nucleophiles. Thus we selected simple epoxy amides,
described in Table 1, to be subjected to the action of the
aforementioned nucleophiles, such as amines, TMSN3 in the
presence of a Lewis acid, sodium azide, organocuprate
reagents and thiols.
In general, all epoxy amides showed very good reactivity
and complete regioselectivity in the opening process at C-2 or
at C-3 positions depending on the reaction conditions. The
exceptions were found in aliphatic epoxy amides which against
TMSN3 and thiols, respectively, did not react, or for the
reactions of aromatic epoxy amides with sodium azide in
which there was a lack of regioselectivity, obtaining a mixture
of regioisomers. For this particular case, interestingly, the
mixture of azido alcohols 46a and 46b was transformed into
one aziridine, 48, by treatment with Ph3P.14 Finally, we
decided to check the chemical behavior of these epoxy amides
against other types of reagents such as SmI2 which has proven
to be a useful reagent for the transformation of simple epoxy
amides into 2-hydroxy amides.15 In our case, when the epoxy
amides were reacted with a freshly prepared solution of SmI2
in THF, we found that the pendant methyl sulfide interfered
with the reaction producing thiocane derivative 55 with epoxy
amide 9a, and a mixture of thiepane 56 and thiocane 57 when
aliphatic epoxy amide 9h was used. Together with these
compounds, a,b-unsaturated amides were also detected as
minor products (o10%) (Scheme 2).
We thank Ministerio de Educacio
´
n
y
Ciencia
(CTQ07-66518) and Junta de Andalucıa (FQM-03329) for
´
financial support.
Notes and references
1 Aziridines and Epoxides in Organic Synthesis, ed. A. K. Yudin,
Wiley-VCH, Weinheim, 2006.
2 A.-H. Li, L.-X. Dai and V. K. Aggarwal, Chem. Rev., 1997, 97,
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3 V. K. Aggarwal and C. L. Winn, Acc. Chem. Res., 2004, 37, 611;
J. Bi and V. K. Aggarwal, Chem. Commun., 2008, 120.
4 M. Valpuesta Ferna
Herrera, Tetrahedron, 1990, 46, 7911–7922; F. J. Lo
F. R. Sarabia-Garcıa and M. S. Pino-Gonzalez, Recent Res. Dev.
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ndez, P. Durante-Lanes and F. J. Lo
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pez-
pez-Herrera,
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´
Org. Chem., 2000, 4, 465–7922, and references therein.
5 S. N. Lakeev, I. Z. Mullagalin, F. Z. Gallin, I. O. Maidanova and
M. F. Abdullin, Russ. Chem. Bull., Int. Ed., 2002, 51, 2230.
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Chem. Soc., 2002, 124, 9964; V. K. Aggarwal and J. Richardson,
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Scheme 2 Opening reactions of epoxy amides with nucleophiles.
Reagents and conditions: (a) 5.0 equiv. of amine or NH3 in H2O,
MeOH, 70 1C, 6–8 h, 69% for 30 (R = Ph, X = NH2), 72% for 31
(R = Ph, X = NHMe), 75% for 32 (R = Ph, X = NHBn), 93% for
33 (R = Ph, X = NHallyl), 54% for 34 (R = Ph, X = NHPh), 68%
for 35 (R = Ph, X = NMe2), 65% for 36 (R = p-MeOC6H4, X =
NH2), 83% for 37 (R = p-MeOC6H4, X = NHMe), 71% for 38
(R = pMeC6H4, X = NHMe), 74% for 39 (R = p-ClC6H4, X =
NHMe), 62% for 40 (R = n-Pr, X = NHMe), 84% for 41 (R = i-Pr,
X = NHMe), 65% for 42 (R = Bn, X = NHMe). (b) 2.5 equiv. of
TMSN3, 0.2 equiv. of Yb(OTf)3, CH2Cl2, 25 1C, 8 h, 85% for 43
(R = p-MeOC6H4), 12% for 44 (R = Ph), 15% for 45 (R = p-MeC6H4).
(c) 10.0 equiv. of NaN3, MeOH, 70 1C, 8 h, 87% for 46a/46b (R = Ph,
2 : 1 mixture), 76% for 47 (R = i-Pr). (d) 1.5 equiv. Ph3P, THF, 25 1C,
6 h, 62% for 48, 89% for 49. (e) 5.0 equiv. Me2CuLi, THF, 0 1C, 8 h.
(f) 1.5 equiv. TBSOTf, 2.0 equiv. 2,6-lutidine, CH2Cl2, 0 1C, 0.5 h,
56% for 50 (R = Ph), 64% for 51 (R = i-Pr), 60% for 52 (R = Chx),
52% for 53 (R = Bn). (g) 2.5 equiv. of PhSH, 0.3 equiv. of Yb(OTf)3,
7 A related bicyclic thioglycolate lactam was prepared by Gleason
for stereoselective alkylation reactions: J. M. Manthorpe and
J. L. Gleason, J. Am. Chem. Soc., 2001, 123, 2091.
8 H. C. Brown and S. C. Kim, Synthesis, 1977, 635.
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J. J. Ortega-Alca
Gonzalez, Tetrahedron: Asymmetry, 1996, 7, 2065.
12 B. Rawlings, Nat. Prod. Rep., 1997, 14, 523.
13 F. Sarabia and S. Chammaa, J. Org. Chem., 2005, 70, 7846;
F. Sarabia, S. Chammaa and M. Garcıa-Castro, J. Org. Chem.,
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´
pez-Herrera, F. Sarabia-Garcı
´
a, A. Heras-Lo
´
´
pez,
´
ntara, G. M. Pedraza-Cebria
n and M. S. Pino-
´
´
CH2Cl2, 25 1C, 1–2 days, 77% for 54 (R
= p-MeOC6H4).
14 S. Hanessian, J. R. del Valle, Y. Xue and N. Blomberg, J. Am.
Chem. Soc., 2006, 128, 10491.
15 J. M. Concellon and E. Bardales, Org. Lett., 2003, 5, 4783.
´
(h) 2.0 equiv. of SmI2, THF, 25 1C, 2 h, 37% for 55 (R = Ph), 80%
for 56 + 57 (R = i-Pr, 1 : 1 mixture).
ꢀc
This journal is The Royal Society of Chemistry 2009
Chem. Commun., 2009, 5763–5765 | 5765