Cationic pathways

Diazirines are in most cases more easily available than linear diazo compounds. Moreover, their decomposition via true carbenes is free of side reactions, whereas linear diazo compounds in presence of H-donors may react by a cationic pathway. Only where reactions of linear diazo compounds are optimized for carbene formation do they give the same products as do decomposing diazirines. 

Carboxylic acids with an electron donating substituent in the a-position decarboxylate in a two-electron oxidation to carbocations (see chap. 7). These can react with the solvent (alcohol, acetic acid, water) or the unreacted carboxylate to ethers, esters, or alcohols (Eq, 14). In some cases the carbon skeleton rearranges, which is a clear indication of the cationic pathway. 

As the mechanism, a radical and a cationic pathway are conceivable (Eq. 31). The stereochemical results with rac- or mcjo-1,2-diphenyl succinic acid, both yield only trans-stilbene [321], and the formation of a tricyclic lactone 51 in the decarboxylation of norbornene dicarboxylic acid 50 (Eq. 32) [309] support a cation (path b, Eq. 31) rather than a biradical as intermediate (path a). 

However, the inhibition of the reaction by lithium perchlorate, that strongly favors the cationic pathway (see chap. 2, 7), contradicts this assumption. With regard to yield and the degree of passivation the decarboxylation/desilylation appears to be a better choice than the bisdecarboxylation for the construction of unsaturated polycyclic compounds (see for example Table 11, No. 12b and No. 22). 

The cationic pathway allows the conversion of carboxylic acids into ethers, acetals or amides. From a-aminoacids versatile chiral building blocks are accessible. The eliminative decarboxylation of vicinal diacids or P-silyl carboxylic acids, combined with cycloaddition reactions, allows the efficient construction of cyclobutenes or cyclohexadienes. The induction of cationic rearrangements or fragmentations is a potent way to specifically substituted cyclopentanoids and ring extensions by one-or four carbons. In view of these favorable qualities of Kolbe electrolysis, numerous useful applications of this old reaction can be expected in the future. 

The membrane-bound preparation from kidney is easily solubilized in non-ionic detergent and analytical ultracentrifugation shows that the preparation consists predominantly (80 85%) of soluble af units with 143000 [28]. The soluble a)S unit maintains full Na,K-ATPase activity, and can undergo the cation or nucleotide induced conformational transitions that are observed in the membrane-bound preparation. A cavity for occlusion of 2K or 3Na ions can be demonstrated within the structure of the soluble a)S unit [29], as an indication that the cation pathway is organized in a pore through the aji unit rather than in the interphase between subunits in an oligomer. 

To understand the Na,K-pump mechanism it is obviously important to identify the cation pathway and the sites for binding and occlusion of Na and K relative to the intramembrane portion of the protein. The groups coordinating the cations should be identified and it should be known if the pump has independent sites for Na" and K" " or if the cations bind alternately to the same set of sites. With a stoichiometry of 3Na /2K per ATP split this would mean that two sites bind Na and alternately, while one site only binds Na". ... 

Barluenga et al. developed a novel exo-endo-cyclization of a,codiynes by use of bis(pyridyl) iodonium(I)-tetrafluoroborate (IPy2BF4) as catalyst.1171 The reaction follows a cationic-cationic pathway (scheme 6). First the electrophilic iodo ion reacts with the triple bond of 26 to give the relative stable vinyl cation 28. Ring closure leads to a seven-... 

Scheme 4.102 Cation and radical-cation pathways for selenoglycoside glycosylation.

Scheme 16 Anodic decarboxylation radical and cationic pathway.

Surface-catalyzed dark and photoassisted phosphate ester hydrolysis (P—O bond rupture) in aqueous suspensions of TiO2 has been proposed [6,7,41]. A number of products indicative of radical cationic pathways have been reported in the TiO2 photocatalysis of benzyl phosphonic acid [44]. 

Recent development of the Heck reaction has also led to greater understanding of its mechanistic details. The general outlines of the mechanism of the Heck reaction have been appreciated since the 1970s and are discussed in numerous reviews [2,3]. More recently, two distinct pathways, termed the neutral and cationic pathways, have been recognized [2c-g,3,7,8,9]. The neutral pathway is followed for unsaturated halide substrates and is outlined in Scheme 8G. 1 for the Heck cyclization of an aryl halide. Thus, oxidative addition of the aryl halide 1.2 to a (bisphosphine)Pd(O) (1.1) catalyst generates intermediate 1.3. Coordination of... 

The cationic pathway is followed for unsaturated triflate substrates, or for unsaturated halide substrates in the presence of halide scavengers such as Ag(I) or Th(I) salts [2,3], and is shown in Scheme 8G.2. The individual steps are similar to the neutral pathway, but the difference in the two mechanisms lies in the nature of the Pd(II) intermediates 2.1-2.3, which are now cationic. As will be discussed in more detail later in this review, this difference has a marked effect on both reactivity and enantioselectivity. 

