(S,S)-(+)-pseudoephedrine as chiral auxiliary in asymmetric aza-Michael reactions. Unexpected selectivity change when manipulating the structure of the auxiliary.
[reaction: see text] The asymmetric aza-Michael reaction of metal benzylamides to alpha,beta-unsaturated amides derived from the chiral amino alcohol (S,S)-(+)-pseudoephedrine has been studied in detail. A deep study of the most important experimental parameters (solvent, temperature, nucleophile structure, influence of additives) has been carried out, showing that the reaction usually proceeds with good yields and diastereoselectivities, although the experimental conditions have to be modified depending on the substitution pattern of the conjugate acceptor. Additionally, a very interesting facial selectivity inversion has been observed when manipulating the structure of the chiral auxiliary, which has allowed a diastereodivergent procedure to be set up for performing asymmetric aza-Michael reactions using the same chirality source. Finally, the adducts obtained in the asymmetric aza-Michael reaction have proven to be very versatile synthetic intermediates in the preparation of other interesting compounds such as beta-amino esters, gamma-amino alcohols, and beta-amino ketones in highly enantioenriched form.
Etxebarria
Juan
J
Departamento de Química Orgánica II, Facultad de Ciencia y Tecnología, Universidad del País Vasco/Euskal Herriko Unibertsitatea, Bilbao, Spain.
Vicario
Jose L
JL
Badia
Dolores
D
Carrillo
Luisa
L
Ruiz
Nerea
N
D000577:Amides / Q000737:chemistry; D000586:Amination; D000596:Amino Acids / Q000138:chemical synthesis / Q000737:chemistry; D000605:Amino Alcohols / Q000737:chemistry; D001372:Aza Compounds / Q000737:chemistry*; D001549:Benzamides / Q000737:chemistry; D004809:Ephedrine / Q000737:chemistry*; D004952:Esters / Q000737:chemistry; D007659:Ketones / Q000737:chemistry; D008094:Lithium / Q000737:chemistry; D015394:Molecular Structure; D013237:Stereoisomerism
D000577:Amides; D000596:Amino Acids; D000605:Amino Alcohols; D001372:Aza Compounds; D001549:Benzamides; D004952:Esters; D007659:Ketones; C037689:benzamide; D008094:Lithium; D004809:Ephedrine