Electron-rich aromatics alkylation

Ferrocene behaves in many respects like an aromatic electron-rich organic compound which is activated toward electrophilic reactions.In Friedel-Crafts type acylation of aromatic compounds with acyl halides, ferrocene is lO times more reactive than benzene and gives yields over 80%. However, ferrocene is different from benzene in respect to reactivity and yields in the Friedel-Crafts alkylation with alkyl halides or olefins. The yields of ferrocene alkylation are often very low. and the separations of the polysubstituted byproducts are tedious. 

Preformed Carbocationic Intermediates. Propargyl cations stabilized by hexacarbonyl dicobalt have been used to effect Friedel-Crafts alkylation of electron-rich aromatics, such as anisole, /V, /V- dim ethyl a n il in e and 1,2,4,-trimethoxybenzene (24). Intramolecular reactions have been found to be regio and stereo-selective, and have been used ia the preparatioa of derivatives of 9JT- uoreaes and dibenzofurans (25). 

In order to achieve high yields, the reaction usually is conducted by application of high pressure. For laboratory use, the need for high-pressure equipment, together with the toxicity of carbon monoxide, makes that reaction less practicable. The scope of that reaction is limited to benzene, alkyl substituted and certain other electron-rich aromatic compounds. With mono-substituted benzenes, thepara-for-mylated product is formed preferentially. Super-acidic catalysts have been developed, for example generated from trifluoromethanesulfonic acid, hydrogen fluoride and boron trifluoride the application of elevated pressure is then not necessary. 

Thiols react more rapidly with nucleophilic radicals than with electrophilic radicals. They have very large Ctr with S and VAc, but near ideal transfer constants (C - 1.0) with acrylic monomers (Table 6.2). Aromatic thiols have higher C,r than aliphatic thiols but also give more retardation. This is a consequence of the poor reinitiation efficiency shown by the phenylthiyl radical. The substitution pattern of the alkanethiol appears to have only a small (<2-fokl) effect on the transfer constant. Studies on the reactions of small alkyl radicals with thiols indicate that the rate of the transfer reaction is accelerated in polar solvents and, in particular, water.5 Similar trends arc observed for transfer to 1 in S polymerization with Clr = 1.4 in benzene 3.6 in CUT and 6.1 in 5% aqueous CifiCN.1 In copolymerizations, the thiyl radicals react preferentially with electron-rich monomers (Section 3.4.3.2). 

Taking into account the close relationship to pyridines one would expect 2-pyridones to express similar type of reactivities, but in fact they are quite different. 2-Pyridones are much less basic than pyridines (pKa 0.8 and 5.2, respectively) and have more in common with electron-rich aromatics. They undergo halogenations (a. Scheme 10) [67] and other electrophilic reactions like Vilsmeier formylation (b. Scheme 10) [68,69] and Mannich reactions quite easily [70,71], with the 3 and 5 positions being favored. N-unsubstituted 2-pyridones are acidic and can be deprotonated (pJCa 11) and alkylated at nitrogen as well as oxygen, depending on the electrophile and the reaction conditions [24-26], and they have also been shown to react in Mitsonobu reactions (c. Scheme 10) [27]. 

Iron porphyrins display pronounced substrate preferences for alkene cyclopro-panation with EDA. In general, electron-rich terminal alkenes in conjunction with aromatic moiety or heteroatoms can efficiently undergo cyclopropanation with high catalyst turnover and selectivity. In contrast, 1,2-disubstituted alkenes cannot undergo cyclopropanation with diazoesters. Alkyl alkenes are poor substrates, giving cyclopropanated products in low yields. In both cases, the dimerization product diethyl maleate was obtained in high yield [53]. 

All examples mentioned so far correspond to reactions between two aromatic groups, however, couplings in which one or both partners are alkyl groups can be achieved using electron-rich boron-based nucleophiles. Fiirstner has reported the use of B-alkyl or 5-allyl methoxy-9-BBN anions for the efficient coupling with some aryl chlorides using an in situ prepared IPr HCl/Pd(OAc)j system [118], Some of the results obtained with these easy-to-handle borate-based nucleophiles are shown below (Scheme 6.34). 

