Taizo Ono

The effect of substituents on the feasibility of azomethine-azomethine isomerization: New synthetic opportunities for biomimetic transamination

Abstract The azomethine-azomethine isomerization of the Schiff bases derived from fluoroalkyl carbonyl compounds and arylmethylamines has been studied as a function of substitution on the amine site. The present study indicates that regardless of the nature of the substitution, the position of the isomerization equilibrium is overwhelmingly controlled by the electron-withdrawing effect of the perfluoroalkyl group, while the reaction rate strongly dependsion both CH acidity and steric availability of the transferring proton. Specifically, we have found that the presence of electron-releasing substituent on the phenyl of the benzylamine site largely retards the isomerization of the corresponding imines. In contrary, azomethine-azomethine isomerizations of the imines derived from the benzylamines containing electron-withdrawing substituent on the phenyl ring or picolylamines, possessing electron-deficient pyridine ring, occur with remarkably higher reaction rates as compared with the established isomerizations of N -benzylimines. In particular, the use of 4-picolylamine allows for truly biomimetic one-stage transamination of fluorocarbonyl compounds to afford the Schiff bases of the corresponding amines. The exciting synthetic aspects of this finding are demonstrated by the improved procedure for transamination of certain fluoroalkyl carbonyl compounds representing aldehydes, ketones, and β-keto carboxylic acids.

Synthesis and biological activity of β-fluoroalkyl β-amino alcohols

Abstract This paper reviews the synthesis of unnatural chiral β-fluoroalkyl β-amino alcohols, with an emphasis on their biological activity and pharmaceutical applications.

Electrochemical fluorination of N-containing carboxylic acids Part 5. Fluorination of the methyl esters of cis-2,6-dimethylmorpholino-group substituted carboxylic acids

Abstract Cis -2,6-dimethylmorpholine and its derivatives having an ester group were subjected to electrochemical fluorination. The electrochemical fluorination of cis -2,6-dimethylmorpholine afforded only a small quantity of F -( N -fluoro-2,6-dimethyl-morpholine), whereas the N -(methoxycarbonylalkyl)-substituted cis -2,6-dimethyl-morpholines gave the corresponding F -acid fluorides in fair yields. Cis -and trans -isomerization on two methyl substituents of the morpholine ring occurred through electrochemical fluorination of pure cis -2,6-dimethylmorpholine to give a 1:0.25–0.5 mixture of cis - and trans -isomers having a F -2,6-dimethylmorpholino-moiety. The formation of a seven-membered ring expanded product was confirmed as a by-product in the fluorination of methyl cis -2,6-dimethylmorpholino-acetate. Spectroscopic data as well as physical properties of new nitrogen-containing F -carboxylic acids are presented.

Theoretical study of reaction of trifluoromethyl radical with hydroxyl and hydrogen radicals

Ab initio molecular orbital theory and density functional theory calculations have been carried out on the reactions of the trifluoromethyl radical with the hydroxyl and the hydrogen radicals. These reactions are key reactions that underlie a new fire extinguishing mechanism of non‐bromine‐containing halon replacements. The activation energies calculated by the MP2 and QCISD methods are in good agreement with the experimental values. The B3LYP, as well as MP2 and QCISD, give good results for the calculations of the heats of reactions. The GAUSSIAN‐1 and GAUSSIAN‐2 theory calculations present the most acxcurate results on both the activation energies and the heats of reactions. The effects of the scaling factors on the activation energies and the heats of reactions are also evaluated.u2003© 1998 John Wiley & Sons, Inc.u2003J Comput Chem 19: 277–289, 1998

Stereoselective Synthesis of Enantiomerically Pure β-Fluoroalkyl γ-Butyrolactones by Sulfoxide-Directed Lactonization

Enantiomerically pure α,α-dichloro β-fluoroalkyl γ-p-tolylthio γ-butyrolactones trans-6a–c have been obtained with excellent stereocontrol (> 98:2) and enantiomeric purity (> 98:2) by sulfoxide-directed lactonization (Marinos annu-lation reaction) of β-fluoroalkyl vinyl sulfoxides (R)-(E)-5a–c with dichloroketene. Highly chemoselective dechlorination and desulfurization reactions performed on trans-6c efficiently provided the β-chlorodifluoromethyl γ-butyrolactone (S)-8c, the absolute stereochemistry of which was determined by X-ray diffraction analysis of its γ-p-tolylthio precursor (2R,3S)-7c.

