[3]Dendralenes: Synthesis, Reactivity Studies and Employment in Diversity-Oriented Synthesis of Complex Polycyclic Scaffolds

Abstract

[3]Dendralenes are exquisite molecules as they exhibit enormous potential for the rapid generation of architecturally esoteric scaffolds when subjected to tandem Diels–Alder reactions, but their synthesis is a tall order. In conjunction with diversity-oriented synthesis, [3]dendralenes satisfy the potential demand for simultaneous and efficient synthesis of intricate collections of molecules that exhibit a range of activities for lead generation in drug discovery. This account chronicles our roller-coaster journey and systematic approach beginning from the synthesis of extremely unstable, non-isolable [3]dendralenes through moderately stable examples and then finally, highly functionalized, stable [3]dendralenes via sequential methylenation (using dimethylsulfonium methylide) and Horner–Wadsworth–Emmons olefination. It also describes the study of the attributes affecting their stability and reactivity with various dienophiles. In addition, it reports on how these dendralenes, upon astute maneuvering, can be engaged in a diene-transmissive Diels–Alder (DTDA) sequence, thus harnessing their full potential by construction of a small but diverse library of complex frameworks in a quick and efficient manner, with step and atom economy.1 Introduction2 Literature Methods for [3]Dendralene Synthesis3 Our Tryst with [3]Dendralenes3.1 Serendipitous Olefination with the Corey–Chaykovsky Ylide3.2 Synthesis of [3]Dendralenes and Reactivity/Stability Studies3.3 Diels–Alder Reactions of [3]Dendralenes3.4 Tuning of [3]Dendralenes for the DTDA Reactions3.5 Diversity-Oriented Synthesis with [3]Dendralenes3.6 Rationalization of Factors Governing the Stability and Reactivity of [3]Dendralenes4 Conclusions

Synthesis of highly polarized [3]dendralenes and their Diels–Alder reactions

“…, those, the electronic effects of which are rather small or conveyed by conjugated π-systems (Ar, HetAr). Several papers 7 a ,10 reported derivatives with one or two EWGs but compounds, in which all terminal sp 2 atoms of the dendralene backbone would be decorated with typical EWGs or EDGs, have not yet been described. Needless to say that, being equipped with strongly polarizing functional groups, rather than just with alkyls, the products can be expected to offer broader synthetic variability via subsequent functional group transformations.…”