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The syntheses of fluorinated cyclopentanone derivatives, which have pharmaceutical and agrochemical importance are reported. The catalytic reaction of copper(I) and nickel(II) difluorocarbenes with silyl dienol ethers afforded 4,4-difluoro- and 5,5-difluorocyclopent-1-en-1-yl silyl ethers, respectively. The fluorine-directed and -activated Nazarov cyclization of 1-fluorovinyl vinyl ketones, which were prepared from silyl dienol ethers and free difluorocarbene, proceeded efficiently to afford 2-fluorocyclopent-2-en-1-ones. Moreover, fluorine-­directed Nazarov cyclizations of 2,2-difluorovinyl vinyl ketones and 1-(trifluoromethyl)vinyl vinyl ketones afforded 3-fluorocyclopent-2-en-1-ones and 5-(trifluoromethyl)cyclopent-2-en-1-ones, respectively. In addition, derivatization of ring-difluorinated products also provided 3-fluorocyclopent-2-en-1-ones.

application/pdf, Disfavored 5-endo-trig cyclizations were achieved in 2-trifluoromethyl-1-alkenes with a nucleophilic nitrogen, oxygen, sulfur, or carbon atom through 1) intramolecular SN2 reaction with loss of a fluoride ion or 2) intramolecular nucleophilic addition to the vinylic group. This reaction manifold provides a versatile method for the synthesis of indolines, indoles, pyrrolidines, tetrahydrofurans, 2,3-dihydrobenzo[b]thiophenes, tetrahydrothiophenes, and cyclopentanes that bear a fluorinated one-carbon unit such as a difluoromethylene, difluoromethyl, or trifluoromethyl group.

o-Formyl-substituted beta,beta-difluorostyrenes readily react with NH(2)OH.HCl or NH(4)OAc to afford 3-fluoroisoquinoline derivatives in good yield via (i) the formation of the corresponding oximes or imines and (ii) subsequent intramolecular replacement of a vinylic fluorine by the sp(2) nitrogen of the iminomethyl group (HON=CH- or HN=CH-). Beta,beta-Difluorostyrenes bearing an o-diazenyl group (HN=N-), generated by reduction of the corresponding diazonium ions, undergo a similar substitution to afford 3-fluorinated cinnolines.

N-[3-(Trifluoromethyl)homoallyl]sulfonamides, prepared via ring opening of (S)-glycidyl ethers or 2-aryloxiranes with 1-(trifluoromethyl)vinyllithium, underwent intramolecular addition or S(N)2'-type reaction in the normally disfavored 5-endo-trig fashion, leading to 2-substituted 4-(trifluoromethyl)- or 4-(difluoromethylene)pyrrolidines. Both alpha- and beta-face-selective hydrogenation of the 4-difluoromethylene group afforded syn- and anti-4-(difluoromethyl)pyrrolidines, respectively. These sequences, followed by the oxidation of a 2-hydroxymethyl or 2-aryl group, successfully provided prolines with a trifluoromethyl, difluoromethylene, or difluoromethyl group at the 4-position, including optically active prolines.

Introduction of a 1-(trifluoromethyl)vinyl group has been accomplished by the reaction of thermally unstable 1-(trifluoromethyl)vinyllithium (1) with strained cyclic ethers. Treatment of 2-bromo-3.3.3-trifluoropropene with butyllithium generates 1. which in turn reacts with several oxiranes or an oxetane at -100 °C in the presence of BF 3 .OEt 2 to afford the corresponding 2-trifluoromethyl- -1-alkenes bearing a hydroxy group on the 4- or 5-position. An enantiopure oxirane undergoes ring-opening without racemization. providing an optically active homoallyllic alcohol with a 3-trifluoromethyl group.

Two protocols are developed for the synthesis of (trifluoromethyl)vinyl compounds by rapid and slow lithium halogen exchange processes generating thermally unstable vinyllithium compounds.

1-(Trifluoromethyl)vinylation is accomplished in two protocols by the in situ generation of thermally unstable 3,3,3-trifluoroprop-1-en-2-yllithium (1): 1) a rapid lithium-halogen-exchange reaction of 2-bromo-3,3,3-trifluoroprop-1-ene (2) takes effect with sec-BuLi at -105 degrees C to generate vinyllithium 1, which reacts with more reactive electrophiles, such as aldehydes and N-tosylimines before its decomposition, to afford 2-(trifluoromethyl)allyl alcohols and N-[2-(trifluoromethyl)allyl] sulfoamides in good yield; 2) treatment of 2 with nBuLi at -100 degrees C causes a slow lithium-halogen exchange of 2, which gives rise to a mixture of 1 and nBuLi. Vinyllithium 1 is preferentially trapped with less reactive electrophiles, such as N,N-dimethylamides in the presence of BF(3)OEt(2), to afford 1-(trifluoromethyl)vinyl ketones in good yield. Versatility of the products toward syntheses of CF(3)-containing ring-fused cyclopentenones is also demonstrated by the Pauson-Khand reaction and the Nazarov cyclization.

