Oxidopyrylium [5+2] cycloaddition chemistry: Historical perspective and recent advances (2008–2018)

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

“…to 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.…”

“…[10] In contrast, the intermolecular version of the oxidopyrylium-based [5+ +2] cycloaddition is much less studied and the substituent effect of the oxidopyrylium ylide on endo/ exo selectivity remained underexplored. [5][6][7] Furthermore, despite the importance of the oxidopyrylium-based [5+ +2] cycloadditions,t he 2p partners have been to date limited to alkenes,d ienamine,t rienamine,a nd alkynes.T ot he best of our knowledge,n oh etero-[5+ +2] cycloaddition of oxidopyrylium ylides with imines has ever been reported.…”

“…

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.

…”

“…[10] In contrast, the intermolecular version of the oxidopyrylium-based [5+ +2] cycloaddition is much less studied and the substituent effect of the oxidopyrylium ylide on endo/ exo selectivity remained underexplored. [5][6][7] Furthermore, despite the importance of the oxidopyrylium-based [5+ +2] cycloadditions,t he 2p partners have been to date limited to alkenes,d ienamine,t rienamine,a nd alkynes.T ot he best of our knowledge,n oh etero-[5+ +2] cycloaddition of oxidopyrylium ylides with imines has ever been reported.As part of our continuing efforts in developing novel [5+ +2] cycloaddition reactions, [11] we became interested in the synthesis of highly substituted nitrogen-containing sevenmembered heterocycles-azepanes-through hetero-[5+ +2] cycloadditions as shown in Scheme 1A.Azepanes are present in numerous natural products such as rubenine, [12] cadambine, [13] and banistenoside [14] (Scheme 1B), which possess complex penta-and even hexa-substituted azepane cores.The feasibility,regio-, and stereoselectivty of the proposed hetero-[5+ +2] cycloaddition are entirely unknown. We herein describe the first hetero-[5+ +2] cycloaddition of oxidopyrylium ylides with cyclic imines with excellent regio-and stereoselectivity.…”

Synthesis of Polycyclic Ether-Benzopyrans and In Vitro Inhibitory Activity against Leishmania tarentolae

“…For example, Diels-Alder [4+2] cycloadditions are ubiquitous among organic reactions [56][57][58], while [5+2] cycloadditions are substantially less recognized [59,60]. However, polycyclic ethers are very important heterocyclic ring systems [61], and oxidopyrylium-based [5+2] cycloadditions ( Figure 2) afford valuable oxabicyclo[3.2.1]-octanes, [62][63][64] which are embedded within such natural products [65][66][67][68][69][70] as englerin A [13][14][15][16], platensimycin [71,72], cortistatins [73,74], and many others [75][76][77]. In addition to the total synthesis of natural products [29][30][31][32][33][34][35][36], there is constant demand for the synthesis of unnatural heterocycles to access novel chemical space [37][38][39][40][41][42][43][44][45].…”