4-alkyl(aryl)-1-germacyclohexa-2,5-diene

enThe 1(Z),4(Z)-1,5-dilithium-3R-3-methoxypenta-1,4-dienes react with diaryldichlorogermanes and dialkyldichlorogermanes to give the 1,1-diaryl- and 1,1-dialkyl-4R-4-methoxy-1-germacyclohexa-2,5-dienes, respectively.With phenyltrichlorogermane, methyl- and ethyl-trichlorogermanes the E/Z-isomeric 1-phenyl(methyl,ethyl)-1-chloro-4R-4-methoxy-1-germacyclohexa-1,3-dienes are obtained, reduction of these with LiAlH₄ makes the corresponding 1-aryl-(alkyl)-1H-4R-4-methoxy-1-germacyclohexa-2,5-dienes available.Reduction of 1-ethyl-1-chloro-4-phenyl-4-methoxy-1-germacyclohexa-2,5-diene with LiAlH₄ yields by additional ether cleavage 1-ethyl-1H-4-phenyl-1-germacyclohexa-2,4-diene.The ¹H NMR (60 MHz, 90 MHz), ¹³C NMR, IR and mass spectra are discussed, several ¹H NMR spectra are calculated according to the LAOCOONLAME program.     

A facile and stereoselective synthetic method for allylic 1,3-dienyl ethers

The 1,4-elimination reaction of 1-allyloxy-4-methoxy-(2Z)-alkenes with n-butyllithium is shown to proceed in a marked preference to the [2,3] Wittig rearrangement to afford the allylic (1Z,3E)-dienyl ethers in high stereoselectivities. The synthetic utility of this method is demonstrated by the Claisen rearrangement of the dienyl ethers thus obtained.     

Synthese und chemie von 4R-silacyclohexa-2,5-dienen und 4R-silacyclohexa-2,4-dienen

The 1(Z),4(Z)-1,5-dilithium-3R-3-methoxypenta-1,4-dienes, available by cleavage of 1,1-di-n-butyl-4R-4-methoxy-1-stannacyclohexane-2,5-dienes with n-BuLi in ether, react with dichlorosilanes (R′R″ SiCl₂; R′, R″ = H, alkyl, aryl, alkoxy) to give 1R′,1R″,4R-4-methoxy-1-silacyclohexa-2,5-dienes.Claevage of the ether group with BBr₃, BCl₃ or PCl₃ gives 6-chloro(bromo)-1-silacyclohexa-2,4-dienes or 1,5-dichloro-1-silacyclohexane-2,4-dienes, respectively.Ether cleavage of 4R-4-methoxy-1-silacyclohexa-2,5-dienes with sodium results in the formation of 4R-1-silacyclohexadienyl anions, which can be hydrolyzed to give 1-silacyclohexa-2,4-dienes which reach further with trichloromethylsilane to give 6-trimethylsilyl-1-silacyclohexa-2,4-dienes.Phase transfer-catalyzed conversion of 1-chlorosilacyclohexadienes into the fluoro derivatives as well as further substitution reactions of 1-chlorosilacyclohexadienes are described.The ¹H NMR, ¹³C NMR, IR and mass spectra of the silacyclohexadienes are discussed.     

A facile method for the stereoselective preparation of (1E,3E)-4-substituted-1-amino-1,3-dienes via 1,4-elimination

The 1,4-elimination reaction of 1-amino-4-methoxy-(2Z)-alkenes is shown to proceed with high (1E,3E)-stereoselectivities to afford the corresponding 4-substituted-1-amino-1,3-dienes in good yield. The scope and stereochemical features of the synthetic method are described.     

Rearrangement of benzylsulfanyl-substituted 2-aza-1,3,5-triene into 5-phenyl-4,5-dihydro-1,3-thiazole in the t-BuOK-THF-DMSO system

Benzylsulfanyl-substituted 2-aza-1,3,5-triene prepared according to one-pot procedure from methoxyallene, isopropyl isothiocyanate, and benzyl bromide underwent unexpected rearrangement in the superbasic t-BuOK-THF-DMSO system with formation of 2-[(Z)-1-methoxyprop-1-en-1-yl]-4,4-dimethyl-5-phenyl-4,5-dihydro-1,3-thiazole via α-deprotonation of the benzylsulfanyl substituent, followed by intramolecular [1,5]-cyclization. Concurrent deprotonation of methyl group in the ketone imine fragment and subsequent [1,7]-electrocyclization of the resulting azatriene carbanion afforded 2-(benzylsulfanyl)-3-methoxy-7-methyl-4,5-dihydro-3H-azepine and 6-methoxy-2-methyl-3H-azepine.     

