Cycloadditions Mediated by Coordination of the Substrate s around a Transition Metal

4 Cycloadditions Mediated by Coordination of the Substrate(s) around a Transition Metal 

Transition metal-mediated [2 + 2+1] cycloadditions are also viable and have numerous applications in total syntheses for the creation of five-membered 

Initially, the Pauson-Khand reaction involved heating the substrate in a hydrocarbon solution at elevated temperatures and, as such, was not applicable to labile polyfunctional substrates. Later it was discovered that this cycloaddition could be greatly accelerated under the action of mild oxidants (morpholine 

An additional advantage of the intramolecular protocol stems from the opportunity to prepare easily the required polyfunctional precursors via cobalt carbonyl stabilized propargyl cations. The approach based on the tandem utilization of Co-mediated alkylation and Pauson-Khand annulation was developed in Schreiber s studies to elaborate short pathways for the synthesis of polycyclic compounds. An example of the efficiency of this protocol is the two-step transformation of the acyclic precursor 409 into the tricyclic derivative 410. The cobalt-complexed acetal 409 was first transformed into the cyclooctyne derivative 411 via intramolecular reaction of the in situ generated propargyl cation 409a with the allylsilane moiety. Cyclooctyne 411 underwent smooth cycloaddition in the presence of carbon monoxide to give the target compound 410 with excellent stereoselectivity. 

Transition metal catalysts were also found to be useful for the mixed cyclo-co-oligomerization of two 1,3-dienes with an alkene or alkyne. This approach was further extended toward the preparation of heterocyclic systems.  

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