Enantioselective addition of vinylzinc reagents to aldehydes catalyzed by modular ligands derived from amino acids.
[reaction: see text] A series of N-acylethylenediamine-based ligands were synthesized from Boc-protected amino acids. The ligands were screened for the ability to catalyze the asymmetric addition of vinylzinc reagents to aldehydes. Three sites of diversity on the ligands were optimized for this reaction using a positional scanning approach. The optimized ligand 3d was found to catalyze the formation of 15 different (E)-allylic alcohols with enantioselectivities that ranged from 52 to 91% ee and yields that ranged from 40 to 90%. This ligand was especially effective for the reaction of aromatic aldehydes with vinylzinc reagents derived from bulky terminal alkynes. Ligand 3d catalyzed the addition of (E)-(3,3-dimethylbut-1-enyl)(ethyl)zinc to 2-naphthaldehyde to give (R,E)-4,4-dimethyl-1-(naphthalene-1-yl)pent-2-en-1-ol in 89% ee. The ee of this product could be increased to 97% through a single recrystallization.
Richmond
Meaghan L
ML
Department of Chemistry, Brown University, Providence, Rhode Island 02912, USA.
Sprout
Christopher M
CM
Seto
Christopher T
CT
D000447:Aldehydes / Q000737:chemistry*; D000577:Amides / Q000737:chemistry; D000596:Amino Acids / Q000737:chemistry*; D002219:Carbamates / Q000737:chemistry; D002384:Catalysis; D008024:Ligands; D015394:Molecular Structure; D011092:Polyethylene Glycols / Q000737:chemistry; D013237:Stereoisomerism; D014753:Vinyl Compounds / Q000737:chemistry*; D015032:Zinc / Q000737:chemistry*
D000447:Aldehydes; D000577:Amides; D000596:Amino Acids; D002219:Carbamates; D008024:Ligands; D014753:Vinyl Compounds; D011092:Polyethylene Glycols; D015032:Zinc