Carbon Friedel-Crafts type addition

Benzyl acetate was prepared by addition of benzyl chloride (containing 0.6% pyridine as stabiliser) to preformed sodium acetate at 70°, followed by heating at 115°, then finally up to 135°C to complete the reaction. On one occasion, gas began to be evolved at the end of the dehydration phase, and the reaction accelerated to a violent explosion, rupturing the 25 mm thick cast iron vessel. This was attributed to presence of insufficient pyridine to maintain basicity, dissolution of iron by the acidic mixture, and catalysis by ferric chloride of a Friedel-Craft type polycondensation reaction to polybenzyls, with evolution of hydrogen chloride, which at 130°C would produce an overpressure approaching 100 bar. Previously the chloride had been supplied in steel drums containing 10% sodium carbonate or 3% sodium hydroxide solutions as... 

The ene reaction,3 6360-365 the addition of a carbon-carbon or carbon-oxygen double bond with concomitant transfer of an allylic hydrogen, can allow for chirality transfer.366-369 The reaction has similarities to the Diels-Alder reaction in that a o-bond is formed at the expense of a 7t-bond. In addition, the use of a Lewis acid as a catalyst allows for control of the relative stereochemistry (Scheme 26.14).370-372 Large-scale reactions will be complicated by the need to use either high temperatures or Lewis acids. In addition, thermal and Friedel-Crafts-type degradation products may be problematic with the use of these conditions.361373... 

The use of naphthols 145 as the carbon nucleophilic readion component in Friedel-Crafts type Michael addition readions was also reported in 2007 by Chen and coworkers [43], In this system, the pronucleophile is activated by the quinuclidine unit of bifundional cinchona-based thiourea catalysts such as 81a. A range of aryl-and alkyl-substituted nitroalkene derivatives 124 were applicable to this system. The corresponding adducts 146 were obtained with 85-95% ee at low temperature... 

Addition of a one carbon unit to phenol in a Friedel-Crafts type of reaction gives rise to a family of perfume ingredients of great... 

Reactions of the imidazole carbon atoms occur easily under basic or neutral conditions however, once protonated, electrophilic substitution is slowed. For example, Friedel-Crafts type alkylations and acylations do not readily occur under protic or Lewis acid conditions, which has led to die development of syntheses of imidazoles that more readily allow the desired carbon alkylated or acylated products. Nitration and halogenations of both 7V-un-substituted and A-substituted imidazoles take place with preferential addition to the 4- or 4- and 5-positions. ... 

From the established carbon-carbon connectivities in 304a, it was proposed that a possible precursor of the bicyclo[7.3.1]enediyne substructure could be C-14 chains such as 329 or 330, or their biogenetic analog, which can be connected with the anthraquinone moiety through a Friedel-Crafts type acylation reaction to form the C-8-C-9 bond and can also cyclize to the bicycle structure through two condensation reactions to form the C-3-C-4 and C-7-C-8 bonds. Introduction of an additional acetate unit at C-5 followed by oxidative degradation to form the carboxyl group and O-methylation from methionine should occur at some point. Tentatively, a heptacar-bonyl acid such as 331 was proposed as a possible precursor of the anthraquinone moiety. Moreover, an enediyne chain such as 329 is also conceivable as a precursor of the anthraquinone portion [332]. 

Carbon-carbon bond forming reactions between carbanionic nucleophiles like enolates or deprotonated nitroalkanes and electron deficient alkenes and alkynes belong to the oldest and most versatile transformations known today (225-229). Moreover, stereoselective variants have proven to possess an enormous potential in the syntheses of complex molecules as already exemplified in Sect. 2.4. Whereas the applications depicted in this previous section utilized nucleophiles activated by enamine formation with a chiral secondary amine catalyst to achieve these highly selective C-C bond formations, the present discussirai will focus on the addition of carbon nucleophiles to iminium-activated Michael acceptors. Herein traditional Michael additions using e.g. enolate nucleophiles will be described whereas the use of aromatic Michael donors with iminium-activated acceptors in Friedel-Crafts type reactions will be discussed separately subsequently. 

In 1977, an article from the authors laboratories [9] reported an TiCV mediated coupling reaction of 1-alkoxy-l-siloxy-cyclopropane with aldehydes (Scheme 1), in which the intermediate formation of a titanium homoenolate (path b) was postulated instead of a then-more-likely Friedel-Crafts-like mechanism (path a). This finding some years later led to the isolation of the first stable metal homoenolate [10] that exhibits considerable nucleophilic reactivity toward (external) electrophiles. Although the metal-carbon bond in this titanium complex is essentially covalent, such titanium species underwent ready nucleophilic addition onto carbonyl compounds to give 4-hydroxy esters in good yield. Since then a number of characterizable metal homoenolates have been prepared from siloxycyclopropanes [11], The repertoire of metal homoenolate reactions now covers most of the standard reaction types ranging from simple... 

C-Alkylations have been performed with both support-bound carbon nucleophiles and support-bound carbon electrophiles. Benzyl, allyl, and aryl halides or triflates have generally been used as the carbon electrophiles. Suitable carbon nucleophiles are boranes, organozinc and organomagnesium compounds. C-Alkylations have also been accomplished by the addition of radicals to alkenes. Polystyrene can also be alkylated under harsh conditions, e.g. by Friedel-Crafts alkylation [11-16] in the presence of strong acids. This type of reaction is incompatible with most linkers and is generally only suitable for the preparation of functionalized supports. Few examples have been reported of the preparation of alkanes by C-C bond formation on solid phase, and general methodologies for such preparations are still scarce. 

While mechanistically distinct, the aldol condensation and the Friedel-Crafts acylation result in the incorporation of additional carbon atoms to the starting structure. This type of extension is extremely important when planning the synthesis of more complex organic molecules. To this end, the greater the number of available reactions, the greater the versatility in synthetic planning. 

Reactions of Hydrocarbons. Several types of reactive hydrocarbon functional groups can be used to polymerize and cross-Unk monomers and ohgomers into thermoset plastics. These include addition polymerization of acetylene-terminated molecules and ring-opening polymerization of strained carbon rings. They also include Friedel-Crafts condensation to form hydrocarbon polymers. 

Friedel-Crafts acylation (RCOCI-AICI3-CH2CI2, 25 °C) of compounds of type [Fe(diene)(CO)3] has been shown to occur by e/nfo-addition of RCO+ (as its ion-pair with [AICI4] ) at carbon. Simple substitution products are obtained because of the stabilization of the intermediate cation by iron. The A -ray structure (PFe salt) of the intermediate formed as in Scheme 23 confirms the geometry... 

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