First Efficient Syntheses of 1‐, 4‐, and 5‐Caffeoylquinic Acid

Efficient synthesis of 1‐, 4‐, and 5‐caffeoylquinic acid was achieved in three or four steps with suitably protected quinic acid precursors, in overall yields of 41%, 36%, and 60% [from quinic acid ( 1 )]. 1‐Caffeoylquinic acid was prepared by esterification of acetone quinide 7 with caffeoyl chloride 6 , followed by a two‐step hydrolysis of all protecting groups. Caffeoylquinic acids 4 and 5 were prepared from known quinic acid derivatives, 13 and 25 , by selective esterification of the secondary hydroxy groups and hydrolysis with 1 M HCl. However, initial attempts to prepare fully protected quinic acid derivatives with a free hydroxy group only at either C‐4 or C‐5, for the synthesis of 4 and 5 , were not successful. Kinetic acetalization of pentasilylated quinic acid 15 using bis(dimethoxy acetals) afforded several crystalline reaction products which were identified by X‐ray diffraction. Diacetal 20 , derived from a vicinal cis ‐diol, was unambiguously identified for the first time. Unexpectedly, it has two trans ‐diaxially oriented methoxy groups, forcing the quinide ring into a twist‐boat conformation.