An Inverse Electron Demand Diels–Alder-Based Total Synthesis of Defucogilvocarcin V and Some C-8 Analogues

Abstract

A concise total synthesis of defucogilvocarcin V is reported. The key features of the approach are the formation of the C-ring using a vinylogous Knoevenagel/transesterification reaction and construction of the D-ring by way of an inverse electron demand Diels-Alder-driven domino reaction. The resulting C-8 ester functionality provides a handle for the synthesis of defucogilvocarcin V as well as some C-8 analogues from a common late-stage intermediate.

π-Expanded coumarins: synthesis, optical properties and applications

“…Notably, in 2011, Bodwell and co-workers developed a method of condensation of coumarin-derived electron-poor dienes with various electron-rich dienophiles (mostly enamines) to afford diverse benzo [c]coumarins through the inverse electron demand Diels-Alder reaction (Scheme 42). [84][85][86] Depending on the desired electron-withdrawing group, dienes have been synthesized through different paths starting from 3-formylcoumarin 70, which have been obtained by ozonolysis of compound 69 which was synthesized from salicylic aldehyde and dimethyl glutaconate. The authors obtained different substituted dienes (71-73) by applying the Wittig reaction, Knoevenagel condensation, and Horner-Wadsworth-Emmons reaction between 3-formylcoumarin (70) and corresponding ylide, such as active methylene, 2-cyanoacetic acid, and dialkylphosphonate, respectively (Scheme 42).…”

“…It seems that classical Hurtley condensation [75][76][77] and oxidative cyclization of the biphenyl-2-carboxylic acids 68 are the most general procedure methodologies. On the other hand, the condensation of hydroxychalcones with b-ketoesters 74 and the chemistry recently developed by Bodwell and co-workers, [84][85][86] are the most interesting ones, since they lead to densely functionalized compounds possessing both electron-donating and electron-withdrawing groups.…”

Benzannulation Reactions: A Case for Perspective Change From Arene Decoration to Arene Construction

“…[34] The synthetic utility of the above [4 + 2] benzannulation was demonstrated by Bodwell and colleagues by constructing a C 2 -symmetric pyrenophane 89 as well as the antitumor agent defucogilvocarcin V. In both the cases, the [4 + 2] benzannulation served as the pivotal step (Scheme 26). [35,36] Nandaluru and Bodwell have reported a multicomponent domino reaction to synthesise 6H-dibenzo [b,d]pyran-6-one derivatives. Both diene and dienophile for the inverse electron demand Diels-Alder (IEDDA) were generated in situ by secondary amine-mediated processes.…”

Stereoselective synthesis and sialidase inhibition properties of KDO-based glycosyloxathiins

“…The huge number of reagents employed in iEDDA also includes heteroatom-containing dienes or dienophiles (inverse electron demand hetero-Diels-Alder, iHDA) to form the corresponding heterocyclic cycloadducts, important intermediates in the synthesis of natural and pharmacologically active products. [11][12][13] From a mechanistic point of view, extensive kinetic and computational studies on iEDDA have been reported, [14][15][16][17][18] confirming the involvement of the HOMO orbital of the dienophile and the LUMO orbital of the diene.…”

“…These reactions have been widely employed to obtain regio-and stereoselectively complex molecules with high atom economy degree. Among these, the inverse electron demand [4+2] Diels-Alder reactions (iEDDA) gained a great deal of attention [1][2][3][4] proving to be of pivotal importance for the synthesis of complex bioactive molecules and natural products [5][6] .…”