Enantioselective Nickel‐Catalyzed Intramolecular Allylic Alkenylations Enabled by Reversible Alkenylnickel E/Z Isomerization

Abstract

Enantioselective nickel‐catalyzed arylative cyclizations of substrates containing a Z‐allylic phosphate tethered to an alkyne are described. These reactions give multisubstituted chiral aza‐ and carbocycles, and are initiated by the addition of an arylboronic acid to the alkyne, followed by cyclization of the resulting alkenylnickel species onto the allylic phosphate. The reversible E/Z isomerization of the alkenylnickel species is essential for the success of the reactions.

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

“…(18) In 2017, the Lam group reported enantioselective nickelcatalyzed intramolecular arylative allylic alkenylations, where the intermediate alkenylnickel species cyclizes onto a Z-allylic phosphate to give chiral 1,4-diene-containing hetero-and carbocycles (Table 7). [66] These reactions used (S)-t-Bu-NeoPHOX (L2) as the chiral ligand in TFE as the solvent, and excellent enantioselectivities were observed. Similar to cyclizations onto cyclohexa-2,5-dienones reported previously (Table 6), [65] small quantities of minor products 50 were observed in most of these reactions.…”

“…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.…”

Sulfonate N‐Heterocyclic Carbene–Copper Complexes: Uniquely Effective Catalysts for Enantioselective Synthesis of C−C, C−B, C−H, and C−Si Bonds

“…Fletcher has introduced as et of efficient enantioselective reactions,c atalyzed by ab inap-Rh complex and involving racemic cyclic allylic chlorides and alkenyl boronic acids (Scheme 18). [41] 4.2.3. With asilyl-substituted propargyl boronate EAS with ap ropargyl moiety can be catalyzed by as ulfonate NHC-Cu complex.…”

Enantioselective Synthesis of Chiral Cyclopent‐2‐enones by Nickel‐Catalyzed Desymmetrization of Malonate Esters

“…Moreover, there are few asymmetric methods for the de novo construction of cyclopent‐2‐enones with a quaternary stereocenter at the 5‐position (as in 3 ) . Although our previous work on enantioselective nickel‐catalyzed arylative cyclizations of alkynyl electrophiles showed that ketones and activated alkenes, are competent reaction partners for alkenylnickel species, the ability of less electrophilic esters to undergo analogous cyclizations was less certain. Herein, we report the successful implementation of this strategy.…”