Towards synthesis of kavalactone derivatives

Kavalactone derivatives were synthesized using a Heck reaction of the 4-methoxy-6-vinyl-5,6-dihydropyran-2-one with aryl iodides. The Suzuki-Miyaura reaction of an aryl boronic acid and (Z)-4-methoxy-6-(2-iodovinyl)-5,6-dihydropyran-2-one has also been successfully used to produce both Z and E isomers of lactones.     

BOTPPI, a new Wittig salt for the synthesis of 12-(S)-hydroxy-eicosatetraenoic acid [12-(S)-HETE]

An efficient route to (Z)-(8-benzyloxy-8-oxooct-3-en-1-yl)triphenylphosphonium iodide, or BOTPPI, is disclosed, complete with full experimental details, NMR spectra, and HRMS data. BOTPPI serves as a surrogate for (Z)-(8-methoxy-8-oxooct-3-en-1-yl)triphenylphosphonium iodide, or MOTPPI, a Wittig salt previously used in two 12-HETE syntheses. BOTPPI has the advantage over MOTPPI of being derived from a sequence for which every intermediate is UV-active and amenable to large-scale chromatographic purification. A formal asymmetric total synthesis of 12-(S)-HETE is also reported, involving a stereoselective phase-transfer catalyzed (PTC) alkylation in its key step.     

Oxidative degradation of eicosapentaenoic acid into polyunsaturated aldehydes

Eicosapentaenoic acid is converted in good overall yield to an α,β-ethylenic epoxide derivative. The oxidative cleavage of the epoxide ring with periodic acid in ether proceeded in part with acid-catalyzed rearrangement of the vinyl epoxide moiety prior to cleavage. Among the products were 2E- and 2Z, 5Z, 8Z, 11Z-tetradecatetraenal, 4-hydroxy-2E,6Z,9Z,12Z-pentadecatetraenal and (all-Z)-2-methoxy-3,6,9,12-pentadecatetraenal.     

Crystal and molecular structures of the potassium salt of 2-methoxy-4-dimethylamino-6-dinitromethyl-1,3,5-triazine

The X-ray diffraction study of the potassium salt of 2-methoxy-4-dimethylamino-6-dinitromethyl-1,3,5-triazine is carried out. The crystals are triclinic; C₇H₉N₆O ₅ ^? ·2K⁺·2H₂O; a = 7.645(7) Å, b = 8.230(7) Å, c = 12.435(9) Å; α = 99.99(8)°, β = 91.52(7)°, γ = 113.86(8)°; V = 701(1) ų, ρ_calc = 1.58 g/cm³, Z = 2, space group P-1. The compound crystallizes as a crystalline hydrate with two water molecules. Two planar fragments of dinitromethyl and 2-methoxy-4-dimethylamino-1,3,5-triazine construct the anion. Their geometrical parameters are explored. The coordination of potassium cations and numerous hydrogen bonds are found which result in the development of a complex 3-D framework.     

Solid-state Structures for 2-Methoxy-1,3-xylyl-18-crown-5 and 2-Methoxy-1, 3-xylyl-21-crown-6: A Search for C–H···O Interactions

Solid-state structures have been determined for 2-methoxy-1,3-xylyl-18-crown-5 (4) (monoclinic, P2₁/n, a = 11.361(3) Å, b = 8.352(3) Å, c = 18.627(4) Å, β = 91.05(2)°, Z = 4) and 2-methoxy-1,3-xylyl-21-crown-6 (5) (monoclinic, Pc, a = 9.996(2) Å, b = 11.321(2) Å, c = 8.642(2) Å, β = 100.095(4)^o, Z = 2). In both molecules, the aromatic units are tilted with respect to the polyether ring and the methoxyl methyl hydrogens are oriented toward ether oxygen atoms of the rings. The interatomic distances, particularly the H···O distance and angles provide important information regarding the strength of the C–H···O interactions.     

