Diego J. Cárdenas

Nickel-catalysed Negishi cross-coupling reactions: scope and mechanisms

The Negishi cross-coupling of organozinc reagents is a valuable tool for the formation of C-C bonds in the presence of functional groups. Although this reaction is catalysed by Ni or Pd complexes, the latter have been much more developed. Nevertheless, Ni derivatives have become important in recent years, especially for their activity in the formation of alkyl-alkyl bonds. The mechanisms involved in Ni-catalysed reactions are different from the usual catalytic cycle involving oxidative addition-transmetalation-reductive elimination that is generally accepted for Pd-catalysed reactions. This tutorial review presents the more recent advances in Ni-catalysed Negishi cross-couplings for the formation of different kinds of C-C bonds and discusses their proposed reaction mechanisms.

Regiocontrolled CuI-Catalyzed Borylation of Propargylic-Functionalized Internal Alkynes

Good to excellent reactivity and regiocontrol have been achieved in the Cu(I)-catalyzed borylation of dialkyl internal alkynes with bis(pinacolato)diboron. The presence of a propargylic polar group (OH, OR, SAr, SO(2)Ar, or NHTs), in combination with PCy(3) as ligand, allowed maximizing the reactivity and site-selectivity (β to the propargylic function). DFT calculations suggest a subtle orbitalic influence from the propargylic group, matched with ligand and substrate size effects, as key factors involved in the high β-selectivity. The vinylboronates allowed the stereoselective synthesis of trisubstituted olefins, while allylic substitution of the SO(2)Py group without affecting the boronate group provided access to formal hydroboration products of unbiased dialkylalkynes.

Towards Efficient and Wide‐Scope Metal‐Catalyzed Alkyl–Alkyl Cross‐Coupling Reactions

The simplest organic fragment, C(sp(3))-C(sp(3)), is unfortunately the most difficult to prepare by metal-catalyzed cross-coupling reactions (shown schematically) in the presence of functional groups. Recent advances show, however, that alkane moieties can be built within functionalized molecules by a careful choice of catalysts and conditions.

Understanding the Exceptional Hydrogen-Atom Donor Characteristics of Water in TiIII-Mediated Free-Radical Chemistry

In recent years solid evidence of HAT reactions involving water as hydrogen atom source have been presented. In this work we demonstrate that the efficiency of titanocene(III) aqua complexes as an unique class of HAT reagents is based on two key features: (a) excellent binding capabilities of water toward titanocene(III) complexes and (b) a low activation energy for the HAT step. The theory has predictive capabilities fitting well with the experimental results and may aid to find more examples of this remarkable radical reaction.

Nickel‐Catalyzed Cross‐Coupling of Alkyl Zinc Halides for the Formation of C(sp2)C(sp3) Bonds: Scope and Mechanism

Optimal conditions for a general Ni-catalysed Negishi cross-coupling of alkyl zinc halides with aryl, heteroaryl and alkenyl halides have been determined. These conditions allow the reaction to take place smoothly, with low catalyst loading, and in the presence of a wide variety of functional groups to afford products in good yields at room temperature. DFT studies on the mechanism support the occurrence of a catalytic cycle involving transmetalation of the alkyl zinc halide to Ni(I) followed by oxidative addition of the haloarene and C-C reductive elimination.

Fe-catalysed Kumada-type alkyl–alkyl cross-coupling. Evidence for the intermediacy of Fe(I) complexes

A novel Fe–NHC catalytic system allows the alkyl–alkyl cross-coupling reaction of alkyl halides and alkylmagnesium reagents has been developed. To our knowledge, this is the first Fe-catalysed Kumada-type coupling for the formation of C(sp3)–C(sp3) bonds in the presence of functional groups. The process takes place under mild conditions, avoiding the formation of β-elimination products. Mechanistic studies suggest the intermediacy of Fe(I) complexes, formed by reduction with the Grignard reagent, as the active species.

Intramolecular coupling of allyl carboxylates with allyl stannanes and allyl silanes: A new type of reductive elimination reaction?

The palladium-catalyzed intramolecular coupling of allyl stannanes with allyl carboxylates provides a general synthesis of five- and six-membered-ring carbocycles. The intramolecular coupling leads selectively to trans five-membered carbocycles and cis six-membered carbocycles, regardless of the cis or trans configuration of the allylic functions in the starting material. For example, the stereoselective synthesis of 10-epi-elemol demonstrated the cis configuration of the six-membered carbocycles. The related Oppolzer cyclization leads to lower yields, or fails completely, with substrates substituted at C-3 of the allyl and/or alkene terminus. The palladium-catalyzed intramolecular coupling of allyl silanes with allyl trifluoroacetates allows the synthesis of trans five-membered-ring carbocycles and requires the use of a bicyclic phosphite as the ligand. DFT calculations suggest that the preferred pathway for the intramolecular allyl/allyl coupling is by formation of the Cbond;C bond between the C-3 termini of the allyl ligands of bis(eta(3)-allyl)palladium complexes.

Copper-Catalyzed Borylative Aromatization of p-Quinone Methides: Enantioselective Synthesis of Dibenzylic Boronates

In this report, we establish that DM-Segphos copper(I) complexes are efficient catalysts for the enantioselective borylation of para-quinone methides. This method provides straightforward access to chiral monobenzylic and dibenzylic boronic esters, with enantiomeric ratios up to 96:4, using a commercially available chiral phosphine. Standard manipulations of the C–B bond afford a variety of chiral diaryl derivatives.

Intramolecular C−H Activation by Alkylpalladium(II) Complexes: Insights into the Mechanism of the Palladium‐Catalyzed Arylation Reaction

The cyclization of [ArOCH2PdL2Cl] complexes proceeds at room temperature in CH3CN in the presence of base, such as KOPh or carbonate, to form palladacycles. The effect of substituents on the aryl moiety (p-MeO > H >p-NO2) is as expected for an electrophilic aromatic substitution by electrophilic Pd(II). The absence of isotopic effect is also consistent with this proposal. Cyclopalladation proceeds with bidentate ligands (dppf, COD and phen); although the C-H activation reactions are slower in these cases. The starting [ArOCH2Pd(PPh3)2Cl] and [ArOCH2Pd(PPh3)Cl]2 complexes were prepared by transmetalation of organostannanes [(ArOCH2)4Sn] with [Pd(PPh3)2Cl2] or [Pd(PPh3)Cl2]2, respectively. Cleavage of palladacycles with HCl also gave [ArOCH2PdL2Cl] complexes.

Pd-Catalyzed Borylative Cyclization of Allenynes and Enallenes

Pd-catalyzed cyclization of 1,5- and 1,6-allenynes and 1,5-enallenes with bis(pinacolato)diboron affords synthetically useful allylboronates and alkylboronates under smooth conditions in a formal hydroborylative carbocyclization reaction. One C-C and one C-B bond are formed in a single operation. The reaction outcome implies that different mechanisms operate for the reactions of allenynes and enallenes, respectively, the actual pathway depending on the relative reactivity of the alkyne or the alkene versus the allene moiety. The cyclized boronates obtained can be functionalized by oxidation or allylation reaction with aldehydes.