Chiral reagents, asymmetric amplification

An amino alcohol was found to accelerate the addition reaction of diethlylzinc to aldehyde [8], and then chiral amino alcohols were proved to be efficient chiral catalysts for asymmetric alkylation by using dialkylzinc reagents [9], Oguni reported a remarkable asymmetric amplification in chiral amino alcohol-promoted alkylation (Scheme 9.4). In the presence of (-)-l-piperidino-3,3-dimethyl-2-butanol (5) of 11% ee, benzaldehyde is alkylated enantioselectively to give (/ )-l-phenylpropanol with 82% ee [10]. Asymmetric amplification was also observed by Noyori using partially resolved (2.S )-3-exo-(dimethylamino)isobomeol (6) [11]. 

It is important to remember that the advantage of increased enantiomeric purity gained during an asymmetric amplification is always accompanied by the disadvantage of reduced reaction rates when compared with the enantiopure chiral auxiliary.35 Although this reduction in reaction rate may not present a problem for fast reactions, it may be necessary to increase the amount of catalyst or chiral reagent in slower reactions in order to have reasonable reaction times. 

Oguni has reported asymmetric amplification [12] ((-i-)-NLE) in an asymmetric carbonyl addition reaction of dialkylzinc reagents catalyzed by chiral ami-noalcohols such as l-piperidino-3,3-dimethyl-2-butanol (PDB) (Eq. (7.1)) [13]. Noyori et al. have reported a highly efficient aminoalcohol catalyst, 2S)-3-exo-(dimethylamino)isobomeol (DAIB) [14] and a beautiful investigation of asymmetric amplification in view of the stability and lower catalytic activity of the het-ero-chiral dimer of the zinc aminoalcohol catalyst than the homo-chiral dimer (Fig. 7-5). We have reported a positive non-linear effect in a carbonyl-ene reaction [15] with glyoxylate catalyzed by binaphthol (binol)-derived chiral titanium complex (Eq. (7.2)) [10]. Bolm has also reported (-i-)-NLE in the 1,4-addition reaction of dialkylzinc by the catalysis of nickel complex with pyridyl alcohols [16]. 

As the mechanism of the reaction and possible intermediates in solution are still unknown, the phenomenon described here cannot yet be used for the targeted development of further reactions. It is, nevertheless, clear that complex formation with the organo-metallic reagents is essential to autocatalysis with asymmetric amplification. For this reason a deeper understanding of the behavior of chiral compounds during the formation of complexes would be very useful for the design and discovery of new autocatalytic processes. 

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