Oxonium ions, stereoselective

Treatment of phenylchalkogen substituted alkenyl alcohols with /-BuOK provided useful tetrahydrofurans stereoselectively <96JOC8200>. A concise synthesis of cis- and trans-theaspirones via oxonium ion-initiated pinacol ring expansion was developed <96JOCl 119>. 

The alkenyl oxonium ion dienophiles generated from dioxolanes can be made diastereoselective by use of chiral diols. For example, acetals derived from anti-pentane-2,4-diol react under the influence of TiCl4/Ti(/-OPr)4 with stereoselectivity ranging from 3 1 to 15 1. 

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. 

The internally stabilized silyl cation (36), formed by hydride transfer as shown, has a 2-silanorbomyl cation structure, and is not coordinated to die solvent or the counterion.78 NMR chemical shifts calculated on the basis of die bridged structure shown are in agreement with the experimental values. The autiiors describe it as free but internally re-stabilized .78 The silicon-stabilized oxonium ion (37) shows considerable stereoselectivity in its reactions (38) is the preferred product isomer by a 92 8 ratio, and (39) by 98 2.79... 

Simpkins et al. used an intramolecular variation of this allylsilane addition to oxonium cations for the synthesis of eight-membered rings [14]. Allylsilane 22, containing the oxonium ion precursor (acetal function) is transformed upon treatment with EtAlCl2 into the medium-sized ring 23 in moderate yield and stereoselectivity (Scheme 13.10). 

A novel strategy for stereoselective glycosylations has been reported in which a chiral auxiliary at the 2-position of a glycosyl donor is used (Scheme 126).189 Upon formation of an oxonium ion, participation of the nucleophilic moiety of the auxiliary is (g) selective and depedent on the chirality. 

On treatment with diethylaluminum trimethylsilylacetylide in the presence of BF3 OEt2, a-acetoxy ether 94 gave the rran5-l,3-dioxane 95 in good yield with excellent stereoselectivity, as reported by Rychonovsky and Dahanukar [91]. The trans alkyne adduct has the configuration expected from axial addition to a cyclic oxonium ion (Sch. 59). 

Taking into account the lack of chemoselectivity and stereoselectivity of these silver ion-mediated reactions, it is reasonable to postulate an SNl-type mechanism for this process, leading to the formation of oxonium ion 14, despite the electron-withdrawing effect of the CF3 group (see Scheme 6.8). The stereochemical outcome should be ascribed to the steric or electronic preference of methanol addition to two possible diastereo-faces of the trifluoromethyl oxonium ion 14, in which the interactions are probably different from those in nonfluorinated DHA derivatives. In order to disfavor the formation of oxonium 14, the reaction was performed without silver salt in MeOH. While the reaction rate did not decrease significantly, only 23% of glycal 18 was obtained. Furthermore, the... 

Under optimized experimental conditions (CH2C12, MeOH (10 equivalents), HFTP (5 equivalents)) the reaction was complete at room temperature in less than 5h. Moreover, the reaction was still chemoselective (less than 5% of the elimination product 18), and completely stereoselective (the a stereoisomer was not detected) (see Scheme 6.9) [47], The nucleophile is delivered on the same P-face as the leaving group. Similar results from DHA glycosyl donor have been rationalized by the formation of the half-chair oxonium ion, and a stereoelectronically preferred axial addition with reactive nucleophiles [18c], Compared to the reaction of 17 with the stronger Ag+ electrophilic assistance (see Schemes 6.7 and 6.8), the low ratio of elimination product 16 and the high p-diastereoselectivity suggest a mechanism different from an addition on the oxonium ion 14. It is also clear... 

In a similar manner, the corresponding cyclopentane annulated spirocyclobutanones 40 were obtained in high yield. Clearly, initial formation of a terminal oxonium ion which undergoes stereoselective addition to the vinyl bond induces the cyclopropylmethyl to cyclobutyl cationic rearrangement. 

Jia et al. [396] have recently disclosed an example of a solid-phase application of their ytterbium] 111) triflate-mediated cyclization of glyoxylate-derived unsaturated imines. Instead of the expected imino-ene products, the authors observed the sole formation of y-lactones, in good to high yields and with good trans stereoselectivity. An explanation of both the mechanism and the observed preferred trans selectivity was presented. The importance of using the lanthanide triflate in its hydrated form in order to fadhtate a catalytic process is also in accordance with the proposed mechanism, in which water plays a role in attacking the oxonium ion intermediate. 

The Prins reaction with formaldehyde is a well-known route to prostaglandins using bicyclic lactone 3 as a precursor. One synthesis of this lactone14 started this sequence with a Prins reaction. Treatment of norbomadiene with paraformaldehyde in the presence of formic acid produced a mixture of epimeric diformates in 67% yield which were transformed in several steps into lactone 3. A second synthesis starts with the unsaturated bicyclic lactone which undergoes attack by the oxonium ion both regio- and stereoselectively from the less hindered face of the double bond, trims Addition of the nucleophilic acetate generates the lactone 3 as the bisacetate derivative15. 

Cyclizations can be initiated by an oxonium ion generated from a carbonyl, acetal or ketal precursor. When dimethylacetal is treated with trimethylsilyl trifluoromethanesulfonate in dichloromethane. 6-exo cyclization takes place forming piperidine 11 with the methyl and vinyl group stereoselectively synls. The remaining methoxy substituent gives a mixture of diastereomers. 

The first tetracyclizations were induced by an oxonium ion by analogy to the first attempted tricyclizations01. The homosteroidal carbon skeleton (six-membered D ring) was found to be stereoselectively trans-anti-tram-anti-trews being generated in four consecutive 6-endo steps. A mixture of diastereomers is formed due to the lack of stereocontrol during initiation and termination of the reaction. 

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