Enantioselective, organocatalytic oxy-michael addition to gamma/delta-hydroxy-alpha,beta-enones: boronate-amine complexes as chiral hydroxide synthons.
An organocatalytic, enantioselective oxy-Michael addition to achiral gamma- and delta-hydroxy-alpha,beta-enones was developed. The key transformation is an unprecedented, asymmetric conjugate addition triggered by complexation between an in situ generated boronic acid hemiester and a chiral amine catalyst. Functionally, the intermediate amine-boronate complex acts as a chiral hydroxide surrogate or synthon. The resultant chiral beta-hydroxy-ketones are obtained in good to excellent yields and high ee following mild oxidative removal of the cyclic boronate. Natural products (R,12Z,15Z)-2-hydroxy-4-oxohenicosa-12,15-dienyl acetate and (+)-(S)-streptenol A were synthesized to demonstrate the utility of this reaction.
Li
De Run
de R
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390.
Murugan
Andiappan
A
Falck
J R
JR
D000588:Amines / Q000737:chemistry*; D001897:Boronic Acids / Q000737:chemistry*; D002384:Catalysis; D006878:Hydroxides; D007659:Ketones / Q000138:chemical synthesis*; D013237:Stereoisomerism
D000588:Amines; D001897:Boronic Acids; D006878:Hydroxides; D007659:Ketones