Total synthesis of (±)-dihydrokawain-5-ol. Regioselective monoprotection of vicinal syn-diols derived from the iodocyclofunctionalization of α-allenic alcohols

Article abstract of DOI:10.1021/jo961653u

The synthesis of (±)-dihydrokawain-5-ol (1) from the vinyl iodo syn-vicinal diol 7a is described. This diol was prepared in a highly diastereoselective fashion via the iodocyclofunctionalization reaction of the N-tosyl carbamate derivative of the corresponding α-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 monoprotection protocol for the introduction of MOM ethers in vicinal diols provided 8a in a highly regioselective fashion (8a:9a > 30:1) from 7a. This regioselective monoprotection was found to be general for vinyl iodo and acetylenic vicinal diols 7 and 10, placing the MOM protecting group on the homoallylic and homopropargylic alcohol of the diol moieties, respectively. Alternatively, a highly regioselective (11.5:1) monosilylation of the homoallylic alcohol in 7a followed by etherification (MOM) of the allylic alcohol provided the differentially protected diol 25. Further manipulation of the vinyl iodide function in 25 (dehydroiodination, carbonylation) followed by desilylation generated the γ-alkoxy-δ-hydroxy-α,β-acetylenic ester 28. Cyclization of 28 produced the unique 4,5-dialkoxypyran-2-one moiety present in (±)-1. This latter transformation involved the interesting acid-catalyzed and thermodynamically driven isomerization of the intermediate β-alkoxy-α,β-unsaturated ester (Z)-29 to the corresponding E-isomer.