Asymmetric Synthesis of Spirocyclopentane Oxindoles via [2+3] Annulation with 2‐(2‐Oxoindolin‐3‐yl)malononitriles as 1,2‐Carbon Bisnucleophiles

Abstract

Carbon bisnucleophiles are important building blocks in organic synthesis and have widespread applications in the construction of carbocyclic compounds. Among them, 1,2‐carbon bisnucleophile has been much less explored. Herein, we developed a [2+3] annulation of 2‐(2‐oxoindolin‐3‐yl)malononitrile with 2‐nitroallylic acetates, where 2‐(2‐oxoindolin‐3‐yl)malononitrile served as a new type of 1,2‐carbon bisnucleophile. Remarkably, the annulation reaction exhibits exclusive chemo‐ and regioselectivity. A Michael addition/SN2 mechanism was proposed to avoid the “anti‐Baldwin” cyclization. This stereoselective strategy provides a facile synthetic route for a new series of spirocyclopentane oxindole derivatives containing three stereogenic centers.

Design, Synthesis, and Biological Evaluation of Tetrahydro‐α‐carbolines as Akt1 Inhibitors That Inhibit Colorectal Cancer Cell Proliferation

“…The (Z)‐4‐methyl‐N‐(1‐methylindolin‐2‐ylidene)benzenesulfonamide were synthesized following the literature procedure [13b] . (E)‐2‐nitro‐3‐phenylallyl acetate were synthesized by following a literature procedure [16g,h] . The relative configurations of compounds 3z were determined unequivocally according to the X‐ray diffraction analysis, and those of other products were deduced on the basis of these results.…”

Kinetic Studies of Hantzsch Ester and Dihydrogen Donors Releasing Two Hydrogen Atoms in Acetonitrile

“…They are very popular in synthesis, catalysis, medicinal chemistry, and biochemistry. 13 − 15 Since they are all good reductants in organic synthesis and industrial production, it is necessary and urgent to study their actual dihydrogen-donating abilities in kinetics quantitatively.…”

“…These three organic compounds are dihydrogen donors usually used to reduce olefins, aldehydes, ketones, imines, alkynes, and quinolines and have received wide attention owing to their study and application prospects in academia and industry. − In addition to these three dihydrogen donors, 2-benzylmalononitrile, 2-(9 H -fluoren-9-yl)­malononitrile, 2-benzyl-1H-indene-1,3­(2 H )-dione, 5-benzyl-2,2-dimethyl-1,3-dioxane-4,6-dione, 5-benzyl-1,3-dimethylpyrimidine-2,4,6­(1 H ,3 H ,5 H )-trione, ethyl 2-cyano-2-(9 H -fluoren-9-yl)­acetate, diethyl 2-(9 H -fluoren-9-yl)­malonate, and the derivatives (Scheme ) are also good dihydrogen donors. They are very popular in synthesis, catalysis, medicinal chemistry, and biochemistry. − Since they are all good reductants in organic synthesis and industrial production, it is necessary and urgent to study their actual dihydrogen-donating abilities in kinetics quantitatively.…”

Access to densely functionalized spirocyclopentenonyl oxindole frameworks via aza- and carbo-Piancatelli rearrangement

“…Among these, spirocyclopentane oxindoles are the ones equipped with a more synthetically challenging all-carbon quaternary centre. 4,5…”

“…The majority of catalytic approaches targeting this scaffold have vastly relied on the formal [3 + 2]-annulation/cycloaddition reactions. 4,5 In these cases, either the oxindole part or the reaction partner was used to serve as the C3 or C2 synthon or vice versa . We also reported a Lewis acid catalyzed [3 + 2]-annulation strategy where spirocyclopropyl oxindoles were employed as a C3 synthon in the form of dipolar donor–acceptor cyclopropane with exo-heterocyclic olefin partners (Scheme 1b).…”