D04 Effect of Coordinating Additives on Chiral Amplification

Effect of Ligand/Ni Ion Ratio:
When equivalent amounts of Ni(ClO4)2´6H2O and DBFOX/Ph are used in the catalyst preparation process, two molecules of DBFOX/Ph ligand are consumed to form heterochiral 2:1 complex (meso-2:1 complex) so that Ni(ClO4)2´6H2O becomes excess toward DBFOX/Ph ligand in the solution. The presence of excess free metal salt Ni(ClO4)2´6H2O appears to be unfavorable since the competitive reaction catalyzed by achiral catalyst should affect the enantioselectivity of reaction. However, the results indicate that this is not actually a serious problem. In the absence of DBFOX ligand, Ni(ClO4)2´6H2O is hardly soluble in dichloromethane. This solubility advantage is supported by the following two observations:
(1) No rate acceleration is observed in the Diels-Alder reaction catalyzed by Ni(ClO4)2´6H2O in the absence of DBFOX/Ph ligand. 3-Acryloyl-2-oxazolidinone as chelating reagent can not solubilize the nickel salt.
(2) Even the reaction using excess Ni(ClO4)2´6H2O together with the enantiopure R,R-DBFOX/Ph gives absolute enantioselectivity . It is interesting that the use of excess ligand DBFOX/Ph leads to a decreased enantioselectivity for endo-cycloadduct, especially when the enantiomeric purity of DBFOX/Ph is low. This phenomenum is closely related with the chirality enrichment mechanism operating in the solution, as will be discussed below. When most of the metal salt has been consumed for the formation of inert meso-2:1 complex, only a little catalytic activity is expected.

Solvent, Metal Ion, and Ligand Effects in Chiral Amplification:
The relative stability between homochiral and heterochiral aggregations of 1:1 complexes should depend upon the polarity of solvents or additives used. We have mentioned above that the addition of coordinating additives such as diethyl ether, acetone, and 1,2-dichloroethane works to activate the DBFOX complex catalyzed Diels-Alder reactions. We therefore examined solvent and additive effects for chiral amplification. 1,2-Dichloromethane and diethyl ether, as solvent and additive respectively, keep high levels of amplifications. This indicates that they solvate the 1:1 complexes to dissociate the weak homochiral oligomers of 1:1 complexes, but the heterochiral oligomers are still stable. On the other hand, a low level of chiral amplification results in the presence of acetone, meaning that acetone is powerful enough to dissociate the strong heterochiral oligomers. Hydrogen bonds of aqua ligands to SbF6 anions are similarly effective as perchlorate ions.Although aqua complexes of magnesium, ion(II), and copper(II) perchlorates are not proper choice for high chiral amplification, zinc perchlorate shows even a more effective amplification than nickel perchlorate (94% ee from 20% ee). Thus, the complex is prepared from DBFOX/Ph (20% ee, 10 mol%) and ZnI2 in dichloromethane, followed by treatment of AgClO4 (20 mol%). After 3 equivalents of water are added, the catalyst is used in the Diels-Alder reaction at -40 ÁC to give the enantiomeric activity of 96% ee (quant, endo:exo = 98:2) for endo-cycloadduct. Thus, the absolute or theoretically maximum chiral amplification has been attained.

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