Friedel-Crafts type reaction alkenes

AICI3 is a moisture-sensitive and strong Lewis acid. It is a first choice for Friedel-Crafts-type reactions, which provide numerous important transformations in laboratory and industry. It can also be applied to the transformation of alkenes to ketones via alkylaluminum halides.303 Hydrozirconation of an olefin and subsequent transmetalation from zirconium to aluminum gives the corresponding alkylaluminum dichloride, and the subsequent acetylation by acetyl chloride affords the corresponding ketone in high yield (Scheme 66). 

Alkyl derivatives of metals such as aluminum, boron and zinc are fairly active Friedel-Crafts catalysts. However, hyperconjugative effects result in a lowering of the electron deficiency. In the case of metal alkoxides this effect is even stronger, and, as a result, they are fairly weak Lewis acids. Metal alkyls, such as alkylaluminums, alkylaluminum halides and sesquihalides are also vital components of Ziegler-Natta catalyst systems which sometimes are utilized for Friedel-Crafts-type reactions. For example, alkylations of aromatics with alkenes in the presence of a Ziegler-Natta catalyst such as AIR3 -1- TiCU results in lower-chain alkylates. Even alkylaluminum halides and sesquihalides serve as Friedel-Crafts catalysts. 

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. 

Traditionally, synthetic approaches toward this framework were charactoized by a lack of generality, involving poorly available starting material that require multistep synthetic transformations [22-25]. More recent approaches include tandem cleavage of hydrogenated / -and a-carbolines [26], ring closing metathesis [27], and metal-catalyzed Friedel-Crafts-type reactions of indole derivatives with several electrophiles (such as alkynes, alkenes or epoxides) (see Refs. [118] and [133] in Chap. 1 [28-32]). 

Simple ruthenium(II) catalysts can now perform heterocycle directed alkylation and Friedel-Crafts type reactions at orf/io-positions of arenes and heteroarenes. The former reaction takes places without p elimination and the latter reaction takes place without addition of Lewis acid to form arenes containing a ketone, amide, or ester functionality. Hydroarylation of strained alkenes can be performed to obtain ortho alkyl (hetero)arenes and alkylation of sp C-H bond can be observed using alcohol as a precursor. 

AICI3 can also catalyze the aliphatic Friedel-Crafts type reaction of propylene oxide with cyclic/acyclic alkenes [86]. As shown in Scheme 6.67, AICI3 promoted the reaction of propylene oxide with cyclododecene to proceed at — 30°C to give aldehyde (86) in 25% yield, furan derivatives (87) in 18% yield, and an F/2 mixture of unsaturated alcohols (88) in 24% yield. 

Extensions of the electrophilic activation of the alkyne moiety as well as an alkene moiety have been developed and applied. The applications include various reactions, for instance, Friedel-Crafts type alkylations,323 anchimeric assistance of heteroatomic moiety generally followed by rearrangements (see below), implementation of more sophisticated functional groups such as ynamides and allenynes, which are discussed below. 

Friedel Crafts type alkylations of benzene by alkenes involve the initial formation of a lattice associated carbenium ion, formed by protonation of the sorbed olefin. The chemisorbed alkene is covalently bound to the zeolite in the form of an alkoxy group and the carbenium ion formed exists only in the transition state. As would be expected fixjm conventional Friedel Crafts alkylation, the reaction rate over acidic molecular sieves also increases with the degree of substitution of the aromatic ring (tetramethyl > trimethyl > dimethyl > methyl > unsubstituted benzene). The spatial restrictions induced by the pore size and geometry frequently inhibit the formation of large multisubstituted products (see also the section on shape selectivity). 

Ipatieff and coworkers carried out the first alkylation with alkenes and branched and normal chain alkanes (except methane and ethane) in the presence of AlCb as the catalyst. The sulfuric acid catalyzed alkylation reaction of arenes and isoalkanes, developed in 1938, is a still widely used industrial process to produce alkylates with high octane numbers. For synthetic applications, however, Friedel-Crafts-type alkylations of alkenes and alkanes have limited value since they tend to give mixtures of products, including oligomers of alkenes. ... 

