Ipso adducts addition

Since the measured yields of the phenolic products corresponded to 30% OH yield, the ipso adduct formation is limited to 10% OH yield. Since the combined G value of m- and -hydroxybenzaldehydes in NjO-saturated solutions in the presence of IrCl is 1.7, only 30% OH seems to add to the ring. The reason for low phenolic yields in the case of benzaldehyde is the possibility of another reaction channel leading to the formation of the exocyclic OH adduct (structure 5) from the addition of OH to the carbonyl group of benzaldehyde [reaction (4)]. 

Formation of phenol very likely requires an ipso addition of C02 to chlorobenzene, as shown in reaction (R35). The ipso position was also reported to be the preferred site for hydroxyl radical addition to chlorobenzene." The bimolecular reaction of the ipso adduct C02 CHD with HO-CHD radicals of chlorobenzene is an alternative reaction channel yielding benzoic acid, HCI and chlorophenol, reaction (R36). Elimination of HC02 from the ipso adduct, reaction (R37), and subsequent reaction with HO-CHD radicals leads to the formation of phenol, HCI and chlorophenol," reaction (R38). 

Alkoxy and acetoxy substituents have been shown to have markedly different directing effects in the addition of Me (MeLi) to coordinated cyclohexadienyl rings. While a 1-ethoxy group in cation (101) leads to the ipso-adduct (102) in a regiospecific fashion, a 1-acetoxy substituent directs nucleophilic addition exclusively to the far end of the dienyl t-system to give (103) (Scheme 15, R = Et or Ac). This reversal of regiocontrol opens up novel possibilities for complementary control strategies in asymmetric synthesis. 

Chloro-l,7-naphthyridine (110 X = Cl) gives on animation with KNH2/ NH3 the tele product 2-amino-1,7-naphthyridine (53) in addition to the ipso product 8-amino-l,7-naphthyridine (54).10 25 The formation of 53 involves as intermediates anionic cr-adduct 111 (X = Cl) (its existence has been proved by NMR spectroscopy see Section I1,B,1) and probably 2-amino-2,8-dihydro-8-chloro-1,7-naphthyridine (112). The latter undergoes a base-catalyzed dehydrochlorination, yielding 53. Because there are four atoms between position 2 and 8. the reaction is called an even tele substitution. 

In benzene derivatives, electron-donating substituents direct into the ortho-and para-positions, while in the case of the electron-withdrawing substituents considerable meta-addition is observed (Table 3.1) otherwise a more equal distribution is established [reactions (6)-(9) and Table 3.1]. In agreement with the pronounced regioselectivity, ipso-addition at a bulky substituent such as the chlorine substituent in chlorobenzene is disfavored. Evidence for this is the low HC1 yield in the case of chlorobenzene, the low yield of para adduct in 4-methyl-phenol (Table 3.1), or the decarboxylation in the case of benzoic acid [reactions (6) and (10)]. 

Pentafluorophenoxy)prop-l-ene upon irradiation in cyclohexane remarkably yields an intramolecular ortho adduct by the addition of the double bond to the ipso,ortho positions of the benzene ring [111], This reaction is exceptional, because the alkene and the arene are connected by a two-atom bridge. 

Several computational studies have been conducted on (Reaction lb) to examine the relative importance of the initial OH addition to the ipso, ortho, meta, and para sites on the aromatic ring. A summary of the computational approaches used by different authors and the reaction energies calculated for the OH-adduct formation for the case of toluene appear in Table 14.3. The data indicate that... 

Addition at the ipso site had been assumed to be unlikely because of steric hindrance arguments. Therefore, past studies by Bartolotti and Edney [26] and Andino et al [27] had not focused on this pathway. For comparison, ortho and ipso toluene-OH adducts are represented in Figure 14.2 as calculated at the MP2/... 

The principal feature of the chemical reactivity of QBA is the addition of a nucleophile to the iminium bond C=N (Scheme 1). The carbon atom C-6 displays the lowest 7C-electron density [97,98]. This process is associated with a number of significant alterations in the constitution, physical appearance, solubility, spectral properties, etc. The quaternary cation is a brightly coloured, polar, water-soluble species. The tertiary-nitrogen adduct has lost the colour and is non-polar and water insoluble. In the case of aminoacetal and aminal derivatives (Scheme 1, Nu = OR, NHR), the reaction is essentially reversible, i.e. the action of acid immediately converts the adduct back to the quaternary salt. Viewed from another perspective the emergence of colour is a sensitive indicator of the presence of some acid and ipso facto of deconq)osition of the adduct. 

Addition of the PhOO radical to the ipso carbon of the phenyl ring has a low barrier (20 kcal mol below the entrance channel) and a tight transition state. This path is important and the addition results in a dioxirane cyclohexadienyl radical (Y(C6 )Y(C02). This bicyclic cyclohexadienyl-dioxirane adduct has resonance between the ortho and para positions on the ring. The formation path has a barrier of 29 kcal mol relatively to the stabilized peroxy... 

A further variation of these functionalizations of cyanoarenes is the NOCAS process [14, 15]. As shown in Scheme 14.2, path g, this involves the addition of a nucleophile (which is often the solvent) to the donor radical cation. The thus-formed neutral radical adds to the acceptor radical anion, while rearomatization by the loss of an anion leads again to an overall ipso-substitution. AUenes could be used as the donors in these reactions, as shown recently by Arnold [50]. Accordingly, the irradiation of TCB in the presence of tetramethylaUene (15) in a 3 1 MeCN/MeOH mixture afforded 1 1 1 arene-allene-methanol adduct 16 in 48% yield (Scheme 14.9, central part). Interestingly, the addition of methanol took place exclusively at the central allene carbon, while aromatic substitution occurred through the terminal carbons. co-Alkenols, in which an O-nucleophile and an easily oxidized moiety are both present, could also be used. In the latter case, the initial ET was followed by a cyclization, yielding aryl-substituted tetra-hydrofurans or tetrahydropyrans as the final products via a tandem Ar—C, C—O bond formation [51]. 

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