Alkylidene Moiety Research Articles

Yb(OTf)3-Catalyzed Reactions of 5-Alkylidene Meldrum's Acids with Phenols: One-Pot Assembly of 3,4-Dihydrocoumarins, 4-Chromanones, Coumarins, and Chromones

[reaction: see text] The Yb(OTf)3-catalyzed annulation reactions of phenols with 5-alkylidene Meldrum's acids enabled the synthesis of structurally diverse heterocycles in high isolated yields. A series of 4-substituted 3,4-dihydrocoumarins, 2,2-disubstituted 4-chromanones, coumarins, and 2-substituted chromones were readily and efficiently assembled, including the naturally occurring coumarins citropten, scoparone, and ayapin. Addition of phenols to biselectrophilic 5-alkylidene Meldrum's acids proceeded through two distinct multibond-forming modes: Friedel-Crafts C-alkylation/O-acylation and Friedel-Crafts C-acylation/O-alkylation. The regioselectivity of the catalytic annulation reaction was controlled by the degree of substitution on the alkylidene moiety.

New N′-alkylidene/cycloalkylidene derivatives of 5-methyl-3-phenyl-1 H-indole-2-carbohydrazide: synthesis, crystal structure, and quantum mechanical calculations

The condensation products of 5-methyl-3-phenyl-1 H-indole-2-carbohydrazide ( 1) with 2-butanone, 3-pentanone and cyclopentanone were prepared. The adducts ( 2a- c) were characterized by microanalysis, UV, IR, 1H NMR, 13C NMR and EI mass spectrometry. 1H NMR spectra of 2a and 2b revealed rotational restriction about the C–N bond in solution (DMSO-d 6) and displayed double resonances associated with the CH 3 and CH 2CH 3 residues of the alkylidene moieties. A variable temperature 1H NMR experiment was run on 2a to overcome the rotational barriers and thus determine the coalescence temperature but no coalescence was observed up to 77 °C. The structural analysis of 2a and 2c were also carried out by single crystal X-ray diffraction and confirmed by theoretical calculations (semiempirical PM3 and ab initio RHF/6-31G(d)).

The Reaction of Diazocyclopentadienyl Compounds with Cyclomanganated Arenes as a Route to Ligand‐Appended Cymantrenes

AbstractThe thermolysis of various cyclomanganated arenes in the presence of 5‐diazocyclopentadiene, 7‐diazoindene or 9‐diazofluorene afforded the corresponding arenes tethered with cymantrenyl, benzocymantrenyl or dibenzocymantrenyl groups in fair to good yields. This reaction implies a multi‐facetted mechanism that consists of three steps: the insertion of an alkylidene moiety into a C−Mn bond, a CAr−C bond formation and several haptotropic ring‐slippages. The coupling reaction has proven to be particularly efficient with Mn(CO)4 chelates derived from acetylarenes and nitrogen‐containing heterocycles. In one case of a 2‐phenyl‐2‐oxazoline complex, the coupling with 9‐diazofluorene yields a new η1‐dibenzocymantrene complex in which the Mn(CO)4 moiety is chelated and is part of a six‐membered metallacycle. The results of this study are mainly supported by the molecular structures of nine new complexes obtained by X‐ray diffraction analyses. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

‘Tucked-in’ titanocene alkyls and alkylidenes

Titanocene neopentyl complexes with one cyclometallated tert-butylcyclopentadienyl group, (η 5-C 5H 4R)(η 5,η 1-C 5H 4CMe 2CH 2)Ti(CHCMe 3), are readily obtained from the corresponding titanocene dichlorides and bis(neopentyl)magnesium. These compounds lose neopentane by α-H abstraction from the cyclometallated ligand to generate alkylidene species in which the alkylidene moiety is connected to one of the cyclopentadienyl ligands. The alkylidene (C 5H 4Me)(C 5H 4CMe 2CH)Ti(PMe 3) reacts with benzene-d 6 by stereoselective addition of a CD bond across the TiC bond. These ‘tucked-in’ alkylidene species also exhibit a wide range of reactivity towards unsaturated substrates (alkynes, ethene, benzonitrile), initiated by cycloaddition to the TiC bond.

