Asymmetric synthesis of the cis- and trans-3,4-dihydro-2,4,8-trihydroxynaphthalen-1(2H)-ones

A short and efficient protocol for the asymmetric synthesis of cis- and trans-3,4-dihydro-2,4,8-trihydroxynaphthalen-1(2H)-one (1 and 2, resp.) is described, with a phthalide annulation as the key step. Introduction of a OH substituent at position 2 was performed by Sharpless dihydroxylation of a silyl enol ether or by means of an N-sulfonyloxaziridine. The absolute configuration of each isomer was determined via Mosher-ester derivatives. By comparison with previously recorded CD spectra of our natural sample, we established that the natural trans- and cis-isomers from Ceratocystis fimbriata sp. platani were the (-)-(2S,4S)-isomer (-)-2 and the (+)-(2S,4R)-isomer (+)-1, respectively.