Synthesis, reactions and structural features of monofluorinated cyclopropanecarboxylates

Abstract Monofluorinated cyclopropanecarboxylates are available in racemic or optically active form by transition metal-catalyzed reactions of vinylfluorides with diazoacetates. From α-fluorostyrene and tert-butyl diazoacetate in the presence of 2 mol% of an enantiopure bis(oxazoline) copper complex, a 81:19 mixture of tert-butyl trans- and cis-2-fluoro-2-phenylcyclopropanecarboxylates was obtained with high enantiomeric excess (ee) of 93 or 89%, respectively. The corresponding racemic ethylesters were used as starting materials for the synthesis of carboxamides, of the cis- and trans-isomers of analogues of tranylcypromine, an anti-depressive drug and several of its homologous fluorinated …

Stereoselective Synthesis of γ-Fluorinated α-Amino Acids Using 2-Hydroxy-3-pinanone as an Auxiliary

(+)-(S)-2-Amino-4-fluorobutanoic acid (5a) (> 96% ee), its α-methylated derivative (+)-(S)-5b (85% ee), and (−)-(S)-2-amino-4-fluoro-4-pentenoic acid (10) (81% ee) were synthesized by diastereoselective alkylation in the presence of LDA at low temperatures. Alkylation of (+)-(R,R,R)-2-hydroxy-3-pinanone based imines of glycine tert-butyl ester 1a or alanine isopropyl ester 1b with 1-bromo-2-fluoroethane (2) or 3-bromo-2-fluoropropene (7), respectively, followed by stepwise deprotection was used. The selectivity of the alkylation increased by lithium/magnesium exchange or for 1b also by addition of DMPU. Differences in the reactivity of enolate alkylations of enantiomerically pure or racemic…

ChemInform Abstract: Olefin Metathesis Reactions with Fluorinated Substrates, Catalysts, and Solvents

One-pot cross-enyne metathesis (CEYM)-Diels-Alder reaction of gem-difluoropropargylic alkynes.

Propargylic difluorides 1 were used as starting substrates in a combination of cross-enyne metathesis and Diels–Alder reactions. Thus, the reaction of 1 with ethylene in the presence of 2nd generation Hoveyda–Grubbs catalyst generates a diene moiety which in situ reacts with a wide variety of dienophiles giving rise to a small family of new fluorinated carbo- and heterocyclic derivatives in moderate to good yields. This is a complementary protocol to the one previously described by our research group, which involved the use of 1,7-octadiene as an internal source of ethylene.

ChemInform Abstract: Asymmetric Synthesis of Monofluorinated 1-Amino-1,2-dihydronaphthalene and 1,3-Amino Alcohol Derivatives.

Enantioenriched 1-amino-4-fluoro-1,2-dihydronaphthalene derivatives are accessed via two complementary synthetic strategies. The careful optimization of the reaction conditions required for the elimination step in one route has allowed both the identification of an anchimerically assisted reaction pathway and, more importantly, access to a divergent reaction pathway toward fluorinated 1,3-amino alcohols from a common intermediate just by adjusting the number of equivalents of base used.

Addition of Nucleophiles to Fluorinated Michael Acceptors

A series of nucleophiles, including primary and secondary amines, primary alcohols, and thiols, as well as diethyl malonate and nitromethane, were added to different fluorinated Michael acceptors including 2-fluoroalk-1-en-3-ones and 2-fluoro-1-phenylprop-2-en-1-one. The resulting beta-substituted afluoro ketones were isolated in 34-92 % yield, depending on the substrate and the nucleophile. The best yields were obtained with secondary amines and with p-methylthiophenol.

Asymmetric Synthesis of Monofluorinated 1-Amino-1,2-dihydronaphthalene and 1,3-Amino Alcohol Derivatives.

Enantioenriched 1-amino-4-fluoro-1,2-dihydronaphthalene derivatives are accessed via two complementary synthetic strategies. The careful optimization of the reaction conditions required for the elimination step in one route has allowed both the identification of an anchimerically assisted reaction pathway and, more importantly, access to a divergent reaction pathway toward fluorinated 1,3-amino alcohols from a common intermediate just by adjusting the number of equivalents of base used.

New indications for the potential involvement of C–F-bonds in hydrogen bonding

Abstract Solid state structures of a selection of 2-fluoro-2-phenylcyclopropane derivatives were examined by X-ray crystallography in order to identify short intermolecular contacts of C–F groups to H–X moieties (X=C, N). Particularly, several cis -configured fluorinated phenylcyclopropane derivatives showed extremely close intermolecular contacts. The shortest of such C–H⋯F–C-distances (2.17 A, C–F–H angle 162°) was found in (1 S ,2 R )-(2-fluoro-2-phenylcyclopropyl)methyl N -(4-bromophenyl)carbamate ( 8 ) and the closest N–H⋯F–C-interaction (2.01 A, C–F–H angle 167°) was found in (±)- cis -2-fluoro-2-phenylcyclopropyl carboxamide ( 4 ). Comparison of the structures of several of the fluor…

ChemInform Abstract: Addition of Nucleophiles to Fluorinated Michael Acceptors.

A series of nucleophiles, including primary and secondary amines, primary alcohols, and thiols, as well as diethyl malonate and nitromethane, were added to different fluorinated Michael acceptors including 2-fluoroalk-1-en-3-ones and 2-fluoro-1-phenylprop-2-en-1-one. The resulting β-substituted α-fluoro ketones were isolated in 34–92 % yield, depending on the substrate and the nucleophile. The best yields were obtained with secondary amines and with p-methylthiophenol.

Olefin metathesis reactions with fluorinated substrates, catalysts, and solvents.