Alkylidenation aldehydes

Tungsten alkylidenes have also been shown to accomplish carbonyl alkylidenation. Aldehydes, ketones, esters and amides have been used as the carbonyl moiety. These reactions involve metallacycle intermediates and appear to parallel much of the metathesis chemistry (equation 32). 

Takeda and co-workers discovered that the easily accessible thioacetals 54 and 56 can be reduced by a low-valent titanium reagent to give Schrock carbenes that are competent to alkylidenate aldehydes, ketones, esters. 

The reaction of an alkylidene phosphorane 1 (i.e. a phosphorus ylide) with an aldehyde or ketone 2 to yield an alkene 3 (i.e. an olefin) and a phosphine oxide 4, is called the Wittig reaction or Wittig olefination reaction. ... 

Safety. Since organic peroxides can be initiated by heat, mechanical shock, friction or contamination, an enormous problem in safety presents itself. Numerous examples of this problem have already been shown in this article. Additional examples include the foilowing methyl and ethyl hydroperoxides expld violently on heating or jarring, and their Ba salts also are extremely expl the alkylidene peroxides derived from low mw aldehydes and ketones are very sensitive and expld with considerable force polymeric peroxides of dimethyl ketene, -K>-0-C(CH3)2C(0)j-n, expld in the dry state by rubbing even at —80° peroxy acids, especially those of low mw, and diacetyl, dimethyl, dipropkmyl and methyl ethyl peroxides, when pure, must be handled only in small amts and... 

Auch komplexe Kupfer(I)-hydride reduzieren hauptsachlich unter 1,4-Addition (Bil-dung gesattigter Aldehyde und Ketone)10. Einfacher ist die Reduktion mit Natrium- bzw. Kalium-tetracarbonyl-hydrido-ferrat einfacher En-one in waBrigem Methanol z.B. 3-Oxo-l-phenyl-butan (90% d.Th.) aus 3-Oxo-l-phenyl-buten11 bzw. von 2-Alkyliden-l,3-dionen in Athanol12 ... 

Many such hydroxyquinoxalines have been made by primary synthesis (see Chapter 1) and some by hydrolysis of extranuclear halogenoquinoxalines (see Section 3.4.2) in addition, during extranuclear alkylidenation of methylquinox-alines (see Section 2.2.1.4) the intermediate secondary alcohols may sometimes be isolated, especially with heavily substituted aldehydes, when dehydration can be difficult or even impossible. ° ... 

Amides can add to aldehydes in the presence of bases (so the nucleophile is actually RCONH ) or acids to give acylated amino alcohols, which often react further to give alkylidene or arylidene bisamides. If the R group contains an a hydrogen, water may split out. 

The cycloaddition of alkynes with the tributylphosphine-carbondisulfide adduct 131 results in the in situ formation of the ylides 132 which react with aldehydes to give the novel 2-arylidene or 2-alkylidene-l,3-dithioles 133 (Scheme 36) [132]. Concerning ylides C-substituted by sulfur we can also mention a publication on the behavior of various keto-stabilized ylides towards acyclic and cyclic a s-disulfides allowing the synthesis of substituted thiazoles, thiols, and dithiols [133]. 

Aldehyde B.P. Alkylidene Dimedone (I) Dimedone "Anhydride (M) 2 4-Dinitro-phenyi hydrazone Send earbuone p-NitrO phenyi hydrazone other Derivatives... 

If competitive aldehydes or ketones are used, preferred or exclusive formation of the sterically least hindered alkylidene dipyrazole is observed.[32] If A -carbonyldipyrazole is heated at 190 °C a pyrazole-transfer reaction also occurs to give tetrapyrazole-l-yl-methane in 50% yield.[33]... 

The synthetic method leading to Nb-alkylidenes and Nb-alkylidynes was particularly successful, due to a quite remarkable difference in the reaction rate of 29 with ketones or aldehydes, vs the subsequent reaction of the alkylidene with ketones and aldehydes (see Scheme 37). The former reaction takes a few minutes at -40°C, while the latter one occurs in hours at room temperature.88 The reaction between 178 and benzaldehyde led to triphenylethylene and the niobyl derivative 184. Due to the difference in reaction rates between a and b in Scheme 37, it was found that the sequential addition of two different ketones or aldehydes to a THF solution of 29 produced a nonsymmetric olefin in a stepwise McMurry-type reaction.84 This is exemplified in the coupling shown in reaction c (Scheme 37). The proposed reaction pathway does not involve the intermediacy of a pinacolato ligand and therefore differs from the mechanism of the McMurry reaction and related reductive couplings at activated metal sites.89... 

