Arenes addition-elimination reactions

We now have some new reactions to use in problems. Put another way, your lives are now even more complicated than before, as even more sadistically difficult problems are within your abilities. There really aren t too many new things to think about. You only have to add the Claisen-like processes that involve the loss of a leaving group from a carbonyl carbon that has been attacked by an enolate. In other words, you always have to keep the addition-elimination reaction in mind. 

Nucleophilic substitutions of halogen by the addition-elimination pathway in electron-deficient six-membered hetarenes by sulfinate anions under formation of sulfones have been described earlier120. The corresponding electron-poor arenes behave similarly121 (equation 30). A special type of this reaction represents the inverse Smiles rearrangement in equation 31122. 

It seems that no general mechanistic description fits all these experiments. Some of the reactions proceed via an addition-elimination mechanism, while in others the primary step is electron transfer from the arene with formation of a radical cation. This second mechanism is then very similar to the electrochemical anodic substitution/addition sequence. 

Intramolecular oxidative cyclizations in the appropriately substituted phenols and phenol ethers provide a powerful tool for the construction of various practically important polycyclic systems. Especially interesting and synthetically useful is the oxidation of the p-substituted phenols 12 with [bis(acyloxy)iodo]-arenes in the presence of an appropriate external or internal nucleophile (Nu) leading to the respective spiro dienones 15 according to Scheme 6. It is assumed that this reaction proceeds via concerted addition-elimination in the intermediate product 13, or via phenoxenium ions 14 [18 - 21]. The recently reported lack of chirality induction in the phenolic oxidation in the presence of dibenzoyltar-taric acid supports the hypothesis that of mechanism proceeding via phenoxenium ions 14 [18]. The o-substituted phenols can be oxidized similarly with the formation of the respective 2,4-cyclohexadienone derivatives. 

Only one example of an attachment of heteroarenes by addition/elimination strategy has been devised [77, 111]. Although arenes are more or less resistant toward addition, heteroaromatic systems such as isoquinolines 118 are prone to addition of nucleophiles. Subsequent reaction with addition of electrophiles furnishes the so-called Reissert compounds 120. These are stable compounds which can, for example, be alkylated. In solid-phase synthesis the electrophile chosen was a polymer-based acid chloride. Detachment can be achieved by simple addition of hydroxide ions (Scheme 6.1.30). 

A brief exploration of annulations with nitro-free fluoro arene 37—readily prepared from ( )-methyl 3-methoxyacrylate (36) by a Michael addition elimination strategy with 2-(2-fluorophenyl)acetonitrile (35)—again revealed that direct SNAr cyclization was impeded under all conditions. Extended conjugation may have contributed however, the necessity for the conjugated sp2-hybridized aryl-propene anion to couple intramolecularly with another sp2-hybridized carbon atom imposed a highly strained reaction trajectory (Scheme 9). 

The facility of arene reductive elimination underpins numerous C-C, C-O and C-N bond-forming reactions, which may be catalysed by late transition metals, in particular palladium (Figure 4.10). Although there are many variants, the general reaction scheme involves introduction of the aryl in electrophilic form via oxidative addition of an aryl halide (or sulfonate), substitution of the palladium halide by a nucleophile (which may also be carbon based) followed by reductive elimination. It is noteworthy that nucleophilic aromatic substitution in the absence of such catalysts can be difficult. 

Addition-elimination to an arene, CF3OF reacts with 4-acetoxypyrene (1) at low temperatures to give the adduct 2, which loses CF3OH at room temperature to give 3. Extended reaction of 1 or of 3 with CF3OF results in the difluoro ketone 4. ... 

In equation (256), haloacetylene and nucleophile could be eliminated and these could form the substitution products by addition-elimination steps, the IIT mechanism or the Arens process. By using LiNRJ as a base in equation (255) and looking for two ynamines, or by adding ArSH to reaction (256) and looking for two thioether products, one can seek evidence of the elimination process. Until such tests are performed, the applicability of the Viehe substitution mechanism remains uncertain. 

An important case is the oxidation of alkenes or alkyl arenes containing at least one hydrogen in an a-position [70-77]. The reaction sequence that leads to a-substitution [Eq. (29)] for alkylbenzenes and -naphthalenes most likely includes Eqs. (1), (3), (7), and (11), whereas for alkylanthracenes there is evidence that substitution may take place as an addition-elimination process (see Sec. IV for details). Typical examples are the oxidation of cyclohexene to 3-acetylcyclohexene in AcOH [Eq. (30)] [76], the oxidation of 1,3,5-cycloheptatriene to 7-methoxy-l,3,5-cycloheptatriene in MeOH [74], and the two-... 

