Asymmetric autocatalysis. Chiral symmetry breaking and the origins of homochirality of organic molecules

Abstract

Biological homochirality, such as that of l-amino acids, has been a puzzle with regards to the chemical origin of life. Asymmetric autocatalysis is a reaction in which a chiral product acts as an asymmetric catalyst to produce more of itself in the same absolute configuration. 5-Pyrimidyl alkanol was found to act as an asymmetric autocatalyst in the enantioselective addition of diisopropylzinc to pyrimidine-5-carbaldehyde. Asymmetric autocatalysis of 2-alkynyl-5-pyrimidyl alkanol with an extremely low enantiomeric excess of ca. 0.00005% exhibited significant asymmetric amplification to afford the same pyrimidyl alkanol with >99.5% enantiomeric excess and with an increase in the quantity of the same compound. We have employed asymmetric autocatalysis to examine the origin of homochirality. Asymmetric autocatalysis triggered by circularly polarized light, chiral minerals such as quartz, chiral organic crystals composed of achiral compounds gave highly enantioenriched pyrimidyl alkanol with absolute configurations corresponding with those of the chiral triggers. Absolute asymmetric synthesis without the intervention of any chiral factor was achieved. Chiral isotopomers acted as chiral triggers of asymmetric autocatalysis.

Keywords: absolute asymmetric synthesis; amplification of chirality; asymmetric autocatalysis; chirality; origin of homochirality; symmetry breaking.

Figure 1.

Concepts of enantiomer, chiral molecule, asymmetric carbon. Implication of biological homochirality.

Scheme 1.

A proposed route to homochirality by asymmetric autocatalysis.

Scheme 2.

The principle of asymmetric autocatalysis and comparison with usual asymmetric catalysis.

Scheme 3.

Asymmetric autocatalysis with amplification of enantiomeric excess of 5-pyrimidyl alkanol 1, multifunctionalized pyrimidyl alkanol 3, 3-quinolyl alkanol 4, and 5-carbamoyl-3-pyridyl alkanol 5 in reactions with the corresponding aldehydes and diisopropylzinc.

Scheme 4.

Enantioselective reactions of pyridine-3-carbaldehyde 6 and benzaldehyde 8 with diethylzinc using (1S,2R)-N,N-dibutylnorephedrine (DBNE) as chiral catalyst.

Scheme 5.

Enantioselective reaction of benzaldehyde with diethylzinc using (S)-DPMPM and its analogs (threo- and erythro-PMPM) as chiral catalysts.

Scheme 6.

The first asymmetric autocatalysis of 3-pyridyl alkanol 10.

Scheme 7.

Practically perfect asymmetric autocatalysis of 2-alkynyl-5-pyrimidyl alkanol 1c.

Scheme 8.

Significant amplification of enantiomeric excess (ee) from extremely low to greater than 99.5% ee in asymmetric autocatalysis of 5-pyrimidyl alkanol 1c.

Figure 2.

Asymmetric autocatalysis of 5-pyrimidyl alkanol 1c with amplification of ee.

Figure 3.

Crystal structures of (a) enantiopure and (b) racemic tetrameric zinc alkoxides of pyrimidyl alkanol 1c determined by X-ray diffraction analysis.

Scheme 9.

Asymmetric autocatalysis triggered by direct irradiation of circularly polarized light.

Scheme 10.

Asymmetric autocatalysis triggered by chiral inorganic crystals and by enantiotopic face of achiral gypsum.

Scheme 11.

Asymmetric autocatalysis triggered by chiral crystals of achiral or racemic organic compounds.

Scheme 12.

Enantioselective addition of diisopropylzinc at the enantiotopic surface of achiral single crystal of 2-(tert-butyldimethylsilylethynyl)pyrimidine-5-carbaldehyde 2f followed by asymmetric autocatalysis.

Scheme 13.

Absolute asymmetric synthesis in conjunction with asymmetric autocatalysis with amplification of ee.

Figure 4.

Histograms of the absolute configurations and ee of the product pyrimidyl alkanol 1c by absolute asymmetric synthesis in the reaction between pyrimidine-5-carbaldehyde 2c and diisopropylzinc.

Scheme 14.

Asymmetric autocatalysis triggered by chiral compounds arising from hydrogen, carbon, nitrogen, and oxygen isotope substitution.

Scheme 15.

Discrimination of chirality by asymmetric autocatalysis.

Scheme 16.

Unusual reversal of the sense of enantioselectivity by the addition of achiral catalyst in asymmetric autocatalysis.