Oxepanes, synthesis

Scheme 8. Oxepane synthesis by photo-induced ring closure of dithioesters. The term dithioester is used in this chapter to describe compounds of type 39 even though such systems are sometimes referred to as dithionoesters or dithioxoesters.

Scheme 11. Bis(oxepane) synthesis using a photochemical dithioester cyclization and a reductive hydroxy ketone cyclization.

Janda, K. D. Shevlin, C. G. Lemer, R. A Oxepane Synthesis Along a Disfavored Pathway The Rerouting of a Chemical Reaction Using a Catalytic Antibody J. Am Chem. Soc 1995,117, 2659-2660. 

A. Kover, M. I. Matheu, Y. Diaz, and S. Castillon, A study of the oxepane synthesis by a 7-endo electrophile-induced cyclization reaction of alkenyisulfides. An approach towards the synthesis of septanosides, Arkivoc (2007) 364-379. 

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. 

In contrast to the IJK system 86, compound 87 (Scheme 17a) poses a much steeper synthetic challenge it is during the course of the synthesis of 87 that the diabolical bis(oxepane) problem would have to be dealt with. At this phase of the project, we had benefited from a good deal of experience with the bis(oxepane) problem, and this experience provided the foundation for a conservative solution. Starting from FG ring system 105, it was hoped that rings E, D, C, B, and A could be annulated sequentially and in that order (Scheme 17c). 

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]. 

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... 

The outcomes of intramolecular cyclizations of hydroxy vinylepoxides in more complicated systems can be difficult to predict. In a study of the synthesis of the JKLM ring fragment of dguatoxin, epoxide 44 was prepared and subjected to acid-mediated cydization conditions (Scheme 9.24) [114]. Somewhat surprisingly, the expected oxepane 45 was not formed, but instead a mixture of tetrahydropyran 46 and tetrahydrofuran 47 was obtained, both compounds products of attack of the C6 and C5 benzyl ether oxygens, respectively, on the allylic oxirane position (C3). Repetition of the reaction with dimsylpotassium gave a low yield of the desired 45 along with considerable amounts of tetrahydropyran 48. 

These reductions of lactols with Et3SiH 84b in combination of BE3 -OEt2, TfOH, or TMSOTf 20 have become standard reactions for synthesis of cyclic ethers [62-69]. Thus even co-hydroxyketones such as 1837 cyclize readily with excess EtsSiH 84b in the presence of TMSOTf 20, in high yields, via the lactols 1838, to give cyclic ethers such as the substituted oxepane 1839 in 90% yield [65] (Scheme 12.18). 

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. 

D. Sabatino and M. J. Damha, Oxepane nucleic acids Synthesis, characterization, and properties of oligonucleotides bearing a seven-membered carbohydrate ring, J. Am. Chem. Soc., 129 (2007) 8259-8270. 

A. Bhattacharjee, S. Datta, P. Chattopadhyay, N. Ghoshal, A. P. Kundu, A. Pal, R. Mukhopadhyay, S. Chowdhury, A. Bhattacharjya, and A. Patra, Synthesis of chiral oxepanes and pyrans by 3-O-allyl-carbohydrate nitrone cycloaddition (3-OACNC), Tetrahedron, 59 (2003) 4623 -639. 

S. Basu, B. Ellinger, S. Rizzo, C.l. Deraeve, M. Schurmann, H. Preut, H.-D. Arndt, and H. Waldmann, Biology-oriented synthesis of a natural-product inspired oxepane. Collection yields a small-molecule activator of the Wnt-pathway, Proc. Natl. Acad. Sci. USA., 108 (2011) 6805-6810. 

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>. 

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