Nickel-catalyzed Enantioselective Hydroarylation and Hydroalkenylation of Styrenes

Abstract

We have developed a Ni-catalyzed enantioselective hydroarylation of styrenes with arylboronic acids using MeOH as the hydrogen source, providing an efficient method to access 1,1-diarylalkanes, which are essential structural units in many biologically active compounds. In addition, Ni-catalyzed enantioselective hydrovinylation of styrenes with vinylboronic acids is also realized with good yields and enantioselectivities. The synthetic utility was demonstrated by the efficient synthesis of (R)-(−)-ibuprofen.

Mechanisms of Nickel-Catalyzed Cross-Coupling Reactions

“…Hydroarylation reactions proceeding through two-electron pathways via Ni(I)/Ni(III) intermediates disregard the position of the olefin in the substrate but form C-C bonds from the most stable benzylic organonickel intermediate via reversible chain walking [83]. Asymmetric variants have been achieved by intramolecular hydroarylation of indoles to form indoline products 63 [84], the coupling of vinylarenes with aryl boron reagents [85], and the coupling of 1,3-dienes with enolates [86]. Most hydroalkylation reactions are conducted with electrophiles under reductive conditions and proceed through radical pathways.…”

Nickel‐Catalyzed Electrochemical Reductive Relay Cross‐Coupling of Alkyl Halides to Aryl Halides

“…Such a transformation would be valuable for the construction of 1,1-diarylalkanes, which are common structural motifs in many natural products and biologically active compounds. [13] As part of our ongoing interest in metal-catalyzed electrochemistry [14] and 1,1-diarylalkane synthesis, [15] we questioned whether electrochemical reductive relay crosscoupling of alkyl bromides and aryl bromides could take place by taking advantage of chain-walking of an alkyl-nickel species. [16][17][18][19] Herein, we report the first such example of Nicatalyzed electrochemical relay cross-coupling of aryl halides and alkyl bromides, affording 1,1-diarylalkanes with good to excellent selectivities and yields (Scheme 1 b).…”

Nickel‐Catalyzed Electrochemical Reductive Relay Cross‐Coupling of Alkyl Halides to Aryl Halides

“…As part of our ongoing interest in metal‐catalyzed electrochemistry and 1,1‐diarylalkane synthesis, we questioned whether electrochemical reductive relay cross‐coupling of alkyl bromides and aryl bromides could take place by taking advantage of chain‐walking of an alkyl‐nickel species . Herein, we report the first such example of Ni‐catalyzed electrochemical relay cross‐coupling of aryl halides and alkyl bromides, affording 1,1‐diarylalkanes with good to excellent selectivities and yields (Scheme b).…”