Polymer-supported l-prolinol-based catalysts for the enantioselective addition of dialkylzinc reagents to N-(diphenylphosphinyl)imines

Abstract

L-Prolinol-based ligands anchored to Merrifield or Wang-type resins have shown to form efficient catalysts for the enantioselective addition of dialkylzinc reagents to N-(diphenylphosphinyl)imines. The enantioselectivity achieved with the polymeric catalyst (ee up to 88%) is slightly lower than the one obtained with the homogeneous ligand N-benzyl-L-prolinol, but the polymersupported ligand presents the advantage of its recyclability: it can be recovered and used in up to six consecutive catalytic cycles with only a slight detriment in the enantiomeric excess. The phosphinamides obtained as addition products can be transformed into the corresponding optically enriched α-branched primary amines under mild acidic conditions.

PFAM catalyzed enantioselective diethylzinc addition to imines

“…Additives are also commonly used for these reactions. Therefore, in order to see the effect of additives on our catalyst system i Pr 2 NEt, Et 3 N, HMPA, DABCO, MeOH, and TMEDA were tried (entries [15][16][17][18][19][20]. After observing that TMEDA increased the enantioselectivity, it was decided to do further optimization by changing the amount and also the type of copper salt.…”

“…polymer-supported L-prolinol catalyst. 15 Besides N -sulfonyl and N -phosphinoyl imines, this reaction was also studied with BOC and formyl protected imines by Aleksakis et al 16 and Feringa et al 17 respectively.…”

“…10 As examples of diethylzinc addition to N-diphenylphosphinoyl arylaldimine, Charatte et al used copper-chiral phosphine ligands, 11 Ha et al used copper-diphosphine and thiophosphoramide ligands, 12 Wang et al used copperferrocenyl amino ketones, 13 Liao et al used copper-chiral tert-butanesulfinylphosphines, 14 and Yus et al used polymer-supported L-prolinol catalyst. 15 Besides N -sulfonyl and N -phosphinoyl imines, this reaction was also studied with BOC and formyl protected imines by Aleksakis et al 16 and Feringa et al 17 respectively. However, due to the unavailability of some chiral ligands, impractical reaction conditions, use of excess amounts of dialkylzinc (3-5 equivalents), and the catalytic turnover problems, researchers are still trying to develop a better catalyst system and practical reaction conditions for this reaction.…”