25073-24-9Relevant academic research and scientific papers
Regioselective and Stereoselective Methods for the Synthesis of the Pentitols
Holland, David,Stoddart, J. Fraser
, p. 1553 - 1571 (2007/10/02)
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-hydroxypent-2-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 70percent diastereoselectivity, yields xylitol penta-acetate (16) as the major product (>80percent 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 (26) -> (27) -> (28) -> DL-(5) -> DL-(3)> provide a highly stereoselective (91percent) synthetic route to DL-arabinitol 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 (20) -> (22)>, provides yet another...
