Ipso-addition

The coupling reaction of 3-methylindole (Scheme 12-21) is complex, as it involves an initial ipso-addition at the 3-position followed by rearrangement of the arylazo group to the 2-position (Jackson and Lynch, 1987 Jackson et al., 1987). However, under slightly different conditions Spande and Glenner (1973) isolated the unusual triazene 12.41. Based on the change in the UV spectrum of the reaction mixture with time, Sarma and Barooah (1977) proposed a mechanism involving initial formation... 

Oxidative dehalogenation of aromatic halogens should not occur because there is no hydrogen atom on the carbon involved however, it often does occur. One mechanism likely involves ipso addition as will be discussed later and as proposed for the dechlorination of pentachlorophenol (Fig. 4.65) (131). 

Based on the observation that 1,4-dimethoxycyclohexadiene cationic iron complex 310 undergoes regiospeciflc nucleophilic addition at C(l) and not at C(S) Stephenson et al [81] developed a new formal synthesis of ( )-lycoramine (300) (Scheme 47). Thus, the arylcarbanion 311, derived from the bromocompound 312 by halogen-metal exchange, reacted with 310 to provide the ipso addition product 313. Oxidative elimination of the C(l) methoxyl group generated the salt 314. 

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)]. 

The addition of two nucleophiles to a coordinated //6-arene is a synthetically important goal. A one-pot synthesis of 1,3-disubstituted cyclohexadienes involving an initial ipso addition to fluoroarene complexes is possible. Indeed, p-fluorotoluenetricarbonylchromium complex 22c reacts with isobutyronitrile carbanion (2 equiv.) in THF to give, after 5 days at —30 °C and acidic treatment under CO atmosphere, the cyclohexadiene 66 in 47 % yield (Scheme 31) [53] the yield can reach 75 % after several weeks Carbon monoxide was used in order to decoordinate the // -cyclohexadiene intermediate and to recover Cr(CO)6 needed for the preparation of the starting material [54]. 

The complex 3-[(//6-4-toluene)tricarbonylchromium indent (69) is obtained in 69 % yield from the ipso nucleophilic substitution of (//6-p-fhiorotoluene)tricarbonylchromium complex 22c with indenyllithium (70) [57]. A 1,3-shift of the benzylic proton probably takes place after the ipso addition of indenyllithium (Scheme 33). 

With monosubstituted benzenes, the tendency of OH to undergo ipso addition seems to be small (<10%). However, if the ipso position is activated by a second substituent like CH3O, HO or 0 , ipso addition may contribute up to 25% to the overall reactivity . Due to the small size of the OH radical, steric effects (i.e. the size of X) do not seem to be of mnch importance in determining the probability of OH attack at the ipso position. Oxidative replacement of halogen has been observed also with pentafluoro-, pentachloro-, pentabromo- and 2,4,6-triiodo-phenol, where it occurs in parallel to electron transfer". ... 

Scheme 2.137 Aromatic nucleophilic substitution and ipso-addition with a variety of Rp " sources [91],...

Intramolecular addition of the peroxy radical to the carbon of the peroxy group (ipso addition), 3-member ring formation... 

Arenium ions possessing a ring fragment of the CHR type or ortho(para)-positioned OH-, NHR- and CHR-type substituents mainly react with rising nucleophilicity of the medium by loss of the proton, as marked earlier. In some cases the Iok of the proton from the substituent competes with the addition of a nucleophile to the ion. For example, arenium ions formed by ipso-addition of N02 capture an acetate-anion (nitroacetoxylation 2-665)j. 

Of particular interest are ipso-additions - of an electrophile, since the respective a-complexes are in most cases unfavourable from the thermodynamic point of view. Therefore, one must be careful to draw conclusions on the initial ratio of isomeric a-complexes from the ratio of isomeric reaction products. Thus, the nitration of 4-isopropyltoluene (p-cymene) by nitronium tetrafluoroborate in sulpholane at 25 C gives 2-nitro- and 3-nitro-4-isopropyltoluenes as well as p-nitro-toluene with the yields 85.2, 5.3 and 9.5 %, respectively Accordingly the reactivity ratio of the 2- and 3-positions of p-cymene in the nitration is 16 1. However, in the nitration of p-cymene by acetylnitrate in acetic anhydride at 0 °C among the above reaction products (with 41.8 and 10% yields, respectively) there is a considerable amount (41%) of cis- and trans-isomers of l-nitro-4-acetoxy-l-methyl-4-isopropylcyclohexa-2,5-diene This may be due to the capture of the acetate-... 

A series of papershave examined the regioselectivity of nucleophilic addition to the arene ligands in a range of [Fe(Cp)(T7 -arene)] cations. The relative distribution of 0-, m-, p-, and ipso-addition products was explained as arising from a combination of electronic, steric, and free valency effects. The nature of the nucleophile was also seen to be important, as shown by the different product distributions obtained from the additions of hydride, cyanide, and acetonyl anions, respectively. 

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). 

Despite these complications with cine and tdc pathways, it turns out that the more obvious ipso-S Ar pathway, in which the nucleophile adds at the position that carries the leaving group (i.e., ipso addition), is also quite common (see Section 14.5.7). In the case of 40 (Scheme 14.16), the indenyl substituent isomerized... 

A synthesis of isopiperitone (71) in Rosenblum s group provides an early synthetic example where the power of the C-1 donor substituent in 72 was employed [16]. Although it only produced one carbon-metal featured twice in this synthesis (Table 14.1 entry 10), and the strategy can be classed as iterative tf tf). Similarly in 74, the metal moves to the least-hindered end, and the relatively large size of the organic group in the donor does not present a problem for ipso addition [297]. This is a key step (Table 14.1 entry 11) in the enantioselec-tive synthesis of ent-sitophilate (73). 

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