Condensations aldol-type

The probable mechanism of the reaction is first addition of piperidine to formaldehyde to form /V-hydroxymethylpiperidine. This reacts with acidic hydrogens of the methyl group of 1,1,1-trifluoroacetone, which is hydrated because the trifluoromethyl group next to carbonyl stabilizes the hydrated form of the carbonyl compound. The resulting dihydrate is further stabilized by hydrogen bonds to the piperidine nitrogen 103.  

Hydrogen atoms on the carbon linked to phosphorus are acidic enough to protonate the oxygen atom of the carbonyl group while the rest of the 

dibromodifluoromethane and hexamethylphosporous amide form a phosphonium salt. The intermediate thus formed reacts with tris(dimethyl-amino)phosphine to give dibromotris(dimethylamino)phosphorane and an ylide with difluoromethylene group attached to phosphorus, difluoro-methylenetris(dimethylamino)phosphorane. 

The ylide reacts with the ketone in the sense of the Wittig reaction in that the difluoromethylene group is attached to the carbonyl carbon while the oxygen forms tris(dimethylamino)phosphine oxide. Another mechanism has been suggested by the author of this reaction [/05], 

This and similar reactions are suitable for the synthesis of fluoro alk-enes with terminal fluorine-containing groups. The final product of this reaction is Q, 2-phenyl-1,1,3,3,3-pentafluoropropene [705], 

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An example of an intermolecular aldol type condensation, which works only under acidic catalysis is the Knoevenagel condensation of a sterically hindered aldehyde group in a formyl-porphyrin with a malonic ester (J.-H. Fuhrhop, 1976). Self-condensations of the components do not occur, because the ester groups of malonic esters are not electrophilic enough, and because the porphyrin-carboxaldehyde cannot form enolates. 

The a-ionization of 7-methylpteridines can also be utilized in aldol-type condensation reactions. 7-Methyl-pterin and -lumazine and 2,4-diaminopteridine condense readily in aqueous base with aromatic aldehydes to afford 7-alkylidenepteridines (77JOC2951). A Claisen condensation requires the protection of the acidic hydrogens of the amide bonds. 

Pteridine, 4-imino-1 -methyl-1,4-dihydro-basicity, 3, 270 Pteridine, 7-methoxy-synthesis, 3, 297 Pteridine, 2-methyl- H NMR, 3, 285 reactions, 3, 288 structure, 3, 266 Pteridine, 4-methyl-Gabriel s synthesis, 3, 309 H NMR, 3, 285 reactions, 3, 288 structure, 3, 266 Pteridine, 6-methyl-bromination, 3, 301 structure, 3, 266 synthesis, 3, 312 Pteridine, 7-methyl-aldol-type condensation, 3, 302 bromination, 3, 301 H NMR, 3, 285 structure, 3, 266 synthesis, 3, 312 Pteridine, 2-methylamino-solubility, 3, 271 Pteridine, 2-methyl-3,4-dihydro-striicture, 3, 279 Pteridine, 6-methyl-3,4-dihydro-structure, 3, 279... 

CLAISEN - GEUTER - OIECKMANN Ester condensation Synthesis ot open chain or cyclic p keloesters by aldol type condensation... 

For some condensations with silylated substrates as starting compounds, trimethylsilyl inflate can be used as a catalyst [103, 104, 105] Atypical example of such a reaction is the aldol type condensation of silyl enol ethers and acetals catalyzed by 1-5 mol% of trimethylsilyl inflate [103] (equation 53)... 

Stannous triflate is an efficient catalyst for aldol-type condensations [ 23, 124, 125 Under conditions of kinetic control, it provides excellent diastereo-selectivity in various cross-aldol reactions (equation 61)... 

The Michael reaction with enamines is exemplified in this procedure. In a second (spontaneous) step of the reaction, an aldol-type condensation occurs resulting in cyclization. Finally, the morpholine enamine of the product forms and is hydrolized by the addition of water to yield a mixture of octalones, which is separated by fractional crystallization. J -Octalone-2 can be reduced by lithium in anhydrous ammonia to the saturated tra/i5-2-decalone (Chapter 3, Section III). 

Thomson -JOnV Click Organic Interactive to learn to draw the structures of products from aldol-type condensation reactions. 

Demailly and coworkers195 found that the asymmetric induction increased markedly when optically active methyl pyridyl sulfoxide was treated with an aldehyde. They also synthesized (S)-chroman-2-carboxylaldehyde 152, which is the cyclic ring part of a-tocopherol, by aldol-type condensation of the optically active lithium salt of a,/3-unsaturated sulfoxide. Although the diastereomeric ratio of allylic alcohol 151 formed from lithium salt 149 and 150 was not determined, the reaction of 149 with salicylaldehyde gave the diastereomeric alcohol in a ratio of 28 72196. 