Synthesis of naturally occurring diene and trienes by Te/Li exchange on (1Z,3Z)-butyltelluro-4-methoxy-1,3-butadiene

(1Z,3Z)-Butyltelluro-4-methoxy-1,3-butadiene 2 was obtained by the hydrotelluration of (Z)-1-methoxy-but-1-en-3-ynes 1. The butadienyllithium 3 obtained by the Te/Li exchange reaction in the (1Z,3Z)-1-butyltelluro-4-methoxy-1,3-butadiene 2 reacted with aldehydes to form the corresponding alcohols 4a-d with total retention of configuration. The alcohols formed undergo hydrolysis, resulting in the α,β,γ,δ-unsaturated aldehydes of (E,E) configuration, which are precursors of trienes obtained from natural sources. The products of this reaction were employed in the synthesis of methyl-(2E,4E)-decadienoate 7, which is a component of the flavor principles of ripe Bartlett pears. Performing the Wittig reaction of the methyl triphenylphosphorane with the deca-(2E,4E)-dienal 5a, we were able to synthesize the undeca-(1,3E,5E)-triene 6a. This compound is a sex-pheromone component of the marine brown algae Fucus serratus, Dictyopteris plagiograma, and Dictyopteris australis. Performing the Wittig reaction of methyl triphenylphosphorane with the octa-(2E,4E)-dienal 5c, the nona-(1,3E,5E)-triene 6b was synthesized. The compound obtained is a sex-pheromone component of the marine brown alga Sargassum horneri. The octa-(1,3E,5E)-triene 6c was easily obtained from hepta-(2E,4E)-dienal 5d by the Wittig reaction with methyl triphenylphophorane. This compound is a sex-pheromone component of the marine brown alga Fucus serratus.     

Heck reaction with 3-fluoro-3-buten-2-one

3-Fluoro-3-buten-2-one (2) is readily prepared from 1-fluoro-1-chloro-2-methoxy-2-methylcyclopropane (1) in 82% yield by heating the cyclopropane in aqueous quinoline solution. Ketone 2 reacts with aryl iodides (3) in a Heck reaction catalyzed by Pd(OAc)₂ to give Z-3-fluorobenzalacetones (4) in 36-86% yield.     

Asymmetric syntheses of 3,4-syn- and 3,4-anti-3-substituted-4-aminopiperidin-2-ones: application to the asymmetric synthesis of (+)-(3S,4R)-cisapride

The conjugate addition of lithium (R)-N-benzyl-N-(α-methylbenzyl)amide to δ-(N-allylamino)-α,β-unsaturated esters, followed by N-deallylation and cyclisation of the resultant β,δ-diamino esters, gives the corresponding 4-aminopiperidin-2-ones as single diastereoisomers (>99:1 dr). Subsequent deprotonation with LiHMDS and functionalisation of the resultant lithium enolate gives 3,4-anti-3-substituted-4-aminopiperidin-2-ones in >99:1 dr. Alternatively, in situ oxidation of the intermediate lithium (Z)-β-amino enolates formed upon conjugate addition gives α-hydroxy-β,δ-diamino esters, which after N-deallylation and cyclisation gives the corresponding 3,4-syn-3-hydroxy-4-aminopiperidin-2-ones in >99:1 dr. The utility of this methodology was successfully demonstrated in a concise asymmetric synthesis of the gastroprokinetic agent (+)-(3S,4R)-cisapride {(+)-(3S,4R)-N(1)-[3′-(4″-fluorophenoxy)propyl]-3-methoxy-4-(2?-methoxy-4?-amino-5?-chlorobenzamido)piperidine} in nine steps from commercially available starting materials with an overall yield of 19%.     