The results obtained with different amines cannot be explained merely on the effects of amine basicity. Thus, to obtain complete hydrogenation of Q to DHQ, the basicity has to be tailored by other factors such as the steric hindrance of the amine and its electronic interaction with the catalyst active sites this seems to be favored by the presence of an electron-rich aromatic ring. Of note, the positive effect of substituted aromatic amines, with a 49% DHQ yield being obtained for ethylanilines, is independent of the substituent position of the alkyl group. 

For some organic compounds, such as phenols, aromatic amines, electron-rich olefins and dienes, alkyl sulfides, and eneamines, chemical oxidation is an important degradation process under environmental conditions. Most of these reactions depend on reactions with free-radicals already in solution and are usually modeled by pseudo-first-order kinetics ... 

Titanium-mediated intramolecular Friedel-Crafts acylation and alkylation are important methods for construction of fused-ring systems (Scheme 29).107 As well as aromatics, olefin units also react in the same way.108 Alkylation of electron-rich olefins such as enol ethers or silyl enol ethers proceeds effectively in the presence of TiCl4.109... 

A clear division of Paterno-Biichi reactions into several distinct categories is possible on the basis of the type of reacting carbonyl compound (alkyl or aromatic), the excited state responsible for reaction (n—71 or Ti—n, singlet or triplet), and the type of olefin (electron deficient or electron-rich). Some examples of these reactions are given in Eqs. 7—11, where only the oxetane products are shown. 

The electronic character of aromatic groups at the a-C of nitrones affects both, the yields and the stereoselections (Table 2.28). Electron-rich aromatic groups increase enantioselectivities but decrease the yields (entries 1-3). Electron-deficient ones slightly decrease enantioselectivities but increase the reaction rates (entries 4 and 5). The electronic properties of A-bound aromatic groups of nitrones has almost no obvious impact on the enantio-selections (entries 6-10). Both, electron-deficient and electron-rich aromatic groups afford good enantioselectivities and diastereoselectivities. Nitrone with a A-bound furyl group furnishes, in moderate yield, the best ee but the lowest diastereoselectivity (entry 9). a-Alkyl and A-alklyl nitrones fail to react (entries 11 and 12). 

In a series of important papers, MacMillan described the alkylation of electron rich aromatic and heteroaromatic nucleophiles with a,P-unsaturated aldehydes, using catalysts based upon the imidazoUdinone scaffold, further establishing the concept and utility of iminium ion activation. In line with the cycloaddition processes described above, the sense of asymmetric induction of these reactions can be rationalised through selective (F)-iminium ion formation between the catalyst and the a,P-unsaturated aldehyde substrate, with the benzyl arm of the catalyst blocking one diastereoface of the reactive Jt-system towards nucleophilic attack (Fig. 3). 

The reaction of 2-aryl-4-phenyl-5(4/b-oxazolones 22 with 4-methylenetriazoles 23 was also studied. The direction of the alkylation was strongly dependent on the nature of the substituent on the aromatic ring at C-2 in 22. Thus, oxazolones with electron-rich aryl substituents gave predominantly alkylation at C-4 to yield 24. In contrast, the isomeric products 25 are preferentially obtained when using substrates with electron-withdrawing substituents (Scheme 7.7). 

The alkylation of 2-aryl-4-phenyl-5(4//)-oxazolones like 22 is strongly dependent upon the nature of the substituent on the aromatic ring at C-2. For electron-rich... 

Carbocations have also been obtained by protonation of photochemically generated carbenes (see Eq. 17), by the fragmentation of photochemically generated cation radicals (see Eq. 18), and by the addition of one photochemically generated cation to an arene (or aUcene) to generate a second cation. As illustrated in Eq. 19, the last method has been employed to convert invisible carbocations into visible ones. Short-hved aryl cations and secondary alkyl cations are quenched by electron-rich aromatics such as mesitylene and 1,3,5-trimethoxybenzene in HEIP to give benzenium ions that can be observed by LEP in this solvent. 

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