Synthesis of Poly(Ethylene Glycol)–Supported (R)-BINOL Derivatives and Their First Application in Enantioselective Mukaiyama Aldol Reactions

Abstract

The Mukaiyama aldol reaction of 2-styryl-oxazole-4-carbaldehyde (1) as model substrate with S-ketene silyl acetal 2 catalyzed by poly(ethylene glycol)-supported binaphthyl-derived chiral titanium(IV) complexes afforded the corresponding aldol product in good to excellent yields and enantioselectivities up to 94% ee. The chemical yields and/or the enantioselectivities are enhanced by generating the active catalyst from Ti(OiPr)₄, polymer-supported ligands (R)-6 or (R)-8, and chiral or achiral promoters. Pyrrolidine derivative (S)-13 and trifluoromethyl-substituted phenol 12 are the most efficient additives found.

Keywords:

• Aldol reaction
• asymmetric catalysis
• binaphthalene
• chiral additives
• poly(ethylene glycol)
• polymer-supported reaction
• thioester

Notes

^a The ee was determined after the desilylation of 10.

^b Result taken from Ref. 22.

^c 60% of conversion.

^d 2 equivalents of BINOL ligand (R)-8 and 1 equivalent of Ti(OiPr)₄.

^a 10 mol% of the ligand was used.

^b The ee was determined after the desilylation of 10.

^c Ca. 80% of conversion.

^d Ca. 85% of conversion.

^e 15 mol% of the ligand was used.