Preparation and synthetic value of π-bond-rich branched hydrocarbons.

Research paper by Michael S MS Sherburn

Indexed on: 08 Jul '15Published on: 08 Jul '15Published in: Accounts of Chemical Research


The two simplest branched acyclic structures comprising only conjugated C═C units, namely, [3]dendralene (3-methylene-1,4-pentadiene) and [4]dendralene (3,4-dimethylene-1,5-hexadiene), were first reported in 1955 and 1962, respectively. No higher members of the series were described in the literature until 2000. This Account describes the modern phase of dendralene chemistry, driven to a large extent by research performed within the author's group. The first synthesis of the parent dendralene family allowed access to the hydrocarbons in batches of up to 5 mg. The synthetic approach took into account the prevailing dogma of the time, specifically that these compounds would be very reactive species and hence difficult to handle in the laboratory. As such, a route involving the cheleotropic elimination of SO2 from stable, and generally insoluble, 3-sulfolene-masked precursors was devised. Our second-generation approach was of significantly higher value in preparative terms, allowing the syntheses of the first six members of the unsubstituted [n]dendralenes (i.e., n = 3-8) directly, on scales of hundreds of milligrams to decagrams, using commercially available precursors and standard laboratory equipment and methods. This work demonstrated that the assumed high reactivity and instability this family of compounds was erroneous and ultimately led to the development of syntheses of structurally related cross-conjugated systems including substituted dendralenes, tetravinylethylene, 1,1-divinylallene, and furan-containing analogues of the dendralenes. Cross-coupling reactions feature strongly in the syntheses of these compounds, and methods involving single- to multifold Stille, Kumada, and Negishi couplings are mainstays of this work. The even parity [n]dendralenes were shown to exhibit enhanced stability over the odd parity congeners, a result that can be attributed to conformational effects. π-Bond-rich branched hydrocarbons are demonstrated to have significant value in the rapid generation of structural complexity. Pericyclic processes are particularly useful in this regard, with the dendralenes and their relatives serving as multidienes, participating in diene-transmissive cycloaddition sequences, sometimes in combination with electrocyclizations, to generate fused and bridged multicyclic systems containing many new covalent bonds. The outcomes of exploratory investigations into pericyclic sequences involving dendralenes are presented, along with methods developed to control chemoselectivity, regioselectivity, and stereoselectivity. Distinct from their use in diene-transmissive sequences, the dendralenes also serve as multialkenes, for the direct synthesis of polyols and oligo-cyclopropanes. Finally, the deployment of π-bond-rich branched hydrocarbons in the shortest total synthesis of a pseudopterosin natural product is summarized, as a prelude to future prospects in the areas of hydrocarbon chemistry and target synthesis.