Disfavored 5-endo-trig cyclizations were achieved in 2-trifluoromethyl-1-alkenes with a nucleophilic nitrogen, oxygen, sulfur, or carbon atom through 1) intramolecular S(N)2' reaction with loss of a fluoride ion or 2) intramolecular nucleophilic addition to the vinylic group. This reaction manifold provides a versatile method for the synthesis of indolines, indoles, pyrrolidines, tetrahydrofurans, 2,3-dihydrobenzo[b]thiophenes, tetrahydrothiophenes, and cyclopentanes that bear a fluorinated one-carbon unit such as a difluoromethylene, difluoromethyl, or trifluoromethyl group.

On treatment with sec-BuLi at −105 °C, 2-bromo-3,3,3-trifluoropropene undergoes rapid lithium–halogen exchange to generate thermally unstable 1-(trifluoromethyl)vinyllithium, which reacts with N-to...

2-(Trifluoromethyl)allyl ketone O-pentafluorobenzoyloximes undergo a palladium-catalyzed 5-endo mode of alkene insertion via oxidative addition of the N-O bond, followed by beta-fluorine elimination to produce 4-difluoromethylene-1-pyrrolines.

o-(1,1-Difluorhex-1-en-2-yl)aniline o′-(1,1-Difluorohex-1-en-2-yl)-p-toluenesulfonanilide 3-Butyl-2-fluoro-1-tosylindole 2,2,2-Trifluoroethyl p-toluenesulfonate Trimethylamine oxide Tetrabutylammonium fluoride o-Iodoaniline Triphenylphosphine Tris(dibenzylideneacetone)dipalladium(0)-chloroform (1/1) Keywords: 5-endo-trig-cyclization; 1,1,-difluoro-1-alkenes; butyl-fluoro-tosylindole; intramolecular substitution; five-membered rings; Baldwin's rules; 2,2-difluorovinylboranes; difluorostyrenes; waste disposal

A variety of phosphorus(V) octaethylporphyrin derivatives of the type [P(OEP)(X)(Y)](+)Z(-) (OEP: octaethylporphyrin) (X = CH(3), CH(2)CH(3), C(6)H(5), F; Y = CH(3), CH(2)CH(3), OH, OCH(3), OCH(2)CH(3), On-Pr, Oi-Pr, Osec-Bu, NHBu, NEt(2), Cl, F, O(-); Z = ClO(4), PF(6)) were prepared. X-ray crystallographic analysis of eleven compounds reveals that the degree of ruffling of the porphyrin core becomes greater and the average P-N bond distance becomes shorter as the axial ligands become more electronegative. Therefore, the electronic effect of the axial substituents plays a major role in determining the degree of ruffling although the steric effect of the substituents plays some role. A comparison of the (1)H NMR chemical shifts for the series of [P(OEP)(CH(2)CH(3))(Y)](+)Z(-) complexes with those of the corresponding arsenic porphyrins, which possess a planar core, indicates a much smaller ring current effect of the porphyrin core in the severely ruffled phosphorus porphyrins. The electrochemistry, spectroelectrochemistry and ESR spectroscopy of the singly reduced compounds are also discussed. The OH protons of [P(OEP)(X)(OH)](+) are acidic enough to generate P(OEP)(X)(O) by treatment with aq dilute NaOH. X-ray analysis of P(OEP)(CH(2)CH(3))(O) reveals that the PO bond length is very short (1.475(7) A) and is comparable to that in triphenylphosphine oxide (1.483 A). The features of the quite unique hexacoordinate hypervalent compounds are investigated by density functional calculation of a model (Por)P(CH(2)CH(3))(O) and (Por)P(F)(O) (Por: unsubstituted porphyrin).

On treatment with sec-BuLi at −105 °C, 2-bromo-3,3,3-trifluoropropene undergoes rapid lithium–halogen exchange to generate thermally unstable 1-(trifluoromethyl)vinyllithium, which reacts with N-to...

µ-Oxo-bridged group 15 element–aluminium heterodinuclear porphyrins, [(oep)(Me)M–O–Al(oep)]ClO 4 (M=P, As, Sb), are synthesized by the reaction of [(oep)(Me)M(OH)]- ClO 4 with (oep)AlMe.

[(oep)As(OH)2]ClO4 is synthesized in good yields by non-nucleophilic oxidative treatment of (oep)AsCl with pyridinium tribromide followed by hydrolysis and is converted to [(oep)AsMe(OH)]ClO4 with AlMe3.