectivities. Some reaction mechanisms for the
aza-Corey-Chaykovsky reaction of an oxosulfonium ylide
have been postulated to date. One mechanism is the
intramolecular attack of the imido anion on the â-carbon in
the betaine (syn or anti), which is formed by the nucleophilic
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10.1021/ol0618499 CCC: $33.50
© 2006 American Chemical Society
Published on Web 09/02/2006

attack of the ylidic carbon on the imine carbon atom, with
elimination of a sulfoxide3b,c or decomposition from a metal-
containing six-membered ring transition state.3d,e,g Another
proposed mechanism is the degradation of a pentacoordinate
1,2-thiazetidine, the [2 + 2]-cycloadducts of an oxosulfonium
ylide and an imine.3e However, the intermediate of the aza-
Corey-Chaykovsky reaction has neither been observed nor
isolated, and the reaction mechanism has not yet been
elucidated.
aniline (1.1 equiv), and an aqueous solution of NH4Cl gave
â-aminoalkyl sulfide 4 (76%), which was converted to 5 with
(n-Bu)4NF (0.84 equiv) (84%) (Scheme 1). The oxidation
Scheme 1. Syntheses of 1,2-Thiazetidines 8 and 9
As a continuation of our work on the four-membered ring
compounds bearing a highly coordinate chalcogen atom,6 we
previously demonstrated the oxirane formation reactions of
tetracoordinate 1,2-oxathietanes 16b and pentacoordinate 1,2-
oxathietanes 26c,d bearing the Martin ligand,7 which are the
[2 + 2]-cycloadducts of a sulfonium ylide and an oxosul-
fonium ylide with a carbonyl compound, respectively (Figure
1). Because some reports have advocated the contribution
Figure 1. Tetracoordinate and pentacoordinate 1,2-oxathietanes 1
and 2 and anti-betaines.
of 5 with m-CPBA (2.0 equiv) in chloroform gave sulfoxide
6 (32%), sulfone 7 (27%), and tetracoordinate 1λ4,2-
thiazetidine 8 (15%). Compounds 6 and 8 were obtained as
a single diastereomer, although the stereochemistry of 6 has
not been determined. Oxidation of 8 with 4.0 equiv of RuO4
in CCl4 at room temperature gave the corresponding oxidized
product, pentacoordinate 1,2-thiazetidine 9 (15%), with
recovery of 8 (74%).11 Either prolonged stirring or heating
at higher temperatures in the last reaction resulted in the
formation of unidentified byproducts, which made it difficult
to separate 9 cleanly.
The molecular structures of 8 (Supporting Information)
and 9 (Figure 2) were established by X-ray crystallographic
analyses.12 Compounds 8 and 9 are the first examples of the
syntheses and structural analyses of a tetracoordinate 1λ4,2-
thiazetidine and a pentacoordinate 1λ6,2-thiazetidine, respec-
tively. The molecular structure of 9 was found to be distorted
of a tetracoordinate 1,2-thiazetidine6,8 and a pentacoordinate
1,2-thiazetidine3e as an intermediate in the aza-Corey-
Chaykovsky reaction, it is important to elucidate the reactiv-
ity of the highly coordinate 1,2-thiazetidines for the study
of the reaction mechanism of the aza-Corey-Chaykovsky
reaction. However, no compound with such a ring system
containing a pentacoordinate sulfur atom has been reported
in contrast to a great number of reports on â-sultams and a
few reports on dicoordinate 1,2-thiazetidine and tricoordinate
1,2-thiazetidine 1-oxides.9 We report here the synthesis,
crystal structure, and thermolysis of the first example of a
pentacoordinate 1λ6,2-thiazetidine, a novel type of sulfurane
oxide.6c,10 We also discuss its comparison with a tetracoor-
dinate 1λ4,2-thiazetidine. The Martin ligand was used to
stabilize these sulfuranes.7
Sequential treatment of benzyl sulfide 36d with lithium
diisopropylamide (2.2 equiv), (hexafluoroisopropylidene)-
(9) (a) Timberlake, J. W.; Elder, E. S. In ComprehensiVe Heterocyclic
Chemistry; Lwowski, W., Vol. Ed.; Pergamon Press: Oxford, 1984; Vol.