Tungsten(0) alkylidene complexes stabilized as pyridinium ylides: new aspects of their synthesis and reactivity

The interaction of dihydropyridines with alkoxycarbene complexes of tungsten has been shown to lead to pyridinium ylid complexes: this transformation has now been applied to the synthesis of a hydroxyl-containing ylid complex by ring-opening of the pentacarbonyl (2-oxacyclopentylidene) tungsten(0) complex and to the synthesis of a series of chiral ylid complexes both from chiral and non-chiral carbene complexes by the use of dihydropyridines and dihydronicotines, respectively. The transfer of the alkylidene moiety of these complexes to nucleophilic olefins will be outlined and discussed. Especially relevant is the interaction of these pyridinium ylid complexes with unsaturated substrates such as dihydropyridines, enamines, and β-alkoxy bis(trimethylsilyl) ketene acetals. This latter reaction leads to conjugated carboxylic acids, and has been be applied to a new synthesis of a honey bee pheromone, the queen substance.

Synthesis and thermal properties of [n]-polyurethanes

Aliphatic [n]-polyurethanes were obtained by catalytic polycondensation of suitable α-hydroxy-ω-O-phenyl urethanes (III). 1H and 13C NMR analyses of the resulting [n]-polyurethanes (3 a–g) show a uniform microstructure consisting of urethane groups only, and with carbonate and urea groups being absent. The [n]-polyurethanes with linear alkylidene moieties (3 a–e) are highly crystalline materials, their melting points show the same odd-even effect as was observed for [n]-polyamides. The [n]-polyurethanes with branched alkylidene groups (3 f, g) show lower crystallinity (3 g) or are amorphous (3 f) materials. Upon heating, the [3]- and all the [4]-polyurethanes (3 a and 3 b, f, g) result in the corresponding cyclic urethanes by ring-closing depolymerization.

Synthesis and Herbicidal Activity of New Oxazolidinedione Derivatives

A series of new 3-(substituted phenyl)-5-alkylidene-1,3-oxazolidine-2,4-dione derivatives was synthesized by reacting substituted phenyl isocyanates with 2-hydroxy-3-alkenoates prepared through an acid-catalyzed isomerization of 3,3-disubstituted glycidates, and their herbicidal activities against various weeds as well as the crop safeties were examined. 1,2) The herbicidal activities of these oxazolidinedione derivatives were primarily influenced by the substituents on the phenyl group and by the structure of the alkylidene moiety. The compounds having a 2,4-dihalo-5-alkoxyphenyl moiety exhibited relatively higher herbicidal activities while the introduction of a long chain alkylidene group at the 5-position of the oxazolidine ring reduced the activity. The crop safety was found to be markedly affected by the substituent at the 5-position of the phenyl group and a cyclopentyloxy group seemed to be the most preferable one. Among the compounds synthesized, 3-(4-chloro-5-cyclopentyloxy-2-fluorophenyl)-5-isopropylidene-1,3-oxazolidine-2,4-dione (KPP-314) was selected as a promising paddy rice herbicide. In greenhouse pot tests, KPP-314 exhibited an excellent activity against annual lowland weeds by pre- and post-emergence soil treatments at 150 to 450 g a.i./ha with a wide safety margin between rice plant and Echinochloa oryzicola.

