Tuning the Stability and the Reactivity of Substituted [3]Dendralenes for Quick Access to Diverse Copiously Functionalized Fused Polycycles with Step and Atom Economy

Abstract

This is the first comprehensive study that details the synthesis of stable acyclic trisubstituted [3]dendralenes and deciphers their structural requisite for a successful diene transmissive Diels-Alder (DTDA) reaction by employing two different dienophiles and eventually generating a small repository of complex molecules, thus exemplifying how substituted [3]dendralenes could be deployed in diversity-oriented synthesis with high selectivities. A balance of reactivity and stability was struck by prudent selection of the position and nature of functional groups on these [3]dendralenes. Upon tandem Diels-Alder reactions with several symmetrical as well as unsymmetrical dienophiles, these dendralenes afforded diversity-oriented quick access to many polycyclic complex motifs possessing several functional groups and multiple stereogenic centers. Thus, the full potential of the dendralenes could be harnessed. The reactions proceeded under mild conditions with step and atom economy and were highly regio- and stereoselective besides being excellent yielding. The DTDA sequence resulted in the generation of four new carbon-carbon bonds, two new rings, and 3-7 stereogenic centers. The key feature of the method is that we could rapidly generate complexity along with functional and structural diversity from a trivial acyclic substrate with no stereogenic centers.

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

“…The dendralene 43f was obtained in 36% yield. 51 Subsequent to successful accomplishment of the synthesis of stable [3]dendralenes, they were engaged in DTDA reactions. Dendralenes 43a-e were reacted with 2 equivalents of N-phenylmaleimide (NPM)/N-methylmaleimide (NMM), to obtain the DTDA adducts 44-48, as depicted in Scheme 16.…”

“…Dendralenes 43a-e were reacted with 2 equivalents of N-phenylmaleimide (NPM)/N-methylmaleimide (NMM), to obtain the DTDA adducts 44-48, as depicted in Scheme 16. 51 All the dendralenes furnished a single diastereoisomer with high regio-and stereoselectivity, except for Scheme 14 DA reactions of [3]dendralenes…”

“…At the outset, this dendralene was reacted with 2 equivalents of NMM, which afforded DTDA adduct 49 (Scheme 17). 51 For the achievement of this diversity, it was decided to perform the DTDA reaction with two different dienophiles in tandem. Hence, 43f was reacted with NMM at -10 °C followed by maleic anhydride (MA) in refluxing toluene to provide the adduct 50 as the sole product.…”

Synthesis of Cross-Conjugated Polyenes via Palladium-Catalyzed Oxidative C–C Bond Forming Cascade Reactions of Allenes

“…In recent years, acyclic cross-conjugated polyenes (dendralenes) have been used in diene transmissive Diels–Alder (DTDA) sequences for rapid generation of complex scaffolds bearing multiple stereogenic centers (Scheme ). Due to regioselective functionalization of the multiple olefinic sites, other applications of dendralenes are found in the synthesis of ivyane family compounds, vinylogous Nazarov reactions, organocatalytic domino cyclizations, oxidative reactions, and metathesis of [3]­dendralene–Fe­(CO) 3 complexes . However, synthetic methods for the preparation of higher cross-conjugated polyenes are quite limited as one-step reactions.…”