7, Chapter 5.15. (b) Harris, P. A. In ComprehensiVe Heterocyclic Chemistry
II; Padwa, A., Vol. Ed.; Pergamon Press: Oxford, 1996; Vol. 1, Chapter
1.32. (c) Otani, T.; Takayama, J.; Sugihara, Y.; Ishii, A.; Nakayama, J. J.
Am. Chem. Soc. 2003, 125, 8255-8263. (d) Page, M. I. Acc. Chem. Res.
2004, 37, 297-303.
(6) (a) Kawashima, T.; Ohno, F.; Okazaki, R. J. Am. Chem. Soc. 1993,
115, 10434-10435. (b) Kawashima, T.; Ohno, F.; Okazaki, R. Angew.
Chem., Int. Ed. Engl. 1994, 33, 2094-2095. (c) Ohno, F.; Kawashima, T.;
Okazaki, R. J. Am. Chem. Soc. 1996, 118, 697-698. (d) Kawashima, T.;
Ohno, F.; Okazaki, R.; Ikeda, H.; Inagaki, S. J. Am. Chem. Soc. 1996, 118,
12455-12456. (e) Ohno, F.; Kawashima, T.; Okazaki, R. Chem. Commun.
1997, 1671-1672. (f) Ohno, F.; Kawashima, T.; Okazaki, R. Chem.
Commun. 2001, 463-464. (g) Kano, N.; Daicho, Y.; Nakanishi, N.;
Kawashima, T. Org. Lett. 2001, 3, 691-694. (h) Kano, N.; Takahashi, T.;
Kawashima, T. Tetrahedron Lett. 2002, 43, 6775-6778. (i) Kawashima,
T. Coord. Chem. ReV. 2003, 244, 137-147.
(10) (a) Martin, J. C.; Perozzi, E. F. J. Am. Chem. Soc. 1974, 96, 3155-
3168. (b) Perrozi, E. F.; Martin, J. C.; Paul, I. C. J. Am. Chem. Soc. 1974,
96, 6735-6744. (c) Adzima, L. J.; Martin, J. C. J. Am. Chem. Soc. 1977,
99, 1657-1659. (d) Lau, P. H. W.; Martin, J. C. J. Am. Chem. Soc. 1977,
99, 5490-5491. (e) Rongione, J. C.; Martin, J. C. J. Am. Chem. Soc. 1990,
112, 1637-1638.
(7) Perozzi, E. F.; Michalak, R. S.; Figuly, G. D.; Stevenson, W. H., III;
Dess, D. B.; Ross, M. R.; Martin, J. C. J. Org. Chem. 1981, 46, 1049-
1053.
(11) Perozzi, E. F.; Martin, J. C. J. Am. Chem. Soc. 1972, 94, 5519-
5520.
(8) (a) Li, A.-H.; Zhou, Y.-G.; Dai, L.-X.; Hou, X.-L.; Xia, L.-J.; Lin,
L. Angew. Chem., Int. Ed. Engl. 1997, 36, 1317-1319. (b) Li, A.-H.; Zhou,
Y.-G.; Dai, L.-X.; Hou, X.-L.; Xia, Li-J.; Lin, L. J. Org. Chem. 1998, 63,
4338-4348.
(12) Crystal data of 9: C25H15F12NO2S, FW ) 621.44, colorless crystals,
orthorhombic, space group Pna21, a ) 10.371(4) Å, b ) 16.811(7) Å, c )
14.108(6) Å, V ) 2459.7(18) Å3, Z ) 4, Fcalcd ) 1.678 g cm-3, T ) 110(2)
K, R1(I > 2σ(I)) ) 0.0243 and wR2(all data) ) 0.0572.
4626
Org. Lett., Vol. 8, No. 20, 2006

mixture, and most of the products could not be identified,
in contrast to thermolysis of the corresponding selenium
analogue.6g On the other hand, thermolysis of the pentaco-
ordinate 1λ6,2-thiazetidine 9 gave a clear result. Upon heating
at 160 °C in toluene-d8 for 17 h, pentacoordinate 1,2-thiaze-
tidine 9 afforded the corresponding aziridine 10 (94%), the
cyclic sulfinate 11 (100%), amine 12 (6%), and benzaldehyde
(13) (6%) (Scheme 2).15 No formation of the corresponding
Scheme 2. Thermolysis of 9
olefin was observed. The latter two compounds, 12 and 13,
must be formed by the hydrolysis of aziridine 10. That is,
the result shows the almost quantitative formation of aziridine
10 and cyclic sulfinate 11 in the thermolysis of 9. Consider-
ing that the oxygen analogue of 9, pentacoordinate 1,2λ6-
oxathietanes 1, gave the corresponding oxirane6 and that the
selenium analogue of 8, a tetracoordinate 1,2λ4-selenazeti-
dine, gave the corresponding aziridine,6g the results show
that the pentacoordinate 1,2-thiazetidine has a similar
reactivity to them at the point of formation of the corre-
sponding three-membered ring compound on thermolysis.