Structure and electrochemical behavior of alkylidene-bridged metalladithiolene complexes (metals: cobalt and rhodium): bond cleavage of alkylidene moieties by electrochemical redox reactions

We prepared thirteen alkylidene-bridged metalladithiolene complexes [(Cp)M(S 2C 2Y 2)(CR 1R 2)] (M=Co and Rh) including two novel ones. We succeeded in X-ray structure analyses of six alkylidene-bridged dithiolene complexes together with three original dithiolene complexes. The Co–S bond distance of the dithiolene ring becomes long due to the formation of alkylidene-bridged complexes. Investigation of the redox process in a series of those alkylidene-bridged metalladithiolene complexes by cyclic voltammetry reveals a large dependence for the redox potentials on the nature of M, Y and R. In the reduction, the radical anion formed in the initial process eliminates the alkylidene moiety slowly to give the radical anion of the original dithiolene complexes. One-electron oxidation gives detectable cation radicals due to some structural change, but when these cation radicals are re-reduced, they rapidly eliminate the bridging moieties to give original dithiolene complexes. We could succeed in detecting the intermediary species in the elimination process. This is one of the very rare and important successes in the trapping of the intermediate in the elimination mechanism. We conclude that both reduction and oxidation weaken the M–C and S–C bonds in the M–S–C triangle ring to regenerate the original metalladithiolene complexes.

On the Synthesis of Unsaturated Oxaspiropentanes

Polyenes bearing an alkylidenecyclopropane moiety are oxidized selectively at the alkylidene moiety or at the other C,C double bond(s) depending upon the nature and the relative number of substituents present at each unsaturation.

Olefin Metathesis in Organic Chemistry

AbstractTransition metal catalyzed CC bond formations belong to the most important reactions in organic synthesis. One particularly interesting reaction is olefin metathesis, a metal‐catalyzed exchange of alkylidene moieties between alkenes. Olefin metathesis can induce both cleavage and formation of CC double bonds. Special functional groups are not necessary. Although this reaction—which can be catalyzed by numerous transition metals—is used in industry, its potential in organic synthesis was not recognized for many years. The recent abrupt end to this Sleeping‐Beauty slumber has several reasons. Novel catalysts can effect the conversion of highly fictionalized and sterically demanding olefins under mild reaction conditions and in high yields. Improved understanding of substrate–catalyst interaction has greatly contributed to the recent establishment of olefin metathesis as a synthetic method. In addition to the preparation of polymers with fine‐tuned characteristics, the metathesis today also provides new routes to compounds of low molecular weight. The highly developed ring‐closing metathesis has been proven to be key step in the synthesis of a growing number of natural products. At the same time interesting applications can be envisioned for newly developed variants of bimolecular metathesis. Improvements in the selective cross‐metathesis of acyclic olefins as well as promising attempts to include alkynes as viable substrates provide for a vivid development of the metathesis chemistry.

Alkylidene-Centered Rearrangement of a Tantalum Alkylidene Alkoxide Species with the N,C,N-Bis-ortho-chelated 1,2,6-Trisubstituted Aryldiamine Ligand [C6H3(CH2NMe2)2-2,6]- to a Product with a C,N-Mono-ortho-chelated 1,2,4-Trisubstituted Aryldiamine Ligand. X-ray Molecular Structure of [TaCl(CH-t-Bu){C6H3(CH2NMe2)2-2,4}(O-t-Bu)

