Oxocarbenium ions preparation

Axial addition to oxocarbenium ions derived from 1,3-dioxanes provides protected a f/-l,3-diols. Our group has developed 4-acetoxy-1,3-dioxanes as oxocarbenium ion precursors. This general strategy for the convergent preparation of anfz-l,3-diols complements cyanohydrin acetonide methodology, which gives access to sy -l,3-diol synthons (Sect. 2). 

Mootoo and co-workers disclosed a procedure for the preparation of C-l substituted galactals based on the intramolecular capture of an oxocarbenium ion by an enol ether residue.79 In their approach, the key intermediate 1 -thio-1,2-O-isopropylidene acetals (TIA) are activated with methyl triflate to generate the crucial annulating synthon (1,2-O-isopropylidenated oxocarbenium ion). 

The best result so far available through a non-EG-acid approach has been obtained with 100% formic acid leading to the desired 69 in 32% yield after alkaline hydrolysis. In contrast, the electrolysis of 67 in an acetone—LiC104—(Pt) system at constant current (3.3 mA/cm2 for 1 h, 0.36 F/mol) in an undivided cell affords the desired alcohol 69 in 52 % yield together with 68 (25 %) (Scheme 3-25). The effect of the solvent is remarkable. Acetone is suitable for the selective preparation of 69, presumably because it traps the cationic intermediate, leading to an oxocarbenium ion, which... 

An acetal tethered compound can easily be prepared by treatment of equimolar amounts of a 2-propenyl ether derivative of a saccharide with a sugar hydroxyl in the presence of a catalytic amount of acid. Activation of the anomeric thio moiety of the tethered compound with N-iodosuccinimide (NIS) in dichloromethane results in the formation of the p-linked disaccharide. In this reaction, no a-linked disaccharide is usually detected. It is of interest to note that when this reaction was performed in the presence of methanol, no methyl glycosides are obtained. This experiment indicates that the glycosylation proceeds via a concerted reaction and not a free anomeric oxocarbenium ion. 

The introduction of a methylene acetal tether needs some further discussion. The 2-propenyl ether is prepared by reaction of a C(2) acetyl group with Tebbe reagent, (C5H5)2TiMe2. Treatment of the resulting enol ether with p-toluenesulfonic acid results in the formation of an oxocarbenium ion, which upon reaction with an alcohol provides an acetal. As can be seen in the reaction scheme, the acid is regenerated, thus only a catalytic amount is required. 

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). 

The use of oxocarbenium ions provides an efficient method for the preparation of heterocycles, especially of medium-sized cyclic ethers. 

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. ... 

E. Suarez and co-workers prepared chiral 7-oxa-2-azabicyclo[3.2.1]octane and 8-oxa-6-azabicyclo[3.2.1]octane ring systems derived from carbohydrates via an intramolecular hydrogen abstraction reaction promoted by A/-centered radicals. The A/-centered radicals were obtained under mild conditions (Suarez modification) from phenyl and benzyl amidophosphates and alkyl and benzyl carbamate derivatives of aminoalditols by treatment with PIDA/I2 or PhlO/l2. The initial A/-radical undergoes a 1,5-hydrogen abstraction to form an alkyl radical, which is oxidized to the corresponding stabilized carbocation (oxocarbenium ion) under the reaction conditions. The overall transformation may be considered as an intramolecular N-glycosidation reaction. 

Due to the lability of some glycosyl halides, the a-chloro or a-bromoglycosyl donors can be prepared in situ (activation step) and reacted with suitable acceptors (glycosidation step) in the presence of halophilic promoters. The reaction proceeds via the oxocarbenium ion 23 (Scheme 6), which is transformed into the corresponding O-glycoside 24. 

To study the conformational equilibria of the mannosyl oxocarbenium ion in solution, Yang and Woerpel [93] prepared a series of monosubstituted and multiply substituted tetrahydropyran dioxocarbenium ions and analyzed their conformational preferences. This approach was employed successfully for determining that the C4 alkoxy-substituted dioxocarbenium ion preferred the pseudoaxial conformation [17]. 

The reaction between carbocations and carbon monoxide affording oxocarbenium ions (acyl cations) is a key step in the well-known Koch-Haaf reaction for preparing carboxylic acids from alkenes. This reaction has been extensively studied under superacidic conditions. An example is indicate below. 

Anhydrides may be prepared by coupling two carboxylic acids under acidic conditions. If ethanoic acid (acetic acid, 21) is heated with HCl, protonation to give an oxocarbenium ion is followed by reaction with a second equivalent of acetic acid to give a tetrahedral intermediate. This reaction is the usual acid-catalyzed acyl addition mechanism. Protonation of the OH unit leads to loss of water and formation of the anhydride. Each step in this process is reversible and steps must be taken to drive the equilibrium (see Chapter 7, Section 7.10, for a discussion of equilibria) toward the anhydride product by removing the water by-product (see Chapter 18, Section 18.6.3). Remember that such techniques are an application of Le Chatelier s principle (discussed in Section 18.3). Even when this is done, isolation of pure anhydrides by this method can be difficult. Unreacted acid may contaminate the product and atternpts to remove the acid with aqueous base may induce hydrolysis of the anhydride. 

Reaction of cyclic acetals with alkynyl ethers promoted by BF3 gives unsaturated lactones in a process proposed to involve initial ketene intermediate 157 which reacts by an intramolecular [2 + 2] cycloaddition giving an in situ generated oxocarbenium ion and then ring expansion (Eqn (4.96)). Both larger and smaller unsaturated lactones can be prepared by the same procedure (Eqn (4.97)). ... 

Finally, a chiral 2-phenylpyrrolidine-derived thiourea was demonstrated to be an efficient organocatalyst to promote the clean substitution of 1-chloro-isochromans by silyl ketene acetals to provide the corresponding chiral substituted isochromans with high yields and enantioselectivities of up to 90% ee. Actually, the 1-chloroisochromans were prepared from the corresponding more stable methyl acetals, which were directly used without purification in the protocol evolving through a cationic oxocarbenium ion (Scheme 5.13). 

Recently, a variety of (3-silylated carboxonium ions have been prepared and characterized by NMR spectroscopy.541 Kira et al.631 used the Corey hydride transfer method, whereas Olah, Prakash, and co-workers applied triphenylmethyl tetrakis (pentafluorophenyl)borate to silylate esters,632 ketones, enones, and carbonates633 [Eq. (3.91)]. The ions thus produced are resonance hybrids of oxocarbenium (327b) and carboxonium (327a) ions with the latter as the major contributors. Calculated (DFT/IGLO) 29 Si NMR chemical shifts agree well with the experimental data. 

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