Intramolecular epoxide opening approach

This synthetic approach to quinine and its diastereomers is based on a simultaneous formation of a quinuclidine ring and a hydroxyl group by intramolecular epoxide opening with the piperidine nitrogen. This process results in an inversion at C-8. 

Additional investigations of chiral salen metal complexes revealed that the corresponding Co-salen complex 142 promotes intramolecular epoxide openings with alcohols in an enantioselective fashion [126]. This approach was elegantly utilized by Danishefsky in an asymmetric total synthesis of the neurotrophic growth factor merrilactone A (144 Scheme 9.17) [127]. 

Scheme 69 Intramolecular epoxide ring-opening approaches toward papulacandin-like spiroacetals [142-144]...

Scheme 70 Tan et al. s intramolecular epoxide ring-opening approach toward acortatarin B [78]...

More structurally complex epoxides can be ring-opened intramolecularly in a synthetically useful fashion. Thus, in their approach to methyl-substituted trmis-fused tetrahydropyran subunits found in marine natural products, Mori and co-workers <99TL8019> treated the polyfunctional arylsulfonyl epoxide 67 with Lewis acid to induce a (s-endo cyclization onto the epoxide moiety, with concomitant ejection of arylsulfinate, to provide the bicyclic ether 68. This system was found to be highly sensitive to the nature of the Lewis acid catalyst used. 

However, these have not been the only approaches to the synthesis of these ring systems. For example, Sasaki et al. were able to use an intramolecular nucleophilic ring opening of an epoxide with sodium dimsylate to form the oxepane ring as illustrated in the conversion of 34 to 35 <99JOC9399>. 

Johnson in 1993 described an approach to racemic p-amyrin involving application of a biomimctic polyene cyclization.7 In the same year Corey accomplished the enantioseleetive synthesis of compound 4. a key intermediate that opened the way to stereoselective preparation of compounds I, 2. and 3 8 A key step in the synthesis of P-amyrin (1) was the introduction of chiral oxazaboroli-dines for enantioseleetive carbonyl reduction. Ba ed on these methods, generation of an enantiomerically pure epoxide and its stereoselective cationic cyclization led to the pentacyclic system of structure 1 Diastereoselective cyclopropanation and an intramolecular protonation of a carbanion represent other interesting steps in this total synthesis. 

The synthesis shown in Scheme 60 exemplifies the first approach <20010L2575, 2004JOC2831>. A rather lengthy series of transformations provides epoxide 311. The epoxide is opened with azide and the resulting alcohol converted to the mesylate. A few additional functional group modifications are then necessary for the synthesis of 312. A standard azide reduction followed by an intramolecular alkylation provides the aziridine 313. This aziridine is then carried on to FR900482 in three additional steps. 

This year has seen several approaches to the core of the zaragozic acids/squalestatins from carbohydrate starting materials. D-Mannose was converted to the glycal 117, elaborated to precursor 118 by a-selective dioxirane oxidation and Cl epoxide ring opening by allyl alcohol, deallylation, oxidation and Grignard addition. Desilylation of 118 with concomitant intramolecular acetalation afforded the core analogue 119 (Schone 30). ... 

The numerous methods for stereoselective epoxide synthesis and the extensive base of knowledge regarding regiocontrol in intramolecular opening reactions combine to create numerous opportunities for natural product synthesis. This section will illustrate many of the routes that have exploited this approach. These routes are often called biomimetic syntheses due to... 

As it turns out, when the epoxide is protonated, the neighboring oxygen atom is able to open the epoxide ring intramolecularly, resulting in a resonance-stabilized cation (4a and 4b). This oxonium ion can then be trapped by hexafluoro-2-propanol, which approaches from the top face of the molecule (the bottom face is blocked by the nearby methyl group, and peroxide bridge), producing compound 5. Finally, loss of a proton forms alcohol 2. 

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