The reaction of 2 equiv of LiO-t-Bu with [TaCl2(CH-t-Bu){C6H3(CH2NMe2)2-2,6}] (1), in which there is an N,C,N-chelated 1,2,6-trisubstituted aryldiamine ligand, affords in a one-pot procedure at 80 °C the new rearranged product [Ta(CH-t-Bu){C6H3(CH2NMe2)2-2,4}(O-t-Bu)2] (2), in which there is a C,N-chelated 1,2,4-trisubstituted aryldiamine ligand. Complex 2 is a yellow solid that has been isolated in 69% yield. The reaction mechanism for the formation of 2 involves a crucial isomerization of the intermediate [TaCl(CH-t-Bu){C6H3(CH2NMe2)2-2,6}(O-t-Bu)] (3) to the rearranged intermediate [TaCl(CH-t-Bu){C6H3(CH2NMe2)2-2,4}(O-t-Bu)] (4). The intermediate complexes 3 and 4 have been independently prepared and characterized. The known complex 3 can be obtained by reaction of 1 with LiO-t-Bu at room temperature. Complex 4 is obtained exclusively, as revealed by 1H NMR spectroscopy, by heating a benzene solution of 3 to 80 °C and has been isolated as a purple solid in 77% yield. In solution 4 exists as two rotational isomers for the TaC(H)-t-Bu moiety; ΔG⧧ = 71 kJ mol-1. The X-ray molecular structure of 3 shows it to be a pentacoordinate Ta(V) species in which the aryl Cipso atom, the alkylidene functionality, and the alkoxide group define the meridional plane of a trigonal bipyramid, with one of the NMe2 nitrogen donors of the C,N-bidentate-bonded aryldiamine and the chloride occupying the axial positions. The lone pair of the N-donor atom of the second ortho amine substituent is oriented toward Ta (Ta···N = 2.629.4 Å), providing incipient η3(N,C,N) facial bonding of the aryldiamine ligand. The structure of 3 also shows a pseudo-parallel orientation of the alkylidene Cα−Hα bond and the Cipso−Ta bond that points to potential C−H activation via a four-membered metallacyclic ring that contains Ta, Cipso, Cα, and Hα. The involvement of the alkylidene functionality in the sequence of highly regiospecific C−H bond-making and -breaking processes necessary to produce complex 4 from 3 was confirmed by deuterium-labeling experiments. The mechanism probably involves an α-H abstraction from the alkylidene moiety in 3 (assisted by the weakly coordinated dimethylamino group) that leads to an intermediate which has a geometry similar to that of a known aryltantalum(V) zinc alkylidene adduct.

Structural Changes Induced by Electron-Transfer Reactions. Isomerization of an Alkylidene Moiety by Reversible Metal−Carbon Bond Cleavage in an Alkylidene-Bridged Cobaltadithiolene Complex

Structural Changes Induced by Electron-Transfer Reactions. Isomerization of an Alkylidene Moiety by Reversible Metal−Carbon Bond Cleavage in an Alkylidene-Bridged Cobaltadithiolene Complex

Synthesis of nitrogen‐containing heterocycles. 7 Reaction of aliphatic diaminomethylenehydrazones with hindered ethoxymethylenecyanoacetate

AbstractAliphatic diaminomethylenehydrazones 1 were reacted with ethyl 2‐cyano‐3‐ethoxy‐2‐pentenoate 2 to give a number of heterocycles in low to moderate yields, according to the substitution pattern and the size of substituent. When 1 carried a single methyl group on the terminal nitrogen, it gave preferentially 6‐oxo‐1,6‐dihydropyrimidines 4 incorporating N(4) into the ring. In contrast, the reaction between 1c or 1d and 2 led to 6‐imino‐ and 6‐oxo‐1, 6‐dihydropyrimidines 7 and 8 along with 3. When the alkylidene moiety was bulky, 1e and 1f, the similar reaction gave 3 in high yields without any cyclized product. Upon exposure to acid, compound 3 yielded 6‐oxo‐1,6‐dihydropyrimidines 6, [1,2,4]triazolo[1,5‐c]pyrimidine‐8‐carboxylate 5 and N‐alkenyl‐1,2,4‐triazoles 9 in addition to 7 and 8 in proportions dictated by the nature of the substituents of 1. The structural assignment and reaction mechanism are discussed.

Synthesis and Applications of RuCl2(CHR‘)(PR3)2: The Influence of the Alkylidene Moiety on Metathesis Activity

