An easy and clean synthesis of chiral 3,4-diaryl-2,5-diazabicyclo[4.4.0]decanes by reductive intramolecular coupling of chiral diimines

Article abstract of DOI:10.1081/SCC-120015698

A clean and efficient reductive intramolecular coupling of diimines prepared from (1R,2R)-cyclohexanediamine gave chiral 2,3-diarylpiperazines.

Full text of DOI:10.1081/SCC-120015698

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An Easy and Clean Synthesis of Chiral 3,4-
Diaryl-2,5-diazabicyclo[4.4.0]decanes by Reductive
Intramolecular Coupling of Chiral Diimines
Peter Hesemann a , Joël J. E. Moreau a b & Thierry Soto a
a Laboratoire de Chimie Organométallique, UMR 5076 E.N.S.C.M., Montpellier Cédex, France
b Laboratoire de Chimie Organométallique, UMR 5076 E.N.S.C.M., 8, rue de l’Ecole Normale,
34296 Montpellier Cédex 05, France Fax:
Version of record first published: 21 Aug 2006.
To cite this article: Peter Hesemann , Joël J. E. Moreau & Thierry Soto (2003): An Easy and Clean Synthesis of Chiral 3,4-
Diaryl-2,5-diazabicyclo[4.4.0]decanes by Reductive Intramolecular Coupling of Chiral Diimines, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 33:2, 183-189
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SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 2, pp. 183–189, 2003
An Easy and Clean Synthesis of Chiral
3,4-Diaryl-2,5-diazabicyclo[4.4.0]decanes
by Reductive Intramolecular Coupling
of Chiral Diimines
*
Peter Hesemann, Joel J. E. Moreau, and Thierry Soto
Laboratoire de Chimie Organometallique, UMR 5076
E.N.S.C.M., Montpellier Cedex, France
ABSTRACT
A clean and efficient reductive intramolecular coupling of diimines
prepared from (1R,2R)-cyclohexanediamine gave chiral 2,3-diaryl-
piperazines.
Key Words: Diimines; Reductive intramolecular coupling; Chiral
building blocks.
*Correspondence: Joel J. E. Moreau, Laboratoire de Chimie Organometallique,
UMR 5076 E.N.S.C.M., 8, rue de l’Ecole Normale, 34296 Montpellier Cedex 05,
France. Fax: þ33 04 67147212; E-mail: jmoreau@cit.enscm.fr.
183
DOI: 10.1081/SCC-120015698
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com

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184
Hesemann, Moreau, and Soto
Environmental considerations and safety regulations define new
challenges and objectives for current chemical research. Chemistry at
interphases offers possibilities to suggest organic process alternatives
for reducing the generation of waste and bringing benefits providing
advantageous synthetic routes.[1] Our interest in advanced materials led
us to study chiral organic–inorganic solids[2] and chiral organic poly-
mers[3] as enantioselective catalytic materials. Rigid and chiral organic
molecules are compounds of growing interest for macromolecular chem-
istry due to their influence on the physical and chemical properties of the
materials.[4] Recent report on the stereoselective synthesis of chiral 3,4-
disubstituted-2,5-diazabicyclo[4.4.0]decanes using low-valent titanium
reagents[5] prompt us to communicate a more practical and efficient
method for the synthesis of various chiral 3,4-diaryl-2,5-diazabicy-
clo[4.4.0]decanes which are useful building blocks for our studies.
The synthesis of aromatic diimines 2(a–f ) by usual procedure
involved the reaction of (1R,2R)-cyclohexanediamine with 2 equi-
valents of the corresponding substituted benzaldehyde in ethanol under
reflux.[6] Isolation of the Schiff bases was facilitated by the precipita-
tion of the products out of the mixture upon cooling. In Table 1,
the results of the reactions of various benzaldehyde derivatives are
summarized.[7]
The piperazine core could be prepared either by use of low-valent
titanium species[9] or by an electroreductive method.[10] In view of the
synthesis of nitrogen-containing macrocycles, Kise et al.[11] reported the
strong protic acid–zinc powder combination as an efficient reductive
Table 1. Preparation of various diaryl (1R,2R)-cyclohexanediimine.
Reagent
R1
R2
R3
R4
Product
Yield (%)d
1a
1b
1c
1d
1e
1f
H
H
H
H
H
OMe
H
H
H
H
H
H
H
Br
OMe
CO2Me
CꢀCSiMe3
H
H
H
H
H
H
Br
2ab
2bb
2cb
2db
2eb
2f c
87
94
98
81
88
81
a
aPrepared by the Krause et al. method.[8]
bPrepared from (1R,2R)-cyclohexanediamine.
cPrepared from racemic trans-(1,2)-cyclohexanediamine.
dIsolated yield.

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Chiral 3,4-Diaryl-2,5-diazabicyclo[4.4.0]decanes
185
intramolecular diimines coupling reagent. This simple chemical reduction
was surprisingly only applied to compound 3a. By use of this method,
we observed that chiral diimines 2(a–f ) are readily conversed to trans-
3,4-diaryl-2,5-diazabicyclo[4.4.0]decanes 3(a–f ) in very high yield
(Sch. 1).[12]
In addition, the reaction treatment was reduced to a simple basic
neutralization–filtration–extraction sequence. Interestingly, the electronic
nature of substituents on the aromatic ring plays a critical role for the
choice of the protic acid used. Indeed the synthesis of compounds 3c
and 3f failed when using methanesulfonic acid (MSA), but the use
of trifluoroacetic acid (TFA) led to single products. The results are
summarized in Table 2.[13]
Scheme 1.
Table 2. Reaction of diimines with the strong protic acid/zinc reagent system.
Reagent
R1
R2
R3
R4
Acida
Product
Yield (%)d
2a
2b
2c
2d
2e
2f
H
H
H
H
H
OMe
H
H
H
H
H
H
H
Br
OMe
CO2Me
CꢀCSiMe3
H
H
H
H
H
H
Br
MSA
MSA
TFA
MSA
MSA
TFA
3ab
3b
3c
3d
3e
3f c
98
95
98
98
94
89
aAcid: MSA (Methanesulfonic acid) or TFA (Trifluoroacetic acid).
bThe product 3a was identified by spectral data (1H NMR, 13C NMR, IR and MS)
and comparison with reported data.[5,10]
cSynthesized starting with racemic diamine.
dYield of isolated products.