Synthesis and Diels–Alder Reactivity of Substituted [4]Dendralenes

Abstract

The first synthesis of all five possible monomethylated [4]dendralenes has been achieved via two distinct synthetic strategies. The Diels-Alder chemistry of these new dendralenes (as multidienes) with an electron poor dienophile, N-methylmaleimide (NMM), has been studied. Thus, simply upon mixing the dendralene and an excess of dienophile at ambient temperature in a common solvent, sequences of cycloadditions result in the rapid generation of complex multicyclic products. Distinct product distributions are obtained with differently substituted dendralenes, demonstrating that dendralene substitution influences the pathway followed, when a matrix of mechanistic possibilities exists. Dendralene site selectivities are traced to electronic, steric and conformational effects, thereby allowing predictive tools for applications of substituted dendralenes in future synthetic endeavors.

Tandem aldol condensation-Diels–Alder-aromatization sequence of reactions: a new pathway for the synthesis of 2-tetralone derivatives

“…interesting strategy involves the use of the DA reaction in tandem protocols 20,21 for rapid and 13 efficient access to diverse libraries of complex products 22 and target molecules. 23,24 14 In the framework of our studies on aldol condensation reactions, we have reported the 15 synthesis of a series of styrylcyclohex-2-enone dienes (e.g.…”

Synthesis of Functionalized [3], [4], [5] and [6]Dendralenes through Palladium‐Catalyzed Cross‐Couplings of Substituted Allenoates

“…[1] No longer simply molecules of curiosity, in large measure due to the efforts of pioneers such as Hopf, and more recently Sherburn, dendralenes of both the cyclic and acyclic varieties have become useful intermediates in targeted syntheses (Figure 1, bottom). [2,3] One of many attractive features is their ready participation in cycloaddition reactions, in particular the diene-transmissive-Diels-Alder (DTDA) reaction. In this regard, they are well configured to maximize "step economy" en route to both natural and unnatural materials that contain polycyclic arrays.…”

“…This multi-catalytic system applied to the synthesis of functionalized dendralenes shows broad substrate compatibility, as well as functional group tolerance. Furthermore, these mild conditions compare very favorably with existing methods, [1,2,4,6] in terms of simplicity, amounts of reagents involved, and environmental concerns (such as organic waste in the form of solvents, and energy invested in the form of low temperatures).…”

Synthesis of Functionalized [3], [4], [5] and [6]Dendralenes through Palladium‐Catalyzed Cross‐Couplings of Substituted Allenoates

“…[1] No longer simply molecules of curiosity,i nl arge measure due to the efforts of pioneers such as Hopf,a nd more recently Sherburn, dendralenes of both the cyclic and acyclicv arieties have become useful intermediates in targeted syntheses (Figure 1, bottom). [2,3] One of many attractive features is their ready participation in cycloaddition reactions,i np articular the diene-transmissive-Diels-Alder (DTDA) reaction. In this regard, they are well configured to maximize "step economy" en route to both natural and unnatural materials that contain polycyclic arrays.N otwithstanding the remarkable advances made in preparing higher homologs that now have reached [12]dendralene, [4] recent papers from the Sherburn group highlight the need for additional inroads to both the parent and especially substituted systems,a sw ell as new chemistry that extends the repertoire of reactions of dendralenes beyond [4+ +2] cycloadditions.I ndeed, in ar ecent Account, [5] Sherburn concludes:" Regarding our deployment of the dendralenes and related unsaturated hydrocarbons in the rapid generation of structural complexity,a gain, we have deployed only knownreactions (and in the main, just one:the venerable Diels-Alder reaction).…”

“…Thus,a crylates,a crylamides,s tyrenes,a nd other alkenes readily participated under similar micellar conditions,p roviding the corre-sponding Heck products in good isolated yields.N oteworthy is the realization of substituted enoates at their b-positions (e.g., 3)w ithout observable isomerization. Furthermore,t hese mild conditions compare very favorably with existing methods, [1,2,4,6] in terms of simplicity,amounts of reagents involved, and environmental concerns (such as organic waste in the form of solvents,a nd energy invested in the form of low temperatures). Borylation was initially [6h] Of note is that homocoupling does not occur under copper catalysis even after extended reaction times (i.e., from 2to48h).…”