Ipso product

Erickson extended these reactions to useful preparations of both 3-chloroindole and several 2,3-dihaloindoles, many of which occur naturally [5], When the C-3 position is already substituted, halogenation usually occurs at C-2. A summary of these halogenations is shown below. Erickson was able to improve Piers synthesis of 2 to a yield of 82%. Interestingly, the action of sulfuryl chloride on 3-iodoindole gives the ipso product 3-chloroindole in 84% yield. 

Interestingly, with only slight difference in the imidazole N-protection, an anomalous Stille reaction occurred for the stannane 43 [29]. When the protecting group of the 5-stannylimidazole was changed from methyl into 1-ethoxymethyl, the reaction between 3-iodoindole 44 and 1-ethoxymethyl-5-bromo-2-methylthioimidazole (46) gave not only the normal ipso product 47 but also the cine product 48. 

The two-electron reduction product of terephthalodinitrile reacts with alkyl halides in liquid ammonia to yield 4-alkylbenzonitriles and 2-alkylterephthalodinitriles. The product ratio strongly depends on the alkyl halide and changes in favour of the ipso product, 4-alkylbenzonitrile, on going from tertiary alkyl to primary and from iodide to chloride. This change is the result of increased contribution of the 5n mechanism relative to the ET mechanism. 

III,B,1 we will deal with reactions in which both cine and ipso products are formed. The mechanism according to which these products are formed has been explained by the occurrence of a didehydronaphthyridine (naphthyri-dyne) intermediate.44 In Section III,B,2 the occurrence of aminodehalogena-tions involving tele substitutions are discussed and in Section 1II,B,3 the reactions in which the aminodehalogenation occurs in an ipso position are examined. 

Reaction of 3-bromoquinoline (62) with KNH2/NH3 gave a mixture of the ipso product 3-aminoquinoline (64) and the cine product 4-aminoquinoline... 

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. 

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. 

The reactivity of 6-haloimidazol[l,2-a]pyridine 135 towards different azoles can be modulated to give ipso product 136 in the presence of copper(l) catalyst or to yield cine product 137 in the absence of copper catalyst <03JOC5614>. Imidazo[l,2-a]pyrimidine 138 can be arylated at the 3-posltion with aryl bromides in the presence of cesium carbonate with catalytic palladium(II) acetate to give 139 <03OL4835>. 

Tanaka et al. have made the intef ting discovery that when cephems undergo vinylation with vinyltributyltin the nature of the product depends on the metal used [214] thus palladium catalysis afford the ipso product while the use of l.Sequiv. of CuCl in N-methylpyrrolidone leads to a double-bond shift in the cephem moiety (Scheme 4-54),... 

Alkyldenitration by the 1-adamantyl radical in / ara-substituted nitrobenzenes (/7-X-C6H4-NO2) is an efficient process only for electron-poor arenes. Thus, while for anisole (X = OMe), benzene (X = H) and toluene (X = Me) derivatives no ipso products were observed, the analogous reaction with nitrobenzenes bearing electron withdrawing substituents (X = NO2, CN, SO2R, CO2R, COMe, CHO) afforded the corresponding alkyldenitration products in 45-60 /) yield [30]. The effect of the... 

Pd(dba)2 in MeCN at room temperature. Two products, namely the expected ipso product 18 and the cine product 19, were obtained [91], On the other hand, reaction of a-trimethylsilylstyrene 20 with 21 afforded the cine product 22 regio-and stereoselectively [92], An application of the coupling of aryldiazonium salt to a,a -bis(trimethylsilyl)-l,4-divinylbenzene derivative 23 afforded the (E,E)-bis(styryl)benzene derivative 24 cleanly [93]. 

The reaction of 17 (or 25) to give 19 (or 31) can not be explained by the oxidative addition-transmetallation-reductive elimination mechanism. In the reaction of 25, carbopalladation to form 26 and 27 is the first step. Desilylpalladation of 26 affords the expected ipso product 28. On the other hand, the intermediate 27 undergoes syn dehydropalladation to give 29, to which syn addition of H-PdX occurs to generate 30. Then anti desilylpalladation provides the cine product 31. This reaction is not completely fluoride-free, because the Bp4 anion is present. 

Coupling of the tram -styrylsilane 35 with iodobenzene gave rise mainly to trans-stilbene (36) as the ipso product and only a small amount of the cine product 37. Under the same conditions, cine product 41 was obtained to some extent from the a-silylstyrene 38 in addition to ipso product 40. The ipso cine ratios change depending on substituents (R) of the aryl iodides 39 [95]. 

Cine substitution is encountered occasionally as a result of a slow transmetallation step when sterically encumbered stannanes are used. Flohr [8] carried out studies designed to find a system suitable for the Stille coupling between sterically congested vinyltins and aryl iodides or trifiates he found that under certain conditions the iodides gave ipso products, while the trifiates under somewhat different conditions afforded cine substitution (Scheme 6.3). He also found that the addition of copper iodide was essential for successful coupling of aryl iodides. Mechanistic explanations of this abnormal cross-coupling mode (cine product)... 

Ipso substitution, as given in the equation below, is sometimes observed in electrophilic aromatic substitution reactions. Explain how the data provided in Figures 15.8-15.11 are inconsistent with the structures of the ipso products shown. 

On the basis of these observations, complex 24 was tested as catalyst for the allylic alkylation of allyl carbonates. In general, Rh complexes led preferentially to the ipso alkylation products [41] while Ir complexes tended to produce the branched and Pd catalysts the linear as the major alkylation product [42]. The catalytic results of complex 24 showed a 6 1 ratio for the ipso product in case of... 

Figure 9.11 Allylic alkylation of allylcarbonates catalyzed by complex 24. In each example, the respective ipso product is dominating, but in case of the linear carbonate a substantial isomerization occurred [13b].

The first example of an allylic alkylation catalyzed by iron compounds was reported in 1979. Allylic halides and carboxylates are treated with a diethyl malonate anion in the presence of sodium tricarbonyl(nitrosyl)ferrate to give the allylated malonates with good regioselectivity in favor of the ipso product (Scheme 4-195). This transformation can be carried out in a carbon monoxide atmosphere catalyzed by the Hieber-type complex [Bu4N][Fe(CO)3NO] (TBAFe) that is easier to handle. The... 

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