Dendralene from dendralenes

Dendralenes From a Neglected Class of Polyenes to Versatile Starting Materials in Organic Synthesis... 

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... 

A considerable number of processes have been described for the preparation of the two simplest dendralenes however, most of them are rather means of formation than efficient preparative methods. As Scheme 2 shows for [3]dendralene 7, thermal methods of preparation predominate (1,2-eliminations and periyclic processes) however, these methods do not always start from readily accessible precursors [5], The most effective procedure - which can hence be employed in subsequent reactivity studies (see below) - consists in the cheletropic decomposition of 11 carried out by Cadogan and Gosney et al. [6] although the preparation of the sulfolene derivative also requires several steps. 

Before the first general synthetic concept for the preparation of the dendralenes is presented, it will be shown that these 7i-systems are interesting not only preparatively but also from a structural point of view. The application of dendralenes in Diels-Alder additions holds particular promise in synthetic chemistry. This is demonstrated in general form in Scheme 4 for the two simplest dendralenes. The [2+4]cycloaddition of 7 with a dienophile 20, not only leads to the expected l l-adduct 21 but also generates a new conjugated diene system which... 

The masked dendralenes 36 are crystalline compounds, stable at room temperature, from which, as hoped, the hydrocarbons 37 could be released on demand in good yields by high-temperature pyrolysis. No solvent is required in these cheletropic reactions which facilitates the work-up. The dendralenes 37 obtained, up to [8]dendralene, have been completely characterized by the usual spectroscopic and analytical methods and can, although they tend to polymerize, be handled under the usual laboratory conditions (see below). The sulfolene decomposition route has recently been applied to the synthesis of many other cross-conjugated compounds, among them the hydrocarbons 39-42 (Scheme 7) [12]. 

Sherbum reported a robust synthesis of the fascinating diene [4]dendralene (97) and its behavior in Diels-Alder reaetions with N-methylmaleimide (89, NMM). Dendralene 97 is available in one step from chloroprene and combines with three equivalents of an A-methylmaleimide-methyl aluminium diehloride complex to provide a diastereomeric mixture of 98 after three Diels-Alder reactions. ... 

Synthesis of a hexasubstituted phenanthrene derivative from [4]dendralene is illustrated in Scheme 16.24 [25]. The poor yields observed in the cycloaddition steps might be due to the thermal instability of [4]dendralene and the initially formed cycloadduct. 

SCHEME 16.24 Synthesis of hexasubstituted phenanthrene derivative from [4]dendralene. 

Higher dendralenes are accessible by double cross-coupling by including branched alkenes into the electrophile unit. For example, in their state-of-the-art synthesis of the parent dendralenes [23], Sherburn and coworkers prepared [6]dendralene (21) by the reaction between 2,3-dichloro-1,3-butadiene (20), and the Grignard reagent (9) prepared from chloroprene, another readily available unsaturated halide produced annually on a megaton scale (Scheme 1.4) [24]. The scope of this reaction in the synthesis of substituted higher dendralenes remains unexplored. 

Scheme 1.5 Syntheses of dendralenes utilizing a double nucleophilic cross-coupling building block, from the Shimizu group [25-27],...

Scheme 1.15 Multi-bond-forming syntheses of [3]dendralenes from the Ma group [68-70].

Despite being a less obvious starting material than a l,3-butadiene-2-yl coupling partner, l,2-butadien-4-yl precursors (such as 166 in Suzuki s pioneering example in Scheme 1.26) have seen the most use in dendralene synthesis [118, 131-136]. A couple of more recent examples include the palladium-catalyzed cross-coupling reaction of alkenyl bromides 179 with, for example, the organoindium derived from allenyl bromide 181, or 1,1-dimethyl allene (183) (via a Mizoroki-Heckreaction) (Scheme 1.28) [132,135]. Palladium(0)-catalyzed dimerizations or homocouplings can also furnish the C2-C3 bond [138-142], as can nickel(O)- [143,144] and rhodium(I)-catalyzed ones [137]. 