Electrochemical fluorination of (N,N-dialkylamino)alcohols

Abstract Series of amino alcohols including 2-( N,N -dialkylamino)ethanols, 3-( N,N -dimethylamino)propanol and 4-( N,N -dimethylamino)butanol were subjected to electrochemical fluorination. In the case of 2-( N,N -dialkylamino)ethanols, the F -(2- N,N -dialkylamino)acetyl fluorides were obtained in fair to good yields. Yields of each target compound were strongly dependent on the kind of the dialkylamino group. Cyclic amines having an N -(2-hydroxylethyl) group afforded the corresponding F -[ N -( c -alkylamino)-substituted acetyl fluorides]. Their yields were generally better than those of acyclic analogs. Several 2-( N,N -dialkylamino)ethanols and 3-( N,N -dimethylamino)propanol were converted into the corresponding trimethylsilylethers, aminoalkyl methyl carbonates and bis-aminoalkyl carbonate, respectively, and they were subjected to fluorination for a comparison of the yield with that obtained from that of the parent aminoalcohol.

PERSISTENT PERFLUOROALKYL RADICAL INVESTIGATIONS UNDER REDUCTIVE ENVIRONMENT : REACTION WITH ELECTRON-DONATING REAGENTS

Abstract The reactivity of persistent perfluoroalkyl radical, perfluoro-3-ethyl-2,4-dimethyl-3-pentyl ( 1 ), with various electron-donating reagents was investigated. It is revealed that 1 which is robust under oxidative conditions is rather vulnerable under reductive conditions. Thus, Lewis bases such as triethylamine and triphenylpnictogens (Ph 3 Pn, Pn=N, P, As, Sb, Bi) and some soft anions such as iodide or tetraphenyl borate reacted with 1 to give perfluoro-3-isopropyl-4-methylpent-2-ene ( 2 ) quantitatively. Even very weak Lewis bases such as diethyl ether and diethylsulfide also reacted with 1 to give 2 and additionally a hydrido product, perfluoro-3-ethyl-3- H -2,4-dimethylpentane ( 4 ). Hydrogen gas did not react with 1 at all without a catalyst, but in the presence of metal Pd adsorbed on charcoal, smoothly reacted to give 2 in quantitative yield. Metal hydrides such as LiAlH 4 , NaBH 4 , NaH, BH 3 (THF complex), Bu 3 SnH, Me 2 PhSiH reacted with 1 to give 2 and 4 . That an electron transfer mechanism is operating in the formation of 2 is obvious, but not conclusive in the formation of 4 .

Inhibition of Combustion by Bromine-Free Polyfluorocarbons 2. Burning Velocities of Methane and n-Heptane Flames with Polyfluorocarbons Containing Oxygen, Nitrogen, or Sulfur

Abstract To estimate the inhibition effect of some polyfluorocarbons containing N, O, or S atoms such as (CF3)3N, (CF3)2NCF2H, (C2F5)2O, CF3SF5, and C2F5SF5 on flame propagation, the laminar burning velocity was measured for mixtures of 9.50 vol% methane, 90.00 vol% air, and 0.50vol% inhibitor and of 1.87 vol% n-heptane, 97.63 vol% air, and 0.50vol% inhibitor. The five compounds have higher ability as fire suppressants than CF3CHFCF3 and CF3H, which have already been put to practical use.

Reactions of perfluorocycloimines with (polyfluoroalkoxy)trimethylsilanes and polyfluoroalkyltrifluoromethanesulfonates

Abstract The reactions of F -(5,6-dihydro-2 H -1,4-oxazine) and F -(3,4-dihydro-2 H -pyrrole) were investigated using two series of reagents: one is the polyfluoroalkylating agent RfOSO 2 CF 3 and the other is the (polyfluoroalkoxy)trimethylsilane RfOSi(CH 3 ) 3 . Systematic study with polyfluoroalkyl groups such as CF 3 CH 2 , C 2 F 5 CH 2 , CHF 2 CH 2 , and (CF 3 ) 2 CH revealed that the regio-chemistry, isomer distribution, product distribution between mono-, di-, and tri-substituted products and even the reaction pathways were subtly changed by the structure of these fluoro substituents as well as by the reagent stoichiometry. A notable substitution effect was found in the reaction of F -(5,6-dihydro-2 H -1,4-oxazine): substitution at the 3-position prevented the N -polyfluoroalkylation by CF 3 CH 2 OSO 2 CF 3 . No particular difference was found between the two different heterocyclic systems in contrast with the reaction of these heterocyclic systems with C 6 F 5 Si(CH 3 ) 3 . The discussion about the reaction mechanisms for both reagents are included.

Synthesis of 2-Fluoro Analogues of Frontalin

The synthesis of enantiomerically and diastereomerically pure (−)-(1R,2R,5R)- and (−)-(1R,2S,5R)-2-fluoro frontalin (7) starting from (+)-(1S)-menthyl-(R)-toluene-4-sulfinate, methylmagnesium bromide, methyl fluoroacetate, 4-pentenyl bromide and diazomethane is described. The absolute stereochemistry was unambiguously determined by X-ray analysis of (+)-(1S,2R,5S,RS)-5, an intermediate in the synthesis of the enantiomeric (+)-(1S,2R,5S)-2-fluoro frontalin (7).