Carbonyl Coupling Reactions Catalytic in Titanium and the Use of Commercial Titanium Powder for Organic Synthesis

Abstract

The high thermodynamic stability of titanium oxides formed as the inorganic byproducts in McMurrytype reactions has so far prevented the development of a catalytic procedure for such reductive carbonyl coupling processes. Similarly, a tightly bound oxide layer passivates the surface of commercial titanium, which is unreactive toward organic substrates under conventional conditions. This paper outlines a way to overcome both of these problems. Thus, oxoamides 1a-h can be reductively cyclized to indoles 2a-h using only catalytic amounts of low-valent titanium if the reaction is carried out in the presence of a chlorosilane. Specifically, the method is based upon the in situ generation of an activated titanium species from TiCl₃ and Zn in the presence of the substrate, followed by regeneration of titanium chloride from the titanium oxides formed via ligand exchange with the admixed chlorosilane. Its proper choice is crucial for obtaining both good turnover numbers and clean conversions. Depending on the product structure, (TMS)Cl, ClMe₂SiCH₂CH₂SiMe₂Cl (5), or ClMe₂Si(CH₂)₃CN (6) was found to be best suited. Similarly, chlorosilanes also effect the activation of commercial titanium powder which may then be used as a performant off-the-shelf reagent for various types of carbonyl and acetal coupling reactions, for the deoxygenation of epoxides and for the reductive cyclization of oxoamides or oxoesters to indoles, benzofurans, and 2-quinolones. Under these conditions retinal can be reductively dimerized to ß-carotene in good yield. Moreover, the titanium/chlorosilane reagent combination exhibits a strong template effect, allowing macrocyclization reactions without recourse to high dilution. Up to 36-membered rings have been closed in that way. ²⁹Si NMR studies provide some insight into the elementary steps responsible for the degradation of the surface oxide layer on titanium by the chlorosilane. The effect of Lewis acid additives on the course of the coupling processes is discussed

Multicomponent Catalysis for Reductive Bond Formations

“…Only recently has it been possible to elaborate a procedure that for the first time enables us to perform intramolecular carbonyl coupling reactions catalyzed by titanium species. [4] This development was triggered by some earlier insights into the essentials of this transformation: it has been shown that a large number of low-valent titanium species, [Ti], differing in their formal oxidation states, ligand spheres, and solubilities promote carbonyl coupling processes with comparable ease. Because this fact refutes previous assumptions that metallic titanium was essential, the strong and aggressive reducing agents required for its preparation can be avoided.…”

“…Other transition metals: The rather general validity of the chlorosilane-based catalysis concept is further substantiated by some recent examples of pinacol coupling processes catalyzed either by low-valent vanadium ([CpV(CO) 4 ] cat., Zn, chlorosilane) [12] or low-valent samarium (SmI 2 cat., Mg, chlorosilane). [13] Likewise, a report from Coreys group on samarium-iodide-catalyzed additions of carbonyl compounds to acrylates deserves mention; these follow essentially the same rationale (SmI 2 cat., Zn(Hg), TMSOTf, LiI).…”

Lewis Acid Catalyzed Reactions of Thioketones with 1,2-Epoxycyclohexane and 1,2-Epoxycyclopentane

“…2.1). For example, workup of the reaction mixture after 1 min at À 788 yielded 31, 32, and bisfluorenylidene (33 [28], Scheme 11) (37, 16, and 2%, resp.). 2.6.…”

Titanocene-Catalyzed Pinacol Couplings: Reagent-ControlledTransition-Metal-Catalyzed Radical Reactions

“…The first succesful realization of this dehydes and ketones only few allow for highly dia-concept was a McMurry reaction catalytic in titanium. [6] stereoselective coupling. [1] An enantioselective coupling has Other examples are Nozaki-Hiyama couplings catalytic in remained elusive so far.…”