Oxepane ring

The reaction processes shown in Scheme 8 not only accomplish the construction of an oxepane system but also furnish a valuable keto function. The realization that this function could, in an appropriate setting, be used to achieve the annulation of the second oxepane ring led to the development of a new strategy for the synthesis of cyclic ethers the reductive cyclization of hydroxy ketones (see Schemes 9 and 10).23 The development of this strategy was inspired by the elegant work of Olah 24 the scenario depicted in Scheme 9 captures its key features. It was anticipated that activation of the Lewis-basic keto function in 43 with a Lewis acid, perhaps trimethylsilyl triflate, would induce nucleophilic attack by the proximal hydroxyl group to give an intermediate of the type 44. 

Mori et al. have demonstrated the most dramatic uses of lithiated epoxides in natural product synthesis [62]. By employing the chemistry developed by Jackson, and subsequently performing a Lewis acid-catalyzed (BF3 OEt2) cyclisation, tetra-hydrofuran, tetrahydropyran, and oxepane rings are readily accessed this strategy is demonstrated by the synthesis of the marine epoxy lipid 173 (Scheme 5.40) [63]. 

Other possible cyclizations may involve 5-epoxy alcohols such as the generic compound 2. In this case, two pathways are theoretically possible a more favored 6-exo cydization mode (Route c) giving rise to a THP ring, or an alternative 7-endo cydization mode providing an oxepane ring (Route d) (Eq. b, Scheme 8.1) [7]. 

For the synthesis of the complex natural product, the terminus six-membered ketone 55 had to be transformed into an oxepane ring. For this necessary transformation, the authors were attracted by the single-carbon homologation of a pyr-anone (a sort of ring-expansion) because, in prindple, it could be used in an iterative sense at any stage of the 6-endo cydization in their poly-TH P-based synthetic approach for the synthesis of trans-fused 6,7,6 (THP-oxepane-THP) and 6,7,7 (THP-oxepane-oxepane) ring systems [28]. Treatment of ketone 55 with TMSCHN2... 

Scheme 8.14 Construction of the bis-oxepane ring moiety of hemibrevetoxin B.

S-adenosylmethionine 406 biosynthesis of epoxide 349 bis(trimethylsilyl) peroxide (BTSP) 448, 450 bis(trimethylsilyl)urea 449 bis-oxepane ring 281... 

S. Tripathi, B. G. Roy, M. G. B. Drew, B. Achari, and S. B. Mandal, Synthesis of oxepane ring containing monocyclic, conformationally restricted bicyclic and spirocyclic nucleosides from D-glucose A cycloaddition approach, J. Org. Chem., 72 (2007) 7427-7430. 

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>. 

Benzoannelation of the oxepane ring system leads to an increase in the barrier to ring inversion. Thus variable temperature NMR spectra on l,2,4,5-tetrahydro-3-benzoxepin (2) suggested that a chair conformation was preferred with a barrier to ring inversion of ca. 39.7 kJ mol"1. 

Acid-catalyzed cyclization of 42 (Equation 15) is a simple and useful method for construction of the oxepane ring <1998TL9601>. 

Stereoselective radical cyclization (Equation 20) initiated by Bu3SnH/AIBN or Bu3SnH/Et3B is suggested as a method for the synthesis of O-linked oxepane ring systems (AIBN = 2,2 -azobisisobutyronitrile) <1998TL2783>. 

An efficient approach for the diastereospecific synthesis (>98 2 of diastereoselectivity) of a model of the ABC ring system of hemibrevetoxin B is described <20060L4231>. One of the key features in the synthesis is a ring expansion to yield the oxepan ring C. 

A stereoselective synthesis of compounds possessing an oxepane ring fused to a diquinane or a bicyclo[4.2.0]octane moieties using photochemical reactions of a common precursor 115 (Scheme 51) is developed the latter compound is related to sterpurane, another class of bioactive sesquiterpenes <2003TL475>. 

In a synthesis of hemibrevetoxin B, isolated from the same species, Yamamoto and coworkers twice used the method outlined in Scheme 5 in the same molecule to form the oxepane ring <95TL5777> and cyclisation of the alcohol (41) afforded the spirooxapane (42), a key intermediate in the synthesis of (-)-ptilomycalin by Overman and co-workers <95JA26S7>. 

Oxonium ions as a source of the oxepane ring are also formed by the irradiation of cyclohexene epoxides <95CPBi62i>. In this work the oxonium ion is also trapped in an intramolecular process to form spiro-derivatives which may undergo further rearrangement as illustrated in Scheme (8). 

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