B03 Stability of the DBFOX/Ph Complexes and Water Tolerance
Tolerance against Water and Alcohol:
Once high water tolerance becomes clear for the
aqua complexes of DBFOX ligands with metal perchlorates, the next question(IJ(Jis:
How much of water can be used without
serious damage for the catalytic activity as well as
enantioselectivity? We therefore examined the effect of water additive in
the catalyzed asymmetric Diels-Alder reactions. After addition of an appropriate
amount of water to the anhydrous complex DBFOX/Ph´Ni(ClO4)2 which was prepared
in the presence of 3-acryloyl-2-oxazolidinone in dichloromethane, the reaction
with an excess amount of cyclopentadiene was performed at room temperature.
Enantioselectivity was as high as 93% ee for the endo-cycloadduct up to
5 equivalents of water added and the satisfactory level of 88% ee was mainteined
when 10 equivalents were added. However, enantioselectivity gradually decreases
with the increased amounts of water added: 83 and 55% ees from 15 and 50
equivalents, respectively. When the reaction temperature goes down to -40
ÁC, the enantioselectivity as high as 98% ee results up to 15 equivalents
of water additive. The effect of methanol at room temperature is quite surprising.
In the presence of 15 and 100 equivalents
of methanol, high levels of enantioselectivities of
88 and 83% ee, respectively, are recorded at the reactions at room temperature.
Tolerance against Amines and Acids:
The effects of a variety of acids and amines are summarized
in the above. As long as amounts of these amine additives are limited to
3 equivalents to the catalyst R,R-DBFOX/Ph, high levels of enantioselectivities
can be obtained for the endo-cycloadduct. The only exception is the reaction
in the presence of diethylamine, where the cycloadduct was racemic.
Effect of Solvent, Cosolvent, and Pretreatment:
Although the high catalytic activity of the complex
DBFOX/Ph´Ni(ClO4)2´3H2O is not affected by water, the enantioselectivity
is modulated by the nature of the reaction solvent, cosolvent, and pretreatment.
The presence of MS 4A did not improve the selectivity (89% ee at rt), but
the preheating of Ni(ClO4)2´6H2O in vacuo with a heat gun prior to complexation
was a useful modification (95% ee at rt). The use of 3-acetyl-2-oxazolidinone
as a model comound of the dienophile in the complexation step increases
the catalytic efficiency, while 1,2-dimethoxyethane is not effective. Choice
of an appropriate reaction solvent is also important. For example, 1,2-dichloroethane
is a better solvent than dichloromethane, but both dibromomethane and toluene
are inferior . Cosolvents such as ethyl
ether or acetone improve the enantioselectivities .
As will be discussed below, the 1:1 DBFOX/Ph´Ni(ClO4)2´3H2O complex forms
a weakly aggregated structure with a resulting decrease in catalytic activity.
We believe that aqua ligands play an important role in this phenomenon.
Weakly coordinating solvents or cosolvents would be replaced with the aqua
ligands to dissociate the oligomeric aggregation. The solvent-coordinating
monomeric complex shows a higher catalytic activity. Less coordinating or
strongly coordinating additives are not effective. Replacement of the perchlorate
counterion with less coordinating hexafluoroantimonate ions was not helpful.