Stereoselective access to tetrahydropyranylacetic acid derivatives. Simple synthesis of (+)-(S,S)-(cis-6-methyltetrahydropyran-2-yl)acetic acid

Article abstract of DOI:10.1055/s-1993-25803

The reaction of the lactols 1a-1d, with malonic acid in hot dimethyl sulfoxide, in the presence of piperidinium acetate as catalyst, gives the corresponding (tetrahydrofuran-2-yl)acetic acids 2a, c and (tetrahydropyran-2-yl)acetic acids 2b, d in high yield (65-75%). While the synthesis of the (6-methyltetrahydropyran-2-yl)acetic acid (2d) is highly stereoselective (cis/trans ratio 20:1), no stereoselection was observed with the (5-methyltetrahydrofuran-2-yl)acetic acid (2c) (cis/trans ratio 1:1). This reaction was applied for the synthesis of natural (+)-(S,S)-(cis-6-methyltetrahydropyran-2-yl)acetic acid (7), minor constituent of the glandular secretion of the civet cat.