A positional scanning approach to the discovery of dipeptide-based catalysts for the enantioselective addition of vinylzinc reagents to aldehydes.
[reaction: see text] A combinatorial library of dipeptide N-acylethylenediamine-based ligands was synthesized by parallel solid-phase methods. These ligands were screened in crude form as catalysts for the asymmetric addition of vinylzinc reagents to aldehydes to give chiral allylic alcohols. Three sites of diversity on the ligands were optimized using a positional scanning approach. The optimized structure from the library, ligand 54, was found to catalyze the formation of 10 different (E)-allylic alcohols with enantioselectivities ranging from 90% to 95% ee. This ligand was effective for both aromatic and alpha-branched aldehydes, and vinylzinc reagents derived from both bulky and straight chain terminal alkynes.
Sprout
Christopher M
CM
Department of Chemistry, Brown University, 324 Brook Street Box H, Providence, Rhode Island 02912, USA.
Richmond
Meaghan L
ML
Seto
Christopher T
CT
D000447:Aldehydes / Q000737:chemistry*; D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D004151:Dipeptides / Q000138:chemical synthesis*; D008024:Ligands; D009942:Organometallic Compounds / Q000737:chemistry*; D013237:Stereoisomerism; D015032:Zinc
D000447:Aldehydes; D004151:Dipeptides; D008024:Ligands; D009942:Organometallic Compounds; D015032:Zinc