ChemInform Abstract: Stereoselective Synthesis of Highly Functionalized Cyclopropanes. Application to the Asymmetric Synthesis of (1S,2S)‐2,3‐Methanoamino Acids.

Abstract

StereoselectiveSynthesis of Highly Functionalized Cyclopropanes.Application to the Asymmetric Synthesis of (1S,2S)-2,3-Methanoamino Acids.-Palladium-catalyzed alkylation-cyclization of dichlorobutene (I) with various substituted acetonitriles (II) in the presence of base proceeds with high diastereoselectivity (88-100% d.e.) to furnish trans-functionalized cyclopropanenitriles (III) in good yields. In contrast, various approaches to realize the asymmetric version of this one-pot alkylationcyclization sequence by utilizing chiral ligands or by reacting chiral ketimines or allyl chlorides provide the corresponding cyclopropanes in low to moderate enantiomeric excess. It is shown, that Pd(0) complexes not only catalyze the diastereoselective cyclization but also ring opening and epimerization reactions and thus cause racemization of cyclopropanes. This can be overcome by performing the cyclization reaction under Mitsunobu conditions. Diimide reduction and hydrolysis then provide chiral methanoamino acids like (VIII). -