October 1998
SYNLETT
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highly reactive model 3a previously studied in our laboratory in the
6b
pyrido[2,3-b]indole series.
ensured leading to a decreasing of the stereodifferentiation during the
hydride equivalent transfer.
Acknowledgement: we thank Sanofi Chimie Co (Gentilly, France) for
financial support of this work.
References
In the case of substrate 6, it can be observed that model 3a in the
pyrido[2,3-b]indole series was superior to model 2b in the quinoline
series during the reduction in the presence of magnesium bromide in
THF (entries 9 and 10). This result justifies the above choice of a model
in the indolopyridine series. Once again, the new conditions are more
efficient than standard conditions (entries 8 and 10). This behaviour is
confirmed in the reduction of substrate 8 (entries 11 and 12).
(1) For reviews see a) Stout, D. M.; Meyers, A. I. Chem. Rev., 1982,
82, 223. b) Ohno, A.; Ushida, S. in Lecture notes in Bio-Organic
Chemistry. Mechanistic Models of Asymmetric Reductions;
Springer-Verlag: Berlin, Heidelberg, New York, Tokyo, 1986; p1-
105. c) Inouye, Y.; Oda, J.; Baba, N. in Asymmetric Synthesis:
Reductions with Chiral Dihydropyridine Reagents; Morrisson, J.
D., Ed.; Academic Press: New York, London, 1983, 2; p92-124. d)
Burgess, V.A. ; Davies, S.G. and Skerly, R.T. Tetrahedron:
Asymmetry, 1991, 2, 299.
In the case of substrate , the β carbon in the nitroethylene group is
8
prochiral. The asymmetric reduction of this substrate was previously
11
studied in our laboratory by using another chiral NADH model
.
In
3b
(2) a) Ohno, A.; Kimura, T.; Yamamoto, H.; Kim, S.G.; Oka, S.;
Ohnishi, Y. Bull. Chem. Soc. Japan, 1977, 50, 1535. b) Ohno, A.;
Yamamoto , H.; Okamoto, T.; Oka, S.; Yamamoto, H. ; Okamoto,
T. ; Oka, S.; Ohnishi, Y. Bull. Chem. Soc. Japan, 1977, 50, 2385.
c) Hughes, M.; Prince, R.H. J. Inorg. Nucl. Chem., 1978, 40, 703.
the presence of magnesium bromide in THF the e.e. was low (entry 13).
As can be seen in the reduction of nitro-unsaturated substrates like 4, 6
and 8 the new conditions i.e. magnesium bromide in THF gave better
yields than magnesium perchlorate in acetonitrile. However the
asymmetric reduction of prochiral 8 with 3b gave a poor e.e.
(3) See for example The Sigma-Aldrich Library of Chemical Safety
nd
Data, 2 edition; Lenga, R. E., Ed; 1988 ; p2180.
(4) Cazin, J.; Trefouel, G.; Dupas, G.; Bourguignon, J.; Quéguiner, G.
8
3) Reduction of prochiral ketones
Tetrahedron, 1988, 44, 1079.
In order to obtain more information concerning the behaviour of the
chiral reagent 3b in reactions promoted by magnesium bromide in THF
we studied two prochiral ketones: methylbenzoylformate 10 which is a
classical substrate in asymmetric reductions performed with NADH
models and 2-benzoylpyridine 12 which was recently involved in
(5) Reagents 2a and 2b are new NADH models which were
synthesized in five steps from previously described 6,7-
dimethoxyquinoline-3-carbonitrile (Charpentier, P.; Lobrégat, V.;
Levacher, V.; Dupas, G.; Quéguiner G.; Bourguignon J.
Tetrahedron Lett., 1998, in press) by following a classical way,
12
asymmetric reductions performed under various conditions.
i.e.: 1) Conversion of the nitrile group into a carboxylic acid with
+
As can be seen, the conversion was in all cases quantitative. On the other
hand the e.e. were higher by using magnesium perchlorate in
acetonitrile than with magnesium bromide in THF. The enantioselective
hydride equivalent transfer from the reagent to the substrate is directed
by the structure of the ternary complex constructed between the model,
a 25 % aqueous solution of NaOH at reflux then H O . 2) The
3
acid chloride was obtained with SOCl 3) The acid chloride was
2.
treated with NH for 2a or with HNEt for 2b 4) Quaternization
3
2
with ICH in CH CN 5) Subsequent regioselective reduction of
3
3
-
the pyridinium salt with Na S O /OH
2
2 4
2+
14
the substrate and Mg ions. The metal ion is hexacoordinated in this
complex and all the ligand-metal bonds ensure the positioning of the
partners during the reduction. It can be assumed that, in the case of
reductions performed with magnesium bromide in THF (a strongly
coordinating solvent) the structure of the ternary complex can be
modified by replacing some of the atoms of the reagent or of the
substrate involved in the hexa coordinated structure by solvent
molecules. As a consequence the positioning of the partners is less well
(6) a) Levacher, V.; Boussad, N.; Dupas, G.; Bourguignon, J.;
Quéguiner, G. Tetrahedron, 1992, 48, 831. b) Berkous, R.; Dupas,
G.; Bourguignon, J.; Quéguiner, G. Bull. Soc. Chim. Fr., 1994,
632.
(7) a) Barett, A. G. M.: Nitroalkanes and Nitroalkenes in Synthesis.
Tetrahedron Symposia-in-print, Tetrahedron, 1990, 46, 7313. b)
Perekalin, V. V. in Conjugated Nitro Compounds; Lipina, E. S.;