Acyclic dendralenes

Our first example of such a sequence comes from the research group of Fallis. 

In many of their contributions to the DTDA chemistry of [3]dendralenes, they illustrated the ease with which multicyclic frameworks can be generated via repetitive cycloadditions. In one of their most striking examples, four rings are generated in a one-pot operation through the combination of five molecules. 

Recognizing the potential of Fallis methodology, Schreiber and coworkers set about applying solid-supported [3]dendralenes in diversity-oriented synthesis [6]. 

A collection of 40 3-aryl-substititued [3]dendralenes were reacted with a library 

The first example of an enantioselective DA reaction of the parent [3] dendralene (6) was conducted by the Sherburn group in 2010 [8]. They demonstrated that 

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By connecting double and single bonds, formally five classes of hydrocarbons can be constructed which differ considerably from one another not only chemically and physically but also in terms of their practical significance [1] the linear polyenes 1, the annulenes 2, which consist exclusively of endocyclic double bonds , the radialenes 3, polyolefins which are characterized by semicyclic double bonds, the fulvenes 4, hybrids containing endo-and semicyclic double bonds, and finally, the dendralenes 5 [2] which are acyclic cross-conjugated polyenes... 

Dendralenes [24] (acyclic cross-conjugated polyenes) have been used as dienes in tandem Diels-Alder reactions, and a methodology for the synthesis of highly functionalized angularly anel-lated aromatic compounds has been developed (Scheme 16.23) [25]. A tandem double Diels-Alder reaction of DMAD with [3]dendralene followed by oxidation with DDQ gave the tetramethyl ester... 

In a very nice titanium-mediated annulation cascade, Cheng and Micalizio [80] synthesized functionalized, bicychc [3] dendralenes 133 in situ as intermediates that were trapped via a subsequent DA reaction (Scheme 1.18). The report includes one example of a DA dimerization product, seven examples of intermolecular metallocycle-mediated annulation followed by intermolecular [4-1-2] cycloaddition reaction to afford (135), and one example of an isolated, acyclic substituted [3]dendralene 137. 

A similar transformation was subsequently reported in 2014 by Fu and coworkers, who used allene and carbamate precursors to generate [3] dendralenes via rhodium(III) catalysis (Scheme 1.34) [158]. A variety of different carbamates 213 successfully rmderwent Rh(III)-catalyzed C-H activation and coupling to generate cychc and acyclic substituted [3] dendralenes 214. While the general route works quite well between the tri-substituted allene and acyclic carbamates, the reaction is not high yielding if the enol ester is cychc or the allene is mono- or tetra-substituted. 

Dendralenes, acyclic cross-conjugated polyenes having a nonplanar structure, containing DT rings (DT[ ]dendralenes) have received considerable attention as novel multistage redox systems. The [3]- and [4]-dendralenes containing... 

We begin by considering the most conceptually simple case intermolecular DTDA reactions of acyclic [3]dendralenes. To date, the majority of studies have been conducted on 3-substituted systems as a consequence of their accessibility [4], and the control they offer over DA site selectivity. In the generalized example illustrated in Scheme 12.3, the [3]dendralene conformation 26 is disfavored due to the steric interaction between the terminal Z-hydrogen atom shown, and the inside substituent R. Thus, assuming the activation barrier for each DA reaction is approximately equal, the reaction should preferably occur at the s-cis diene site depicted in 25 as a result of its increased population. 

Scheme 12.9 The DTDA chemistry of Cl, C2, and C3-tethered acyclic [3]dendralenes.

Interestingly, there has yet to be a DTDA sequence involving a dienophile tethered at Cl or C2. Most incorporate a tether at C3 [10-12], but at least one separate example, involving an inter- and then intramolecular DA sequence of an acyclic [3] dendralene where the second dienophile is tethered to the first, has been reported (discussed in section 12.5) [13]. 

Only one study detailing DTDA reactions of the pseudo-acyclic 1,1- or 3,3-cyclo[3]dendralenes has been reported, most likely owing to the difficulties associated with DA reactions of such highly substituted dienes. The prototypical, and not yet reahzed, DTDA cascade of l,l-cyclo[3]dendralene 17 is presented in Scheme 12.12. If the first DA reaction occurs at the more sterically demanding exocyclic diene site, spiro-bicycle 65 is produced, which could react further to generate the... 

Cyclo [3] dendralenes contain both a semicyclic and acyclic diene site, and, in principle, either of the two tricyclic frameworks 92 or 94 can be accessed through alternative DTDA sequences (Scheme 12.19). 

The first (and only) detailed DTDA study of parent [4] dendralene (14) was reported by the Sherburn group in 2005 [35]. Upon addition of an excess of NMM, at ambient pressure and temperature, a mixture of five products was obtained in excellent overall yield (Scheme 12.26). The first DA reaction occurred primarily at the terminal diene site to provide l,2-monocyclic[3]dendralene 119, as well as 21% of the internal adduct 120. Triene 119 could not be isolated, and a second cycloaddition, predominately at the internal site, afforded the two endo-DA adducts 121 and 122. The major diastereomer arises via approach of the dienophile anti with respect to the succinimide ring in compound 119. The tris-adducts 123 and 124 originate from reaction at the acyclic diene site of 119, and from the less hindered top face (as drawn). The two intermediates generated... 

Altogether there are three fundamental classes of oligo-olefins that exhibit cross-conjugation the dendralenes (acyclic and branched), the radialenes (cyclic and branched), and the fulvenes. The fulvenes contain both branched and linear conjugation within the same it-system, and are therefore hybrid systems. As they are widely regarded as cross-conjugated molecules in the chemical literature, we follow this convention here. 

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