Alkenes from condensation reactions

A -Isoxazolines are readily available from the 1,3-dipolar cycloaddition of nitrile -oxides with alkenes and from the condensation reaction of ehones with hydroxylamine. Therefore, methods of conversion of -isoxazolines into isoxazoles are of particular interest and of synthetic importance. 

When the reactant is of the form ZCH2Z, aldehydes react much better than ketones and few successful reactions with ketones have been reported. However, it is possible to get good yields of alkene from the condensation of diethyl malonate, CH2(COOEt)2, with ketones, as well as with aldehydes, if the reaction is run with TiCU and pyridine in THF. In reactions with ZCH2Z, the catalyst is most often a secondary amine (piperidine is the most common), though many other catalysts have been used. When the catalyst is pyridine (to which piperidine may or may not be added) the reaction is known as the Doebner modification of the Knoevenagel reaction. Alkoxides are also common catalysts. 

Examples of name reactions can be found by first considering the nature of the starting material and product. The Wittig reaction, for instance, is in Section 199 (Alkenes from Aldehydes) and Section 207 (Alkenes frorm Ketones). The aldol condensation can be found in the chapters on difunctional compounds in Section 324 (Alcohol, Thiol-Aldehyde) and in Section 330 (Alcohol, Thiol-Ketone). 

Another important reaction in synthetic chemistry leading to C-C bond formation is the Michael addition. The reaction typically involves a conjugate or nucleophilic 1,4-addition of carbanions to a,/l-unsaturated aldehydes, ketones, esters, nitriles, or sulfones 157) (Scheme 21). A base is used to form the carbanion by abstracting a proton from an activated methylene precursor (donor), which attacks the alkene (acceptor). Strong bases are usually used in this reaction, leading to the formation of byproducts arising from side reactions such as condensations, dimerizations, or rearrangements. 

A simple, efficient, one-step synthesis of quinoxaline 1,4-dioxides from the reaction of benzofurazan oxide 179 with activated alkenes such as enamines was named the Beirut reaction in honor of the city of its discovery. Developments up to 1993 were surveyed by Haddadin and Issidorides <1993H(35)1503>, who first demonstrated this reaction. The benzofurazan oxide 179 (Scheme 52) also condenses with 1,3-diketones <1995M1217, 1996JHC1057, 1999CHE459, 2003EJM791, 2005H(65)1589>, /3-keto acid derivatives <1995H(41)2203,... 

Pyrano[2,3- ]-l,2,4-trioxines 260a-c arise in low yield from the reaction of the appropriate alkene, 3,4-dihydro-277-pyran 258, with singlet oxygen in the presence of methylene blue (MB), followed by condensation of the intermediate oxetane 259 with acetaldehyde or acetone as appropriate (Scheme 43) <1997H(46)451>. 

However, Forstner et al. (1997a) also point out that the formation of furanones from the cyclization of -y-hydroxycarboxylic acids (e.g., C3H7CH(OH)CH2CH2COOH) in the condensed phase is well known. If -y-hydroxycarboxylic acids are formed from OH reactions with the alkenes, the furanones can be formed from this cyclization in the particles. However, Forstner and co-workers also indicated that such a reaction could occur during sample workup and hence the true yields of the furanones could be significantly smaller. 

Siloxane polymerization differs mechanistically from the formation of hydrocarbon polymers in that it is essentially an acid-base process, as might be expected from the strong alternation of electronegativites along the het-eroatomic chain, and the radical initiators that catalyze the homocatenation of alkenes do not work for siloxanes. Long, unbranched polysiloxane chains are favored by higher condensation reaction temperatures and basic catalysts such as alkali metal hydroxides. Acidic condensation catalysts tend to produce polymers of lower molar mass, or cyclic oligomers. 

The different reactivity of 1,2- and 1,1-acceptor/donor-substituted alkenes is paralleled by the readiness with which these compounds can be prepared. Thus, /3-amino acrylates are often spontaneously formed by mixing amines with /3-keto esters, and these derivatives have been used as protective groups for amines because of their low reactivity. a-Amino acrylates can, similarly, be prepared from a-keto esters [40], but this condensation reaction does not proceed spontaneously and requires chemical or azeotropic removal of water [41—43]. a-Amino acrylates are unstable compounds which must be stored at low temperatures [41] or N-acylated immediately after their generation [43]. 

Homer-Wadsworth-Emmons reactions are C=C-forming condensation reactions between the Li, Na, or K salt of a /1-koto- or an a-(alkoxycarbonyl )phosphomc acid dialkyl ester and a carbonyl compound (see Figure 4.46). These reactions furnish a,/3-unsaturated ketones or 0 ,/3-unsaturated esters, respectively, as the desired products and a phosphoric acid diester anion as a water-soluble by-product. In general, starting from aldehydes, the desired compounds are produced /ra/ov-selectively or, in the case of alkenes with trisubstituted C=C double bonds, -selectively. 

Fig. 11.23. Julia-Kocienski olefination to obtain tmns-alkenes from aldehydes in a single step their condensation reaction with the sulfonyl anion B, followed by an Ar-SN reaction (- E) and a fragmentation.

Another report describes the synthesis of pyrazino[2,3-6]quinoxaline 1,4-dioxides (123) by condensation of furoxano[3,4-Z>]quinoxaline (121) with alkynes and alkenes. The pyrazino[2,3-A]quin-oxaline 1,4-dioxides (123) are also isolated as the final products from the reaction with alkenes and oxidation of the initially formed dihydro derivatives (122) (Scheme 21) <88JHC813>. 

The last stages arc shown below. The ketone is protected, and the alkene oxidized to a carbonyl group, cleaving off one of the C atoms (you will meet this reaction—ozonolysis—in Chapter 35). The diester can be cyclized by a Claisen ester condensation. The stereogenic centres in the ring are not affected by any of these reactions so a Irans ring junction must result from this reaction. >... 

In case of the direct reaction of the natural oil or lower alkyl ester of natural fatty acid and the amine the reaction method for producing the amide derivatives is as follows That is, about 1 mol of the said oils and 1 to 100 equivalent mols of the said amines are mixed in the absence or presence of solvents such alcohols as methanol, ethanol or the like, such aromatic hydrocarbons as benzene, toluene, xylene or the like, such halogenoalkanes as methylene chloride, chloroform, carbon tetrachloride or the like, and such alkenes or alkanes as petroleum ether, benzene, gasoline, ligroin or cyclohexane, such ethers as tetrahyrofuran, dioxane and the like, or a mixture thereof, and the mixture is subjected to the reaction in the absence or presence of catalyst amount or equimolar amount to the amine of an auxiliary agent of condensation, such as alkoholate of alkali metal, i.e. lithium, methylate, lithium ethylate, sodium methylate, sodium ethylate, potassium-t-butylate and the like, or acidic auxiliary agents, i.e. p-toluenesulfonic acid and the like, thereby to yield the amide derivatives. In this reaction, a formal alcohol may be removed from the reaction system. 

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