lactams prepared by organotin hydride mediated cyclisations of
1-amidoalkyl radicals.12–14
from ring closures of 4-unsaturated aminoacyl radicals. Sim-
ilarly, b-lactams can be obtained from secondary amines with
alk-2-enyl substituents, and related amines, in a two-step
process. If the unsaturated bond is functionalised with an aryl or
alkyl group at the 3-position in the amine, the cyclised
azetidinylalkyl radical is stabilised and consequently a hydroxy-
benzyl or hydroxyalkyl side chain is introduced with potential
for additional functional group manipulation.
An interesting feature was that both 10 and 11 were obtained
as hydroxyl derivatives, the former as a 5+1 mixture of anti- and
syn-isomers15 and the latter as a pair of diastereoisomers (3+1)
(Scheme 2). Probably hydrogen abstraction from the toluene
solvent was slower for the secondary precursor radical for 10
and the benzylic precursor radical for 11, so that addition of
dissolved dioxygen supervened. The peroxyl radicals formed in
this way would be converted to more reactive oxyl radicals (by
self-coupling and O2 loss)16 that did abstract hydrogen, hence
affording the hydroxyl derivatives.
We thank the EPSRC for financial support (Grant GR/
N37674/01).
Notes and references
1 P. A. Baguley and J. C. Walton, Angew. Chem., Int. Ed., 1998, 37,
3072.
2 A. Studer and S. Amrein, Synthesis, 2002, 835.
3 M. Hasebe, K. Kogawa and T. Tsuchiya, Tetrahedron Lett., 1984, 25,
3887; M. Hasebe and T. Tsuchiya, Tetrahedron Lett., 1986, 27, 3239.
4 M. Hasebe and T. Tsuchiya, Tetrahedron Lett., 1987, 28, 6207; M.
Hasebe and T. Tsuchiya, Tetrahedron Lett., 1988, 29, 6287.
5 A. J. McCarroll and J. C. Walton, J. Chem. Soc., Perkin Trans. 2, 2000,
2399.
6 J. C. Jochims, S. Hehl and S. Herzberger, Synthesis, 1990, 12, 1128.
7 A. J. McCarroll and J. C. Walton, Angew. Chem., Int. Ed., 2001, 40,
2225; A. J. McCarroll and J. C. Walton, J. Chem. Soc., Perkin Trans. 1,
2001, 3215.
8 EPR parameters for the radicals derived from 3g in tert-butylbenzene at
220 K were: iminyl (I) g = 2.0034, a(N) = 9.9, a(H) = 79.9 G;
aminoacyl (A) g = 2.0017, a(N) = 21.7 G; cyclised radical 7g (C) g =
2.0025, a(2H) = 22.3, a(1H) = 31.6 G (1G = 10 mT).
9 A solution of oxime oxalate amide 3g (0.8 g, 2.38 mmol), and MAP (1.0
g, 7.14 mmol) in toluene 400 cm3 was heated to 100 °C and photolysed
with a 400 W UV lamp in a quartz cold finger immersed in the solution
for 5 h. The mixture was allowed to cool to room temperature and then
evaporated to dryness to give the crude lactam. Column chromatog-
raphy (DCM: 1.0% MeOH) gave the pure cyclised product, 1-benzyl-
3-methyl-pyrrolidin-2-one (9g) as a colourless oil (378 mg; 84%); dH
(300 MHz, CDCl3) 1.25 (3 H, d, J = 7.2 Hz, CH3), 1.60 (1 H, m, CH),
2.25 (1 H, m, CH), 2.52 (1 H, m, J = 7.2 Hz), 3.19 (2 H, m, CH2) 3.19
(2 H, m, CH2), 4.42 (1 H, AB, CH), 4.48 (1 H, AB, CH), 7.21–7.37 (5
H, m, ArH); dC (75 MHz, CDCl3) 16.4 (CH3), 27.1 (CH2), 36.8 (CH),
44.7 (CH2), 46.8 (CH2), 127.5, 128.1, 128.6 (5 3 CH), 136.7 (C), 177.4
(CNO); m/z (relative intensity) 189 (100, M+), 174 (11), 161 (12), 91
(90); found M+ 189.1153, C12H15NO requires 189.1154.
10 G. B. Gill, G. Pattenden and S. J. Reynolds, J. Chem. Soc., Perkin Trans.
1, 1994, 369; G. Pattenden and S. J. Reynolds, ibid., 1994, 379.
11 L. V. Jackson and J. C. Walton, Chem. Commun., 2000, 2327.
12 H. Ishibashi, C. Kameoka, H. Iriyama, K. Kodama, T. Sato and M.
Ikeda, J. Org. Chem., 1995, 60, 1276.
Scheme 2 Preparation of b- and g-lactams via photosensitised reactions of
oxime oxalate amides.
Iminyl radicals 5 are inevitably formed as co-intermediates
with the desired aminoacyls 4. However, the only significant
product derived in each case from 5 (d–g) was benzaldehyde.
Evidently 5 abstracts hydrogen from the solvent to give
PhC(H)NNH that is hydrolysed on work-up. Under the experi-
mental conditions described above, hydrogen abstraction prior
to cyclisation was unimportant and negligible amounts of
formamides 8 were produced. In practice, therefore, inter-
ference from undesired by-products was unproblematic.
13 H. Ishibashi, C. Kameoka, K. Kodama, T. Sato and M. Ikeda,
Tetrahedron, 1996, 52, 489.
14 A. J. Clark and J. L. Peacock, Tetrahedron Lett., 1998, 39, 1265.
15 Note that this compound (stereochemistry undefined) was previously
obtained, as a mixture with the 6- and 7-hydroxylated analogues, by
biohydroxylation of the parent azabicycle with Beauveria sulfurescens:
A. Archelas, J. D. Fourneron and J. D. Furstoss, Tetrahedron Lett.,
1988, 29, 6611.
We conclude that photosensitised decompositions of oxime
amide oxalates provide an efficient and general route to
aminoacyl radicals. Good yields of g-lactams can be obtained
16 J. A. Howard, in Free Radicals, ed. J. K. Kochi, Wiley, New York,
1973, vol. II, ch. 12, p. 3.
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