Regioselective and stereoselective methods for the synthesis of the pentitols

David Holland, J. Fraser Stoddart*

*Corresponding author for this work

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18 Scopus citations


Several different approaches to the stereoselective synthesis of xylitol (1), as well as the other two pentitols, ribitol (2) and DL-arabinitol DL-(3), from the (Z)- and (E)-1-hydroxypentadienes (4) and (5) and the (Z)- and (E)-4,5-epoxypent-2-enals (6) and (7) are described. They rely upon either (a) epoxidations of allylic C=C double bonds followed by stereospecific (anti) and sometimes regioselective epoxide cleavages, or (b) syn-hydroxylations of allylic C=C double bonds. Employing approach (a), the (Z)-isomers (4) and (6) do not afford any ribitol (2) among the products and the (E)-isomers do not afford any xylitol (1). The consequences are reversed when approach (b) is adopted. The most convenient synthesis of xylitol (1) starts from the (Z)-isomer (6) of 4,5-epoxypent-2-enal. The formyl group in (6) is reduced, provided acidic work-up conditions are employed, to yield (Z) - (4RS) -4,5-epoxy-1-hydroxypent2- ene (9), which is characterised as its acetate (10). Opening of the epoxide ring in (10) with acetate ion gives the triacetate (11), which is deacetylated to afford a key intermediate, (Z)-(4RS)-1,4,5-trihydroxypent-2-ene (12). Epoxidation of (12) with peracids (e.g. p-nitroperbenzoic acid) yields (t-butyl hydroperoxide with catalytically active Ti4+, V5+, and Mo6+ complexes fails) two epoxides (13) and (14), arbitrarily named isomers A (13) and B (14) subsequently shown to have the relative stereochemistries (2S,3R,4R) and (2R,3R,4R), respectively. Epoxide ring opening with acetate ion in acetic anhydride of the more abundant isomer B (14), obtained with 70% diastereoselectivity, yields xylitol penta-acetate (16) as the major product (>80% diastereoselectivity) along with small and trace amounts of the other two pentitol penta-acetates. Epoxide ring opening of isomer A with acetate ion in acetic anhydride is not a straightforward reaction for the most part and has been found to involve the intermediacy of an isolatable bicyclic orthoester (23) en route to some of the xylitol penta-acetate (16) formed as the principal stable product during this reaction. These variations of approach (a) constitute stereoselective syntheses of xylitol (1), which are claimed to be acceptable on a laboratory scale. They provide a slightly better route than an alternative one involving the transformations (4) → (33) → (34) → (39) → (16) → (1), starting from (Z)-1-hydroxypenta-2,4-diene (4), principally because this particular precursor is less readily accessible than (Z)-4,5-epoxypent-2-enal (6). By contrast, the (E)-isomer (5) of 1-hydroxypenta-2,5-diene is obtainable in high yield from the reduction of vinyl acrylic acid and the analogous transformations [(5) → (26) → (27) → (28) → DL-(5) → DL-(3)] provide a highly stereoselective (91%) synthetic route to DL-arabinitiol DL-(3). Osmium-catalysed syn-hydroxylation of (E)-(4RS)-triacetoxypent-2-ene (22), prepared from (E)-4,5-epoxypent-2-enal (7) in two steps [(7) → (20) → (22)], provides yet another approach to DL-arabinitol DL-(3), but the stereoselectivity (76%) of this oxidation is not as good as that observed for the epoxidation of rel-(3R,4R)-3,4,5- triacetoxypent-1-ene (27) in the above transformation. The synthesis of ribitol (2) by osmium-catalysed synhydroxylation of the (Z)-isomer (11) of (22) was achieved with a modest stereoselectivity of 66% for the oxidation step.

Original languageEnglish (US)
Pages (from-to)1553-1571
Number of pages19
JournalJournal of the Chemical Society, Perkin Transactions 1
StatePublished - 1983

ASJC Scopus subject areas

  • Chemistry(all)


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