1440
S. Kuduk et al. / Tetrahedron Letters 44 (2003) 1437–1440
ture was heated to 50°C for 2 h. The mixture was
Acknowledgements
concentrated in vacuo and purified by HPLC to afford
the product (Table 1, entry 5) TFA salt (71 mg, 69%) as
a white foam that gave a proton NMR spectrum consis-
tent with theory and a mass ion (ES+) of 302.1 for
M+H+: 1H NMR (300 MHz, MeOH-d4): l 7.34 (bm,
5H), 5.22 (bt, J=5.4 Hz, 1H), 5.12 (m, 1H), 3.85 (m, 1H),
3.66 (m, 2H), 3.39 (m, 1H), 2.62 (m, 1H), 2.13 (m, 1H),
1.37–1.71 (m, 6H).
The authors would like to thank Dr. Mike Wood for
helpful discussions.
References
7. Rokach, J.; Hamel, P.; Hunter, N. R.; Reader, G.;
Rooney, C. S.; Anderson, P. S.; Cragoe, E. J.; Mandel, L.
R. J. Med. Chem. 1979, 22, 237–244.
8. (a) Boeckman, R. K.; Jackson, P. F.; Sabatucci, J. P. J.
Am. Chem. Soc. 1985, 107, 2191; (b) Boeckman, R. K.;
Goldstein, S. W.; Walters, M. A. J. Am. Chem. Soc. 1988,
100, 8250.
9. Additional support for this mechanism was gained by
using dimethyl sulfate in place of methyl iodide in the
reaction with thioamide 1. In this case we only observed
the unrearranged product 2, and not 3, consistent with
the poor nucleophilicity of the sulfate counterion. We
have also prepared the O-methylimidate of benzyl 1-
(aminocarbonyl)cyclopropylcarbamate using trimethylox-
onium tetrafluoroborate. All attempts to rearrange this
material were unsuccessful. We believe the failure of this
imidate to undergo rearrangement is because the resulting
HBF4 salt is not conducive for nucleophilic ring opening.
Similar observations have been noted in the classical
cyclopropyliminium ion rearrangement (Ref. 3). Interest-
ingly, addition of halide salts to the tetrafluoroborates
did not result in rearrangement of the O-methyl imidates.
We are continuing to investigate O-methyl imidates as
substrates for this rearrangement.
1. Cloke, J. B. J. Am. Chem. Soc. 1929, 51, 1174.
2. Stevens, R. V. Acc. Chem. Res. 1977, 10, 193–198.
3. Boeckman, R. K.; Walter, M. A. Advances in Hetero-
cyclic Natural Product Synthesis; JAI Press: New York,
1990; Vol. 1, pp. 1–40.
4. Typical procedure for the imidate formation and rear-
rangement: To a stirred solution of benzyl 1-(aminocar-
bonothioyl)cyclopropylcarbamate 1 (1.60 g, 6.83 mmol)
in 60 mL of acetone was added methyl iodide (1.70 mL,
27.3 mmol). Additional methyl iodide was added to the
reaction as needed. The mixture was refluxed under N2
for 2 h and concentrated in vacuo to obtain a yellow
foam 3 that gave proton NMR spectra consistent with
theory and a mass ion (ES+) of 265.2 for M+H+: 1H
NMR (300 MHz, MeOH-d4): l 7.33 (bm, 5H), 5.34 (d,
J=6.5 Hz, 2H), 5.13 (s, 2H), 3.93–4.16 (m, 2H), 2.73 (s,
3H), 2.69 (m, 1H), 2.39 (m, 1H).
5. We have also carried out the reaction with Boc protection
as a complement to the Cbz examples shown. While the
rearrangement occurred under identical conditions, the
amine addition products were more difficult to isolate
and purify.
6. Typical procedure for the formation of diaminodihydropyr-
rolidines: To a solution of the crude rearrangement
product HI salt 3 (0.10 g, 0.255 mmol) in 1 mL of THF
was added piperidine (0.66 g, 0.77 mmol), and the mix-
10. Wasserman, H. H.; Dion, R. P. Tetrahedron Lett. 1983,
24, 3409–3412.