3 For selected instances of intramolecular aminohalogenation reactions, see:
(a) T. Bach, B. Schlummer and K. Harms, Chem. Commun., 2000, 287;
(b) T. Bach, B. Schlummer and K. Harms, Chem.–Eur. J., 2001, 7, 2581;
(c) H. Danielec, J. Klugge, B. Schlummer and T. Bach, Synthesis, 2006,
551; (d) D. G. Churchill and C. M. Rojas, Tetrahedron Lett., 2002, 43,
7225; (e) S. C. Bergmeier and D. M. Stanchina, J. Org. Chem., 1997, 62,
4449; (f) M. R. Manzoni, T. P. Zabawa, D. Kasi and S. R. Chemler, Orga-
nometallics, 2004, 23, 5618; (g) S. D. R. Christie, A. D. Warrington and
C. J. Lunniss, Synthesis, 2009, 146; (h) K. Muñiz, C. H. Hövelmann and
J. Streuff, J. Am. Chem. Soc., 2008, 130, 763.
4 T. Yoshimitsu, T. Ino, N. Futamura, T. Kamon and T. Tanaka, Org. Lett.,
2009, 11, 3402.
5 Peroxides are known to react with Fe(II) to produce oxyradical species.
This process is known as the Fenton reaction: C. Walling, Acc. Chem. Res.,
1975, 8, 125.
6 For examples of utility of N-tosyloxycarbamates and related compounds in
organic synthesis, see: (a) H. Lebel, K. Huard and S. Lectard, J. Am.
Chem. Soc., 2005, 127, 14198; (b) T. J. Donohoe, M. J. Chughtai, D.
J. Klauber, D. Griffin and A. D. Campbell, J. Am. Chem. Soc., 2006, 128,
2514; (c) H. Lebel and K. Huard, Org. Lett., 2007, 9, 639; (d) H. Lebel,
S. Lectard and M. Parmentier, Org. Lett., 2007, 9, 4797; (e) R. Liu, S.
R. Herron and S. A. Fleming, J. Org. Chem., 2007, 72, 5587; (f) K. Huard
and H. Lebel, Chem.–Eur. J., 2008, 14, 6222.
7 For instance, FeBr2 has been shown to form a stable tetrahydrate complex
with water, see: K. Waizumi, H. Masuda and H. Ohtaki, Inorg. Chim.
Acta, 1992, 192, 173. It is thus likely that iron(II) complexes are solvated
in the reaction mixture.
8 Authentic bromides 4b, 13a, and 13b were prepared by the stereospecific
SN2 opening of aziridines. Thus, the bromination of aziridines 17–19 with
FeBr2/Bu4NBr afforded the corresponding bromides. However, since an
aziridine derived from (Z)-cinnamyl substrate was unobtainable due to its
significant instability, bromination could not be conducted. The stereo-
chemistry of bromide 14 was unambiguously confirmed by nOe exper-
iments. The structure of compound 15a was established by coupling
constant analysis of the 1H NMR spectrum.
Fig. 1 Minor product generated by aminobromination of 11
complete stereocontrol in transferring a bromine atom. Com-
pound 14 was obtained in 85% yield as a single isomer having
syn-arrangement with respect to the vicinal nitrogen and bromine
atoms. Interestingly, aziridine 16 (4%) was found to be produced
in this case (Fig. 1).
In this context, it could be assumed that the moderate syn : anti
diastereoselectivities obtained for the acyclic substrates were
attributable to the formation of the diastereomers through the
bromination of the corresponding aziridines. To elucidate the
extent of involvement of the non-radical pathway, the aminobro-
mination of substrate 12 that bears an internal double bond was
investigated (entry 5). The reaction of 12 was found to provide
15a (75%) along with diastereomer 15b (20%) that was likely to
be produced by the brominative opening of an aziridine,
suggesting again that the radical pathway was predominant.
