A convenient route to the enantiomers of 4-TIPS-3-butyn-2-ol of >95% enantiomeric purity by reduction of the ynone precursor 4 with the Noyori N-tosyl-1,2-diphenylethylenediamineruthenium cymene catalyst is described. The mesylate derivative of the (S) enantiomer (1c) is converted in situ to an allenylzinc or indium reagent in the presence of a catalyst derived from Pd(OAc) 2 and Ph 3 P and either Et 2 Zn or InI. A second in situ addition of these reagents to aldehydes leads to anti homopropargylic alcohol adducts. The additions proceed in generally high (60−90%) yield with modest to excellent diastereoselectivity and high enantioselectivity. Only slight mismatching (<5%) is observed with chiral α-methyl and α-silyloxy aldehydes. Additions to α-substituted enals are highly diastereoselective, while β,β-disubstituted enals afford ca. 2:1 mixtures of anti and syn adducts.
A detailed route for the synthesis of the "S" enantiomer of 4-TIPS-3-butyn-2-ol in 90% enantiomeric purity by reduction of the ynone precursor by the Noyori catalytic system was reported by Marshall et al. The ease of catalyst preparation, operational simplicity and potential...
Synthesis of the optically active TIPS-functionalized acetylenic alcohols