Access to enantioenriched alpha-amino esters via rhodium-catalyzed 1,4-addition/enantioselective protonation.
Conjugate addition of potassium trifluoro(organo)borates 2 to dehydroalanine derivatives 1, mediated by a chiral rhodium catalyst and in situ enantioselective protonation, afforded straightforward access to a variety of protected alpha-amino esters 3 with high yields and enantiomeric excesses up to 95%. Among the tested chiral ligands and proton sources, Binap, in combination with guaiacol (2-methoxyphenol), an inexpensive and nontoxic phenol, afforded the highest asymmetric inductions. Organostannanes have also shown to participate in this reaction. By a fine-tuning of the ester moiety, and using Difluorophos as chiral ligand, increased levels of enantioselectivity, generally close to 95%, were achieved. Deuterium labeling experiments revealed, and DFT calculation supported, an unusual mechanism involving a hydride transfer from the amido substituent to the alpha carbon explaining the high levels of enantioselectivity attained in controlling this alpha chiral center.
Navarre
Laure
L
Laboratoire de Synthèse Sélective Organique (UMR 7573, CNRS), Ecole Nationale Supérieure de Chimie de Paris, 11 rue P&M Curie, 75231 Paris cedex 05, France.
Martinez
Rémi
R
Genet
Jean-Pierre
JP
Darses
Sylvain
S
D000475:Alkenes / Q000737:chemistry; D000596:Amino Acids / Q000138:chemical synthesis*; D002384:Catalysis; D004952:Esters / Q000138:chemical synthesis*; D008956:Models, Chemical; D008958:Models, Molecular; D009947:Organotin Compounds / Q000737:chemistry; D010636:Phenols / Q000737:chemistry; D011522:Protons; D012238:Rhodium / Q000737:chemistry*; D013237:Stereoisomerism; D013816:Thermodynamics
D000475:Alkenes; D000596:Amino Acids; D004952:Esters; D009947:Organotin Compounds; D010636:Phenols; D011522:Protons; D012238:Rhodium