Extensive studies by Amatore, Jutand, and co-workers have shed light on the structure and oxidative addition chemistry of a number of synthetically important palladium complexes [42], In particular, these workers have shown that the major species in a solution of Pd(dba)2 and BINAP is Pd(dba)BINAP and that oxidative addition of Phi to this complex generates (Bl-NAP)Pd(Ph)I [42d,43], In addition, it has been demonstrated that palladium halide complexes such as (PhjP jaryljPdCl do not dissociate the halide ligand in DMF solution [44], whereas the corresponding triflate complex is completely dissociated [44,45], As noted earlier, the nature of the oxidative addition intermediates defines two mechanistic pathways for the Heck reaction the neutral pathway for unsaturated halide substrates and the cationic pathway for unsaturated triflate substrates [2c-g,3,7-9]. Further, it is possible for halide substrates to be diverted to the cationic pathway by addition of Ag(I) orTh(I) salts [3], and it is possible to divert some triflate substrates to the neutral pathway by addition of halide additives [38]. Individual steps of these two pathways have recently received some scrutiny. 

Salient features of the cationic pathway, which was introduced independently by Cabri [8] and Hayashi [9], are presented in Scheme 8G.20. Thus, subsequent to oxidative addition, a vacant coordination site is generated either by triflate dissociation or by halide abstraction by the Ag(I) salt in intermediate 20,4. This vacant coordination site facilitates double-bond coordination to form cationic intermediate 20.5, which ultimately forms the Heck product. 

The first detailed study of the individual steps of the cationic pathway of the intramolecular Heck reaction was recently described by Brown (Scheme 8G.21) [46], Oxidative addition of aryl iodide 21.1 to [l,l -bis(diphenylphosphino)ferrocene](cyclooctatetraene)palladium generated 21,2. Complex 21.2 was stable at room temperature and was characterized by X-ray crystallography no interaction between the palladium center and the tethered alkene was observed in this intermediate. Treatment of 21.2 with AgOTf at -78°C removed iodide from the palladium coordination sphere, which facilitated a rapid alkene coordination and subsequent... 

A key feature of the cationic mechanism is that removal (or dissociation) of an anionic ligand from the palladium coordination sphere allows alkene complexation to occur while maintaining coordination of both phosphines of a bisphosphine ligand. That both phosphines can be accommodated in a square-planar four-coordinate intermediate during the insertion step has provided a simple rationalization for the higher enantioselectivities often observed for the cationic pathway. Concrete information on the enantioselective step of asymmetric Heck reactions proceeding by the cationic pathway has not been reported to date. It is likely to be either coordination of the alkene to generate 20.S or the insertion step (20.5 —> 20.6, Scheme 8G.20). 

The neutral pathway differs from the cationic pathway in the absence of a vacant coordination site in the square-planar four-coordinate palladium(II) intermediate prior to alkene coordination. The key question is then how does alkene coordination take place. Early studies pointed out that Heck reactions of aryl or vinyl halides promoted by (bisphosphine)palladium complexes could be sluggish, and this sluggishness was attributed to a reluctance of one of the phosphines of the... 

Pyridylarenes undergo Cu(II)-catalysed diverse oxidative C-H functionalization reactions. The tolerance of alkene, alkoxy, and aldehyde functionality is a synthetically useful feature of this reaction. A radical-cation pathway (Scheme 4) has been postulated to explain the data from mechanistic studies. A single electron transfer (SET) from the aryl ring to the coordinated Cu(II) leading to the cation-radical intermediate is the rate-limiting step. The lack of reactivity of biphenyl led to the suggestion that the coordination of Cu(II) to the pyridine is necessary for the SET process. The observed ortho selectivity is explained by an intramolecular anion transfer from a nitrogen-bound Cu(I) complex.53... 

According to Kiirti and Czako,36 there is an important interaction between the HOMO of the ene component CH2=CH-C-H and the LUMO of the enophile. In agreement with this interpretation, the reaction is favored by electron-withdrawing substituents on the enophile. However, the rate is also enhanced if electrons are withdrawn from the ene component. For example, according to the same authors, the mechanism of the Lewis acid promoted ene reaction is believed to involve both a concerted and a cationic pathway.37 Whether the mechanism is concerted or stepwise, a partial or full positive charge is developed at the ene component in Lewis acid promoted ene reaction.36 Explain this contradiction. 

In this example, significant chiral induction can only be realized if silver salts are added to trap the iodide ions, and thus a chelating coordination mode of the chiral bidentate ligand is facilitated during coordination of the olefin (Scheme 2, cationic pathway). Even better results are obtained from substrates with non-coordinating leaving groups such as vinyl triflates. 

Scheme 10. Reverse enantioselectivity for the neutral and cationic pathways.

The competition between the radical and cationic pathway in the Kolbe reaction is strongly influenced by the presence of foreign anions, e.g. CIO4 and F", as has been known for a long time (for reviews, see Eberson, 1968, 1973). Exactly how strong this influence is was recently shown for the oxidation of phenylacetate ion the addition of only one hundredth molar proportion of perchlorate relative to phenylacetate ion completely suppressed formation of the... 

To confirm the 1,3-hydrogen shift, the prerequisite for the cyclization of the cyclodecadienyl cation to the bicyclodecenyl cation (pathway a, Scheme 55), Jommi et al. used [2—5— H2]-mevalonate [( )-463 ]. The ratio of to in dendrobine (82) and its derivatives was expected to determine the correctness of the hypothesis (226). 

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