Ring-closing metathesis for the synthesis of novel 9- and 10-membered silicon-containing benzo-fused heterocycles

A ring-closing metathesis (RCM) strategy afforded a number of novel 9- and 10-membered benzo-fused compounds containing at least one silicon atom as part of the heterocyclic portion. In this manner, the following compounds containing heterocyclic rings of 9-10 atoms were synthesized: (Z)-2,2-dimethyl-7-[(4-methylphenyl)sulfonyl]-2,3,6,7-tetrahydrobenzo[h][1,7,2]oxazasilonine, (Z)-2,2-dimethyl-3,6-dihydro-2H-benzo[h][1,7,2]dioxasilonine, (Z)-8-isopropoxy-9-methoxy-3,3-dimethyl-1,3,4,7-tetrahydrobenzo[g][1,2]oxasilonine and (Z)-2,2,7,7-tetramethyl-2,3,6,7-tetrahydrobenzo[i][1,8,2,7]dioxadisilecine.     

Synthesis of 4-(2-hydroxy-1-methyl-5-oxo-1H-imidazol-4(5H)-ylidene)-5-oxo-1-aryl-4,5-dihydro-1H-pyrrole-3-carboxylates, a new triazafulvalene system

(2E,3Z)-2-(1-Methyl-2,5-dioxoimidazolidin-4-ylidene)-3-[(arylamino- or heteroarylamino)methylene]succinate 5 obtained by [2+2] cycloaddition of (5Z)-5-[(dimethylamino)methylene]-3-methylimidazolidine-2,4-dione (1) and dimethyl acetylenedicarboxylate (2) followed by substitution of the dimethylamino group with aromatic or heteroaromatic amines, afforded by heating in ethanol in the presence of potassium hydroxide, potassium salts 6. Acidification of 6 with hydrochloric acid afforded mixtures of (E)- and (Z)-isomers of methyl 4-(2-hydroxy-1-methyl-5-oxo-1H-imidazol-4(5H)-ylidene)-5-oxo-1-phenyl-4,5-dihydro-1H-pyrrole-3-carboxylates. On the other hand, alkylation of compounds 6 with methyl iodide or benzyl bromide produced the corresponding methyl (E)-4-(2-methoxy- or 2-benzyloxy-1-methyl-5-oxo-1H-imidazol-4(5H)-ylidene)-5-oxo-1-phenyl-4,5-dihydro-1H-pyrrole-3-carboxylates 9, derivatives of a new triazafulvalene system.     

Reaction of metal-Carbene complexes with vinyllithium reagents

The reaction of vinyllithium with (CO)₅CrC(OCH₃)C₆H₅ (Ic) at?78° followed by the treatment with HCl at ?78° gave 43% (Z)-1-methoxy-1-phenylpropene (IIIa) and 21% 1,4-dimethoxy-1,4-diphenyl-1,3-butadiene (IVa) and no trace of a vinylphenylcarbene complex or its expected decomposition products. IIIa and IVa are proposed to arise from electrophilic attack at the carbon-carbon double bond of a σ-allychromium intermediate. The reaction of phenyllithium with (CO)₅CrC(OCH₃)CH=CHC₆H₅ (V) gave 9% (CO)₅CrC(OCH₃)CH₂CH- (C₆H₅)₂(VI) and 17% (E)-1-methoxy-1,3-diphenylpropene (VII). Reaction of V with lithium diphenylcuprate gave 30% of the conjugate addition product VI.     

Rearrangements of tetrahydroimidazo[1,5-b]isoxazole-2,3-dicarboxylates to pyrrolo[1,2-e]imidazol-6-ols, precursors of 2,5-dihydro-1H-pyrrole derivatives

Isoxazolines 2 from the cycloaddition of imidazoline 3-oxides 1 with DMAD rearrange in the presence of methoxide to give cis-3-methoxy-7-(methoxycarbonyl)-2,7a-diaryl-5-oxo-2,3,5,7a-tetrahydro-1H-pyrrolo[1,2-e]imidazol-6-olates 3 with 100% de. The acidic hydrolysis of 3 led to kinetically controlled formation of methyl 1-formyl-4-hydroxy-5-oxo-2-phenyl-2-((arylamino)methyl)-2,5-dihydro-1H-pyrrole-3-carboxylates 6a-e. The intramolecular transformylations of the latter to the corresponding (E)- and (Z)-methyl 4-hydroxy-2-((N-(aryl)formamido)methyl)-5-oxo-2-phenyl-2,5-dihydro-1H-pyrrole-3-carboxylates 7a-e were shown to be substituent dependent (correlate with σ) and characterized by Hammett type equations. The effect of temperature was investigated and the ρ constants determined for the same reaction series at 50, 60 and 70 °C. The amide diastereomeric ratio [(E)-7]/[(Z)-7] is substituent dependent and can be described by the equation log[(E)]/[(Z)]_x=−ρσ_I+log[(E)]/[(Z)]_x=H.     

