Synthesis of Axially Chiral Biaryls via Enantioselective Ullmann Coupling ofortho‐Chlorinated Aryl Aldehydes Enabled by a Chiral 2,2′‐Bipyridine Ligand

Abstract

The first nickel‐catalyzed highly enantioselective reductive Ullmann coupling of ortho‐chlorinated aryl aldehyde was achieved under mild reaction conditions with a chiral 2,2′‐bipyridine ligand (+)‐DTB‐SBpy, thus providing axially chiral biphenyl or binaphthyl dials with up to 99 % yield and 99.5:0.5 er. The versatility of the products as common synthetic intermediates for diverse axially chiral ligands, catalysts, and functional molecules was demonstrated by short‐step transformations. This protocol also allowed the concise and highly enantioselective formal total synthesis of biologically active natural products (+)‐kotanin, (−)‐isoschizandrin and (+)‐gossypol.

A fruitful century for the scalable synthesis and reactions of biphenyl derivatives: applications and biological aspects

“…38 Whereas, enantioselective biphenyls 2 were obtained via the reaction of ortho -chlorinated benzaldehyde derivatives 1 in the presence of Ni catalyst (Scheme 2). 39…”

Access to Axially Chiral Aryl Aldehydes via Carbene-Catalyzed Nitrile Formation and Desymmetrization Reaction

“…[ 11 – 14 ], and others [ 15 , 16 ]. In a broader picture, aldehyde moieties have versatile applications in chemical synthesis [ 17 – 21 ] and exhibit various functions in natural products and bioactive molecules [ 22 – 25 ] (Fig. 1 A).…”

“…1 A). A number of synthetic approaches are now available to prepare axially chiral aryl aldehydes via enzymatic catalysis [ 26 ], transition metal catalysis [ 17 , 19 – 21 , 27 – 29 ], or organic catalysis [ 18 , 30 , 31 ]. Elegant examples include metal-catalyzed C-H activation or cross-coupling reactions, as demonstrated by Liao et al.…”

“…[ 17 ], Yang et al. [ 20 ], and others [ 19 , 21 , 28 , 29 ]. In the area of organic catalysis, Sparr et al.…”

Asymmetric Bioreduction of Ethyl 4-Chloroacetoacetate into Ethyl 4-Chloro-3-hydroxybutyrate by Recombinant Escherichia coli CgCR in Ethyl Acetate-Betaine:Lactic Acid-Water

“…In an ideal bioreduction system, carbonyl reductase coupled with dehydrogenase for cofactor regeneration in the same kind of bacterial cells is a good strategy for bioreduction. This strategy can be applied to biologically reduce COBE to (R)-CHBE with high activity and substrate-tolerance of the biocatalyst, which has the potential to replace traditional chemical reduction processes [61][62][63][64].…”