Hydroxyalkylation arenes

We have found several examples in which adjacent cationic charge centers are shown to activate carboxonium electrophiles. A convenient method for studying this activation is through the use of the hydroxyalkylation reaction, a commercially important, acid-catalyzed condensation of aldehydes and ketones with arenes.10 It is used for example in the synthesis of bis-phenol A from acetone and phenol (eq 6). While protonated acetone is able to react with activated arenes like phenol, it is not capable of reacting with less nucleophilic... 

Diprotonated, superelectrophilic intermediates were suggested to be involved in both conversions. Considering protonated aldehydes, benzal-dehyde gives a carboxonium ion that is significantly resonance stabilized and thus unreactive towards aromatic substrates such as o-dichlorobenzene or nitrobenzene. Pyridinecarboxaldehydes, however, show much higher electrophilic reactivities due to their ability to form via TV-protonation the superelectrophile (5, eq 8).10 A similar situation is seen in the hydroxyalkylation reactions of acetyl-substituted arenes. Acetophenone is fully protonated in excess triflic acid, but the resulting carboxonium ion (6) is... 

Several types of nitrogen-containing heteroaromatic compounds are also capable of producing carboxonium-centered dications (Table 3).45 Among the dications 108-113, all have been shown to react with weak nucleophiles such as benzene, deactivated arenes, and even saturated hydrocarbons. Moreover, their reactivities greatly exceed that of comparable monocationic electrophiles. In the case of dication 111, for example, it is shown that it will condense with benzene in a hydroxyalkylative conversion (eq 36).45d... 

Heterobimetallic homogeneous catalysts [e.g. (12)] have been developed26 for the alkylation of a range of aromatic compounds by n-activated alcohols. The superior electrophilicity is attributed to the high-valent T-Sn core in the structures. A review has appeared of reactions involving the hydroxyalkylation and cycloalkylation of arenes by hydrofurans, lactones, and unsaturated acids 27... 

The hydroxyalkylation of activated arenes (containing functional groups such as the hydroxy or methoxy groups) [1-4] with aldehydes and ketones is a reaction of... 

Cyclic ketals of acetophenone can be prepared directly under basic conditions by the reaction of aryl triflates, bromides or iodides with hydroxyalkyl vinyl ethers in the presence of a catalytic amount of palladium(II) acetate and 1,3-bis(diphenylphosphino)propane (DPPP). The example illustrated in Scheme 2.39 is noteworthy since a protected methyl ketone was appended to an arene in the presence of a reactive aldehyde functionality. 

Bis(acyloxy)iodo]arenes in the presence of bromide anion in water also oxidize primary and secondary alcohols similarly to the (PhIO) /KBr system [11,12]. The oxidation of primary alcohols using ArI(OAc)2/KBr in water or aqueous methanol affords carboxylic acids or esters [9, 13], while the oxidation of secondary alcohols under similar conditions results in the formation of the respective ketones in excellent yields [14]. Aldehydes can be converted into methyl esters by a similar procedure using PhI(OAc)2/NaBr in an acidic aqueous methanol solution [15]. Likewise, acetals 3 can be converted into the corresponding hydroxyalkyl carboxylic esters 4 by oxidation with PhI(OAc)2/LiBr in water (Scheme 6.3) [16]. 

Different from the hydroxyalkylation reactions using carbonyl compounds as substrates, Nicolaou s and Macmillan s groups developed independently the intramolecular asymmetric Friedel-Crafts-type a-arylation of aldehydes with electron-enriched arenes based on the SOMO activation strategy. Using chiral imidazolidione as catalyst, a series of cyclic aldehydes were obtained in good yields and enantioselectivities with cerium ammonium nitrate (CAN) as single electron transfer oxidant [46]. 

Ethyl trifluoropyruvate has been activated in TfOH medium for the hydroxyalkylation of arenes to give valuable Mosher s acid derivatives in good to excellent yields. Even Selectfluor has been activated in TfOH to effect electrophilic fluorination of arenes including fluorobenzene and chlorobenzene. ... 

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