TOTAL SYNTHESIS OF (+ -)-DIHYDROKAWAIN-5-OL - REGIOSELECTIVE MONOPROTECTION OF VICINAL SYN-DIOLS DERIVED FROM THE IODOCYCLOFUNCTIONALIZATION OF ALPHA-ALLENIC ALCOHOLS/

The synthesis of (+/-)-dihydrokawain-5-ol (1) from the vinyl iodo syn- vicinal diol 7a is described. This diol was prepared in a highly diast ereoselective fashion via the iodocyclofunctionaliztion reaction of th e N-tosyl carbamate derivative of the corresponding a-allenic alcohol (6a). A key to the synthesis of 1 involved the differentiation of the alcohol groups of the diol moiety in 7a. Application of Yamamoto's mon oprotection protocol for the introduction of MOM ethers in vicinal dio ls provided 8a in a highly regioselective fashion (8a:9a > 30:1) from 7a. This regioselective monoprotection was found to be general for vin yl iodo and acetylenic vicinal diols 7 and PO, placing the MOM protect ing group on the homoallylic and homopropargylic alcohol of the diol m oieties, respectively. Alternatively, a highly regioselective (11.5:1) monosilylation of the homoallylic alcohol in 7a followed by etherific ation (MOM) of the allylic alcohol provided the differentially protect ed diol 25. Further manipulation of the vinyl iodide function in 25 (d ehydroiodination, carbonylation) followed by desilylation generated th e gamma-alkoxy-delta-hydroxy-alpha,beta-acetylenic ester 28. Cyclizati on of 28 produced the unique 4,5-dialkoxypyran-2-one moiety present in (+/-)-1. This latter transformation involved the interesting acid-cat alyzed and thermodynamically driven isomerization of the intermediate beta-alkoxy-alpha,beta-unsaturated ester (Z)-29 to the corresponding E -isomer.