N-Acyliminium ion pools react with various carbon nucleophiles as summarized in Scheme 5.16. For example, allylsilanes, silyl enol ethers, Grignard reagents, and 1,3-dicarbonyl compounds serve as good nucleophiles. Aromatic and heteroaromatic compounds also react as nucleophiles with N-acyliminium ion pools to give Friedel-Crafts-type alkylation products.N-Acyliminium ions are known to serve as electron-deficient 4n components and undergo [4 -F 2] cycloaddition with alkenes and alkynes. Usually these reactions take place very quickly, and therefore N-acyliminium ion pools serve as effective reagents for flash chemistry. 

In feet, Norman et ol disclosed the first example of an intramolecular Fujiwara-Moritani reaction back in 1970 [124] it was. however, understood as a Friedel-Crafts-type process involving alkene activation by palladium(II). Aside from this seminal report, a few oxidative cydizations of 1.4-quinones using stoichiometric amounts of... 

Functionalized alkenes containing a phenyl or carboxylic acid group at appropriate distance from the double bond undergo intramolecular cyclization during the sulfonation. On reaction of ( -4-hexenoIc add with SO3 a sulfo 5 lactone is formed (eq 8), and a Friedel-Crafts type cyclization is observed on sulfonation of ( )-5 phenyl-2-pentene (eq 9) both cyclizations proceed quantitatively and stereospedfically. 

Carbocations are formed by several reactions. One example has been discussed already in the context of the SnI reaction (Scheme 2.2.8a). Other important options include the addition of protons to double bonds, for example, the addition of a Br0nsted acid to an alkene or ketone (Scheme 2.2.8b and c, respectively). The addition of a Lewis acid to a carbonyl group can also lead to a type of carbocation, an effect that is exploited in all kinds of technical Friedel-Crafts acylation reactions (Scheme 2.2.8d). Finally, in high-temperature refinery processes, the formation of carbocations from alkanes is of highest relevance. Here acidic catalysts are usually applied that abstract a hydride from the alkane to form hydrogen and a carbocation at the alkane substrate (Scheme 2.2.8e). 

We will show here the classification procedure with a specific dataset [28]. A reaction center, the addition of a C-H bond to a C=C double bond, was chosen that comprised a variety of different reaction types such as Michael additions, Friedel-Crafts alkylation of aromatic compounds by alkenes, or photochemical reactions. We wanted to see whether these different reaction types can be discerned by this... 

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. 

Aromatic compounds are usually readily alkylated or acylated by a Friedel-Crafts reaction.150 The combination of reagents used most commonly for aromatic alkylation is an alkyl halide with a strong Lewis acid (Equation 7.65). However, alkenes, alcohols, mercaptans, and a number of other types of organic... 

Olah and coworkers, ° and Mayr and Striepe discussed the scope and limitations of aliphatic Friedel-Crafts alkylations. In particular, they considered factors that would favor reactions of the type shown in equation (121), where an alkene is alkylated by an alkyl halide. ° They reasoned that formation of the 1 1 addition products (42) can be expected, if (41) reacts faster with the alkene than (42), otherwise higher addition products will be formed. Mayr ° suggested that the relative dissociation rates of (41) and (42) induced by the Lewis acid should reflect their relative rates of addition to a common alkene. Furthermore, it was assumed that the solvolysis rates in 80% ethanol were proportional to the Lewis acid induced dissociation constants. A few examples where good yields of alkylated (addition) products were obtained are shown in equations (122) and (123). 

This section will expand the theme of reactions between a carbocation and a nucleophilic species such as an alkene or an alcohol. In this section, however, the carbocation will be attacked by an aromatic ring to form a Wheland-type intermediate, which leads to a substituted aromatic system. These are the Friedel-Crafts reactions and they are among the most important reactions in organic chemistry. 

It is clear that many Lewis acids and protonic acids can be used to catalyze various Friedel-Crafts reactions. The choice of halide, alkene, or alcohol substrate will largely determine which catalyst is used, although, as seen in Table 12.11, the type of reaction that is of interest is also dependent on the choice of catalyst. The following sections provide several examples to illustrate common catalysts used in various reactions, as well as the synthetic utility of the reaction. 

The iR NMR spectrum of pyrrole is slightly less convincing as the two types of proton on the ring resonate at higher field (6.5 and 6.2 ppm) than those of benzene or pyridine but they still fall in the aromatic rather than the alkene region. Pyrrole is also more reactive towards electrophiles than benzene or pyridine, but it does the usual aromatic substitution reactions (Friedel— Crafts, nitration, halogenation) rather than addition reactions pyrrole is also aromatic. 

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