Enantioselective Synthesis of α-All-Carbon Quaternary Center-Containing Carbazolones via Amino-palladation/Desymmetrizing Nitrile Addition Cascade

Abstract

An enantioselective Pd(II)-catalyzed amino-cyclization and desymmetrizing nitrile addition cascade reaction of alkyne-tethered malononitriles is reported. This reaction forms two rings and one quaternary carbon center in a single step and serves as an efficient strategy for the construction of α-quaternary carbazolones with high enantioselectivities (up to 98:2 er). The utility of this method is demonstrated by product derivatization into a diverse array of heterocycles and a nitrile-containing leucomidine A analog.

Sequential Pd0‐ and PdII‐Catalyzed Cyclizations: Enantioselective Heck and Nucleopalladation Reactions

“…We envisioned that a halogenated indole could be a suitable precursor for an intramolecular C(sp 2 )‐H arylation reaction [18] . The resulting class of indole‐fused polycyclic scaffolds [27] is commonly observed in natural products [17a] . Treating compound 3 t with ICl gave the corresponding iodinated product, which could be converted to polycyclic indole 6 in the presence of catalytic Pd(PPh 3 ) 4 and Cs 2 CO 3 .…”

Enantioselective Nickel-Catalyzed Reductive Aryl/Alkenyl–Cyano Cyclization Coupling to All-Carbon Quaternary Stereocenters

“…Extensive methods have been developed to enantioselectively append α-all-carbon quaternary centers onto these motifs: asymmetric decarboxylative Tsuji allylation of allyl enol carbonates or allyl β-keto esters and enantioselective α-alkylation of β-substituted cycloketones are among the most broadly applied methods, although the scope is often limited by the availability of the presynthesized benzocyclic ketone starting materials. Continuing our quest toward catalytic desymmetrization of disubstituted malononitriles, , we show in this report that asymmetric intramolecular nickel-catalyzed reductive coupling between aryl halides and malononitriles 1 provides access to enantioenriched α-quaternary indanones and tetralones 2 (Scheme d). Although the addition of arylnickel species I onto nitriles is feasible and precedented, , enantiotopic differentiation of the two miniscule CN groups and suppression of possible β-C elimination of intermediate II (vide infra) or reductive decyanation of 2 would represent significant challenges toward achieving our planned transformation.…”

Controlled Synthesis of One-Handed Helical Polymers Carrying Achiral Organoiodine Pendants for Enantioselective Synthesis of Quaternary All-Carbon Stereogenic Centers

“…In this context, asymmetric dearomatization of phenols and the relevant electron-rich aromatic compounds has been regarded as an effective method for the synthesis of such cyclic molecules. − Chiral hypervalent iodine organocatalysts can effectively catalyze dearomatization of phenols, giving a variety of transformations that are hard to be achieved by others catalysts. ,− Thanks to the pathbreaking contributions by Kita et al, Ishihara et al, and so on, remarkable progress has been achieved using chiral organoiodine catalysts for enantioselective spirolactonization and hydroxylative phenol dearomatization. , However, developing chiral hypervalent iodine organocatalysts with high catalytic efficiency and satisfactory enantioselectivity still remains a challenging task. Moreover, asymmetric synthesis of a spiro-stereogenic quaternary all-carbon center is a daunting and long-standing challenge in organic synthesis. − Therefore, creating novel and green catalysts to realize this end is very interesting and of great value.…”