Stereoselective synthesis of highly functionalized cyclopropanes. Application to the asymmetric synthesis of (1S,2S)-2,3-methanoamino acids

One-pot palladium(0)-catalyzed alkylation and S-N, cyclization of 1,4-dichl orobut-2-ene 1 by the anion of or-substituted carbonitriles 2a-d can provid e highly functionalized cyclopropanes (E)-4a-d, diastereoselectivity, (de 8 8-100%). Several attempts to achieve the asymmetric synthesis of the 1-amin o-2-ethenylcyclopropanecarbonitriles (E)-9, by means of this new procedure, i.e., using chiral palladium ligands, chiral aminoacetonitriles (-)- and ( +)-12 (from 1-hydroxypinanone) or chiral allyl chlorides (4S)-20b-d and (4R )-20e (from (2S) ethyl lactate) have pointed up the reversibility of the pa lladium-catalyzed cyclization step, responsible for the low enantioselectiv ity observed (ee less than or equal to 32%) and for the formation of byprod ucts, i.e., azepine derivatives 8a,b arising from subsequent aza Cope ring expansion. Molecular mechanics calculations using a modified MM2 type force field adapted to the pi-allyl palladium complexes have explained these res ults. However, when performed under the Mitsunobu reaction conditions (DEAD , PMe3), therefore, in the absence of palladium catalyst, the S-N, cyclizat ion occurred also diastereoselectively (de > 88%) and provided the enantiom erically enriched 1-amino-2-propenylcyclopropanecarbonitrile (E)-22 (ee > 8 3%) suitable precursor of (1S,2S)-2,3-methanoamino acids.