Cross-coupling Of Alkyl Electrophiles Research Articles

Enantioselective Nickel Hydride Catalyzed Cross Coupling of Alkyl Electrophiles

Key words nickel hydride catalysis - enantioselectivity - cross-coupling - alkyl electrophiles

Decarboxylative C(sp3 )-O Cross-Coupling.

Alkyl aryl ethers are an important class of compounds in medicinal and agricultural chemistry. Catalytic C(sp3 )-O cross-coupling of alkyl electrophiles with phenols is an unexplored disconnection strategy to the synthesis of alkyl aryl ethers, with the potential to overcome some of the major limitations of existing methods such as C(sp2 )-O cross-coupling and SN 2 reactions. Reported here is a tandem photoredox and copper catalysis to achieve decarboxylative C(sp3 )-O coupling of alkyl N-hydroxyphthalimide (NHPI) esters with phenols under mild reaction conditions. This method was used to synthesize a diverse set of alkyl aryl ethers using readily available alkyl carboxylic acids, including many natural products and drug molecules. Complementarity in scope and functional-group tolerance to existing methods was demonstrated.

Stereospecific and stereoconvergent cross-couplings between alkyl electrophiles

The development of metal-catalysed cross-coupling reactions between one electrophilic and one organometallic nucleophilic partner has revolutionized the practice of chemical synthesis, with coupling reactions between sp2 centres now commonplace in both academic and industrial research. Methods to allow coupling of sp3 centres are rapidly being developed, with many recent advances even enabling control of the absolute configuration of newly formed stereogenic centres. The related cross-electrophile couplings have not been developed as thoroughly owing to the challenge of obtaining cross-selectivity between two substrates with similar reactivity. However, the discovery of improved methods to address this challenge has led to significant recent progress. The development of enantioselective cross-electrophile coupling reactions is an emerging area of research. Both stereoconvergent and stereospecific variants have been reported for the synthesis of a range of products containing tertiary stereogenic centres. Many of these transformations build on lessons learnt from traditional (electrophile–nucleophile) cross-couplings of alkyl electrophiles. For example, all enantioselective transformations described to date use a nickel catalyst. Continued progression is likely to provide strategic disconnections for asymmetric synthesis of natural products and medicinal agents. The cross-electrophile coupling approach to stereocontrolled C–C bond formation provides a complementary alternative to traditional cross-coupling methods. This Perspective provides an overview of the recent development of nickel-catalysed asymmetric cross-electrophile coupling reactions. Both stereoconvergent and stereospecific examples are considered and mechanistic details are highlighted.

Iron-Catalyzed Cross-Coupling of Alkyl Electrophiles with B2pin2

Iron-Catalyzed Cross-Coupling of Alkyl Electrophiles with B2pin2

Synthesis and reactivity of new aminophenolate complexes of nickel.

New well-defined, paramagnetic nickel complexes have been prepared and characterized by X-ray crystallography. The complexes were found to be active for the cross-coupling of alkyl electrophiles (especially ethyl 2-bromobutyrate) with alkyl Grignard reagents. The ligand architecture in these new complexes could potentially be rendered chiral, opening up future possibilities for performing asymmetric cross-coupling reactions.

Cross-couplings of alkyl electrophiles under "ligandless" conditions: Negishi reactions of organozirconium reagents.

This report establishes that simple, "ligandless" palladium complexes can catalyze the first zirconium-Negishi reactions of alkyl electrophiles. In view of the attractiveness of ligandless catalysts (cost, simplicity, and ease of purification), these observations add a significant and intriguing new dimension to the development of effective palladium-based processes for coupling alkyl electrophiles.

The first applications of carbene ligands in cross-couplings of alkyl electrophiles: sonogashira reactions of unactivated alkyl bromides and iodides.

A Pd/N-heterocyclic carbene-based catalyst achieves the Sonogashira coupling of an array of functionalized, beta-hydrogen-containing alkyl bromides and iodides under mild conditions. By furnishing the first example of a nonphosphine-based palladium catalyst for cross-coupling unactivated alkyl electrophiles, this study provides an impetus for future efforts at catalyst development that extend beyond phosphine ligands.