Robert Filler

Further studies on the synthesis of α-fluoro carbonyl compounds [1]

Abstract The trimethylsilyl enol ethers of cycloalkanones and acid esters are converted in high yields (70–90%) to the corresponding α-fluoro carbonyl derivative using XeF 2 in CH 2 Cl 2 . Non-cyclic α-hydroxy ketones such as ethyl mandelate are efficiently transformed to the α-fluoro product by DAST and by Ishikawas reagent. Nucleophilic displacement of halogen by fluoride failed in cyclic systems, giving instead, α,β-unsaturated ketones in DMF or CH 3 CN (18-crown-6) and 1,2-diones in DMSO, with KF acting as a base. Attempts at DMSO oxidation of I(Br)F adducts failed to give the α-fluoro ketones, but resulted in dehydrohalogenation to the trans -vinyl fluorides.

New Developments in the Chemistry of Oxazolones

Publisher Summary This chapter considers the recently reported 2-oxazolin-5-ones and 3-oxazolin-5-ones. The classical Erlenmeyer synthesis of azlactones, which includes condensation of aldehydes with hippuric or aceturic acid in the presence of acetic anhydride and sodium acetate, is considered the most commonly used method for preparation of 2-oxazolin-5-ones. Other methods for synthesis include the use of polyphosphoric acid, from 5-oxazolonium perchlorates and other heterocycles and open-chain compounds. The chapter describes oxidation, cycloaddition, conversion into other heterocycles, hydrolysis, and photolysis. With regard to stereochemistry, the chapter describes optically active oxazolones and racemization and geometrical isomerism. Moreover, it illustrates the methods of preparation and reactions for 3-oxazolin-5-ones, 2-oxazolin-4-ones, 4-oxazolin-2-ones, and 3-oxazolin-2-ones, respectively and considers the nomenclature as per the chemical abstracts.

Fluorination of nitrogen-containing aromatics with xenon difluoride

Abstract Pyridine reacts with xenon difluoride to give a mixture of 2-fluoropyridine 3-fluoropyridine, and 2,6-difluoropyridine, while 8-hydroxyquinoline is converted to 5-fluoro-8-quinolinol. Aniline and benzylamine react vigorously with XeF2 to yield mixtures of monofluoro isomers derived from the parent amines.

Synthesis of polyfluoroaryl [2.2] cyclophanes

Abstract New and improved syntheses of 4,5,7,8-tetrafluoro- and 4,5,7,8,12,13,15,16-octafluoro[2.2]paracyclophanes are described. The preparation of the new compound, 4,5,7,8-tetrafluoro[2.2]metaparacyclophane, is outlined.

Recent Advances in Oxazolone Chemistry

Publisher Summary This chapter discusses the significant recent advances in oxazolone chemistry. Five different structures can be written for the oxazolones—namely, 5(4H)-oxazolone, 5(2H)-oxazolone, 4(5H)-oxazolone, 2(3H)-oxazolone, and 2(5H)-oxazolone. The methods of preparation of 2-oxazolin-5-ones [5(4H)-Oxazolone], the reactions related to it, and its stereochemistry are also reviewed in the chapter. The behavior of unsaturated azlactones with organometallic reagents has been described in the chapter. The 4-unsaturated-5-oxazolones provide convenient starting materials for the synthesis of several nitrogen-containing heterocyclic systems. The chapter also discusses the preparation of tetrazoles and isoquinolines and the isolation of several pairs of the geometric isomers of 4-unsaturated-5-oxazolones. The chemical properties of the pseudooxazolones depend to some extent on the type of substitution at the 2-position of the hetero ring; it is divided into two parts—(1) 2-arylidenepseudooxazolones and (2) 2-trifluoromethylpseudooxazolones.

Introduction of α-fluorophosphonomethyl ether functionality and its application to the synthesis of fluorinated acyclic phosphonate nucleosides

Abstract Introduction of the α-fluorophosphonomethyl ether functionality has been achieved by electrophilic fluorination of the corresponding phosphonomethyl ether carbanion. Coupling of the synthesized 2-[(diethoxyphosphono)fluoromethoxy]ethanol (9) with adenine and 6-chloropurine under Mitsunobu conditions afforded novel fluorinated acyclic phosphonate nucleosides 11a and 11b, respectively.

Synthesis of fluorovinylsalicylic acids and their derivatives

Abstract Palladium-catalyzed cross-coupling of lodosalicylic acid derivatives with polyfluorovinyl zinc reagents provided the corresponding fluorovinyl-substituted salicylates. Methyl-5-(β,β)-difluorovinyl methyl salicylate was prepared by a Wittig reaction of the 5-formyl compound with the strongly nucleophilic ylide. ((Et2N),P-CF2. In one sequence, a fluorine-free benzofuran was obtained, instead of a difluorovinyl-salicylate.

Reaction of ethyl 4,4,4-trifluoroacetoacetate enolate with 3-bromo-1,1,1-trifluoroacetone: synthesis of 2,4-bis (trifluoromethyl) furan

Abstract The potassium enolate of ethyl 4,4,4-trifluoroacetoacetate 1 reacts with 3-bromo-1,1,1-trifluoroacetone 2 in DMSO solution to yield three products. Ethyl 2,4-bis(trifluoromethyl)-4-hydroxydihydro-3-furoate 3 is generated via C-acylation. The hydrated trifluoromethyl ketone 4 is formed by O-alkylation and 4 reacts further with 2 to give the di-O-alkylated ketone hydrate 5 . Compound 3 undergoes dehydration to the furan derivative 6 on reaction with Ac 2 O-ZnCl 2 .

Stable mono-arenium ions of poly-fluorinated [2.2] paracyclophanes

Abstract Stable Monocations (σ-complexes) of tetrafluoro[2.2] paracyclophane and octafluoro[2.2] paracyclophane are generated by ipso protonation in superacid media and their NMR parameters are compared with the σ-complex of protonation of the parent [2.2] paracyclophane.

AN IMPROVED SYNTHESIS OF 9-[2-(DIETHOXYPHOSPHONOMETHOXY)ETHYL]ADENINE AND ITS ANALOGUES WITH OTHER PURINE BASES UTILIZING THE MITSUNOBU REACTION

Abstract Unprotected adenine, 6-chloropurine, 2.6-diaminopurine. and 2-amino-6-chluropurine have been directly coupled with 2-(diethoxyphosphonomethoxy)ethanol under Mitsunobu reaction conditions to provide acyclic phosphonate nucleotide analogues which are intermediates for antiviral agents such as PMEA.