C-5-Substituted Pyrimidine Nucleosides. 3. Reaction of Allylic Chlorides, Alcohols, and Acetates with Pyrimidine Nucleoside Derived Organopalladium Intermediates

Article abstract of DOI:10.1021/jo00320a039

The reaction of allylic chlorides with pyrimidine nucleoside derived organopalladium intermediates was investigated.The organopalladium intermediates were generated in situ by the reaction of 5-(chloromercuri)-2'-deoxyuridine (1), 5-(chloromercuri)cytidine, and 5-(chloromercuri)-2'-deoxycytidine with a catalytic amount of Li2PdCl4 in methanol.With allyl chloride, 1 gives principally 5-allyl-2'-deoxyuridine, some of which reacts further with 1 to give the cross-linked nucleosides (E)-5-<3-(2'-deoxyuridin-5-yl)-1-propen-1-yl>-2'-deoxyuridine (5) and5-<3-(2'-deoxyuridin-5-yl)-1-methoxyprop-1-yl>-2'-deoxyuridine (6). 3-Chloro-1-butene couples with 1 to give mainly (E)-5-(2-buten-1-yl)-2'-deoxyuridine (9) and lesser amounts of the Z isomer 10 and 5-(1-methyl-2-propen-1-yl)-2'-deoxyuridine (11).Nucleoside 11 appears to be the product of a coupling reaction between 1-methoxy-2-butene and the organopalladium intermediate derived from 1.Allylic chlorides are transformed to allyl methyl ethers in 0.1 M Li2PdCl4 at a slightly slower rate than the coupling reaction.Higher allylic chloride homologues show greater regioselectivity and stereoselectivity. 3-Chloro-1-pentene leads to (E)-5-(2-penten-1-yl)-2'-deoxyuridine (14) as the sole major product in 50percent yield.When a cyano group was attached to C-5 of 3-chloro-1-pentene, the resultant allylic chloride coupled regioselectivity but gave both cis and trans isomers.The mechanism of the coupling reaction is discussed and a basis for stereoselectivity proposed.Allylic alcohols and acetates couple more slowly and less cleanly, leading to lower yields of the same allylic-substituted pyrimidine nucleosides obtained with allylic chlorides.In some instances other products could be isolated.Nucleoside 1 and 3-hydroxy-4-methyl-1-pentene gave 5-(4-methyl-2-penten-1-yl)-2'-deoxyuridine (16) as well as 5-(4-methyl-3-oxopentyl)-2'-deoxyuridine (20). 3-Acetoxy-4-methyl-1-pentene led to (E)-5-(4-methyl-1,3-pentadien-1-yl)-2'-deoxyuridine (23).Mechanisms leading to these products are discussed.