A considerable body of the data on the Sn reactions accumulated in the literature [11-49] shows that these reactions are of fundamental value for the chemistry of electron-deficient arenes and heteroarenes. The Sn reactions can be realized through the following pathways (1) the addition-oxidation protocol Sn (AO) which is based on using an outer oxidant (Scheme 13) [11-14] and (2) the addition-elimination scheme Sn (AE) which suggests the presence of... 

In summary, photochemical methods exploit the high energy of the adsorbed photon in various ways - that is, either via reaction of the electronically excited state itself, whether involving the usual addition-elimination mechanism of arenes or unimolecular fragmentations, or via electron transfer followed by fragmentation of one of the charged radical ions. 

Theoretical studies on timgstenocene complexes suggest the intermediacy of arene C-H (j-complexes on the pathway of the oxidative addition and reductive elimination reactions that cleave and form arene C-H bonds. ° Thus, the ri -arene complexes likely rearrange to C-H (j-complexes prior to C-H bond cleavage, as depicted in Equation 8.25. 

Carbon-heteroatom bond-forming reductive elimination from transient intermediates has been proposed as the product release step of a variety of important Pd-catalyzed transformations, including arene and alkane C-H bond functionahza-tion [1,2], ally lie acetoxylation [3], alkene borylation [4], and olefin difunctionalization [5]. Over the past 25 years, a variety of Pd " model complexes have been synthesized to study reductive elimination reactions at Pd centers. For instance, in 1986, Canty reported the first example of a crystallographically characterized organometallic Pd complex, /ac-[(bpy)Pd (CH3)3(l)] (bpy = 2,2 -bipyridine) (1). In addition, his group has demonstrated that this species undergoes facile C-C bond-forming reductive elimination to release ethane (Eq. 1) [6],... 

The reductive elimination from metal-alkyl-hydride complexes L MR(H) (M = Ir, R = Cy or M = Rh, R = Ph) giving the alkane or arene occurs with inverse kinetic isotope effects which were taken into account by a preequilibrium with the a-alkane or r -arene complex. These reactions represent the microscopic reverse of oxidative addition of an alkane or arene C-Fl bond on electron-rich 16-electron metal centers... 

The use of cyclic alkenes as substrates or the preparation of cyclic structures in the Heck reaction allows an asymmetric variation of the Heck reaction. An example of an intermolecular process is the addition of arenes to 1,2-dihydro furan using BINAP as the ligand, reported by Hayashi [23], Since the addition of palladium-aryl occurs in a syn fashion to a cyclic compound, the 13-hydride elimination cannot take place at the carbon that carries the phenyl group just added (carbon 1), and therefore it takes place at the carbon atom at the other side of palladium (carbon 3). The normal Heck products would not be chiral because an alkene is formed at the position where the aryl group is added. A side-reaction that occurs is the isomerisation of the alkene. Figure 13.20 illustrates this, omitting catalyst details and isomerisation products. 

The alkylation reaction is limited to nitro-substituted arenes and heteroarenes and is highly chemoselec-tive nucleophilic displacement of activated halogens, including fluorine, was not observed. The regio-selectivity is determined by the bulkiness of the silicon reagent. With unhindered silyl derivatives a strong preference for ortho addition was observed, as in the example of equation (6). With bulkier reagents attack took place exclusively at the para position (Scheme 1). The success of this reaction, which could not be reproduced with alkali enolates, was attributed at least in part to the essentially nonbasic reaction conditions under which side processes due to base-induced reactions of nitroarenes can be effectively eliminated.12... 

This chapter covers reactions in which coordination of a transition metal to the ir-system of an arene ring activates the ring toward addition of nucleophiles, to give V-cyclohexadienyl-metal complexes (1 Scheme 1). If an electronegative atom is present in the ipso position, elimination of that atom (X in 1) leads to nucleophilic aromatic substitution (path a). Reaction of the intermediate with an electrophile (E+) can give disubstituted 1,3-cyclohexadiene derivatives (path b). If a hydrogen occupies the ipso posi-... 

---