Table 2 Efficiency of the substitution of b-CD
Method
Electrophile reagent Total substitution yield (%) Polysubstitution yield (%) Monosubstitution yield at O3/at O2 (%)
Aa Benzylic reagents
3
4
5
47.5
95
Traces
41
85
0
23
32
29
9.5
33
0
14
47
0
0
5
9
4
38/0
42/20
Traces
0/27
38/0
0/0
0/23
8/19
0/20
0/25
0/30
0/13
Allylic reagents
Bb Benzylic reagents
Allylic reagents
9
10
11
3
4
5
9
10
11
29
35
13
5
0
a
b
H2O, CuSO4, NaOH; EtONa, DMSO.
presumably due to steric hindrance, the trans isomer being less
bulky than the cis.
common procedure (i.e. chromatography on silica gel column followed
by a recrystallization) described in the ESI.w
A new methodology based on a temporary copper(II)–b-CD
complexation allowed the synthesis of 3I-O-derivatives using bulky
electrophilic reagents as benzylic compounds 3, 4 or a bulky allylic
reagent 10. Monosubstitution isolated yields (38–42%) were high-
er than those obtained at O-2 with a previous method using
dimethyl sulfoxide as solvent and sodium ethoxide as a basic agent
(Method B, Table 2).5c Method B was previously described for
introducing a benzylic moiety at O-2 and it was extended here to
allylic compounds. The quite common 2I-O-substituted derivatives
were generally obtained when the substitution reaction was carried
out in dimethyl sulfoxide. In contrast to that, the paramount
interest of the new method A based on a temporary complexation
of some secondary hydroxy groups in aqueous medium is to
mainly obtain 3I-O-substituted derivatives, such as versatile inter-
mediates 6b and 13b easy to use in CD chemistry. Compound 6b
which is obtained from cheap and commercially available b-CD, is
an important intermediate to access 3-hydroxy permethylated
b-CD as a good precursor for a wide variety of monofunction-
alized ‘permethyl’ b-CDs used in chromatography.11 Compound
13b contains a halogeno alkenyl substituent which is particularly
convenient for palladium-catalyzed coupling reactions. It could
then serve as a versatile intermediate to access CD dimers.12 And
finally, this new methodology will soon be applied to the synthesis
of functionalized CDs displaying catalytic scavenger properties
against xenobiotics and toxicants such as potent nerve agents and
organophosphorus pesticides.
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This work was supported by DGA (a–DGA/CNRS fellowships
to N.M. and R.L.P. b–DSP/STTC contract PEA010807 to
F.E./O.L. and P.M), and ANR (contract BLAN06-1_134538).
The authors thank C. Dubouilh and A. Martinet for excellent
technical assistance, and they also acknowledge B. Brasme,
J.C. Debouzy and B. Lefevre for hepful compound analysis.
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Notes and references
z Final purification by HPLC was used for analytical reasons. O-3
Regioisomers can be isolated with a satisfactory degree of purity by a
ꢀc
This journal is The Royal Society of Chemistry 2009
Chem. Commun., 2009, 589–591 | 591