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 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.
Dorizon
Philippe
P
Laboratoire des Carbocycles (Associé au CNRS), Institut de Chimie Moléculaire d'Orsay, Bât. 420, Université de Paris-Sud, 91405 Orsay, France.
Su
Guifa
G
Ludvig
Gitte
G
Nikitina
Lilyia
L
Paugam
Renée
R
Ollivier
Jean
J
Salaün
Jacques
J