Chiral Synthesis via Organoboranes. 18. Selective Reductions. 43. Diisopinocampheylchloroborane as an Excellent Chiral Reducing Reagent for the Synthesis of Halo Alcohols of High Enantiomeric Purity. A Highly Enantioselective Synt

摘要

Diisopinocampheylchloroborane, Ipc2BCI, reduces ring and chain substituted haloaralkyl ketones to the corresponding halo alcohols in excellent enantiomeric excess. In certain cases these alcohols can be upgraded by simple methods to essentially 100% ee. For instance, (+)- or (-)-3-chloro-1-phenyl-1-propanol is initially obtained in 97% ee. Simple recrystallization then furnishes the pure enantiomers. These chiral halo alcohols are highly versatile intermediates. They can be readily cyclized to oxiranes and 2-substituted tetrahydrofurans with retention of chirality. Utilizing this methodology, we have developed an efficient, highly enantioselective synthesis of both optical isomers of the antidepressant drugs, Tomoxetine, Fluoxetine, and Nisoxetine, from the common intermediates (+)- or (-)-3-chloro-1-phenyl-1-propanol. Organoboranes, Chlorine compounds, Reprints. (mjm)