Asymmetric amplification during self-replication is a key feature that is used to explain the origin of homochirality. Asymmetric autocatalysis of pyrimidyl alkanol in the asymmetric addition of diisopropylzinc to pyrimidine-5-carbaldehyde is a unique example of this phenomenon. Crystallization of zinc alkoxides of this 5-pyrimidyl alkanol and single-crystal X-ray diffraction analysis of the alkoxide crystals reveal the existence of tetramer or higher oligomer structures in this asymmetric autocatalytic system.

The achiral hydrocarbon tetraphenylethylene crystallizes in enantiomorphous forms (chiral space group: P2(1)) to afford right- and left-handed hemihedral crystals, which can be recognized by solid-state circular dichroism spectroscopic analysis. Chiral organic crystals of tetraphenylethylene mediated enantioselective addition of diisopropylzinc to pyrimidine-5-carbaldehyde to give, in conjunction with asymmetric autocatalysis with amplification of chirality, almost enantiomerically pure (S)- and (R)-5-pyrimidyl alkanols whose absolute configurations were controlled efficiently by the crystalline chirality of the tetraphenylethylene substrate. Tetrakis(p-chlorophenyl)ethylene and tetrakis(p-bromophenyl)ethylene also show chirality in the crystalline state, which can also act as a chiral substrate and induce enantioselectivity of diisopropylzinc addition to pyrimidine-5-carbaldehyde in asymmetric autocatalysis to give enantiomerically enriched 5-pyrimidyl alkanols with the absolute configuration correlated with that of the chiral crystals. Highly enantioselective synthesis has been achieved using chiral crystals composed of achiral hydrocarbons, tetraphenylethylenes, as chiral inducers. This chemical system enables significant amplification of the amount of chirality using spontaneously formed chiral crystals of achiral organic compounds as the seed for the chirality of asymmetric autocatalysis.

Asymmetric amplification during self-replication is akey feature that is used to explain the origin of homochirality. Asymmetric autocatalysis of pyrimidyl alkanol in the asymmetric addition of diisopropylzinc to pyrimidine-5-carbaldehyde is aunique example of this phenomenon. Crystallization of zinc alkoxides of this 5-pyrimidyl alkanol and single-crystal X-ray diffraction analysis of the alkoxide crystals reveal the existence of tetramer or higher oligomer structures in this asymmetric autocatalytic system.The origin of biological homochirality,such as that found in l-amino acids,i safundamental question that has attracted the interest of scientists from awide range of research areas. [1] Although there are several possible origins of homochirality, propagation and amplification of chirality generated from the initial breaking of symmetry are also key topics for the evolution of homochirality.A symmetric autocatalysis with amplification of chirality has been suggested as amechanistic model for the evolution of homochirality.I nt his reaction, ac hiral product serves as an asymmetric catalyst to produce more of itself;the process is thus an automultiplication of the chiral compound.We found asymmetric autocatalysis with amplification of the enantiomeric excess (ee)i nareal chemical reaction (Scheme 1).[2-4] When diisopropylzinc (iPr 2 Zn) is added to pyrimidine-5-carbaldehyde 1 in the presence of ac atalytic amount of (S)-pyrimidyl alkanol 2 with alow ee,asymmetric autocatalytic amplification of the ee produces (S)-2 with high ee as the final product. Early autocatalytic work with pyrimidine-5-carbaldehyde [2a] and 2-methylpyrimidine-5-carbaldehyde was succeeded by the use of superior 2-alkynyl analogues [2b] and the amplification efficiencywas dramatically increased to obtain product 2 with more than 99.5 % ee after consecutive asymmetric autocatalytic amplification, even when the initial catalyst has only ca. 510 À5 % ee.T his unique property means that, in addition to chiral molecules, at race imbalance of chirality induced by chiral triggers such as circularly polarized light, [5] crystal chirality, [6] various chiral materials, [7] or isotope chirality [8] can also be amplified to afford enantioenriched alkanol 2 with corresponding absolute configurations.Furthermore,spontaneous absolute asymmetric synthesis can be achieved by using this reaction. [9] Although the theory of asymmetric amplification during self-replication was first proposed in 1953, [10] the above reaction remains the only practical example of ac hemical reaction involving asymmetric autocatalysis that leads to high levels of amplification of ee.S everal studies have been undertaken to understand the mechanism of this reaction. Thel arge amplification of ee observed in this autocatalytic reaction is often explained by the formation of aggregates, which has been proposed to account for the positive nonlinear effect observed during asymmetric catalysis.[11] Mechanistic studies based on kinetic experiments, [12] reaction mo...

Much interest has been paid to the origin of homochirality, such as that of L-amino acids. The proposed origins of chirality have usually induced only low enantiomeric excess. Thus, asymmetric amplification by asymmetric autocatalysis has been invoked. Asymmetric autocatalysis of 5-pyrimidyl alkanol in the enantioselective addition of diisopropylzinc to pyrimidine-5-carbaldehyde is a unique example of amplification of chirality. Crystallization of possible intermediates, specifically zinc alkoxides of this 5-pyrimidyl alkanol, was investigated to obtain mechanistic insights into this reaction. Single-crystal X-ray crystallography of the formed zinc alkoxide crystals shows the existence of tetramer or higher oligomer structures in this asymmetric autocatalytic system.

Asymmetric autocatalysis initiated by chiral crystals containing racemic DL-serine was achieved. P- and M-crystals of DL-serine acted as the source of chirality of asymmetric autocatalysis to afford highly enantioenriched (>99.5% ee) (S)- and (R)-pyrimidylalkanols after the amplification of ee. This is the first example of the usage of the crystal, which contains the same number of D- and L-enantiomers as an origin of chirality in enantioselective synthesis.