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Novel and Efficient Synthesis of gem ‐Difluorinated Derivatives of Acyclic Nucleoside Phosphonates (ANPs)
Author(s) -
Pomeisl Karel,
Beier Petr,
Pohl Radek,
Krečmerová Marcela
Publication year - 2016
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.201600445
Subject(s) - chemistry , reagent , nucleophile , combinatorial chemistry , nucleoside , organic chemistry , stereochemistry , catalysis
A novel efficient method for the synthesis of gem ‐difluorinated derivatives of acyclic nucleotide analogues has been developed. The method is based on utilization of diethyl difluoromethylphosphonate as a nucleophilic difluoromethylation reagent. In contrast to previous difluoromethylation procedures using commercially available DAST or deoxofluor, this process is very robust, proceeds under mild conditions and is accompanied only by small amounts of by‐products. The reaction of diethyl difluoromethylphosphonate with 2‐benzyloxyacetaldehyde afforded 3‐(benzyloxy)‐1,1‐difluoropropan‐2‐ol ( 6 ) a key precursor for syntheses of difluoromethylated analogues of various acyclic nucleoside phosphonates.