Enantioselective Nickel‐Catalyzed anti‐Arylmetallative Cyclizations onto Acyclic Ketones

Abstract

Domino reactions involving nickel‐catalyzed additions of (hetero)arylboronic acids to alkynes, followed by cyclization of the alkenylnickel intermediates onto tethered acyclic ketones to give chiral tertiary‐alcohol‐containing products in high enantioselectivities, are described. The reversible E/Z isomerization of the alkenylnickel intermediates enables overall anti‐arylmetallative cyclization to occur. The ring system of the products are substructures of certain diarylindolizidine alkaloids.

Precatalyst‐Enabled Selectivity: Enantioselective NiH‐Catalyzed anti‐Hydrometalative Cyclization of Alkynones to Endo‐ and Heterocyclic Allylic Alcohols

“…Taken all these clues together, a postulated mechanism is depicted in Scheme 2 e. Reaction of Ni( L1 ) 2 ( I ) and (EtO) 2 MeSiH forms Ni II ‐H species II , followed by alkyne insertion to deliver cis ‐alkenylnickel cis ‐ III [15d] . Then reversible cis / trans isomerization provides E ‐alkenylnickel trans ‐ III followed by coordination of ketone to the nickel center and an intramolecular addition affording the allylic alkoxide nickel IV .…”

Nickel‐Catalyzed Arylative Cyclizations of Alkyne‐ and Allene‐Tethered Electrophiles using Arylboron Reagents

“…[90] The first of these is anti-arylmetallative cyclization. [17,18,[61][62][63][64][65][66][67][68][69][70] Here, the reactions are initiated by transmetalation of the arylboronic acid with the nickel complex 8 (formed by coordination of a ligand to a nickel(II) salt) to give arylnickel species 9 (Scheme 2A). Coordination of 9 to the alkyne of the substrate 1, followed by syn-stereospecific migratory insertion of the alkyne places nickel distal to the electrophile.…”

“…In nickel‐catalyzed arylative cyclizations of alkyne‐tethered electrophiles, two modes of cyclization are generally possible, which differ in both their regio‐ and stereochemical outcomes [90] . The first of these is anti ‐arylmetallative cyclization [17,18,61–70] . Here, the reactions are initiated by transmetalation of the arylboronic acid with the nickel complex 8 (formed by coordination of a ligand to a nickel(II) salt) to give arylnickel species 9 (Scheme 2A).…”

“…More recently, nickel catalysis has also been shown to be highly effective in these reactions. [61][62][63][64][65][66][67][68][69][70][71][72][73][74][75] As well as being less expensive and more readily available than the more commonly used rhodium or palladium catalysts, nickel catalysis can offer unique possibilities in reaction development not readily available to these other catalyst systems. [76][77][78][79][80][81][82][83][84][85][86][87][88][89] This review will describe nickel-catalyzed arylative cyclizations of alkyne-and allene-tethered electrophiles using arylboron reagents, that proceed by the general mechanistic pathways shown in Scheme 1.…”

“…By varying the tether or the electrophile of the substrate, a variety of cyclic products can be obtained, and by employing non‐racemic chiral ligands, enantioselective reactions can be achieved. More recently, nickel catalysis has also been shown to be highly effective in these reactions [61–75] . As well as being less expensive and more readily available than the more commonly used rhodium or palladium catalysts, nickel catalysis can offer unique possibilities in reaction development not readily available to these other catalyst systems [76–89] …”