Asymmetric synthesis of oxygen heterocycles via Pd-catalyzed dynamic kinetic asymmetric transformations: application to nucleosides.
Racemic butadiene and isoprene monoepoxide react with unsaturated alcohols in the presence of a chiral palladium catalyst and a boron co-catalyst to give 3-alkoxy-4-hydroxy-1-butene and 3-alkoxy-4-hydroxy-3-methyl-1-butene, respectively, with excellent regio- and enantioselectivity in a dynamic kinetic asymmetric transformation whereby both enantiomers of the starting epoxides provide the same enantiomeric product. In the case of 2-phenylbutadiene monoepoxide, easily available from phenacyl chloride and vinylmagnesium bromide, the reaction proceeds by kinetic resolution. A model to rationalize the result is presented. The bis-olefin products are ideal substrates for the Ru catalyzed ring closing metathesis. In this way, five-, six-, and seven-membered oxygen heterocycles are readily available enantiomerically pure. The value of this very simple two step process is demonstrated by the use of the five-membered ring heterocycles to form unnatural and unusual nucleosides that cannot be easily accessed by other means. The sequence involves a Ru catalyzed isomerization of the initial 2,5-dihydrofuran to a 2,3-dihydrofuran followed by a selenium promoted addition of a pyrimidine or purine base. One advantage of this strategy is the easy access to either enantiomeric series, both of which have important biological applications.
D000438:Alcohols / Q000138:chemical synthesis / Q000737:chemistry; D002384:Catalysis; D003500:Cyclization; D004852:Epoxy Compounds / Q000138:chemical synthesis / Q000737:chemistry; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D007700:Kinetics; D008956:Models, Chemical; D015394:Molecular Structure; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry; D009942:Organometallic Compounds / Q000737:chemistry; D010100:Oxygen / Q000737:chemistry*; D010165:Palladium / Q000737:chemistry*; D012428:Ruthenium / Q000737:chemistry; D013237:Stereoisomerism
D000438:Alcohols; D004852:Epoxy Compounds; D006571:Heterocyclic Compounds; D009705:Nucleosides; D009942:Organometallic Compounds; D010165:Palladium; D012428:Ruthenium; D010100:Oxygen