New Dihydroxy Bis(Oxazoline) Ligands for the Palladium-Catalyzed Asymmetric Allylic Alkylation: Experimental Investigations of the Origin of the Reversal of the Enantioselectivity

• Published in: Chemistry : a European journal Vol. 10; no. 3; pp. 699 - 707
• Main Authors: Aït-Haddou, Hassan, Hoarau, Olivier, Cramailére, Dimitri, Pezet, Frédéric, Daran, Jean-Claude, Balavoine, Gilbert G. A.
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 06-02-2004; WILEY‐VCH Verlag
• Subjects: allylic alkylation; asymmetric catalysis; enantioselectivity; N ligands; palladium
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.200204649

The origin of the reversal of the enantioselectivity in the palladium‐catalyzed allylic alkylation of rac‐1,3‐diphenyl‐2‐propenyl acetate with dimethyl malonate anion using chiral dihydroxy bis(oxazoline) “BO” ligands derived from (1S,2S)‐(+)‐2‐amino‐1‐phenyl‐1,3‐propanediol was investigated. To determine the structural effects of the dihydroxy BO ligand on this unique phenomenon, new homochiral dihydroxy BO ligands were prepared from L‐threonine and L‐serine and were assessed in the transformation. The results obtained with these novel BO ligands, compared with the one obtained by using the dihydroxy BO ligands derived from (1S,2S)‐(+)‐2‐amino‐1‐phenyl‐1,3‐propanediol, reveal that the reversal in the enantioselectivity observed with the dihydroxy BO ligand depends on the structure of the ligand. The effect of different bases used to generate the dimethyl malonate anion was also examined. The results are discussed in terms of the interaction of one hydroxy group in the intermediate π‐allyl palladium complex with the dimethyl malonate anion.
A remarkable shift of the enantioselectivity was observed in the application of a dihydroxy bis(oxazoline) ligand with a defined structure in a palladium‐catalyzed asymmetric allylic alkylation (see scheme). The origin of this intriguing phenomenon was investigated and the effect of the ligand structures was established.