An amino alcohol ligand for highly enantioselective addition of organozinc reagents to aldehydes: serendipity rules.
[reaction: see text] Amino alcohol 4 (or its enantiomer) is prepared in two simple steps. Commercial (1R,2S)-2-amino-1,2-diphenylethanol is dialkylated with bis(2-bromoethyl) ether. Subsequent hydrogenation over 5% Rh on alumina in the presence of morpholine unexpectedly stops at the hexahydro derivative 4. Amino alcohol 4 promotes the enantioselective addition of diethylzinc to aldehydes at room temperature in up to 99% enantiomeric excess.
Nugent
William A
WA
Bristol-Myers Squibb Company, Process Research and Development Department, Chambers Works, P.O. Box 269, Deepwater, New Jersey 08023-0269, USA. william.nugent@bms.com
D000447:Aldehydes / Q000737:chemistry; D000605:Amino Alcohols / Q000138:chemical synthesis* / Q000737:chemistry; D008024:Ligands; D009025:Morpholines / Q000737:chemistry; D009942:Organometallic Compounds / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D015032:Zinc / Q000737:chemistry
D000447:Aldehydes; D000605:Amino Alcohols; D008024:Ligands; D009025:Morpholines; D009942:Organometallic Compounds; C037574:morpholine; D015032:Zinc