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-dichlorobut-2-ene 1 by the anion of or-substituted carbonitriles 2a-d can provide highly functionalized cyclopropanes (E)-4a-d, diastereoselectivity, (de 88-100%). Several attempts to achieve the asymmetric synthesis of the 1-amino-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 palladium-catalyzed cyclization step, responsible for the low enantioselectivity observed (ee less than or equal to 32%) and for the formation of byproducts, 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 results. However, when performed under the Mitsunobu reaction conditions (DEAD, PMe3), therefore, in the absence of palladium catalyst, the S-N, cyclization occurred also diastereoselectively (de > 88%) and provided the enantiomerically enriched 1-amino-2-propenylcyclopropanecarbonitrile (E)-22 (ee > 83%) suitable precursor of (1S,2S)-2,3-methanoamino acids.