Synthetic 10-membered: synthesis from fused ring

Hi) By formation of seven- from six-membered rings The expansion of a di- or a tetra-hydropyran ring fused to a three-membered ring has been used as a synthetic approach to oxepins. Thus the synthesis of oxepin (193) was attempted by thermal dehydrochlorination of a tetrahydropyran (equation 57) obtained from a dichlorocarbene addition reaction (65CI(L)184). Unfortunately the equilibrium appeared to favor the keto tautomer to the apparent exclusion of the enolic oxepin form (193). 

Intramolecular phosphonate-based olefination has been used to construct five-membered rings in a number of syntheses for example in a novel approach to [3.3.0] fused pyrazolidinones (244) (Scheme 35), a totally synthetic class of antibacterial agents. 44 new, convergent synthesis of the fungal metabolite and useful synthetic intermediate (+)-terrein (248) has been reported. 45 The method is based on two phosphonate olefination steps. The diphosphonate (245), obtained from L-tartaric acid, gives, on treatment with base, a mixture of the required phosphonate (24 6) and the diphosphonate (247). However, under appropriate conditions (246) is the major product and can be converted into (+)-terrein by reaction with acetaldehyde (Scheme 36). Olefination of the ketone (249) with dimethyl diazomethylphosphonate (250) provides, via carbene insertion, the cyclopentene (251) and hence a new route to (-)-frontalin (252) (Scheme 37).146... 

The fundamental idea of sterically restricted cis-fused 5-membered bicyclic structure as an efficient chiral environment for enhanced asymmetric induction was extended to the synthesis of several synthetically useful, optically active aldehydes. The reaction of aminals (l,3-diazabicyclo[3.3.0] octane derivatives) having a fixed cis-fused 5-membered bicyclic ring structure, obtained from the diamine la and appropriate aldehydes, with nucleophiles was investigated. Several functionalized aldehydes were obtained in high e.e. and successfully applied to the synthesis of selected optically active natural products. 

Nowadays, many elegant syntheses of steroids, alkaloids and affiliated products are prepared from several five- or six-membered rings. Usually, the preferred steps of such syntheses correspond to the polycyclizations of educts, that contain many multiple bonds, and one or two other functional groups of further educts can often also participate [17]. However, in recent years a new type of the radical chemistry of the isocyanides has been introduced [47].This is illustrated by the one-pot synthesis of (20S)-camptothecin 25 from phenyl isocyanide 13a and 24. Such preparations of cyclopenta-fused quinolines are seldom found in tandem-domino chemistry [16], and this procedure is also closely related to the MCRs of the isocyanides. The previous multistep synthesis of 25 was accomplished by Danishefsky and Volkmann [47b], and uses a large number of linear synthetic steps with only small overall transformations towards the target. 

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