Rh-catalyzed asymmetric hydrogenation of prochiral olefins with a dynamic library of chiral TROPOS phosphorus ligands.
A library of 19 chiral tropos phosphorus ligands, based on a flexible (tropos) biphenol unit and a chiral P-bound alcohol (11 phosphites) or secondary amine (8 phosphoramidites), was synthesized. These ligands were screened, individually and as a combination of two, in the rhodium-catalyzed asymmetric hydrogenation of dehydro-alpha-amino acids, dehydro-beta-amino acids, enamides and dimethyl itaconate. ee values up to 98% were obtained for the dehydro-alpha-amino acids, by using the best combination of ligands, a phosphite [4-P(O)2O] and a phosphoramidite [13-P(O)2N]. Kinetic studies of the reactions with the single ligands and with the combination of phosphite [4-P(O)2O] and phosphoramidite [13-P(O)2N] have shown that the phosphite, despite being less enantioselective, promotes the hydrogenation of methyl 2-acetamidoacrylate and methyl 2-acetamidocinnamate faster than the mixture of the same phosphite with the phosphoramidite, while the phosphoramidite alone is much less active. In this way, the reaction was optimized by lowering the phosphite/phosphoramidite ratio (the best ratio is 0.25 equiv phosphite/1.75 equiv phosphoramidite) with a resulting improvement of the product enantiomeric excess. A simple mathematical model for a better understanding of the variation of the enantiomeric excess with the phosphite/phosphoramidite ratio is also presented.
Monti
Chiara
C
Dipartimento di Chimica Organica e Industriale, Centro di Eccellenza C.I.S.I. Università degli Studi di Milano, Istituto di Scienze e Tecnologie Molecolari del CNR, Via G. Venezian 21, 20133 Milano, Italy.
Gennari
Cesare
C
Piarulli
Umberto
U
de Vries
Johannes G
JG
de Vries
André H M
AH
Lefort
Laurent
L
D000438:Alcohols / Q000737:chemistry; D000475:Alkenes / Q000138:chemical synthesis* / Q000737:chemistry; D000588:Amines / Q000737:chemistry; D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D006865:Hydrogenation; D008024:Ligands; D015394:Molecular Structure; D009943:Organophosphorus Compounds / Q000737:chemistry*; D012238:Rhodium / Q000737:chemistry*; D013237:Stereoisomerism
D000438:Alcohols; D000475:Alkenes; D000588:Amines; D008024:Ligands; D009943:Organophosphorus Compounds; D012238:Rhodium