Recent Developments in the [5+2] Cycloaddition

Abstract

The rapid generation of molecular complexity in a relatively easy manner has made the [5 + 2] cycloaddition approach a highly useful tool in the synthesis of a wide number of complex natural products and important biologically active products containing seven-membered rings. Besides the common and highly efficient [5 + 2] cycloadditions of oxidopyrylium and oxidopyridinium ions with p-systems which offer an easy access to a wide range of novel heterocyclic seven-membered ring molecules with a oxygen or nitrogen bridge, and the less employed [5 + 2] photocycloadditions, the metal-catalyzed [5 + 2] cycloadditions have attracted a lot of attention and have become one of the most popular ways of constructing seven-membered ring products. All these cycloadducts can be synthetically manipulated easily toward a number of interesting molecular structures with high potential applications.

Highly trans‐Selective Arylation of Achmatowicz Rearrangement Products by Reductive γ‐Deoxygenation and Heck–Matsuda Reaction: Asymmetric Total Synthesis of (−)‐Musellarins A–C and Their Analogues

“…[1] The syntheticu tility [2] of AR products has been considerably expanded in recent decades by identification of new oxidants [3] (e.g., meta-chloroperbenzoic acid and N-bromosuccinimide) and the development of highly efficient transformationso fd ihydropyranone acetals (II), such as Kishi reduction [4] (II!III;F igure 1), Feringa-O'Doherty O-glycosylation [5] (II!IV;F igure 1), [5+ +2] cycloaddition [6] (II!V;F igure 1), and bicycloketalization [7] (II!VI;F igure 1). Exploiting these reactions as the key step provided efficient routesfor the synthesis of complex natural products [2] and al ibrary of skeletallyd iverse compounds for biological activity studies. [8] In particular, Kishi reduction hasb een widely recognized as the methodo f choice for the synthesis of functionalized cis-2,6-dihydropyranones (cis-DHPOs; III)d ue to the reproducibly high yield and predictable excellent cis diastereoselectivity (diastereomeric ratio (d.r.)…”

Synthesis of substituted tropones by sequential Rh-catalyzed [5+2] cycloaddition and elimination

“…We have recently completed the first total synthesis of harringtonolide 4 via a [5+2] cycloaddition 10 of oxidopyrylium ion 6 and alkene (Scheme 1). 5 Although we were able to assemble the carbon skeleton of 4 very efficiently, it took us a number of steps to remove the extra oxygen bridge in 7 for the formation of tropone in target 4 .…”

Synthesis of naturally occurring tropones and tropolones

“…The subsequent section was organized by how the 7-membered rings were formed. Although seven-membered ring syntheses have been reviewed several times, these reviews often focus on one type of method, such as the [4+3] cycloaddition, 85–87 [5+2] cycloaddition, 88–89 or other reactions. 90–91 A recent review on synthetic strategies to access seven-membered carbocycles in natural products only discussed the total synthesis of a few tropone- and tropolone-containing natural products including pareitropone, imerubrine, isoimerubrine and grandirubrine.…”