Stereoselective approach to alk-2-yne-1,4-diols. Application to the synthesis of musclide B

An expedient method for the stereoselective preparation of alk-2-yne-1,4-diols has been achieved, based on the addition of chiral alk-1-yn-3-ols (or their protected derivatives) to aldehydes mediated by zinc triflate, Et3N, and (+)- or (–)-N-methylephedrine. In general, the configuration observed at the emergent stereocenter depends on the N-methylephedrine employed resulting in good to excellent diastereoselectivities. This strategy has been applied to the enantioselective synthesis of musclide B, a bioactive metabolite from musk.