"Ring Closing Metathesis of Substrates Containing more than two C-Cdouble Bonds: Rapid Access to Functionalized Heterocycles"

Abstract

In most cases where ring closing metathesis is applied to the synthesis of heterocycles, α,ω-dienes are used as precursors. If substrates containing more than two double bonds are subjected to a metathesis reaction, carba-or heterocycles bearing additional exocyclic alkene functionality result, or multiple ring closing processes occur. This offers interesting and potentially very useful synthetic perspectives. On the other hand, selectivity problems need to be addressed as the cyclization of substrates with more than two double bonds available for olefin metathesis may result in constitutional isomers or stereoisomers. This review highlights problems and opportunities evolving from ring closing metathesis of tri-, tetra-, and polyenes as a strategy for the selective synthesis of functionalized heterocycles. The chapter on RCM of trienes is subdivided according to the symmetry of the metathesis precursor. The following two chapters deal with the double or multiple RCM of tetra-or polyenes. These processes are further classified according to the preferred cyclization mode. Finally, the application of cascade or domino metathesis reactions to the synthesis of heterocycles will be discussed. These processes can be classified into those where exclusively C-C-double bonds take part in the metathesis reaction, and those where one or more C-C-triple bonds are involved.

One‐Flask Tethered Ring Closing Metathesis–Electrocyclic Ring Opening for the Highly Stereoselective Synthesis of Conjugated Z/E‐Dienes

“…Thus, it was not necessary to use the allylic alcohols 8 as single stereoisomers and, in most cases, the addition of a vinyl-Grignard reagent to the appropriate aldehyde should be the method of choice for their synthesis. The conversion of 5p into 1p proceeds, in addition to the high Z/E-selectivity observed for all examples listed in Table 2, with very high ring-size selectivity [54] in the RCM step. There is no indication that the alternative cyclization mode, leading to a seven-membered ring, is relevant under these conditions.…”

Synthesis of Dihydrofurans and Dihydropyrans with Unsaturated Side Chains Based on Ring Size‐Selective Ring‐Closing Metathesis

“…This aspect of olefin metathesis has recently been reviewed by us. [29] Particularly relevant for the subject of this study are reports where different modes of cyclization result in different ring sizes, [30] such as the RCM-based synthesis of fused vs. "dumbbell"-type bicyclic lactams, [31,32] the strong preference for "dumbbell"-type oxacycles in the RCM of tetra- [33,34] or hexaenes. [35] Parallel to our preliminary account on the control of ring size-selectivity in RCM reactions of trienes 2, [36] two reports by Crimmins et al were published where the regioselective ring closure of structurally closely related trienes is described and efficiently used in the total syntheses of the Annonaceous acetogenin (À)-mucocin [37] and the microbial metabolite (+)-SCH 351448.…”

Regioselective Tandem Ring Closing/Cross Metathesis of 1,5‐Hexadien‐3‐ol Derivatives: Application to the Total Synthesis of Rugulactone

“…Otherwise, the reaction between the unsaturation fixed on the acid chain could take place more favorably with the vinyl group to form a 6-allylpyrone structure compared to the reaction involving the allyl rest leading to a 7-vinyl caprolactone. [14,16,17] Treatment of 13 with alcohol 14a in the presence of Grubbs type II catalyst 5 afforded dimer structure 18, ketone 19 [18] resulting from the isomerization of the terminal double bond [19] and further reketonization, and also 5064 Scheme 3. Retrosynthetic analyses for 3 and related 6-allyl hexenolides 12.…”