Aromatic rearrangements intermolecular reactions

In these reactions, a group is detached from a side chain and then attacks the ring, but in other aspects they resemble the reactions already treated in this chapter. Since a group moves from one position to another in a molecule, these are rearrangements. In all these reactions, the question arises as to whether the group that cleaves from a given molecule attacks the same molecule or another one, that is is the reaction intramolecular or intermolecular For intermolecular reactions the mechanism is the same as ordinary aromatic substitution, but for intramolecular... 

It has been found that benzo[c ]-l,3-azasilolines (141) can be prepared by the intermolecular reaction of A,A-dimethyl-2-triorganosilylethylamines (137) with benzyne in the presence of excess -butyllithium <76JOCi962>. It is postulated that deprotonation of the first betaine intermediate (138) with butyllithium affords the second intermediate (139) which undergoes silyl rearrangement with loss of ethylene. Cyclization of the resultant aromatic anion (140) onto silicon with concomitant loss of an R group then gives the heterocycle (141) (Scheme 15). 

As the intermolecular multicomponent reactions, three-component cycloaddition reactions (21.2 [2+2-1-2] cycloaddition and 21.3 [3+2+1] cycloaddition) and two-component cycloaddition reactions (21.4 [4+2] cycloaddition) are described. As the intramolecnlar single-component reactions, cycloaromatization reactions (21.5 intramolecular hydroarylation of alkynes and cychzation via transition metal vinybdenes) are described. Aromatic ring constrnction reactions involving aryne reactions (Chapter 12), rearrangement reactions (Chapters 16 and 18), metathesis reactions (Chapter 17), and coupling reactions (Chapters 19 and 20) are described in these different chapters. 

The retrosynthetic concept of the Nicolaou group is shown in Scheme 22. The target molecule 36 is disconnected via an IMDA cyclization of the diene quinone precursor 138, which would be generated from the tetraline derivative 139 using Wittig chemistry followed by aromatic oxidation. A Claisen-type rearrangement would provide access to 139 whereby the side chain required for the rearrangement of 140 would be introduced by 0-acylation. The core of 141 would be formed via an intermolecular Diels-Alder reaction between diene 142 andp-benzoquinone 130 [42]. 

They also applied this method to the intermolecular ene reactions of aliphatic and aromatic aldehydes with alkenes containing a disubstituted vinylic carbon, a potentially valuable route to homoallylic alcohols [50]. Proton-initiated rearrangements do not take place, because the alcohol-Lewis acid complex formed in the ene reaction reacts readily to give methane and a non-acidic aluminum alkoxide. Formaldehyde and excess Me2AlCl gave good yield of ene adducts with all types of alkene, as exemplified in Sch. 26. 

The exact mechanism has still not been completely worked out. " Opinions have been expressed that it is completely intermolecular, ° completely intramolecular, and partially inter- and intramolecular. One way to decide between inter- and intramolecular processes is to run the reaction of the phenolic ester in the presence of another aromatic compound, say, toluene. If some of the toluene is acylated, the reaction must be, at least in part, intermolecular. If the toluene is not acylated, the presumption is that the reaction is intramolecular, though this is not certain, for it may be that the toluene is not attacked because it is less active than the other. A number of such experiments (called crossover experiments) have been carried out sometimes crossover products have been found and sometimes not. As in 11-17, an initial complex (68) is formed between the substrate and the catalyst, so that a catalyst/substrate molar ratio of at least 1 1 is required. In the presence of aluminum chloride, the Fries rearrangement can be induced with micro-wave irradiationSimply heating phenyl acetate with microwave irradiation gives the Fries rearrangement. " The Fries rearrangement has been carried out in ionic melts. 

One of the major problems encountered in this synthesis is the difficulty of obtaining the starting materials (either the a-aminocarbonyl compounds or their acylated derivatives). The former may be prepared by Neber rearrangement of ketoxime tosylates with a base such as ethoxide or pyridine.46 a-Acylamino carbonyl compounds can be prepared directly by the reductive acetylation of oximino ketones.28 38 Balaban and his collaborators47-60 have developed an excellent method for the synthesis of a-acylamino ketones (5). They are obtained in yields of 50-90% by the reaction of azlactones (2-aryl-5-oxazolone, 4) with aromatic hydrocarbons in the presence of aluminum chloride under Friedel-Crafts conditions the reaction may proceed either intermolecularly or intramolecularly. 

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