Another C-H activation method that has potential in the synthesis of dendralenes was reported by Gulras and coworkers in 2015 (Scheme 1.35) [159]. A stable dendralene intermediate 217 was prepared from substituted phenol 215 and allene 216, as an intermediate in the Rh(III)-catalyzed synthesis of 2f/-chromenes. In principle, this method could be adapted to target substituted dendralenes. 

Another way to circumvent the stereoselectivity issues that may arise from olefination or addition/elimination sequences to l,4-dien-3-ones is to switch the polarity of components and olefinate a carbonyl compound with a symmetrical nucleophilic pentadienyl anion equivalent. A seminal contribution was reported by Paul and Tchelitcheff in 1951, who combined trivinylmethane (235) and carbon dioxide to form a [3]dendralene 237 (Scheme 1.40 (a)) [190]. In this instance, the anion of trivinyl methane 236 is indeed a pentadienyl anion, but bond formation occurs with allylic transposition through a vinyl unit. 

Aside from the synthesis of dendralenes from nondendralenic materials, there also exist a variety of transformations that can be applied to a preexisting dendralene framework to add further functionality. Most of these examples form part of exploratory studies to test the reactivity of dendralenes nevertheless, they show potential for the synthesis of a variety of functionalized dendralenes. Broadly, these can be divided into transformations that reduce the length of the [ ]dendralene framework (e.g., n- n—1), ones that functionalize and preserve an existing [n] dendralene framework (i.e., n n), or ones that add extra branched alkenes to form a higher [njdendralene (e.g., n- n+1). 

Scheme 1.43 Hetero-DA and enantioselective DA reactions of dendralenes from the Sherburn group [205, 206].

Singly complexed tricarbonyliron-[4]dendralene 261 (prepared from [4]den-dralene (259)) [89, 207] can be reacted with NMM (262) to undergo a single DA reaction at a terminal diene site to produce, after decomplexation, a reactive [3]dendralene 263 (Scheme 1.44), which cannot be isolated by reacting uncom-plexed [4]dendralene (259) and dienophiles (see Chapter 12). Complexation and reaction, therefore, provides a viable avenue toward dendralenes not isolable from other reaction conditions. 

Cadogan et al. [27] reported the DTHDA cycloaddition of parent cross-conjugated carbotriene ([3]dendralene) 106 with some representative electron-withdrawing dienophiles including heterodienophiles (Scheme 2.16). They applied a flash vacuum pyrolysis technique to synthesize parent carbotriene 106 in pure form from 3-vinyl-3-sulfolene. The initial DA reaction with p-benzoquinone (PBQ) at 40 °C afforded mono-adduct 107 (90%), followed by the second HDA reaction with Ph-TAD at 40 °C to provide the mixed bis-adduct 108 (63%). Triene 106 gave mono-adduct 109 in the presence of even an excess amount of TCNE at 40 °C. Ph-TAD was able to react with mono-adduct 109 at 40°C to provide crossed bis-adduct 110 (63%). Bis-adduct 111 was directly obtained (21%) by reaction of 106 with excess Ph-TAD at 40 °C, as same as the reaction with Ph-MI. 

The unique titanocene- or hafnocene-substituted [4]radialenes 86 [78] and 87 [79] were formed in low yields from diphenylbutadiyne and Cp2H(Ti -MegSiC CSiMej) or Cp2Hf(n-Bu)2, respectively (Scheme 4.18). Other 1,3-diynes did not react analogously. Efforts to liberate the free radialene from these organometallics by acidolysis were only partly successful treatment of 86 with hydrogen chloride led to the [3]dendralene 88 in high yield, while 87 furnished the tetraphenyl[4] radialene 89 only as an unstable, impure product. 

Section 4.2.3. The parent [5]radialene has been synthesized at last [147]. Key to success was a low-temperature decomplexation of a [5]radialene-bis(Fe(CO)3) complex, that had been prepared from a 2,6-dichloro-3-oxa-[5]dendralene precursor. A 30 mM solution of the hydrocarbon in acetone had a half-life time of around 16 min at -20 °C. According to G4(MP2) calculations for the gas phase, a Diels-Alder reaction, which leads to dimerization/polymerization, is outstandingly facile. 

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