undergoes rearrangement in warm CH2Cl2 to give a novel
tetrahydrooxazine 6, which shows coupling reactions typical of
a lactol.
H(1)
O(2)
We thank the EPSRC for their support of this work (grant
GR/K50719). I.A.O.N. thanks the James Black Foundation for
their continued financial support and Zeneca for a generous
unrestricted research grant.
H(3)
H(14)
C(1)
H(15)
C(10)
O(1)
H(4)
C(2)
H(2)
H(8)
Notes and References
H(9)
H(13)
C(6)
C(11)
C(8)
† E-mail: ion@liv.ac.uk
‡ Present address: Ribotargets Ltd, Kett House, 1 Station Road, Cambridge,
C(9)
C(3)
UK CB1 2JP.
N(1)
C(5)
H(5)
C(4)
H(7)
C(7)
H(12)
H(6)
1 R. Yoneda, Y. Sakamoto, Y. Oketo, S. Harusawa and T. Kurihara,
Tetrahedron, 1996, 52, 14563; T. Kurihara, Y. Sakamoto, M. Takai, K.
Ohuchi, S. Harusawa and R. Yoneda, Chem. Pharm. Bull., 1993, 41,
1221.
2 T. Kurihara, K. Ohuchi, M. Kawamoto, S. Harusawa and R. Yoneda,
Chem. Lett., 1991, 1781.
H(10)
H(11)
Fig. 2 Crystal structure of 6
exemplified by the conversion of physostigimine N-oxide to
geneserine.7 The structure of tetrahydrooxazine 6 was con-
firmed by single crystal X-ray analysis of the product (Fig.
2).6
3 J. C. Espie, R. Ramasseul and A. Rassat, Tetrahedron Lett., 1978, 795;
J. B. Aragao and M. H. Loucheux, Bull. Soc. Chim. Fr., 1971, 4387;
A. D. de Wit, M. L. M. Pennings, W. P. Trompenaars, D. N. Reinhoudt,
S. Harkema and O. Nevestveit, J. Chem. Soc., Chem. Commun., 1979,
993.
This 6-hydroxytetrahydrooxazine in which the nitrogen bears
a benzyl group has not been previously prepared. Interestingly,
the crystal structure shows that the anomeric hydroxy group is
in an equatorial position. We have carried out some preliminary
studies on the chemistry of this ring system and have established
that it undergoes reactions typical of a lactol. For example,
treatment of tetrahydrooxazine 6 with the stabilised ylide shown
gave the ester 7 via initial alkene formation followed by an
intramolecular Michael addition.8 Conversion of the tetra-
hydrooxazine 6 to its acetate followed by reaction with
allyltrimethylsilane in the presence of BF3–OEt2 yielded the
allyl adduct 8 (Scheme 5).
4 I. A. O'Neil, N. D. Miller, J. Peake, J. V. Barkley, C. M. R. Low and
S. B. Kalindjian, Synlett., 1993, 515; I. A. O'Neil, N. D. Miller, J. V.
Barkley, C. M. R. Low and S. B. Kalindjian, Synlett, 1995, 617; I. A.
O'Neil, N. D. Miller, J. V. Barkley, C. M. R. Low and S. B. Kalindjian,
Synlett, 1995, 619; I. A. O'Neil, C. D. Turner and S. B. Kalindjian,
Synlett, 1997, 777; I. A. O'Neil and A. J. Potter, Tetrahedron Lett., 1997,
38, 5731.
5 H. H. Wasserman, B. H. Lipshutz, A. W. Tremper and J. S. Wu, J. Org.
Chem., 1981, 46, 2991.
6 Crystal data for 3 (from CH2Cl2): C11H13NO3, M = 207.23, ortho-
rhombic, space group Pbca, Z = 8, a = 10.998(3), b = 16.750(4), c =
10.837 Å, U = 1996.3(10) Å3, Dc = 1.379 g cm23; T = 153 K; max 2q
= 49.9°, graphite-monochromated Mo-Ka radiation (l = 0.71069Å),
2020 reflections were measured; of these, 1277 with F > 0.30s(F) were
used in the refinement; R = 0.077, Rw = 0.081, residual electron density
0.44/20.48 e Å23. For 6 (from CH2Cl2): C11H15NO2, M = 193.24,
monoclinic, space group P21/c (no 14), Z = 4, a = 9.036(6), b =
CO2Me
OH
˚
13.551(6), c = 8.478(4) Å, b = 99.70(4), U = 1023.4(9) Å3, Dc = 1.254
ii, iii
i
O
N
O
N
O
N
g cm23; T = 153 K; max 2q = 50.0°, graphite-monochromated Mo-Ka
radiation (l = 0.71069Å), 2008 reflections were measured; of these,
1877 were unique with 1325 F > 1.00s(F) used in the refinement; R =
0.052, Rw = 0.040, residual electron density 0.81/20.96 e Å23. CCDC
182/893.
Bn
Bn
Bn
7
6
8
Scheme 5 Reagents and conditions: i, Ph3P = CHCO2Me, THF, 68%; ii,
7 S. Takano and K. Ogasawara, Alkaloids of the Calabar Bean, in The
Alkaloids, Chemistry and Pharmacology, Academic Press, San Diego,
1989, vol. 36, pp. 225–251; C. Hootelé, Tetrahedron Lett., 1969, 2713.
8 B. Maurer, A. Grieder and W. Thommen, Helv. Chim. Acta., 1979, 62,
44.
AcCl, NEt3, CH2Cl2; iii, AllylSiMe3, BF3·OEt2, 30% over 2 steps
In summary, we have prepared and characterised the first
stable simple azetidine N-oxide 3 and shown that it is stabilised
by intramolecular hydrogen bonding to the carboxylic acid. The
corresponding N-benzyl-2-hydroxymethylazetidine N-oxide 5
Received in Cambridge, UK, 2nd April 1998; 8/02503G
1488
Chem. Commun., 1998