The reactions of RuCl2(PPh3)3 with a number of diazoalkanes were surveyed, and alkylidene transfer to give RuCl2(CHR)(PPh3)2 (R = Me (1), Et (2)) and RuCl2(CH-p-C6H4X)(PPh3)2 (X = H (3), NMe2 (4), OMe (5), Me (6), F (7), Cl (8), NO2 (9)) was observed for alkyl diazoalkanes RCHN2 and various para-substituted aryl diazoalkanes p-C6H4XCHN2. Kinetic studies on the living ring-opening metathesis polymerization (ROMP) of norbornene using complexes 3−9 as catalysts have shown that initiation is in all cases faster than propagation (ki/kp = 9 for 3) and that the electronic effect of X on the metathesis activity of 3−9 is relatively small. Phosphine exchange in 3−9 with tricyclohexylphosphine leads to RuCl2(CH-p-C6H4X)(PCy3)2 10−16, which are efficient catalysts for ROMP of cyclooctene (PDI = 1.51−1.63) and 1,5-cyclooctadiene (PDI = 1.56−1.67). The crystal structure of RuCl2(CH-p-C6H4Cl)(PCy3)2 (15) indicated a distorted square-pyramidal geometry, in which the two phosphines are trans to each other, and the alkyli...

Synthesis of some derivatives of 1-[2-deoxy-3,5-O-(1-diethylphosphono)alkylidene-β-D-threo-pentofuranosyl]thymine substituted in the ω-position of the alkylidene moiety

Synthesis of some derivatives of 1-[2-deoxy-3,5-O-(1-diethylphosphono)alkylidene-β-D-threo-pentofuranosyl]thymine substituted in the ω-position of the alkylidene moiety

Intermolecular C–H activation by reactive titanocene alkylidene intermediates

Thermal α-H abstraction from (C5H4R)2Ti(CH2CMe3)2(R = H, Me) produces reactive titanocene neopentylidene intermediates under mild conditions, that can either be trapped with PMe3 to yield the alkylidene complexes (C5H4R)2Ti(CHCMe3)PMe3, or add C–H bonds of hydrocarbon substrates R′H (R′H = benzene, p-xylene) to the TiC double bond to produce (C5H4R)2Ti(CH2CMe3)R′; an alternative reaction pathway, insertion of the alkylidene moiety into the cyclopentadienyl C–C bond, has been observed in the presence of THF.

Synthesis and anti-cancer activity of 2-alkylaminomethyl- 5-( E)-alkylidene cyclopentanone hydrochlorides

A series of 2-alkylaminomethyl-5-( E)-alkylidene cyclopentanone hydrochlorides ( 2), have been synthesized and evaluated as anti-cancer agents. These compounds were designed as masked α-methylenecyclopentanones, which appear in many cytotoxic or anti- cancer natural products. Most of the synthesized compounds were found to be active towards various human cancer cell lines and many showed significant subpanel selectivity. For compounds containing the same alkylidene moiety (from C 3 to C 9), the dimethylamino- methyl analogs were more active than structures possessing morpholino-, pyrrolidino-, or piperidino-methyl groups. Alteration of the alkylidene moiety had little effect on anti-cancer potency. The mass spectrum of a glutathione adduct of 2h indicated that the mechanism of action for these anti-cancer agents may be related to the attack at the aminomethyl carbon atom by biological nucleophilic thiols.

Mass spectrometric fragmentation of isomeric 2‐alkyl‐substituted 1,3‐indandiones and 3‐alkylidenephthalides: a seven‐step consecutive isomerization of regular and distonic molecular radical cations