Taking these observations into account, we are currently postu-
lating that the loss of the syn/anti specificity mainly stems from
the flexibility of the radical intermediates, and that the aziridina-
tion–bromination is partially involved.
In conclusion, we have demonstrated that allyl N-tosyloxycar-
bamates serve as an allyl azidoformate surrogate for aminohalo-
genation. Further investigation of the reaction mechanisms and
the application of the present method to the synthesis of nitro-
gen-containing molecules is currently being pursued in our
laboratory.
Acknowledgements
This work was supported in part by Hoansha Foundation, the
Program for Promotion of Fundamental Sciences in Health
Sciences of the National Institute of Biomedical Innovation
(NIBIO), and a Grant-in-Aid for Scientific Research on Innova-
tive Areas [No. 22136006] from the Ministry of Education,
Culture, Sports, Science and Technology of Japan (MEXT).
.
9 Typical experimental procedures (entry 3, Table 1): n-Bu4NBr (109 mg,
0.34 mmol) and FeBr2 (6.2 mg, 0.028 mmol) were added to a stirred sol-
ution of N-tosyloxycarbamate 1 (98.0 mg, 0.28 mmol) in t-BuOH (5 mL)
at room temperature . After sonicating for 3 min, the mixture was stirred at
room temperature for a further 4 h. The mixture was transferred to a separa-
tory funnel where it was partitioned between H2O and EtOAc. The organic
phase was washed with brine, dried over MgSO4, filtered, and concentrated
under reduced pressure. The residue was purified by silica gel flash column
chromatography (EtOAc/n-hexane 2 : 5 to 2 : 3) to give N-tosyloxycarba-
mate 1 (3.7 mg, 4%) as a colorless solid, more polar carbamate 7 (2.6 mg,
5%) as a colorless solid, and the most polar inseparable mixture of bro-
mides 4a and 4b (60.4 mg, 84%, dr = 4 : 1) as a colorless solid. The dia-
stereomeric ratio of bromides 4a and 4b was determined by 1H NMR
analysis of the mixture. The spectroscopic data of carbamate 7 were identi-
cal to those reported in the literature. syn-Bromide 4a: colorless needles of
mp 113–114 °C (EtOAc/n-hexane); IR (neat) ν 3262, 1755 cm−1; 1H NMR
(500 MHz, CDCl3) δ 7.44–7.30 (m, 5H), 6.01 (brs, 1H), 4.88 (d, 1H, J =
9.8 Hz), 4.49 (m, 1H), 4.24 (t, 1H, J = 9.2 Hz), 3.94 (dd, 1H, J = 9.8, 5.5
Hz); 13C NMR (125 MHz, CDCl3) δ 158.0, 136.4, 129.7, 129.3, 127.9,
67.3, 58.7, 56.7; MS m/z: 256 [M + H]+, 154 (100%); HRMS (FAB) calcd
for C10H1179BrNO2 [M + H]+: 255.9973, found: 255.9977. anti-Bromide
4b: colorless needles of mp 171–173 °C (EtOAc/n-hexane); IR (neat) ν
3219, 1736 cm−1; 1H NMR (400 MHz, CDCl3) δ 7.46–7.34 (m, 5H), 4.96
(brs, 1H), 4.76 (m, 1H), 4.66 (ddd, 1H, J = 11.0, 7.3, 2.7 Hz), 4.51–4.41
(m, 2H); 13C NMR (100 MHz, CDCl3) δ 157.9, 137.0, 129.7, 129.4,
128.0, 69.5, 58.0, 54.4; MS m/z: 256 [M + H]+, 154 (100%); HRMS
(FAB) calcd for C10H1179BrNO2 [M + H]+: 255.9973, found: 255.9969.
Notes and references
1 For a pertinent review, see: G. Li, S. R. S. S. Kotti and C. Timmons,
Eur. J. Org. Chem., 2007, 2745.
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This journal is © The Royal Society of Chemistry 2012
Org. Biomol. Chem., 2012, 10, 2363–2365 | 2365