Molecular Structure of a Chiral 3,5-Bridged Pyridine and the Effect of Structure on Circular Dichroic Spectra

Article abstract of DOI:10.1021/jo00266a012

The crystal structure of the 3,5-bridged chiral macrocyclic pyridine (4S,14S)-4,14-di(2-propyl)-6,9,12-trioxa-3,15,19-triazabicyclo<15.3.1>heneicosa-1(21),17,19-triene-2,5,13,16-tetrone (5a) has been determined by crystallographic means.Each unit cell contains two nonequivalent molecules.In each molecule the amide groups are twisted out-of-plane in a conrotatory fashion righ-handedly with respect to the molecular C2 axis viewed along the line from C4 to N1 of the pyridine ring.This twist allows avoidance of potential interaction between the amide nitrogen bonded protons and that bonded to C4 of the pyridine ring.The macrocyclic framework is inherently dissymmetric as a result of this helical twist.This is reflected in the circular dichroism spectrum of 5a, which has two strongly negative effects in the 200-400-nm region, at 218 nm, <θ> -58800 and 273 nm, <θ> -45600.Very similar CD effects are found for analogues of 5a with at the chiral atoms at the 4,14-positions, methyl groups (6a), tert-butyl groups (6b), and proline (7).Comparison are also made with compounds (8b) derived (in thought) from 5a by transposition of the macrocyclic bridge from the 3,5- to the 2,6-positions.Compound 8a is analogous to 8b save that it is a benzene rather than a pyridine derivative.Several nonmacrocyclic analogues of 5a have also been examined as well as the thiamide derivative of 5a (compound 9) for which a synthesis has been developed.The longer wavelength CD effect in 5a is assigned to the pyridine n-?^* transition and the shorter wavelength effect to ?-?^* transitions.Attempts to correlate the absolute signs with a recently postulated model fail.A method for synthesis of the unnatural amino acids, (S)-(+)-2-amino-3,3,-dimethylbutanoic acid (13), in enantiomerically pure form is described as well as an NMR method for the determination of the enantiomeric purity of samples of 13.