Oxocarbenium ions synthesis

Scheme 18 Synthesis of C-glycals based on oxocarbenium ion-enol ether cyclization.

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. 

From a strictly chemical point of view, the synthesis of glycosides still presents a formidable challenge to synthetic chemists in spite of major advances in the area [1], Unlike peptidic bonds, the formation of the glycosidic linkage is subject to various factors that include, among others, electronic, stereoelectronic, conformational, substituent, and reactivity effects generally associated with incipient oxocarbenium ions derived from carbohydrates. 

The facile synthesis of (24) from (22) has the oxonium cation (23) as an intermediate.62 Vinyl oxocarbenium ions are reported to take part in intermolecular... 

The enantioselective synthesis of the C(18)-C(25) segment of lasanolide A 324 can be achieved via an oxonia-Cope-Prins cascade cyclization of a-acetoxy ether 325. The in situ reduction of the oxocarbenium ion intermediate 326 with Bu3SnH prevents the formation of a tetrahydropyran 4-one side product (Scheme 81) <20050L1589>. 

Figure 12.25 shows how acetals can be brominated electrophihcally because of the (weakly) acidic reaction conditions. Proper acidity and electrophihcity is ensured by the use of pyri-dinium tribromide (B). This reagent is produced from pyridinium hydrobromide and one equivalent of bromine. Pyridinium tribromide is acidic enough to cleave the acetal A into the enol ether G. This cleavage succeeds by way of an El elimination like the one encountered in Figure 9.32 as an enol ether synthesis. The enol ether G reacts with the tribromide ion via the bromine-containing oxocarbenium ion H and the protonated acetal D to form the finally isolated neutral bromoacetal C. (The reaction can be conducted despite the unfavorable equilibrium between the acetal A and the enol ether G, since G continuously reacts and is thus eliminated from the equilibrium.)... 

SCHEME 4.10 Trapping of an intermediate oxocarbenium ion using a 3-0-TMS ether in the synthesis of fS-L-rhamnosides. Naph, 2-naphthyl. 

Arnold s demonstration" that oxocarbenium ion intermediates can be formed through homobenzylic ether radical cation fragmentation reactions shows that mild oxidizing conditions can be used to prepare important reactive intermediates. Scheme 3.2 illustrates a critical observation in the development of an explanatory model that allows for the application of radical cation fragmentation reactions in complex molecule synthesis. In Arnold s seminal work, cleavage of the benzylic carbon-carbon bond in substrate 1 is promoted by 1,4-dicyanobenzene (DCB) with photoirradiation by a medium-pressure mercury vapor lamp. With methanol as the solvent, the resulting products were diphenylmethane (2) and formaldehyde dimethyl acetal (3). 

A diastereoselective ewrfo-cyclization into an oxidatively generated oxocarbenium ion was a key step in a formal synthesis of leucascandrolide A. Exposing 56 to CAN provided cw-tetrahydropyran 57 in high yield and with excellent stereocontrol (Scheme 3.20). This transformation provides further evidence that oxidative electrophile formation is tolerant of several functional groups and can be applied to complex molecule synthesis. The synthetic sequence also utilized a Lewis acid mediated ionization reaction to form an oxocarbenium ion in the presence of the homobenzylic ether (58, 59), illustrating that two carbocation precursors that ionize through chemically orthogonal conditions can be incorporated into the same structure. 

Exo- and endo-cyclic ring closure reactions using 0-nucleophiles transform oxocarbenium ions into cyclic acetals. As an example of an endocyclic cyclization, epoxide ring opening of (96) with lithium dimethyl cuprate, and subsequent treatment of the resulting alcohol with acid, smoothly gives the bicyclic acetal (97), ° a key intermediate in the total synthesis of tirandamycic acid (Scheme 47). ... 

Vinylsilanes as nucleophilic terminators offer several additional advantages over ordinary nonactivated alkenes (c/. Section 4.2.2.1). The silyl group is readily substituted stereo- and regio-selectively by the electrophilic carbon atom of the oxocarbenium ion, as demonstrated in Overman s synthesis of alkyl-idenetetrahydropyran (109 Scheme 53). This strategy was also applied to the preparation of five- and seven-membered cyclic ethers. ... 

An impressive application is the highly stereocontrolled and enandoselective synthesis of (-)-laure-nyne (113 Scheme 54). The key step is the cyclization of the mixed acetal (110) to give the oxocene (112), with the required endocyclic unsaturation at the correct position. The formation of this eight-mem-bered cyclic ether, instead of the corresponding seven-membered ring with an exocyclic double bond, may be rationalized by an intramolecular ene-type reaction of the intermediate oxocarbenium ion (111). 

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