Ipso-directing effect

The presence of activating substituent on the carbocyclic ring can, of course, affect the position of substitution. For example, Entries 4 and 5 in Table 14.1 reflect such orientational effects. Entry 6 involves using the ipso-directing effect of a trimethylsilyl substituent to achieve 4-acetylation. 

Halogen Substituents with Ipso-Directing Effects in Synthetic Applications of M ulti hapto-Complexes... 

Trialkyltin substituents are also powerful ipso-directing groups. The overall electronic effects are similar to those in silanes, but the tin substituent is a better electron donor. The electron density at carbon is increased, as is the stabilization of /S-carbocation character. Acidic cleavage of arylstannanes is formulated as an electrophilic aromatic substitution proceeding through an ipso-oriented c-complex. ... 

Since trimethylsilylarenes can be prepared by metallation of the arene followed by treatment with chlorotrimethylsilane, this provides an alternative route into a range of difficult substitution patterns. For example, the ortho/para directing effects of the methoxy groups in 1,3-dimethoxybenzene 75 direct the electrophile to the 4-position. However, lithiation of 1,3-dimethoxybenzene takes place at the 2-position. Reaction with chlorotrimethylsilane then gives the 2-trimethylsilyl compound 76, which undergoes ipso substitution with the electrophile to give the 1,2,3-trisubstituted product 77 (equation 39)101,102. 

Exactly the same sort of mechanism accounts for the reactions of aryl silanes with electrophiles under Friedel-Crafts conditions. Instead of the usual rules governing ortho, meta, and para substitution using the directing effects of the substituents, there is just one rule the silyl group is replaced by the electrophile at the same atom on the ring—this is known as ipso substitution. Actually, this selectivity comes from the same principles as those used for ordinary aromatic substitution (Chapter 22) the electrophile reacts to produce the most stable cation—in this case (3 to silicon. Cleavage of the weakened C-Si bond by any nucleophile leads directly to the ipso product. 

Moreover, the powerful directing effect was observed with ortAo-methoxycarbonyl group which favours the ipso-attack [3]. Further improvements have been introduced by using the diazonium salts as parent substrates, similarily to the Pschorr reaction [4]. 

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. 

The main purpose of this chapter is to discuss the directing effects of functional groups in these reactions. As one would expect, steric effects direct internal nucleophile addition to the less hindered of the electrophilic centers as in the formation of 49. With a C-1 OMe substituent, a addition has been proposed [235]. Internal nucleophile addition to the less hindered of the electrophilic centers has also been reported for 50 [236]. Other examples give mixtures [237]. On the other hand, 1,4-dimethyl substitution on the tj cydoheptadienyl ligand shows regiocon-trol dominated by the C-1 Me group (y selectivity ipso to the C-4Me group) [229]. 

The presence of a 4-methoxy substituent on the 2-phenylethyloxyl or 3-phenylpropyl-oxyl side chains radically altered the course of these cyclizations (Scheme 4). 31a and 31b afforded the spiro-fused ring systems 32 and 33 in 26 and 69% yields, respectively, as the only cyclization products. With this substituent, cyclization onto the activated ipso positions was favoured over direct attack, even where the strained transition state for Atj -5 cyclization of 31a to 32 was involved. Demethylation of the intermediate spirocyclohexa-dienyl cation is favoured over rearrangement in these cases. Kikugawa and coworkers effected the formation of 32 (82%) and 33 (39%) with reverse efficiencies using AgaCOs in TFA . 

In view of the extensive documentation outlined above, the usefulness of the polarity alternation concept as a primary guide for evaluation of substituent effects can hardly be denied. The influence of a substituent on the ipso site has not been discussed in this article but an even more direct and important effect is implicit. Among the innumerable examples one may cite the preferential formation of geminal dimetallic species [5] in hydrometalation and carbometalation of vinylmetals and acetylenes. On the other hand, chemical systems are usually very complex, inter- and intramolecular forces including steric and stereoelectronic factors may dominate over polarity alternation. Thus, chelation by a proximal donor often directs metalation and stabilizes certain organometallic entities. In these instances the stability gaining from polarity alternation is overwhelmed. 

Some differences in the change of 13C NMR chemical shifts of nitrobenzothiazoles compared with nitrobenzimidazoles and nitrobenzoxazoles have been discussed. In Table 3.30 the 13C NMR chemical shifts of nitrobenzothiazoles are presented. The nitro group introduction into position 2 leads to a 10 ppm down field shift of the ipso-carbon resonance, whereas a similar effect of the ipso-substitution in the phenylene fragment of benzothiazoles is 20 ppm [778-781], The results of regression analysis of the 13C NMR chemical shifts of benzothiazoles in terms of the inductive and resonance constants of substituents (F and R, c, and cR, c, and aR°) provide evidence for the fact that the substituent effect transmission from positions 2-6 is approximately 30% weaker than in the opposite direction [779], As stated previously, an analogous picture is observed for benzimidazoles. 

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