Allene-Alkene Coupling

We had established in previous catalytic reactions involving complex 24 that this precatalyst was activated by the removal of the cod (1,5-cyclooctadiene) from the ruthenium by its reaction with the alkyne substrate via a [2 + 2 + 2] cydization as illustrated in Equation 1.64 [57]. Thus, not only does this reaction constitute an activation of the Ru complex 24 by reacting off the cod, it also serves as a novel atom economic reaction in its own right. Both internal and terminal alkynes participate. The overall atom economy of this process is outstanding since cod itself is simply available by the nickel-catalyzed dimerization of butadiene. Thus, the tricyclic product is available by the simple addition to two molecules of butadiene and an alkyne with anything else only needed catalytically. 

Adding a catalytic amount of an alkyne to the reaction in Equation 1.63 indeed enhanced the yield dramatically. The quantitative yield for the activation step obtained using 3-hexyn-l-ol made this alkyne the one of choice as the activator for the allene addition. Taking advantage of this atom economic synthesis of 1,3-dienes by employing the [4 + 2] cydoaddition then allows complex cyclic entities to be available with high atom economy. 

Both 1,1- and 1,2-disubstituted allenes participate well. If both substituents bear allylic hydrogen, the issue becomes regioselectivity of (3-hydrogen elimination. An obvious solution is to activate one of the possible (3-Hs by proper choice of the substituent. A carbonyl group serves that role, as illustrated in Equations 1.65 and 1.66 [58]. In these cases, the tris-acetonitrile precatalyst was employed, which does not require the addition of an alkyne as a cocatalyst. Interestingly, competing the reaction of a propargyl alcohol with that of an allene as in the case of allenyne 58 (Equation 1.67) showed complete chemoselectivity for reaction of the allene. 

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In Section 9.2, intermolecular reactions of titanium—acetylene complexes with acetylenes, allenes, alkenes, and allylic compounds were discussed. This section describes the intramolecular coupling of bis-unsaturated compounds, including dienes, enynes, and diynes, as formulated in Eq. 9.49. As the titanium alkoxide is very inexpensive, the reactions in Eq. 9.49 represent one of the most economical methods for accomplishing the formation of metallacycles of this type [1,2]. Moreover, the titanium alkoxide based method enables several new synthetic transformations that are not viable by conventional metallocene-mediated methods. 

Crossed Alkene-Alkene Coupling 2323 Allene Synthesis by sp -sp Coupling... 

Scheme 10.154 Proposed reaction steps in the titanium-mediated reductive allene-alkene cross-coupling [125].

Melhylenecydobutane-l,2-dicar-boxylic anhydride, 43,27 Methylenecydobutanes by addition of allenes to alkenes, 43, 30 Methylenecyclohexane, 40, 66 Methylene iodide, reaction with zinc-copper couple and cyclohexene, 41, 73... 

Trost et al 2 briefly explored using non-enone enophiles. Simple alkenes led to the formation of complex mixtures of isomers due to the presence of an additional set of /3-hydrogens. Many other types of substrates were incompatible with reaction conditions. Vinyl ketones were, therefore, the only coupling partners shown to be effective in the ruthenium-catalyzed Alder-ene couplings of allenes and alkenes. 

The transition metal cross-couplings of allenes described here offer practical solutions for the modification of 1,2-dienes and access to the preparation of highly functionalized 1,3-dienes, alkynes and alkenes, which are often not easily accessible in a regio- and stereoselective manner by classical methods. Some of the prepared alkynes or functionalized allenes serve as important intermediates in syntheses of natural products, biologically active compounds, e.g. enynes and enyne-allenes, and new materials. It can be predicted that further synthetic efforts will surely be focused on new applications of allenes in transition metal-catalyzed cross-coupling reactions. 

Nickel-catalyzed cyclizations, couplings, and cycloadditions involving three reactive components have been an active area of research for the past decade [39,40]. Central to these reactions is the involvement of a low-valent nickel capable of facilitating oxidative coupling of an unsaturated hydrocarbon (such as an alkyne, allene, or alkene) and a carbonyl substrate (such as an aldehyde or ketone). The use of NHCs as ligands has been evaluated for couplings of aldehydes. Such reactions typically afford O-protected allylic alcohols in good yields. 

The synthesis of unsaturated compounds by C-C bond formation can also be carried out by coupling of alkenes with allenes, intermolecularly or intra-molecularly. Thus, 1,3-dienes were selectively obtained by coupling of allenes and vinyl ketones [28-30]. The reaction was catalyzed by the complex CpRuCl(COD) and with CeCl3 as a cocatalyst (Eq. 19). This cocatalyst is expected to decrease the chloride ion concentration to keep the active cationic ruthenium complex coordinatively unsaturated. 

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