Alkynes reductive coupling

Scheme 25 Hydroboration and hydrozirconation strategies for aldehyde/alkyne reductive coupling...

A variety of aldehyde/alkyne reductive couplings involving the stoichiometric use of early transition metals (Ti and Zr) have been developed (Scheme 27) [68-70]. The low cost and ease of handling of titanium alkox-ides render these stoichiometric processes very practical despite the lack of catalytic turnover. Recent variants of stoichiometric processes involving titanium alkoxides have demonstrated impressive scope in relatively complex applications [71-73]. 

Although the titanium-based methods are typically stoichiometric, catalytic turnover was achieved in one isolated example with trialkoxysilane reducing agents with titanocene catalysts (Scheme 28) [74], This example (as part of a broader study of enal cyclizations [74,75]) was indeed the first process to demonstrate catalysis in a silane-based aldehyde/alkyne reductive coupling and provided important guidance in the development of the nickel-catalyzed processes that are generally more tolerant of functionality and broader in scope. 

This Pd(0)/formic acid system was effective for the cyclization of substituted 5-allene-l-ynes to give diene 140 (Eq. 25) through initial insertion into the internal 7r-bond of the allene followed by insertion into the alkyne [79]. All of the examples provided were geminally substituted within the backbone to facilitate cyclization. Intramolecular allene-alkyne reductive couplings to generate six-membered rings were not achieved. 

Several mechanistic pathways have been proposed for nickel-catalyzed aldehyde/ alkyne reductive couplings, and an overview of the possible mechanisms has been provided elsewhere [3]. Therefore, this description will focus on what is generally believed to be the operative mechanism. The key features of this mechanism are the oxidahve cyclizahon of a zero-valent nickel aldehyde-alkyne complex to form a five-membered oxametallacycle, followed by reductive cleavage of the nickel-carbon bond, and carbon-hydrogen bond formation via reduchve elimination (Scheme 8.30). 

Intermolecular aldehyde/alkyne reductive couplings involving PBua and EtaB have been explored on a variety of systems ranging from simple to quite complex [22]. Aromatic alkynes are generally the best substrates, whereas more substrate generahty is observed on the aldehyde component (Scheme 7). In the course of examining asymmetric couplings (see Sect. 2.2.4), a variety of different monodentate phosphines were examined [23]. 

M. R. Chaulagain, G. J. Sormunene, J. Montgomery, J. Am. Chem. Soc. 2007, 129, 9568-9569. New N-heterocyclic carbene ligand and its application in asymmetric nickel-catalyzed aldehyde/alkyne reductive couplings. 

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