Oxonium ion intermediate

The synthesis of different substituted finans by cyclization of 4-pentynones using potassium tert-butoxide in DMF was reported <96TL3387>. Dihydrofuran 32 can be prepared by a destannylative acylation of l-[(2-methoxyethoxy)methoxy]-2-(phenylsulfonyl)-2-(tributylstannyl)-cyclopropane. Treatment of 32 with BFj-EtjO yields 3-acyUurans via an intramolecular Prins-type reaction of the resulting oxonium ion intermediate <96TL4585>. 

Ring expansion of tetrahydrofurans to dihydropyrans results when their 2-W-aziiidinyl imines are heated <96CC909> and when their 2-ca-alkyl bromides are treated with Ag20 in a nucleophilic acidic solvent <96JCS(P1)413>. Alkyl carbenes and bicyclic oxonium ion intermediates are invoked, respectively. 

The use of iodotrimethylsilane for this purpose provides an effective alternative to known methods. Thus the reaction of primary and secondary methyl ethers with iodotrimethylsilane in chloroform or acetonitrile at 25—60° for 2—64 hours affords the corresponding trimethylsilyl ethers in high yield. The alcohols may be liberated from the trimethylsilyl ethers by methanolysis. The mechanism of the ether cleavage is presumed to involve initial formation of a trimethylsilyl oxonium ion which is converted to the silyl ether by nucleophilic attack of iodide at the methyl group. tert-Butyl, trityl, and benzyl ethers of primary and secondary alcohols are rapidly converted to trimethylsilyl ethers by the action of iodotrimethylsilane, probably via heterolysis of silyl oxonium ion intermediates. The cleavage of aryl methyl ethers to aryl trimethylsilyl ethers may also be effected more slowly by reaction with iodotrimethylsilane at 25—50° in chloroform or sulfolane for 12-125 hours, with iodotrimethylsilane at 100—110° in the absence of solvent, " and with iodotrimethylsilane generated in situ from iodine and trimcthylphenylsilane at 100°. ... 

This reaction has been used to construct the carbon skeleton found in dysidiolide, a cell cycle inhibitor isolated from a marine sponge.73 In this case, the reactive oxonium ion intermediate was generated by O-silylation. 

This chemistry was mechanistically interesting, and in order to rationalize the observed diastereoselectivities, molecular modeling calculations were conducted on the proposed oxonium ion intermediates.4 There are E- and Z-oxonium ion conformers. Since the major Z-oxonium ion conformers (86, 87) from these calculations were approximately 3 kcalmol-1 higher in energy, these conformers most likely did not significantly contribute to the stereochemical outcome of the reaction (Figure 7.3). 

The reversible acid-catalyzed transacetalation of the cyclophane formal 3 has been shown to undergo a ring-fusion/ring-fission process to generate a mixture of polymer cyclic formaldehyde acetals by means of oxonium ion intermediates <06CEJ8566>. The stepwise... 

Unlike cyclohexene, its oxa analog, 3,4-dihydro-2//-pyran, undergoes facile reduction to tetrahydropyran in yields ranging from 70 to 92% when treated with a slight excess of triethylsilane and an excess of either trifluoroacetic acid or a combination of hydrogen chloride and aluminum chloride (Eq. 69).146 This difference in behavior can be understood in terms of the accessibility of the resonance-stabilized oxonium ion intermediate formed upon protonation. 

Overman reported the synthesis of highly enantiopure 3-acyltetrahydrofurans with C5 substituents from formaldehyde acetals of allylic diols <00TL9431>. An example of Overman s procedure is depicted below, which involves the generation of a formaldehyde oxonium ion intermediate 92 before the cyclization. 

The bioactivity of imino sugars is due to the fact that they inhibit glycosidases. Once protonated, the imino sugar mime the oxonium ion intermediate of the reaction catalysed by those enzymes (Fig. 32), and therefore binds the active site. 

Selective Transformation Glycosidic bond formation is complicated by the potential for both a- and P-epimeric products. As most of these reactions proceed through an oxonium ion intermediate, the a/p ratio is derived from substituents on the pyranose ring. The number of required building blocks doubles even with the oversimplification that the stereoselectivity is derived solely from the nature of C2 substituent. 

Common Anomeric Groups, Common Activators Both conformational and electronic factors have been exploited to obtain selectivity in one-pot glycosylations using common anomeric groups and activators. Selectivity results from differences in the stability of oxonium ion intermediate between the two prospective glycosyl donors. 

The driving force provided by alkoxy-group participation is low and such participation in aliphatic compounds is favoured when a five- or six-membered oxonium ion intermediate is involved... 

The oxonium ion intermediate of the type 34 normally collapses by the attack of a nucleophile OH or OAc to yield a masked aldehyde or hemi-acetal-acetate group. However, in this particular case the approach of... 

Tetrahydropyrans bearing halides at C4 can be accessed by a modified Taddei-Ricci reaction. The reaction involves condensation of allyltrimethylsilane, aldehydes and a cyclic acetal 371 in the presence of a Lewis acid to afford all ry -tetrahydropyrans 372 as a single diastereomer. The reaction proceeds via anion mediated ring closure of oxonium ion intermediate 373 (Scheme 89). This methodology was successfully applied to the synthesis of a model compound bearing all the structural motifs present in the eastern subunit of okadaic acid <1997TL2895>. 

A titanium(lv)-promoted coupling of ethyl glyoxylate and dihydropyran provides an oxonium ion intermediate 388 which can be trapped with nucleophiles (NuH) providing access to 2,3-disubstituted tetrahydropyrans 389 (Scheme 91, Table 20) <1999TL1083>. This methodology is incorporated into the total synthesis of the antitumor agent mucocin <2002AGE4751>. 

The conversion of enol ether 80 to cyclic ketal 83 in water in 12% yield exemplifies the chemoselectivity possible with 14D9.79 Although 83 is the normal product of the acid-catalyzed hydrolysis of 80 in organic solvents, it is never observed in water because the highly reactive oxocarbenium intermediate is rapidly trapped by the solvent to give ketone 82 (via hemiacetal 81) as the sole product. The ability of the antibody to protect the reactive oxonium ion intermediate from hydrolysis and partition it toward a product that is not typically observed under these conditions (i.e., 83) mimics the capabilities of rather sophisticated enzymes. Extension to other reactions involving reactive, water-incompatible intermediates can be easily imagined. 

The difference in reactivity between alkylated and acylated pentenyl glycosides can be rationalised as follows the elctrophilic iodonium ion will add to the double bond of the pentenyl moiety to give a cyclic iodonium ion. Nucleophilic attack by the oxygen will lead to an oxonium ion intermediate which then forms an oxocarbenium ion and an iodo-tetrahydrofuran derivative. The aglycone oxygen will be of low... 

---