Palladium and nickel are used in conjunction with titanocene(III) complexes to perform selective allylations of carbonyl compounds and alkenes, respectively. Pd/Ti‐catalyzed allylation of ketones ...proceeds diastereoselectively under mild conditions, whereas Ni/Ti‐promoted cyclizations provide polyalkyl‐substituted carbo‐ and heterocycles with excellent control over regio‐ and stereoselectivity.
Cp2TiCl: An Ideal Reagent for Green Chemistry? Castro Rodríguez, María; Rodríguez García, Ignacio; Rodríguez Maecker, Roman Nicolay ...
Organic process research & development,
07/2017, Volume:
21, Issue:
7
Journal Article
Peer reviewed
The development of Green Chemistry inevitably involves the development of green reagents. In this review, we highlight that Cp2TiCl is a reagent widely used in radical and organometallic chemistry, ...which shows, if not all, at least some of the 12 principles summarized for Green Chemistry, such as waste minimization, catalysis, safer solvents, toxicity, energy efficiency, and atom economy. Also, this complex has proved to be an ideal reagent for green C–C and C–O bond forming reactions, green reduction, isomerization, and deoxygenation reactions of several functional organic groups as we demonstrate throughout the review.
A general method for the straightforward synthesis of exocyclic allenes on five‐, six‐, seven‐, and eight‐membered oxygen heterocycles is described. A Barbier‐type titanocene(III)‐catalyzed ...cyclization of propargyl halides with a pendant carbonyl group is the key step of the process. This reaction is compatible with many functional groups, and can be smoothly carried out under neutral and mild conditions at room temperature.
The synthesis of exocyclic allenes on five‐, six‐, seven‐, and eight‐membered oxygen heterocycles can be achieved through a Barbier‐type titanocene(III)‐catalyzed cyclization of propargyl halides with a pendant carbonyl group.
The titanocene‐catalyzed cascade cyclization of epoxypolyenes, which are easily prepared from commercially available polyprenoids, has proven to be a useful procedure for the synthesis of C10, C15, ...C20, and C30 terpenoids, including monocyclic, bicyclic, and tricyclic natural products. Both theoretical and experimental evidence suggests that this cyclization takes place in a nonconcerted fashion via discrete carbon‐centered radicals. Nevertheless, the termination step of the process seems to be subjected to a kind of water‐dependent control, which is unusual in free‐radical chemistry. The catalytic cycle is based on the use of the novel combination Me3SiCl/2,4,6‐collidine to regenerate the titanocene catalyst. In practice this procedure has several advantages: it takes place at room temperature under mild conditions compatible with different functional groups, uses inexpensive reagents, and its end step can easily be controlled to give exocyclic double bonds by simply excluding water from the medium.
The total synthesis of a wide range of complex terpenoid skeletons, including monocyclic, bicyclic, and tricyclic natural products, is facilitated by employing a novel reaction cascade based on the combination of biomimetic strategies with titanocene catalysis. For example, the titanocene‐catalyzed radical cyclization of 2,3‐oxidosqualene mainly gave malabaricatrienes (see scheme). Mechanistically the reaction presumably occurs via discrete carbon‐centered radicals.
We describe a comprehensive study into the Cp2TiCl‐mediated reductive epoxide ring opening using either water as a hydrogen source or deuterium oxide as a deuterium source. The remarkable chemical ...profile of this reaction allows access to alcohols with anti‐Markovnikov regiochemistry from different epoxides. The use of D2O as a deuterium source leads to an efficient synthesis of β‐deuterated alcohols, including a deuterated sample of tyrosol, a bioactive compound contained in the leaves of the olive, which was successfully applied as an internal standard in food analysis.
The reductive opening of epoxides mediated by Cp2TiCl is described. Water was used to access alcohols with anti‐Markovnikov regiochemistry. The use of D2O led to the efficient synthesis of β‐deuterated alcohols. A deuterated sample of tyrosol, a bioactive compound contained in the leaf of the olive tree, was prepared and successfully applied as an internal standard in food analysis.
The formation of either deoxygenation products or allylic alcohols from epoxides is observed when these substrates are treated with Cp
2TiCl under anhydrous conditions. It seems that processes via ...trisubstituted radicals give allylic alcohols whereas processes via disubstituted radicals may give deoxygenation products or allylic alcohols depending on the structure of the original epoxide. This method allows a controlled access to these functional groups, providing a useful tool in organic synthesis. A mechanistic discussion for these transformations is reported.
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The half‐sandwich titanocene reagent CpTiIIICl2, obtained by in situ reduction of commercial CpTiCl3 with manganese, is an excellent system for the Barbier‐type reaction between aldehydes and ...propargylic halides, leading to homopropargylic alcohols and α‐allenols. An efficient and straightforward methodology for the conversion of aldehydes into 2,5‐dihydrofurans involving a two‐step sequence (TiIII addition‐AgI cyclization) is presented. The usefulness of the method is proved by the preparation of a Natural Product: a dihydrofuranic labdane, isolated from the leaves of Mikania sp. nov.
CpTiIIICl2, prepared from commercial CpTiCl3, is an excellent reagent for the Barbier‐type allenylation and propargylation of aldehydes. It can be used for the synthesis of 2,5‐dihydrofurans through a straightforward methodology involving a two‐step sequence: Ti (III) addition ‐ Ag(I) cyclization.
A general procedure for the synthesis of both 12,6- and 12,8-eudesmanolides has been developed. The key step is the titanocene-catalyzed radical cyclization of accessible epoxygermacrolides. The ...novel reagent 2,4,6-trimethyl-1-trimethylsilylpyridinium chloride, both compatible with oxiranes and capable of regenerating Cp2TiCl2 from Cp2Ti(Cl)H and Cp2Ti(Cl)OAc, played an important role in the catalytic cycle leading to exocyclic alkenes.
We describe a novel convergent procedure that has proved useful in the synthesis of a wide range of meroterpenoid-related structures containing a mono-, sesqui-, or diterpenoid moiety linked to a ...nonfused aromatic subunit with various substitution patterns. The key steps were the Stille-type coupling of aryl stannanes and allylic carbonates, followed by the titanocene-catalyzed domino cyclization of aryl epoxypolyprenes. The coupling reaction was perfectly compatible with preformed epoxides, while the sequential cyclization, which presumably proceeded via alkyl radicals inert to benzene derivatives, selectively provided exocyclic alkenes.
