Chiral Selectivity in the Achiral Amino Acid Glycine

A Cambridge Structural Database (CSD) search for the zwitterion of glycine, the only natural amino acid which does not have a chiral center at C_α, and its derivatives H₃N–C_αH₂–C′(O_cis)­O_trans(H/R/M) gave 425 hits, 420 of which are chiral because of the ψ conformation with regard to the central C′–C_α bond (ψ = O_cisC′C_αN ≠ 0 or 180°). Chiral ψ conformations distort the planar carboxylic group C_αC′(O_cis)­O_trans group stereoselectively to an asymmetric flat tetrahedron with four different corners, specified by (R_θ)/(S_θ). Negative rotation angles ψ predominantly induce pyramidalization angles θ = O_transC′C_αO_cis below −180°, resulting in a high diastereoselectivity for (M_ψ,S_θ)-glycine. Positive rotation angles ψ preferentially give (P_ψ,R_θ)-glycine. Density functional theory calculations confirm the results of the data analysis, indicating an increase of pyramidalization θ for increasing rotation angles ψ. This is corroborated by the analysis of section averages of the structural data, showing an increase of the ψ/θ selectivity in the series 1.5, 2.8, 3.5, and 6.0 for increasing rotation angles ψ. Without any chiral bias, 419 glycine derivatives crystallize in the ratio racemate/conglomerate 359:65.