the allylation in the tandem reactions, on mechanistic and synthetic
aspects as well as on combinatorial applications of this chemistry
are currently ongoing.
We are grateful to Dr Lerner and The Scripps Research Institute
for support.
To further explore the scope of the one-pot reactions, a series of
aliphatic aldehydes were tried under the same reaction conditions.
The experimental procedure involves only mixing and stirring, and
comprises these steps: 1) the mixture of the aldehyde (1.2 equiv.),
nitrosobenzene (1.0 equiv.) and the catalyst proline (20 mol%) in
DMSO was stirred at ambient temperature for 10–20 minutes; 2)
allyl bromide (1.5 equiv.), indium (1.5% equiv.) and sodium iodide
(1.5 equiv.) were added and then the reaction mixture was kept
stirring for 3–5 minutes. The reaction does not require anhydrous or
oxygen-free conditions. Table 1 shows this chemistry. In every
case, the tandem reactions afforded the products syn-/anti-3b–3f in
good overall yields (65–82%) with excellent enantioselectivities
(syn-3b to syn-3f with 98–99% ee’s and anti-3b to anti-3f with 97
– over 99% ee’s). The diastereomeric ratios (dr) ranged from 3 : 2
to 4 : 1. It is noteworthy that the terminal allylic group in the
products 3a–3f could be easily converted to new aldehydes for
further dihydroxylation using the same tandem strategy, so that
chiral polyols might be synthesized step by step. All racemic
standard products required to establish HPLC conditions were
made by using racemic proline.
The observed diastereoselectivity (syn-selective)11 of the trans-
formation is in accord with the previously proposed model for the
indium promoted allylation.8 When the hydroxyl group in the
transition state is substituted by the N-phenylamino group, a big
dropoff in p-facial discrimination materializes, presumably due to
increased steric hindrance. This caused a decrease in diaster-
eoselectivity while the unsubstituted a-hydroxyaldehydes gave
excellent dr.8b
Notes and references
1 (a) For Sharpless AD, see: Review: H. C. Kolb, M. S. VanNieuwenhze
and K. B. Sharpless, Chem. Rev., 1994, 94, 2483; (b) For asymmetric
epoxidation/epoxide-ring-opening, see: S. Y. Ko, A. W. M. Lee, S.
Masamune, L. A. Reed III, K. B. Sharpless and F. J. Walker,
Tetrahedron, 1990, 46, 245; (c) For the catalytic asymmetric synthesis
of syn-1,2-diols by Mukaiyama aldol reactions, see: S. Kobayashi and T.
Kawasuji, Synlett, 1993, 911; For the enzymatic catalysis, see: (d)
Review: H. J. M. Gijsen, L. Qiao, W. Fitz and C.-H. Wong, Chem. Rev.,
1996, 96, 443; (e) M. D. Bednarski, E. S. Simon, N. Bischofberger, W.-
D. Fessner, M.-J. Kim, W. Lees, T. Saito, H. Waldmann and G. M.
Whitesides, J. Am. Chem. Soc., 1989, 111, 627; (f) W.-D. Fessner, G.
Sinerius, A. Schneider, M. Dreyer, G. E. Schulz, J. Badia and J. Aguilar,
Angew. Chem., Int. Ed. Engl., 1991, 30, 555; For the antibody catalysis,
see: (g) C. F. Barbas III, A. Heine, G. Zhong, T. Hoffmann, S.
Gramatikova, R. Björnestedt, B. List, J. Anderson, E. A. Stura, E. A.
Wilson and R. A. Lerner, Science, 1997, 278, 2085; (h) T. Hoffmann, G.
Zhong, B. List, D. Shabat, J. Anderson, S. Gramatikova, R. A. Lerner
and C. F. Barbas III, J. Am. Chem. Soc., 1998, 120, 2768; (i) G. Zhong,
D. Shabat, B. List, J. Anderson, S. C. Sinha, R. A. Lerner and C. F.
Barbas III, Angew. Chem., Int. Ed., 1998, 37, 2481.
2 H. Hanessian, Total Synthesis of Natural Products: the ‘Chiron’
Approach, Pergamon Press, Oxford, 1983.
3 J. Seyden-Penne, in Chiral Auxiliaries and Ligands in Asymmetric
Synthesis, Wiley-Interscience, New York, 1995.
