Recent Developments in the [5+2] Cycloaddition

Abstract

The [5+2] cycloaddition allows the synthesis of a diversity of complex highly functionalized seven-membered products in a single step. These cycloadducts can readily be further manipulated synthetically for use in the synthesis of a number of complex natural products and important biologically active products containing seven-membered rings. In addition to the common and highly efficient [5+2] cycloadditions of (oxido)pyrylium and (oxido)pyridinium ions with various p-systems, providing an easy access to a wide range of novel heterocyclic sevenmembered rings exhibiting an oxygen or nitrogen bridge, the metal-catalyzed [5+2] cycloadditions still attract a great attention and have become one of the most popular ways of constructing seven-membered compounds. Among the most important reactions are metal-catalyzed (hetero) [5+2] cycloadditions of vinyl-substituted three-membered rings, rhodium-catalyzed [5+2] cycloadditions of 3-acyloxy-1,4-enynes, and metal-catalyzed [5+2] cycloadditions of ortho-vinylphenols and ortho-vinyl/arylanilines.

(3+3)‐Annulation of Donor–Acceptor Cyclopropanes with Diaziridines

“…[1,2] In contrast to alkenes, imines,a lkynes,a nd so forth, three-membered rings remain significantly underexplored as starting compounds for the synthesis of larger rings except for their involvement into (3+ +2)-cycloadditions.M eanwhile,t hree-membered heterocycles have ah igh potential for organic synthesis;t he high strain energy and facile cleavage of the polarized carbonheteroatom bond ensure their efficient use as synthetic equivalents of 1,3-zwitter-ionic synthon I(Scheme 1a). [1,2] In contrast to alkenes, imines,a lkynes,a nd so forth, three-membered rings remain significantly underexplored as starting compounds for the synthesis of larger rings except for their involvement into (3+ +2)-cycloadditions.M eanwhile,t hree-membered heterocycles have ah igh potential for organic synthesis;t he high strain energy and facile cleavage of the polarized carbonheteroatom bond ensure their efficient use as synthetic equivalents of 1,3-zwitter-ionic synthon I(Scheme 1a).…”

Intermolecular Regio‐ and Stereoselective Hetero‐[5+2] Cycloaddition of Oxidopyrylium Ylides and Cyclic Imines

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We have developed the first intermolecular hetero-[5+ +2] cycloaddition reaction between oxidopyrylium ylides and cyclic imines with excellent control of regio-and stereoselectivity.S urprisingly,d ivergent stereochemistry was observed depending on the substitution pattern of the oxidopyrylium ylide.T his new reaction provides quicka ccess to highly substituted nitrogen-containing seven-membered rings-azepanes.N otably,abroad range of oxidopyrylium ylides and cyclic imines participate in this novel hetero-[5+ +2] cycloaddition reaction and the cycloadducts can be readily transformed into the core skeletons of bioactive natural products.D FT calculations revealed that the cycloaddition proceeds through as tepwise pathway and the imine nitrogen atom serves as the nucleophile to initiate the cycloaddition.

Cycloadditionisoneofthemostefficientandpowerfulwaysto build molecular complexity.A lthough various cycloaddition reactions have been developed for the synthesis of complex four-, five-, and six-membered rings with excellent control of regio-and stereoselectivity,far fewer methods are available for the formation of highly substituted sevenmembered rings. [1][2][3] Since the first report by Hendrickson in 1980, [4] oxidopyrylium ylide based [5+ +2] cycloaddition [5] has emerged as apowerful transformation for the construction of seven-membered carbocycles. [2,6,7] Most previous studies have focused on intramolecular oxidopyrylium-alkene cycloaddition with the alkene 2p components tethered to C2 or C6 position, that is,type Ioxidopyrylium-alkene cycloaddition.

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(3+3)‐Annulation of Donor–Acceptor Cyclopropanes with Diaziridines

“…One-step construction of cyclic molecules from simple building blocks with ac onsiderable increase in as tructure complexity is one of the most important challenges of contemporary organic chemistry.T he essential processes for this purpose are various cycloadditions,a nnulations and domino reactions with diverse unsaturated compounds being typical building blocks. [1,2] In contrast to alkenes, imines,a lkynes,a nd so forth, three-membered rings remain significantly underexplored as starting compounds for the synthesis of larger rings except for their involvement into (3+ +2)-cycloadditions.M eanwhile,t hree-membered heterocycles have ah igh potential for organic synthesis;t he high strain energy and facile cleavage of the polarized carbonheteroatom bond ensure their efficient use as synthetic equivalents of 1,3-zwitter-ionic synthon I(Scheme 1a). [3] Cyclopropanes were for al ong time considered as rather kinetically inert species due to the absence of highly polarized bonds in the all-carbon ring.…”