Enantioselective Synthesis Induced by the Helical Molecular Arrangement in the Chiral Crystal of Achiral Tris(2-hydroxyethyl) 1,3,5-Benzenetricarboxylate in Conjunction with Asymmetric Autocatalysis

Abstract

5-Pyrimidyl alkanol with an enantiomeric excess of up to >99.5% was formed using chiral crystals of achiral tris(2-hydroxyethyl) 1,3,5-benzenetricarboxylate as a chiral initiator.In the enantioselective addition of diisopropylzinc to pyrimidine-5-carbaldehyde, the helicity of the molecular arrangement of achiral tricarboxylate in the crystalline state could be successfully used as a source of chirality to afford enantioenriched alkanol in conjunction with asymmetric autocatalysis with amplification of enantiomeric excess.Spontaneous chiral crystallization of achiral compounds is suspected as a possible origin of biological homochirality such as that found in L-amino acids and D-sugars.1 There are achiral organic compounds that crystallize in chiral space groups to form enantiomorphous crystals.2 Stereospecific reactions have been reported to form enantioenriched organic compounds using enantiomorphous crystals as reactants in the solid state. 2We have been studying asymmetric autocatalysis with amplification of enantiomeric excess (ee), 36 in which a chiral product acts as the chiral catalyst for its own production. Chiral crystals formed from achiral compounds can act as the source of chirality in the addition reaction of dialkylzinc to aldehyde to give a highly enantioenriched product in combination with asymmetric autocatalysis. 7 In this process, the spontaneously generated chiral crystals of the achiral molecules induce enantioselectivity upon the organic compound, and then the asymmetric autocatalysis increases the initial tiny imbalance of chirality to afford a large amount of enantioenriched organic compound. Asymmetric autocatalysis with amplification of ee can correlate the origins of chirality with the homochirality of organic compounds. Azumaya, Yokozawa, and co-workers reported that tris(2-hydroxyethyl) 1,3,5-benzenetricarboxylate (1) formed helically arranged enantiomorphous crystals, which belong to the chiral space group P6 1 or P6 5 (Scheme 1). 9 The planar molecules 1 helically connected with neighboring molecules to generate chirality in the crystalline state by aromaticaromatic interactions and hydrogen bonds. Because the columnar stacks within individual crystals have the same sense of helicity, the crystal shows chirality.Asymmetric synthesis 10 and separation 11 using a chiral substance with helical structure 12 are an intriguing research topic in chiral chemistry. In this paper, we report on the use of chiral crystals of tricarboxylate 1 as a chiral inducer in asymmetric autocatalysis. Therefore, highly enantioenriched organic compounds can be synthesized based on the helicity of 1 in conjunction with asymmetric autocatalytic amplification of ee (Scheme 2).The enantiomorphs of 1 could be obtained by stirred crystallization from methanol solution (Scheme 1). The chirality of the crystal can be discriminated by using the solid-state circular dichroism (CD) spectrum; therefore, right-handed Pcrystals of 1 show a positive Cotton effect at 224 nm with the KBr method ([CD(+)224 KBr ]-1), while...

Asymmetric Autocatalysis as a Link Between Crystal Chirality and Highly Enantioenriched Organic Compounds

“…In addition, chiral crystals composed of achiral Nbenzoylglycine, [44] 2-thenoylglycine, [45] cocrystals composed of two achiral compounds, [46] benzil, [47] tetraphenylethylene, [48] ethylenediammonium sulfate, [49] benzenecarboxylate, [50] and 2,6-di-tert-butyl-p-cresol (BHT) [51] are found to be chiral triggers of asymmetric autocatalysis (Scheme 6).…”

Role of Asymmetric Autocatalysis in the Elucidation of Origins of Homochirality of Organic Compounds

“…Enantiomorphous crystals formed from achiral N-benzoylglycine (hippuric acid) [96], 2-thenoylglycine [97], certain chiral cocrystals consisting of two achiral compounds [98], benzil [99], tetraphenylethylene [100], ethylenediammonium sulfate [101], aromatic triester [102], and 2,6-di-tert-butyl-p-cresol (BHT) [103] serve as chiral initiators of asymmetric autocatalysis (Scheme 7). It should be added that a chiral crystal composed of a racemic serine initiates asymmetric autocatalysis.…”

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

“…It was also found that enantiomorphous crystals composed of achiral N -benzoylglycine, 84) N -(2-thienylcarbonyl)glycine, 85) cocrystal of tryptamine and p -chlorobenzoic acid, 86) benzil, 87) tetraphenylethylene, 88) ethylenediamine sulfate, 89) benzene triester 90) and 2,6-di- t -butyl- p -cresol (BHT) 91) act as chiral triggers for asymmetric autocatalysis of 1c . Thus, asymmetric autocatalysis could serve as a macroscopic observation tool of molecular-level information on the structure of crystal surfaces.…”