Asymmetric synthesis of 4'-ethoxy-2',3'-didehydro-2',3'-dideoxynucleosides by palladium-catalyzed kinetic discrimination between the corresponding diastereoisomeric lactol acetates.
4'-Substituted nucleoside analogues have been synthesized using palladium-catalyzed asymmetric allylic amination conditions. A kinetic discrimination between the diastereomeric lactol acetates (3) produced the desired aminated products (6a-d) and recovered acetate (alpha-3) in high yields and <97:3 diastereoselectivity. Epimerization of the recovered lactol acetate (alpha-3) produced a 60:40 alpha/beta mixture of (3), which could be resubjected, in principle, to the palladium-catalyzed asymmetric allylic amination conditions.
Hegedus
Louis S
LS
Department of Chemistry, Colorado State University, Fort Collins 80523, USA. hegedus@lamar.colostate.edu
Hervert
Katherine L
KL
Matsui
Satoshi
S
D000085:Acetates / Q000737:chemistry*; D000225:Adenine / Q000737:chemistry; D000478:Alkylation; D002384:Catalysis; D002625:Chemistry, Organic / Q000379:methods*; D002855:Chromatography, Thin Layer; D003596:Cytosine / Q000737:chemistry; D015224:Dideoxynucleosides / Q000138:chemical synthesis* / Q000737:chemistry*; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry*; D013237:Stereoisomerism; D013941:Thymine / Q000737:chemistry; D014498:Uracil / Q000737:chemistry
D000085:Acetates; D015224:Dideoxynucleosides; D014498:Uracil; D010165:Palladium; D003596:Cytosine; D000225:Adenine; D013941:Thymine