A pentacoordinate 1λ6,2-thiazetidine can be regarded as a
[2 + 2]-cycloadduct of the polarized C--S+ bond of an oxo-
sulfonium ylide to the CdN bond of an imine. Formation
of the aziridine from 1,2-thiazetidine 9 suggests that a penta-
coordinate 1,2λ6-thiazetidine might be an intermediate of the
aziridine formation reaction from an oxosulfonium ylide with
an imine, i.e., the aza-Corey-Chaykovsky reaction.3e
In summary, we have not only succeeded in the first syn-
thesis and isolation of both a tetracoordinate 1,2λ4-thiazetidine
and a pentacoordinate 1,2λ6-thiazetidine but also proved the
aziridine formation from the 1,2λ6-thiazetidine. These experi-
mental results suggest the participation of the 1,2λ6-thiazeti-
dine as a transition state or an intermediate in the aza-Corey-
Chaykovsky reaction of an oxosulfonium ylide. A study of
the stereochemistry of the aziridine formation reaction from
a 1,2λ6-thiazetidine and its reaction pathway is in progress.
Figure 2. ORTEP drawing of 9 with thermal ellipsoids plot (50%
probability). Selected bond lengths (Å), angles (deg), and torsion
angles (deg) for 9: S1-N1, 1.7751(15); S1-C1, 1.8455(17); C1-
C2, 1.556(3); C2-N1, 1.455(2); S1-O1, 1.8383(14); S1-O2,
1.4476(14); S1-C3, 1.7930(19); C1-S1-N1, 75.75(8); S1-C1-
C2, 90.91(11); C1-C2-N1, 95.11(13); C2-N1-S1, 97.22(11);
O1-S1-N1, 159.42(6); C1-S1-C3, 119.09(8); C1-S1-O2,
125.96(9); O2-S1-C3, 114.74(8); S1-N1-C2-C1, 8.42(12);
S1-C1-C2-N1, 8.03(12).
trigonal bipyramidal structures at a sulfur atom with O1 and
N1 atoms at apical positions and with C1, C3, and O2 atoms
at equatorial positions. The bond angle of two apical bonds
of 9 deviates by 20.58(6)° from 180°, due to their ring strain.
Configuration on the central sulfur atom in 8 and 9 indicates
that oxidation of 8 proceeded with retention of configuration.
The S1-N1 bond length of 9 (1.7751(15) Å) is somewhat
longer than those of â-sultams (1.638-1.698 Å)13 and the
sum of the corresponding covalent radii (1.74 Å)14 because
of the hypervalency. The equatorial S1-O2 bond length of
9 (1.4476(14) Å) is similar to that of the previously reported
sulfurane oxides (1.439(4)-1.445(6) Å).6c,10 The 1,2-thiaz-
etidine ring of 9 deviates from planarity, as indicated by their
S1-N1-C2-C1 torsion angle [8.42(12)°].
On one hand, thermolysis of tetracoordinate 1λ4,2-thiaz-
etidine 8 at 210 °C in o-xylene-d10 for 81 h gave a complex
Acknowledgment. We thank Central Glass, Shin-etsu
Chemical Co., Ltd., and Tosoh Finechem Corp. for the gifts
of organofluorine compounds, organosilicon compounds, and
alkyllithiums, respectively. We also thank the Ministry of
Education, Culture, Sports, Science and Technology of Japan
for financial support.
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Supporting Information Available: Synthetic procedures
and spectral data for 4-9; X-ray crystallographic files for 8
and 9 (CIF). This material is available free of charge via the
Internet at http://pubs.acs.org.
OL0618499
(14) Pauling, L. In The Nature of the Chemical Bond, 3rd ed.; Cornell
University Press: New York, 1960; p 246.
(15) The yields of these products were determined on the basis of the
1
integral of H and 19F NMR spectra of the reaction solution.
Org. Lett., Vol. 8, No. 20, 2006
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