Asymmetric Allylic Alkylation of β-Ketoesters via C–N Bond Cleavage of N-Allyl-N-methylaniline Derivatives Catalyzed by a Nickel–Diphosphine System

Abstract

Nickel complexes bearing chiral diphosphine ligands, such as (S)-Tol-MeO-BIPHEP and (S)-H 8 -BINAP, serve as efficient catalysts for asymmetric allylic alkylation (AAA) of β-ketoesters using allylic amines as allyl sources. The reactions proceed with high catalytic activity and high enantioselectivity. N-Methyl-N-phenyl allylic amines were indispensable to achieve the high catalytic activity and high enantioselectivity, and to expand the substrate scope to 5-and 7-membered β-ketoesters, whose nickel-catalyzed AAA with allylic alcohols results in low enantioselectivity. On the basis of the kinetics using a catalyst system made of Ni(cod) 2 and (S)-Tol-MeO-BIPHEP, and DFT calculations for the reaction pathway of the AAA reaction mediated by an isolated olefin-coordinated nickel-DPPF complex 4b, we propose a mechanism where protonation of the nitrogen atom of the coordinating allylic amine by β-ketoester is key to cleaving the C-N bond and delivering a cationic π-allyl nickel(II) intermediate. ASSOCIATED CONTENT Supporting InformationDetails of experimental procedures, optimization of reaction conditions, kinetic studies, NMR spectra, HPLC chart for all new compounds, and Cartesian coordinates of DFT-computed structures (PDF) were included in a Supporting Information. X-ray crystallographic data for complex 4b (CIF).

Mechanistic Insights into the Nickel-Catalyzed Regioselective Carboxylation of Allylic Alcohols

“…The sextet state of manganese species was used for all the following discussions due to its higher stability than the related doublet and quartet states (Figure S2 & Scheme S1). From the Ni­(I) intermediate IN4 , approaching of CO 2 generates an η 1 -C coordinated intermediate IN5 , and such an η 1 -C coordination mode is typical for electron-rich organometallic complexes. , Thereafter, carboxylation occurs to generate the Ni­(II) metallacycle species ( IN6 ), and the energy barrier is only 3.7 kcal/mol. After carboxylation, reduction, dissociation of the β, γ-unsaturated carboxylate ( P1 ), and the coordination of the substrate S1 occur to regenerate the Ni(0) intermediate IN1 .…”

Asymmetric Redox Allylic Alkylation to Access 3,3′‐Disubstituted Oxindoles Enabled by Ni/NHC Cooperative Catalysis

“…Owing to the low cost and exceptional synthetic versatility of the first‐row transition metals, [10] great interest has been devoted to revealing the potential of nickel catalysts [11] in catalyzing asymmetric allylic alkylation reactions to build up quaternary stereocenters [12e] . However, only a limited number of “soft” nucleophiles, such as β‐ketoesters, [14a,c] α‐carbonyl lactones, [14b] and transient enamines [14d] have been reported to participate in these transformations thus far. Cognizant of this, we considered NHC‐bound homoenolate equivalents as transient nucleophiles, which can engage in the enantioselective carbon−carbon bond formation event with electrophiles mediated by nickel catalysts [15] .…”

Enantioselective Synthesis of Quaternary Carbon Stereocenters by Asymmetric Allylic Alkylation: A Review

“…In 2020, Mashima and co-workers reported the AAA reaction of β-ketoesters with allylic amines as the allyl precursor to construct quaternary chiral centers catalyzed by a catalyst system consisting of cheap and readily nickel with chiral diphosphine ligand L7 (Scheme 8). [18] They explored the mechanism of the above alkylation reactions by some stoichiometric reactions as well as DFT calculations, which demonstrated that Table 1. Substrate scope of palladium-catalyzed AAA through CÀ H alkylation.…”

“…AAA reaction of β-ketoesters via CÀ N bond cleavage catalyzed by a nickel-diphosphine system. [18] Scheme 9. Pd-catalyzed C-3 allylation of 3-substituted-1H-indoles by using trialkylboranes.…”

“…In 2020, Mashima and co‐workers reported the AAA reaction of β ‐ketoesters with allylic amines as the allyl precursor to construct quaternary chiral centers catalyzed by a catalyst system consisting of cheap and readily nickel with chiral diphosphine ligand L7 (Scheme 8). [18] They explored the mechanism of the above alkylation reactions by some stoichiometric reactions as well as DFT calculations, which demonstrated that the deprotonation of β ‐ketoesters by the N ‐methylaniline moiety of allylic amines is the significant step to cleave the C−N bond, delivering a cationic π ‐allyl nickel(II) intermediate. Based on the DFT calculations, the C−N bond cleavage pathway of this reaction was found completely different from that of palladium‐catalyzed systems.…”