Fischer Indole Synthesis with Selected 2,3-Dideoxy-D-glycero-aldopentose Derivatives. Conversion of D-Xylose to (2S)-3-(Indol-3-yl)propane-1,2-diol

Abstract

Two independent routes towards (2S)-3-(indol-3-yl)propane-1,2-diol (11) were achieved starting from 3,5-di-O-acetyl-1,2-O-cyclohexylidene-α-D-xylofuranose (1). Ethanethiolysis of 1 afforded acyclic diethyl dithioacetal 2 which was further O-deacetylated to give 3. Selective benzoylation of 3 gave 5-O-benzoyl derivative 4. Treatment of 4 with N-bromosuccinimide in methanol gave methyl furanoside 5 which was further desulfurized over Raney nickel to afford 6. An acid hydrolysis of 6 gave hemiacetal 7 which upon treatment with phenylhydrazine, according to standard Fischer indolization procedure, yielded a mixture of chiral indoles 10. O-Debenzoylation of 10 gave the crystalline diol 11. A more efficient route towards the chiral indole 11 included the initial dethioacetalation of 2 into dimethyl acetal 8 which was further desulfurized over Raney nickel to give the corresponding 2,3-dideoxy derivative 9. Direct Fischer indolization of 9 with phenylhydrazine, followed by O-deacetylation of intermediate 12, afforded the expected indole 11 in good yield.