Photoinduced Nonstabilized Azomethine Ylide Formation for the Preparation of Fluorine Containing Pyrrolidines.

A mild and reproducible method for the formation of a nonstabilized azomethine ylide was developed by photoinduced reaction catalyzed with eosin Y under green light irradiation. Resulting 1,3-dipole was trapped with fluoroalkenes, fluoroalkylated alkenes, and representative dipolarophiles to access pyrrolidine scaffolds, including spirocyclic compounds. The mechanism involved in this transformation was investigated, showing clearly a catalytic redox cycle with eosin Y.

Access to Fluoropyrrolidines by Intramolecular Aza-Michael Addition Reaction.

Study of the intramolecular aza-Michael addition reaction from an aminofluorovinylsulfone opens a new route for the synthesis of pyrrolidine derivatives. An unexpected diastereoselective cyclization reaction was observed, leading preferentially to the anti-N-benzylpyrrolidine sulfone. The resulting sulfone was reacted with aldehydes to access ß-substituted α-fluoroalkenyl pyrrolidines in one step.

Synthesis of fluorophosphonylated acyclic nucleotide analogues via copper(I)-catalyzed Huisgen 1-3 dipolar cycloaddition.

Preparation of several acyclonucleosides containing both a difluoromethylphosphonate group and a triazole moiety is described starting from a difluorophosphonosulfide. The key step of the synthesis involves a copper(I)-catalyzed Huisgen 1-3 dipolar cycloaddition between difluorophosphonylated azides and propargylated nucleobases derived from thymine and 2-amino-6-chloropurine.

Difluorophosphonylated Allylic Ether Moiety as a 2'-Modification of RNA-Type Molecules: Synthesis, Thermal, and Metabolic Studies.

The first synthesis of oligonucleotides incorporating URF, a uridine modified with a difluorophosphonylated allylic ether onto the 2'-position, is described. Fluorinated homouridylates and miR-342-3p analogues are efficiently prepared. UV-melting experiments and enzymatic degradation studies indicate this new series of fluorinated oligonucleotides exhibit good and thermal metabolic stability as well as an increased lipophilicity. Comparison with oligonucleotides containing 2'- O-allyluridine instead of URF reveals improvement of these chemical properties is related to the presence of the difluoromethylphosphonate group.

Modified Julia fluoroolefination: selective preparation of fluoroalkenoates.

The modified Julia olefination reaction has been applied to develop a stereoselective synthesis of fluoroalkenoate derivatives from a fluorobenzothiazolyl sulfone and aldehydes or a ketone. The olefination reaction can be achieved by using a variety of bases. DBU and DBU in the presence of MgBr2 were found to be the most efficient systems to prepare either (Z)- or (E)-alkenoates in moderate to excellent stereoselectivity.