racemic 4-trimethylsilyl-3-butyn-2-ol can
be prepared by deprotonation with strong bases (BuLi, LDA,
Grignards reagents) of trimethylsilylacetylene followed
by addition to acetaldehyde.Deprotonation of 3-butyn-2-
ol followed by quenching with excess trimethylsilyl chloride
followed by concomitant hydrolysis of the trimethylsilyl ether
is generally the most straightforward route.Enzymatic reduction
of 4-TMS-3-butyn-2-one has also been used to prepare the
reagent using alcohol dehydrogenase.
Preparation of nonracemic 4-TMS-3-butyn-2-ol has been
accomplished by asymmetric addition of dimethylzinc to
acetaldehyde promoted by TADDOL or addition of a
trimethylsilylvinylsulfoxide to acetaldehyde followed by thermal
elimination of the sulfoxide.Asymmetric reduction of 4-
TMS-3-butyn-2-one using stoichiometric reducing reagents,
catalytic transfer hydrodrogenation,and enzymatic reduction
with isolated protein or whole cells afford the 4-TMS-3-butyn-
2-ol with varying degrees of enantioenrichment.Enzymatic resolution by esterification of the racemic alcohol is the method
of choice for the large-scale preparation.