AbstractThe electron impact‐induced fragmentation of 2,2‐dimethyl‐ and 2‐ethyl‐1,3‐indandione, 1 and 2, and their isomers, 3‐isopropylidene‐ and 3‐propylidenephthalide, 3 and 4, respectively, was studied in detail by mass‐analysed ion kinetic energy (MIKE) and collision‐induced dissociation (CID‐MIKE) spectrometry, including 2H and 13C. labelled analogues of 1 and 2. In all regimes of internal energy, the molecular ions 1+. 4+. interconvert by up to seven consecutive, reversible isomerization steps prior to the main fragmentation processes, viz. loss of CH3. and C2H4. 1,3‐Indandione and 3‐methylenephthalide ions with identical alkylidene moieties (i.e. 1+.⇌3+. and 2+.⇌4+.) equilibrate rapidly and completely prior to fragmentation, whereas these pairs of isomers interconvert only slowly via a five‐step rearrangement of the indandione ions 1+.⇌2+.. Distinct from the behaviour of simpler ionized carbonyl species, a 1,2‐C shift of a (formally) neutral carbonyl group is found to occur along with that of a protonated one. Also distinct from simpler cases, methyl loss does not take place from the ionized enol intermediates formed within the interconversion 1+.⇌2+. of the diketone ions but rather from the n‐propylidenephthalide ions 4+.. This follows from CID‐MIKE spectrometry of the [M  CH3]+ ions of 1–4 and two reference C10H7O2+ (m/z 159) ions of authentic structures (protonated 2‐methylene‐1,3‐indandione and protonated 1,4‐naphthoquinone). The characteristic CID fragmentation of the C10H7O2+ ions is rationalized. Finally, the multistep isomerization of ionized 1,3‐indandiones apparently also extends to higher homologues [e.g. 5+. from 2‐ethyl‐2‐methyl‐1,3‐indandione (5) and 6+. from 2,2‐diethyl‐1,3‐indandione (6)]: the ionized phthaloyl group of 1,3‐indandione radical cations 1+., 2+., 5+. and 6+., originally attached with its two acyl functionalities to the same carbon of the aliphatic chain, performs, in fact, a ‘multi‐step migration’.

Semiempirical molecular orbital study on the transition states for the anti-selective Michael addition reactions of the lithium Z-enolates of N-alkylideneglycinates to α,β-unsaturated esters

Semiempirical molecular orbital calculations (MNDO and PM3) show that the lithium Z-enolates derived from N-alkylideneglycinates react with α,β-unsaturated esters through a stepwise mechanism via the intermediate formation of Michael adducts. The initial step involves an anti-selective carbon–carbon bond formation through a Michael addition process and the second step consists of stereoselective ring formation or a 1,3-dipolar cycloaddition. The energy difference between the transition states for each step depends upon the steric hindrance caused by the alkylidene moiety: bulky alkylidene substituents prefer the formation of Michael adducts and small ones prefer 1,3-dipolar cycloadducts. The exclusively high anti-selectivity observed in the Michael addition step is due to the attractive molecular orbital interaction working between the imine moiety of donor molecules and the α-carbon of the acceptors.

Erste röntgenographische Charakterisierung N‐lithiierter 4‐Alkyliden‐1,4‐dihydropyridine des Typs [{4‐(CH3CR)C5H4N}Li(TMEDA)]2: Vergleich von Kristall‐ und MNDO‐Strukturdaten sowie Untersuchungen zur Lithium‐Koordination in Lösung

The First X‐ray Structures of N‐Lithiated 4‐Alkylidene‐1,4‐dihydropyridines [{4‐(CH3CR)C5H4N}Li(TMEDA)]2: Comparison of the X‐ray and MNDO Geometries and Investigation of Lithium Coordination in SolutionThe 4‐ethyl‐ and ‐isopropylpyridines 5a and b were transformed into the lithiated compounds [{4‐(CH3CH)C5H4N}‐Li(TMEDA)]2 (6a) and [{4‐(CH3CCH3)C5H4N}Li(TMEDA)]2 (6b) by reaction with LDA and in the presence of TMEDA. These compounds were recrystallized from a toluene/hexane solution to obtain suitable crystals for X‐ray investigations. Both structures are dimeric containing nonstoichiometric amounts of toluene in the crystals. The structural parameters of the heterocyclic moieties of 6a or b are typical of N‐lithiated 4‐alkylidene‐1,4‐dihydropyridines. MNDO geometries compare quite well with the X‐ray structure of 6a. The lithium atom of 6a in solution prefers the same type of coordination as in the crystal: Two‐dimensional 6Li,1H‐HOESY showed Li contacts only to ortho‐hydrogen atoms (Figure 3). 6a and b react differently with chlorotrimethylsilane (8). The variations of the alkylidene moieties of 6a and b, although seemingly small, are decisive: While the α,α‐dimethyl compound 6b reacts exclusively as an N nucleophile, the α‐methyl compound 6a functions also exclusively as a Cα nucleophile.