One-pot palladium(0)-catalyzed alkylation and S(N)(') cyclization of 1,4-dichlorobut-2-ene 1 by the anion of alpha-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-ethenylcyclopropanecarbonitrile (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 = 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, PMe(3)), 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.
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). -
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