Spontaneous absolute asymmetric synthesis promoted by achiral amines in conjunction with asymmetric autocatalysis

We report herein the reaction of pyrimidine-5-carbaldehyde and diisopropylzinc in the presence of achiral amine such as N,N'-dimethylpiperazine, N,N'-diethylpiperazine or N-methylmorpholine but in the absence of a chiral substance. The stochastic formation of (S)- and (R)-pyrimidyl alkanols with detectable ee was observed. This study shows that the slight fluctuation of the enantiomeric ratio of pyrimidyl alkanol produced at the initial reaction step can be enhanced significantly in conjunction with asymmetric autocatalysis with amplification of enantiomeric excess. We believe that the stochastic behavior in the formation of pyrimidyl alkanol constitutes one of the conditions necessary for spontaneous absolute asymmetric synthesis.The origin of biomolecular homochirality such as L-amino acids and D-sugars is an interesting mystery [1-6]. Spontaneous absolute asymmetric synthesis [1], that is, the synthesis of enantioenriched products from achiral conditions in the absence of a chiral substance, has been proposed as one of the origins of chirality. Spontaneous asymmetric crystallization of achiral compounds is another of the proposed mechanisms of homochirality [7-10]. However, spontaneous absolute asymmetric synthesis without using chiral compounds differs from crystallization in that it is possible for an increase in the amount of chiral compound to occur. Experimental realization of spontaneous absolute asymmetric synthesis via asymmetric autocatalysis has been a challenge, although the theories have been proposed [11-13].During our continuing studies of asymmetric autocatalysis [14-25], we have observed asymmetric autocatalysis of 5-pyrimidyl alkanols in the enantioselective addition of diisopropylzinc (i-Pr2Zn) to pyrimidine-5-carbaldehyde. It is noteworthy that, even when an asymmetric autocatalyst with an extremely low ee was used as the initial catalyst, an almost enantiomerically pure product, i.e., asymmetric autocatalysis, could be obtained by consecutive