The synthesis of enantiomerically pure 5-menthyloxy-2(5B)-furanones is described as well as the diastereoselective 1,4-addition of thiols to these butenolides to yield new homochiral CQ-synthons. Kinetic resolution of 5-methoxy-2(5H)-furanone, with an enautiameric excess of 139, wae achieved by cinchonidine catalyzed thiophemol addition. The synthetic utility of the aeyzmetric th 01 additions is illustrated in an efficient route to enant 1 omerically pure (R)-and (S)-3,4-epoxy-1-butanol.
Optically active 2,3-epoxyalcohols have served as starting materials in the synthesis of numerous complex chiral coappaunds x ever since the discovery, by Katsuki and Sharpless', of an efficient zmthod for their preparation by asyzmetric epoxidation. Similarly 3,4-epoxyalcohols might be applied as key chiral building blocks in synthesis. These developments have been hampered sofar by limited availability of enantiomerically pure 3,4-epoxyalcohols.
In contrast to the asymmetric epoxidation of allylic alcohols, the titaniumtetraisopropoxide (Ti(OiPr).), diethyltartrate, t-butylhydroperoxide msdiated epoxidation of homoallylic alcohols gives rise to low to medium range enantiomeric excemes (e.e. '8 23-55%)= whereas chdcal yields are rather low. Similar results were reported for the formation of 3,4-epoxy-1-butanol using Zr(OiPr). instead of Ti(OiPr). (e.e. 40%).. For substituted hoztoallylic alcohols e.e.' s up to 77% have been reached=... Currently the most frequently applied route to optically active 3,4epoxyalcohols relies on natural products as chiral starting materials. A convenient, though multietep conversion of S-malic acid (-1) into both (R)and (S)-3,4-epoxy-1-butanol (A) has been described by several groups~~~~' (scheme 1). An efficient enantioselective synthesis of (R)and (S)-malic acid was developed by Wynberg and Staring. based on the cinchonidine catalyzed addition of ketene to chloral.
Vandewalle and coworkersm reported a route to 2 and related CI-chiral synthons fram (S)-Erythrulose (1) containing the unnatural sugar configuration (scheme 1). Purthemore amtric syntheses of 1 are based on: i.
kinetic resolution using a lipase catalyzed hydrolysis of esters of epoxyalcohols (e.e. 73% for recovered ester)xo. if. asymetric thiophenol addition to maleic esters zmdiated by cinchonidine followed by convereion into 5 (e.e. 81%)7.