Synthesis, circular dichroism, and absolute stereochemistry of a Fecht acid analog and related compounds

Abstract

2,6-Dimethylspiro[3.3]heptane-2,6-dicarboxylic acid (2), an analog of the Fecht acid (1), was enantioresolved by the method of (1S,2R,4R)-(-)-2,10-camphorsultam yielding enantiopure acid (+)-2, the S absolute configuration of which was unambiguously determined by X-ray crystallography of camphorsultam amide derivative (R)-(-)-12b and chemical correlation. To determine the absolute configuration of chiral spiro[3.3]heptane compounds by the circular dichroism (CD) exciton chirality method, acid (+)-2 was converted to (+)-2,6-bis(phenylacetylenyl)-2,6-dimethylspiro[3.3]heptane (3) and (+)-2,6-bis(4-methoxyphenylacetylenyl)-2,6-dimethylspiro[3.3]heptane (4). The CD spectra of (+)-3 and (+)-4 exhibit intense exciton split Cotton effects of positive chirality, from which their S absolute configurations were confirmed.