In conclusion, we have developed a highly efficient tandem
aminoxylation–allylation reaction – the proline catalyzed asym-
metric a-aminoxylation of aldehydes and subsequent in situ
allylation – for the direct, rapid and enantioselective conversion of
aldehydes to both syn- and anti-mono amino-substituted 1,2-diols
in high yields with excellent enantioselectivities. Since proline is
commercially available in both enantiomerically pure forms, this
methodology provides an extremely facile route to all four
stereoisomers of both syn- and anti-1,2-diols, important building
blocks and ligands in organic synthesis and asymmetric catalysis.
Studies on the further improvement of the diastereoselectivities of
4 (a) E. N. Jacobsen, I. Markó, W. S. Mungall, G. Schröder and K. B.
Sharpless, J. Am. Chem. Soc., 1988, 110, 1968; (b) L. Wang and K. B.
Sharpless, J. Am. Chem. Soc., 1992, 114, 7568.
5 (a) W. Notz and B. List, J. Am. Chem. Soc., 2000, 122, 7386; (b) N.
Yoshikawa, N. Kumagai, S. Matsunaga, G. Moll, T. Ohshima, T. Suzuki
and M. Shibasaki, J. Am. Chem. Soc., 2001, 123, 2466; (c) B. M. Trost,
H. Ito and E. R. Silcoff, J. Am. Chem. Soc., 2001, 123, 3367.
6 G. Zhong, Angew. Chem., Int. Ed., 2003, 42, 4247.
7 For other proline-catalysis using aldehydes as donors, in aldol reaction,
see: (a) A. Cordova, W. Notz and C. F. Barbas III, J. Org. Chem., 2002,
67, 301; (b) A. Northrup and D. W. C. MacMillan, J. Am. Chem. Soc.,
2002, 124, 6798; (c) in Mannich reaction, see: A. Cordova, S.-i.
Watanabe, F. Tanaka, W. Notz and C. F. Barbas III, J. Am. Chem. Soc.,
2002, 124, 1866; (d) in a-amination, see: A. Bøgevig, K. Juhl, N.
Kumaragurubaran, W. Zhuang and K. A. Jørgensen, Angew. Chem., Int.
Ed., 2002, 41, 1790; (e) B. List, J. Am. Chem. Soc., 2002, 124, 5656; (f)
For the a-hydroxylation of aldehydes, see: D. Enders, in Asymmetric
Synthesis Vol. 3 (Ed.: J. D. Morrison), Academic Press, Orlando, 1984,
p. 275; (g) D. Enders, P. Fey and H. Kipphardt, Org. Synth., 1987, 65,
173 and 183; (h) A. Job, C. F. Janeck, W. Bettray, R. Peters and D.
Enders, Tetrahedron, 2002, 58, 2253.
Table 1 One-pot asymmetric synthesis of both syn- and anti-diol units
drb
(syn : anti)
eec
8 (a) L. A. Paquette and T. M. Mitzel, J. Am. Chem. Soc., 1996, 118, 1931;
(b) L. A. Paquette, Synthesis, 2003, 765.
Product
R
Yielda
(syn/anti, %)
9 (a) Review: C.-J. Li, Chem. Rev., 1993, 93, 2023; (b) A. Lubineau, J.
Augé and Y. Queneau, Synlett, 1995, 1087; (c) C.-J. Li, Tetrahedron,
1996, 52, 5643; (d) L. A. Paquette, in Green Chemistry: Recent
Advances in Chemical Processing, ACS Symposium Series, Vol. 767;
ACS, Washington DC, 2000, p. 100.
10 (a) N. Momiyama and H. Yamamoto, J. Am. Chem. Soc., 2003, 125,
6038; (b) N. Momiyama and H. Yamamoto, Angew. Chem., Int. Ed.,
2002, 41, 2986.
11 The stereochemistry of this tandem transformation was established by
1H-NMR determination of syn- and anti-structures of the products
together with the known absolute configuration of the a-aminoxyl
aldehydes (see ref. 6).
3a
3b
3c
3d
3e
3f
70%
80%
71%
65%
82%
74%
4 : 1
3 : 2
5 : 3
3 : 2
3 : 2
3 : 2
97/ > 99
98/98
99/97
98/98
98/98
methyl
isopropyl
propyl
butyl
benzyl
99/ > 99
a All were yields of isolated products. b The syn : anti ratio was determined
by weighing the separated isomers and/or by H-NMR spectra. c The ee’s
were determined by chiral phase HPLC columns (see Supporting In-
formation).
1
C h e m . C o m m u n . , 2 0 0 4 , 6 0 6 – 6 0 7
607