On the use of multi-parameter free energy relationships: the rearrangement of (Z)-arylhydrazones of 5-amino-3-benzoyl-1,2,4-oxadiazole into (2-aryl-5-phenyl-2H-1,2,3-triazol-4-yl)ureas

By using a multi-parameter approach (a combination of Hammett/Ingold-Yukawa-Tsuno/Fujita-Nishioka free energy relationships) the mononuclear rearrangements of heterocycles (MRH) rates for five new ortho-substituted and ten new di-, tri-, or tetra-substituted (Z)-arylhydrazones of 5-amino-3-benzoyl-1,2,4-oxadiazole into the relevant (2-aryl-5-phenyl-2H-1,2,3-triazol-4-yl)ureas (in dioxane/water and in a large range of pS⁺ values) have been related to the electronic and proximity effects exerted by the present substituents, also considering previous results on some mono meta- and para-substituted (Z)-arylhydrazones. In every case, excellent correlation coefficients have been calculated (r² or R²≥0.996). Once more the study of MRH has furnished an interesting panel of different reactivity (three pathways of reaction have been evidenced: general-base-catalyzed, uncatalyzed, and specific-acid-catalyzed) and this has been useful in enlightening how polysubstitution can differently affect the MRH rates. Moreover 2,6-disubstitution on the (Z)-arylhydrazono moiety causes a significant increase of the reactivity in all of the three studied pathways. All of the collected data appear useful for understanding structure-reactivity/activity relationships in polysubstituted compounds.     

Hexafluorothioacetone based synthesis of fluorinated heterocycles

Cycloadducts of hexafluorothioacetone (HFTA) were prepared in high yield by a CsF catalyzed reaction between readily available 2,2,4,4-tetrakis-(trifluoromethyl)-1,3-dithietane (as a source of HFTA) with conjugated electron-rich hydrocarbon dienes, such as cyclopentadiene, 2,3-dimethylbuta-1,3-diene, cyclohexa-1,3-diene or (1Z,3Z)-cyclohepta-1,3-diene. Cyclohexa-1,4- and (1Z,5Z)-cycloocta-1,5-dienes, also undergo the reaction with in situ generated HFTA, but form the products of insertion of HFTA into the C-H bond of the diene as a result of ene-reaction. The highly selective reaction of HFTA with (1Z,3Z,5Z)-cyclohepta-1,3,5-triene and (1Z,3Z,5Z,7Z)-cycloocta-1,3,5,7-tetraene leads to the formation of cycloadducts derived from exclusive addition of thioacetone to the corresponding bicyclic isomers—bicyclo[4.1.0]hepta-2,4-diene or bicyclo[4.2.0]octa-2,4,7-triene, respectively. The corresponding cycloadducts of HFTA with 2,3-dimethylbutadiene-1,3-cyclohexa-1,3-cyclohexa-1,4-dienes and (1Z,3Z,5Z)-cyclohepta-1,3,5-triene were also prepared by direct reaction of sulfur/hexafluoropropene/KF and the corresponding hydrocarbon substrate at 35-45 °C in DMF.     

<Emphasis Type="Italic">N</Emphasis>-(4-methoxy-3-nitrobenzyl) derivatives of some nitrogen-containing heterocycles

A number of nitrogen heterocycles reacted with 4-methoxy-3-nitrobenzyl chloride in dimethyl-formamide in the presence of potassium carbonate to give the corresponding N-(4-methoxy-3-nitrobenzyl) derivatives. The reaction of 5-fluoro-1,3-bis(4-methoxy-3-nitrobenzyl)pyrimidine-2,4(1H,3H)-dione with aqueous methylamine afforded N,N′-bis(4-methylamino-3-nitrobenzyl)urea, whereas analogous reaction with 1-(4-methoxy-3-nitrobenzyl)-2-(methylsulfanyl)-1H-benzimidazole resulted in substitution of the methoxy group by methylamino.