Fluoride ion catalyzed alkylation of nucleic acid derivatives using trialkyl phosphates, dialkyl sulfates and alkyl methanesulfonates

Abstract

Trimethyl phosphate, dimethyl and diethyl sulfate and methyl and ethyl methanesulfonate all give high yields of alkylation on purines and pyrimidines in the presence of tetrabutylammonium fluoride. Trimethyl phosphate produces near quantitative yields of diesters of nucleic acids but gives virtually no triester formation. The alkyl sulfates produce very high yields of triesters of nucleic acids including cyclic phosphates while the alkyl methanesulfonates are intermediate in reactivity. It was observed that in the absence of fluoride ion the dialkylsulfates gave reasonable yields of thymidine monosulfates.

Fluoride ion as a base in organic synthesis

“…14 Previous methods for carrying out cyclizations of this type invariably relied on strongly alkaline media with resulting side reactions and often very low yields (typically 20-40 %). It is interesting to note that protic solvents and low polarity solvents diminished the product yields and that salts of anions other than fluoride such as tetrabutylammonium chloride or bromide failed to catalyze the cyclization.11 Indirect evidence of another type of TBAF-promoted cyclization was provided alongside the above results on hydantoin syntheses.11 When carbobenzoxy-u-phenylalanine methyl ester (64) was treated with TBAF, the only product isolated, in nearly quantitative yields, was the carbobenzoxy-oL-phenylalanine (65).…”

Synthesis and Reaction of Pyrimidine Nucleosides

“…(228) The preparation of 5-hydroxymethyl-2' -deoxyuridine 5'-phosphate labeled at the 5-hydroxymethyl carbon with 13C or 14C was accomplished by using the labeled styrene in the above reaction, followed by oxidative cleavage of the styrene function with osmium tetroxide-sodium perchlorate and successive borohydride reduction of the 5-formyl group. (229) The reaction of 5-chloromercuricytidines with methyl acrylate in the presence of Li2 PdCl 4 gave the 5-(E)-acrylate (78). Compound (78) was cyclized by photoisomerization to give 3-(0ribofuranosyl )-2,7 -dioxopyrido [2,4] pyrimidine (79).…”

“…(229) The reaction of 5-chloromercuricytidines with methyl acrylate in the presence of Li2 PdCl 4 gave the 5-(E)-acrylate (78). Compound (78) was cyclized by photoisomerization to give 3-(0ribofuranosyl )-2,7 -dioxopyrido [2,4] pyrimidine (79). (230.22'» 5-(E)-Carboxyvinyl-2'-deoxyuridine (80) was converted to 5-(E-2-bromovinyl )-2' -deoxyuridine (81), a very potent anti herpes agent, (231) by treatment with N-bromosuccinimide.…”

Simple and efficient anionic polymerization of N‐phenylmaleimide with fluorides as an initiator

“…Generally, fluoride anion catalyzed reactions via strong H bonding of the fluoride anion to the reactant protic molecule, with resulting enhancement of the nucleophilicity of the protic compound. Fluoride anion as a catalyst can assist many reactions such as alkylation and arylation of phenols, catechols, alcohols, and other compounds, esterification reactions, Michael addition reactions, aldol condensations, Knoevenagel reactions, intramolecular cyclization reactions, oxidations, nucleophilic fluorination reactions, multicomponent reactions, and some special polymerizations . Fluoride ion facilely breaks CSi and OSi bond to remove protecting groups .…”