Asymmetric Synthesis of Multicyclic Spirooxindole Derivatives Bearing Stereogenic Quaternary Carbon Atoms

Abstract

An organocatalyzed stereoselective domino reaction as a facile approach to multicyclic spirooxindole derivatives bearing two stereogenic quaternary carbon atoms is reported. The alkylsubstituted chiral thiourea catalyst was efficient for the reaction to tolerate a wide range of substrates, furnishing a new class of spirooxindole derivatives bearing an O,O-acetal-fused tricyclic skeleton or tetrahydroxanthone moiety in moderate to good yields with good to excellent selectivities. The products generated from this method have promising anticancer activities.

Metal-Free Regioselective Oxa-Michael Approach to Access Spirooxindole-Fused Tetrahydrofuran/Tetrahydropyran through [3 + 2]/ [4 + 2] Spirocyclization of Methyleneindolinones with Haloalcohols

“…Methyleneindolinones have emerged as a useful synthon for preparing spirocyclic compounds and significant achievements have been made with various nucleophiles . Michael addition reactions are highly efficient to construct spirooxindole-fused derivatives, through nucleophilic addition on electrophilic methyleneindolinones at C3′ or C3 position. , Organocatalytic asymmetric oxa-Michael reaction provides an alternative powerful strategy for the synthesis of complex molecules with contiguous multiple stereocenters . Along with this the regioselective [3 + 2] and [4 + 2] reactions of methyleneindolinones allow for the facile construction of spirocyclic oxindoles with one or two contiguous quaternary centers …”

Controllable Synthesis of N- and O-Containing Heterocycles via Formal [3 + 2] and [5 + 2] Cyclizations

“…On the basis of the experimental observation and literature precedents, , a plausible mechanism was proposed, as shown in Scheme . First, the reaction is initiated by coordination of scandium to carbonyl of oxindole moiety 1 and aldehyde 2 to form a six-membered ring chair confirmation, rendering the carbonyl α position of the oxindole moiety more nucleophilic than the malonate moiety.…”