Alkoxycarbenium ions generation

The alkoxycarbenium ions generated by the cation pool method react with various carbon nucleophiles such as substituted allylsilanes and enol silyl ethers to give the corresponding coupling products in good yields. It should be noted that the reactions of alkoxycarbenium ion pools with such nucleophiles are much faster than the Lewis acid promoted reactions of acetals with similar nucleophiles. A higher concentration of the cationic species in the cation pool method seems to be responsible. 

Focusing on the synthetic/preparative aspects, in Chapter 10 by J-i. Yoshida, novel approaches to generation of N-acyliminium and alkoxycarbenium ions are presented and their synthetic applications are discussed. 

Alkoxycarbenium ions are important reactive intermediates in modem organic synthesis.28 It should be noted that other names such as oxonium ions, oxocarbenium ions, and carboxonium ions have also been used for carbocations stabilized by an adjacent oxygen atom and that we often draw structures having a carbon-oxygen double bond for this type of cations.2 Alkoxycarbenium ions are often generated from the corresponding acetals by treatment with Lewis acids in the presence of carbon nucleophiles. This type of reaction serves as efficient methods for carbon-carbon bond formation. 

If we consider the generation of alkoxycarbenium ions by C-H bond dissociation, ethers should be of our first choice as precursors of alkoxycarbenium ions by analogy to carbamates. The oxidation potentials of ethers, especially aliphatic ethers, however, are very positive, and therefore, it is rather difficult to oxidize ethers selectively under usual conditions. The regioselectivity is also a problem. Usually a mixture of two regioisomers of products is obtained because two regioisomeric alkoxycarbenium ions are generated. 

Generation of Alkoxycarbenium Ion Pools by Oxidative C-S Bond Cleavage... 

We chose to study the generation of alkoxycarbenium ion 26 from thioacetal 28. The electrochemically generated ArS(ArSSAr)+, 37 which was well characterized by CSI-MS, was found to be quite effective for the generation of alkoxycarbenium ions, presumably because of its high thiophilicity (Scheme 17). The conversion of 28 to 26 requires 5 min at -78 °C. The alkoxycarbenium ion pool 26 thus obtained exhibited similar stability and reactivity to that obtained with the direct electrochemical method. The indirect cation pool method serves a powerful tool not only for mechanistic studies on highly reactive cations but also for rapid parallel synthesis. 

Alkoxycarbenium ion pools can also be generated by oxidative C-C bond dissociation. Oxidative C-C bond dissociation is well known in the literature.38 Thus, the electrochemical oxidation of l,2-dimethoxy-l,2-diphenylethane 32... 

S. Suzuki, K. Matsumoto, K. Kawamura, S. Suga, and J.-I. Yoshida, Generation of alkoxycarbenium ion pools from thioacetals and applications in glycosylation chemistry, Org. Lett., 6 (2004) 3755-3758. 

Generation of alkoxycarbenium ions is often carried out by treatment of the corresponding acetals or their derivatives with a Lewis acid in the presence of a carbon nucleophile. This type of reaction serves as an efficient method for carbon-carbon bond formation under acidic conditions. Mechanistic studies of Lewis-acid promoted reactions of acetals using NMR spectroscopy showed the presence of Lewis acid-acetal complexes in the solution, but alkoxycarbenium ions were never detected. The absence of signals resulting from alkoxycarbenium ions in the NMR spectra, however, does not necessarily rule out their intermediacy in the reactions with nucleophiles. Therefore, it was imperative to accomplish the reactions of spectroscopically characterized, nonsta-bilized alkoxycarbenium ions with carbon nucleophiles. The cation-pool method made this possible and opened a new chapter in the chemistry of alkoxycarbenium ions. 

The thus-generated alkoxycarbenium ion is stable only at temperatures below approximately —50 °C. Above this temperature, it decomposes. 

Generation of alkoxycarbenium ion pools by oxidative C—S bond cleavage... 

Alkoxycarbenium ion pools can also be generated by electrochemical oxidative C—S bond dissociation (Scheme 5.20). " Arylthio (ArS) groups are known to also serve as effective electroauxiliaries for the electrochemical oxidation of heteroatom compounds. " The introduction of an ArS group decreases the oxidation potential and the C—S bond... 

Problems have been observed when attempting to carry out reactions with either diacid chlorides or half-ester half-acid chlorides when the two carbonyl functions are separated by either two or three carbon atoms. Rearrangement reactions occur with those compounds and so Friedel-Crafts acylation reactions may yield mixtures of products. Optically active methyl 3-methylglutarate was shown to racemize easily Suggested explanations of these effects include the involvement of alkyl diacyloxonium and acyl-oxy-alkoxycarbenium ions. NMR studies have shown that the half methyl ester-half acid chloride from phthalic acid forms the acyloxy-alkoxycarbenium ion very easilyj and that the related ions derived from succinic and glutaric acids can also be generated under stable ion conditions. ... 

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