Williams56 argues that these aldol-type condensations do not proceed via cyclic, chairlike six-membered transition states, in contrast to previous arguments to the contrary58., ... 

Due to the high a-C,H acidity in the alkoxyethylidene complexes 6 (e.g.,piCa=8 (R=Me)) [ 16], transformations via an enolate analog are possible and have been used to introduce additional functionality into the carbene side chain to access various Fischer carbene complexes [3]. The a,/J-unsaturated complex 8 could be obtained from 6 (R=Et) by an aldol-type condensation with benzaldehyde 7 in the presence of triethylamine and trimethylsilyl chloride (Scheme 2) [17]. This reaction proceeds completely diastereoselectively to yield only the trans-isomer. Analogously, binuclear complexes have been prepared from 6 and 1,3-and 1,4-phthaldialdehyde in good yields [17]. This type of condensation has... 

O-Trimethylsilyl nitronates 1036 have been used in fluoride-catalyzed aldol-type condensations with aldehydes and ketones to give a-trimethylsilyloxy-nitro com-... 

Addition of such a-lithiosulfinyl carbanions to aldehydes could proceed with asymmetric induction at the newly formed carbinol functionality. One study of this process, including variation of solvent, reaction temperature, base used for deprotonation, structure of aldehyde, and various metal salts additives (e.g., MgBrj, AlMej, ZnClj, Cul), has shown only about 20-25% asymmetric induction (equation 22) . Another study, however, has been much more successful Solladie and Moine obtain the highly diastereocontrolled aldol-type condensation as shown in equation 23, in which dias-tereomer 24 is the only observed product, isolated in 75% yield This intermediate is then transformed stereospecifically via a sulfoxide-assisted intramolecular 8, 2 process into formylchromene 25, which is a valuable chiron precursor to enantiomerically pure a-Tocopherol (Vitamin E, 26). 

It was probably Kozlov et al., studying the condensation of acetylene with aniline, who observed the first homogeneously catalyzed hydroamination of an alkyne [239]. They give experimental evidence that N-phenylethylideneamine is an intermediate, which evolves to an aldol-type condensation product (Scheme 4-9), known as an Ek-stein-Eibner base [240-242]. 

Nucleophilic additions to carbonyl groups lead to alcohols which on dehydration, furnish alkenes70,71. This two-step protocol has been extremely useful for diene and polyene synthesis with wide variation in the carbonyl substrate and the nucleophilic addendum. Diene synthesis using aldol-type condensation as well as phenyl sulphonyl carbanion (the Julia reaction) are also discussed in this section. 

Murahashi and co-workers developed an aldol-type condensation between various activated nitriles and aldehydes or ketones, catalyzed by cyclopentadienylruthenium enolate complexes (Equation (30)).351,351a 351b... 

The heteroatom version of the vinylcyclopropane rearrangement serves to facilitate alkaloid construction. Scheme 13 outlines a strategy for the pyrrolizidine alkaloid isoretronecanol 211 90). Use of a carboxaldehyde (i.e. 213) as a synthon for the primary alcohol provides an ability to adjust stereochemistry. It also sets up formation of the pyrrolidine ring bearing the aldehyde by an aldol-type condensation of an enol of the aldehyde onto an imine derived from 214. Because of the lability of such systems, introduction of X=PhS imparts stability. The resultant azacyclopentene translates to an imine 215 using the iminocyclopropane rearrangement methodology. Simple condensation of the primary amine 216 with aldehyde 37a then initiates this... 

Zirconium tetrachloride promotes a tandem nucleophilic addition and aldol-type condensation reaction of methyl propynoate, or /V,/V-dimethylpropynamidc, with aldehydes, or ketones, in the presence of tetra-n-butylammonium iodide (Scheme 6.13) [8] with a high selectivity towards the formation of Z-isomers. A similar reaction occurs between aliphatic and aromatic aldehydes and penta-3,4-dien-2-one to yield 1-substituted 2-acetyl-3-iodobut-3-enols (50-75%) [9]. 

Aldol-type condensation of carbanions generated by tetra-n-butylammonium triphenyldifluorosilicate... 

A stereoselective tandem iodination and aldol-type condensation has been described for the reaction of methyl propiolate and carbonyl compounds in the presence of a stoichiometric amount of tetra-n-butylammonium iodide and zirconium chloride to yield Z-3-iodo-2-(l-hydroxyalkyl)propenoates, as the major products [48]. No reaction occurs in the absence of the Lewis acid. There does not appear to be any control on the chirality of the hydroxyl centre. 

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