Recent development on the [5+2] cycloadditions and their application in natural product synthesis

Abstract

The recent developments on the [5+2] cycloadditions and their application in the synthesis of complex natural products are discussed.

Anodic Oxidation as an Enabling Tool for the Synthesis of Natural Products

“…tection generated quinolactacin B (9) in 61% yield over three steps. 71 Similarly, anodic oxidation of chilenamine (10) to the hydroxyisoindolo-benzazepine 11 and further Ley-Griffith oxidation 73 delivered lennoxamine (12) in 63% yield over two steps (Scheme 2). 70 The Shono oxidation, especially the -functionalization of amines, has been applied in a variety of natural product syntheses, including for instance nazlinine (13), 74 (+)myrtine 14, 75 (+)-calvine (15), 76 (+)-crispine A (16), 77…”

“…While polar reactions of closed-shell species dominated in the early ages of organic synthesis, cycloadditions and reactions of radicals and radical ions gradually gained in importance and proved to be particularly suitable techniques for constructing complex molecular frameworks while possessing a high functional group tolerance. [10][11][12][13][14][15][16] Neutral radicals are often generated by thermally induced homolysis of labile bonds in 'radical starters' such as organic peroxides or AIBN, but as in the case of radical ions, they can also be generated by electrochemical methods. Replacing stoichiometric one-or two-electron reductants and oxidants with electric current is economically and ecologically advantageous and goes well with the worldwide trend towards sustainable chemistry.…”

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].…”

“…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 ].…”

Synthesis of Pyridothiazepines via a 1,5‐Dipolar Cycloaddition Reaction between Pyridinium 1,4‐Zwitterionic Thiolates and Activated Allenes

“…[7] It is noteworthy that the [5 + 2]-cycloaddition reaction has only been sporadically reported in the literature due to the inherent difficulties in forming the seven-membered ring and most of them involve transition-metal catalysis. [8] Herein, we describe our preliminary results on this reaction.…”