Angewandte
Chemie
has been realized. Finally, a new mild procedure for the
cleavage of dithianes with IBX has been unveiled. Although
these novel reactions induced by IBX are expected to find
considerable applications in organic synthesis, new modes of
reactivity for this rather old reagent are still anticipated.
Experimental Section
Typical oxidation procedure: IBX (1.0–1.5 equiv) was added to a
solution of the amine substrate (1.0 mmol) dissolved in DMSO
(
2.5 mL, 0.4m) at ambient temperature. The resulting mixture was
1
heated (458C) and the reaction progress was monitored by H NMR
spectroscopy ([D ]DMSO). Upon completion, the reaction mixture
6
was diluted with saturated aqueous Na S O (2.5 mL) and an equal
2
2
3
volume of EtOAc. The suspension was stirred for about 5 min, and, if
necessary, any remaining solids were filtered off through a pad of
celite and washed with EtOAc (3 1 mL). The combined solution was
basified with saturated aqueous NaHCO (2.5 mL) and subsequently
extracted with EtOAc (2 2.5 mL). The organic solution was then
washed with saturated aqueous NaHCO3 (2 5 mL) and brine
3
Scheme 4. Postulated mechanistic rationale for the deprotection of
dithianes by IBX under neutral conditions.
(
5 mL). After drying (MgSO ), the solvent was removed in vacuo to
4
yield the crude product, which rarely required further purification.
Table 4: Relative reactivity of IBX towards secondary amine 5 versus
alcohol 58, ketone 59, and dithiane 60.
[
a]
Received: June 6, 2003 [Z52076]
Keywords: imines · nitrogen heterocycles · oxidation · oximes ·
.
[
b]
[c]
synthetic methods
Entry
1
Starting materials
Conditions
Conversion ([%])
IBX ð1:5 equivÞ
!
DMSO
[
[
1] C. Hartman, V. Meyer, Ber. Dtsch. Chem. Ges. 1893, 26, 1727.
2] For a leading reference, see: D. B. Dess, J. C. Martin, J. Am.
Chem. Soc. 1991, 113, 7277.
[
3] M. Frigerio, M. Santagostino, S. Sputore, J. Org. Chem. 1999, 64,
4537.
IBX ð1:0 equivÞ
2
3
!
DMSO
[
4] K. C. Nicolaou, T. Montagnon, P. S. Baran in Electronic Ency-
clopedia of Reagents for Organic Synthesis (e-EROS) (Ed.: L. A.
Paquette), Wiley-VCH, Weinheim, in press, and references
therein. See also references [5–11] as leading references.
5] K. C. Nicolaou, T. Montagnon, P. S. Baran, Y.-L. Zhong, J. Am.
Chem. Soc. 2002, 124, 2245.
[
[
[
IBX ð1:5 equivÞ
!½cꢁ
DMSO=CH2Cl2 ð10:1Þ
6] K. C. Nicolaou, T. Montagnon, P. S. Baran, Angew. Chem. 2002,
114, 1035; Angew. Chem. Int. Ed. 2002, 41, 993.
7] K. C. Nicolaou, D. L. F. Gray, T. Montagnon, S. T. Harrison,
Angew. Chem. 2002, 114, 1038; Angew. Chem. Int. Ed. 2002, 41,
996.
[
4
[
a] Reactions were carried out on a 0.2–0.5-mmol scale at 458C for
5 min. [b] 1 equivalent each of 5 and 58, 59, or 60 was used.
c] Determined by H NMR spectroscopy. [d] Dichloromethane was
added to improve substrate solubility.
1
[
8] K. C. Nicolaou, Y.-L. Zhong, P. S. Baran, Angew. Chem. 2000,
112, 639; Angew. Chem. Int. Ed. 2000, 39, 625.
[
9] K. C. Nicolaou, P. S. Baran, R. Kranich, Y.-L. Zhong, K. Sugita,
the formation of imine 6 was convincingly favored in each
case. In the case in which ketone a,b-unsaturation was
evaluated in the presence of dibenzylamine 5 (Table 1,
entry 2), N-benzylidene formation could not be driven to
completion, as substrate degradation became a factor with
increased amounts of IBX.
In conclusion, we have discovered a number of new
reactions of IBX with heteroatom-containing substrates and
demonstrated their utility in organic synthesis. Specifically, we
have developed general IBX-induced procedures for the
generation of imines from secondary amines under mild
conditions and in notably high yields. Furthermore, the
oxidative aromatization of nitrogen heterocycles from
simple substrates, including those with no activating groups,
N. Zou, Angew. Chem. 2001, 113, 208; Angew. Chem. Int. Ed.
2001, 40, 202.
[
[
[
10] K. C. Nicolaou, P. S. Baran, Y.-L. Zhong, J. A. Vega, Angew.
Chem. 2000, 112, 2625; Angew. Chem. Int. Ed. 2000, 39, 2525.
11] K. C. Nicolaou, P. S. Baran, Y.-L. Zhong, S. Barluenga, K. W.
Hunt, R. Kranich, J. A. Vega, J. Am. Chem. Soc. 2002, 124, 2233.
12] a) T. Sueda, D. Kajishima, S. Goto, J. Org. Chem. 2003, 68, 3307;
b) M. Ochiai, D. Kajishima, T. Sueda, Heterocycles 1997, 46, 71.
[13] K. Yamaguchi, N. Mizuno, Angew. Chem. 2003, 115, 1518;
Angew. Chem. Int. Ed. 2003, 42, 1480.
14] A. Goti, M. Romani, Tetrahedron Lett. 1994, 35, 6567.
[
[
[
15] J. Yamaguchi, T. Takeda, Chem. Lett. 1992, 1933.
16] J. Larsen, K. A. Jørgensen, J. Chem. Soc. Perkin Trans. 2 1992,
1213.
[
17] K. Maruyama, T. Kusukawa, Y. Higuchi, A. Nishinaga, Chem.
Lett. 1991, 1093.
Angew. Chem. Int. Ed. 2003, 42, 4077 –4082
ꢀ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4081