Enantioselective Rh-catalyzed hydrogenation of N-formyl dehydroamino esters with monodentate phosphoramidite ligands
Enantioselectivities up to >99% ee were achieved in the rhodium-catalyzed asymmetric hydrogenation of N-formyl dehydroamino esters using monodentate phosphoramidites as chiral ligands. The substrates were synthesized by condensation of methyl isocyanoacetate with a range of aldehydes and with cyclohexanone. A highly convenient multigram scale one step synthesis of methyl 2-(formamido)acrylate was developed. This compound was used in the synthesis of methyl 2-(formamido)cinnamate via a solvent free Heck reaction. Moreover, full conversion and >99% ee were obtained in 1 h in the hydrogenation of methyl 2-(formamido)acrylate with 0.2 mol% catalyst and 2 bar hydrogen pressure. The versatility of the formyl protection was established by its removal under mild conditions.
Panella, Lavinia,Aleixandre, Alicia Marco,Kruidhof, Gerlof J.,Robertus, Jort,Feringa, Ben L.,De Vries, Johannes G.,Minnaard, Adriaan J.
p. 2026 - 2036
(2007/10/03)
(Z)-selective β-bromination of N-formyl-α,β-dehydroamino acid esters
Stereoselective β-bromination of N-formyl-α,β-dehydroamino acid esters 5 was investigated. A reaction of 5 with NBS afforded α-bromo-N-formylimines 10 which successively isomerized to give β-bromo-N-formyl-α,β-dehydroamino acid esters 4. The migration of the double bond of the intermediates 10 with bulky substituents at the β-position resulted in highly stereoselective formation of (Z)-4, while that of the substrates with less bulky substituents proceeded non-stereoselectively. A mechanism of the stereoselective bromination was proposed on the basis of semiempirical calculations using AM1.
SYNTHESIS OF Β-FUNCTIONALIZED α,β-DEHYDROAMINO ACID DERIVATIVES
β-functionalized α,β-unsaturated amino acids were synthesized by an addition-elimination pathway.Reaction of methyl β-bromo-α-formylaminoacrylates ( 3a-e ), which were prepared by the condensation of methyl isocyanoacetate ( 1 ) with aldehydes followed by