(R)- and (S)-4-TIPS-3-butyn-2-ol. Useful Precursors of Chiral Allenylzinc and Indium Reagents

  • 10.1021/jo060542k
  • The Journal of Organic Chemistry
  • p 4840-4844, Volume 71, Issue 13,
  • journal-article
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.


Synthesis of the optically active TIPS-functionalized acetylenic alcohols

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...