Maneuvering the stability and reactivity of ‘Dendralenes”, an exciting class of oligo-enes for diversity oriented organic synthesis
Organic synthesis is mainly concerned with C-C and C-X (X = heteroatom) bond forming reactions. The biggest challenge is to perform them under strict control of regio-, stereo- and enantio-selectivity, and also to achieve diverse structural complexity in fewer steps. Carbon-carbon double bond (olefin) is an important synthon in organic chemistry for further C–C bond formation, diverse functional group generation and for construction of complex organic structures. Olefins also exhibit great structural diversity when several such bonds are put together in a molecule. Depending upon the type of connectivity of the ethylene units, conjugated polyenes can be classified into various classes. A geminal linkage results in a class of cross conjugated polyenes called as "Dendralenes". Despite being in existence in Nature and having been synthesized as early as in 1955, they remained "unmanageable" until the turn of this century mainly owing to their unpredictable stability and reactivity.
Due to the abundance of fused hetero- and carbocyclic ring systems in numerous bio-active compounds, such motifs have intrigued synthetic organic chemists. Besides, an efficient synthesis of such architecturally complex scaffolds is an uphill task and hence poses a formidable challenge. In this regard, dendralenes are fascinating molecules because they possess huge potential for the quick generation of diverse and complex multicyclic scaffolds when subjected to tandem Diels–Alder (DA) reactions, also known as diene transmissive Diels–Alder (DTDA) sequences. But their synthesis is a tall order.
The chronicles of our roller-coaster journey and systematic approach beginning from the development of new olefination protocols, synthesis of extremely unstable, non-isolable dendralenes through moderately stable examples and finally, highly functionalized stable dendralenes will be presented. The attributes affecting their stability and reactivity have been recognized. Also, how these dendralenes, upon judicious maneuvering, can be engaged in a 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 will be discussed.
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