Bis(oxazoline) Lewis acid catalyzed aldol reactions of pyridine N-oxide aldehydes--synthesis of optically active 2-(1-hydroxyalkyl)pyridine derivatives: development, scope, and total synthesis of an indolizine alkaloid.
A new, short, and simplified procedure for the synthesis of optically active pyridine derivatives from pro-chiral pyridine-N-oxides is presented. The catalytic and asymmetric Mukaiyama aldol reaction between ketene silyl acetals and 1-oxypyridine-2-carbaldehyde derivatives catalyzed by chiral copper(II)-bis(oxazoline) complexes gave optically active 2-(hydroxyalkyl)- and 2-(anti-1,2-dihydroxyalkyl)pyridine derivatives in good yields and diastereoselectivities, and in excellent enantioselectivities-up to 99 % enantiomeric excess. As a synthetic application of the developed method, a full account for the asymmetric total synthesis of a nonnatural indolizine alkaloid is provided.
Danish National Research Foundation, Center for Catalysis, Department of Chemistry, Aarhus University, 8000 Aarhus C, Denmark.
Aitor
A
Landa
Anna
A
Minkkilä
Gonzalo
G
Blay
Karl Anker
KA
Jørgensen
D000143:Acids / Q000737:chemistry; D000447:Aldehydes; D000470:Alkaloids / Q000138:chemical synthesis / Q000737:chemistry*; D002384:Catalysis; D002621:Chemistry / Q000379:methods*; D003497:Cyclic N-Oxides / Q000138:chemical synthesis / Q000737:chemistry*; D007212:Indolizines / Q000737:chemistry*; D055095:Optics and Photonics; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry*; D013237:Stereoisomerism
D000143:Acids; D000447:Aldehydes; D000470:Alkaloids; D003497:Cyclic N-Oxides; D007212:Indolizines; D011725:Pyridines; C035094:indolizine; C116609:3-hydroxybutanal; C023666:pyridine