The second method leads to the formation 3-alkyl- and 3-arylindoles from the reaction of indole with aldehydes in the presence of alkali metal tetra-carbonylhydridoferrate (Scheme 40).67 It is possible that this novel process may occur via reduction of intermediate 3-alkylidene- or 3-arylidene indolenines. 

The Williamson ether synthesis remains the most practical method for the preparation of tetrahydrofurans, as can be exemplified by the two examples shown in the following schemes. A simple synthesis of 2-substituted tetrahydrofuran-3-carbonitriles 84 is achieved by generating the alkoxide under a phase transfer condition via reaction between 4-chlorobutyronitrile and non-enolizable aldehydes <00SL1773>. A synthesis of 2-alkylidene-tetrahydrofuran 85 was recorded, in which a dianion can be generated through treatment of the amide shown below with an excess of LDA, and is followed by addition of l-bromo-2-chloroethane. In this way, the more basic y-carbon is alkylated and leads eventually to the nucleophilic cyclization <00SL743>. 

The ruthenium carbene catalysts 1 developed by Grubbs are distinguished by an exceptional tolerance towards polar functional groups [3]. Although generalizations are difficult and further experimental data are necessary in order to obtain a fully comprehensive picture, some trends may be deduced from the literature reports. Thus, many examples indicate that ethers, silyl ethers, acetals, esters, amides, carbamates, sulfonamides, silanes and various heterocyclic entities do not disturb. Moreover, ketones and even aldehyde functions are compatible, in contrast to reactions catalyzed by the molybdenum alkylidene complex 24 which is known to react with these groups under certain conditions [26]. Even unprotected alcohols and free carboxylic acids seem to be tolerated by 1. It should also be emphasized that the sensitivity of 1 toward the substitution pattern of alkenes outlined above usually leaves pre-existing di-, tri- and tetrasubstituted double bonds in the substrates unaffected. A nice example that illustrates many of these features is the clean dimerization of FK-506 45 to compound 46 reported by Schreiber et al. (Scheme 12) [27]. 

The organotitanium compounds produced by desulfurization of the diphenyl thioacetals of aldehydes 28 with the titanocene(II) species Cp2Ti[P(OEt)3]2 29 react with carbon—carbon double bonds to form the olefin metathesis-type products. Thioacetals 28 may be transformed into terminal olefins by desulfurization with 29 under an ethene atmosphere (Scheme 14.15) [27]. This reaction is believed to proceed through a titanacyclobutane intermediate, formed by cycloaddition of the titanocene-alkylidene with ethene. 

As noted above, titanocene-alkylidenes can be prepared using various methods and starting materials. Like the methylidene complex, higher alkylidene complexes are useful for the transformation of carbonyl compounds to highly substituted olefins. Ketones and aldehydes are converted into substituted allenes by treatment with titanocene-alkenylidenes prepared by olefin metathesis between titanocene-methylidene and substituted allenes (see Scheme 14.7) [17]. Titanocene-alkenylidene complexes can also be prepared from... 

The utilization of copper complexes (47) based on bisisoxazolines allows various silyl enol ethers to be added to aldehydes and ketones which possess an adjacent heteroatom e.g. pyruvate esters. An example is shown is Scheme 43[126]. C2-Symmetric Cu(II) complexes have also been used as chiral Lewis acids for the catalysis of enantioselective Michael additions of silylketene acetals to alkylidene malonates[127]. 

The Groebke-type multi-component reaction between 3-amino-l,2,4-triazole, aromatic aldehydes and benzylic isonitriles afforded iV-alkylidene-4//-imidazo[l,2-A [l,2,4]triazol-6-amines in moderate to good yields <2006TL6891>. 

Reactions with other gem-diiodoalkanes under these conditions proceed in low yield however, addition of DMF (and ultrasonic irradiation) provides a very general method for alkylidenation of aldehydes with good (E)-selectivity (equation II). 

The synthesis of the pyridine ring from ethyl acetoacetate, aldehydes, and ammonia proceeds extraordinarily readily. The mechanism is as follows. In the first phase the aldehydes react with the acetoacetic ester to form alkylidene bis-acetoacetic esters. The 1 5-diketone derivatives so formed undergo ring closure by introduction of a molecule of ammonia and elimination of two molecules of water ... 

Otherwise, the same products can be obtained by a Knovenagel-type reaction between )3-cyanosulphones and aromatic aldehydes in the presence of sodium telluride (behaving as a base). This result is consistent with the above-formulated desulphonylation of an intermediate a-alkylidene )3-cyanosulphone at the expense of the sodium hydrogen telluride formed during the reaction. 

Alkylidenation of aldehydes and cyclopropanation of o jS-unsatu-rated carbonyl compounds with dibromomalonic esters... 

Dibromomalonates react with aldehydes under the assistance of dibutyl telluride (2 equiv) to afford alkylidene malonates. ... 

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