Enantioselective Pictet–Spengler reactions of isatins for the synthesis of spiroindolones

Abstract

The condensation cyclization between isatins and 5-methoxy tryptamine catalyzed by chiral phosphoric acids provides spirooxindole tetrahydro-β-carboline products in excellent yields (up to 99%) and enantioselectivity (up to 98:2 er). A comparison of catalysts provides insight for the substrate scope and factors responsible for efficient catalytic activity and selectivity in the spirocyclization. Chiral phosphoric acids with different 3,3′-substitution on the binaphthyl system and opposite axial chirality afford the spiroindolone product with the same absolute configuration.

Recent Advances in Asymmetric Organocatalytic Construction of 3,3′‐Spirocyclic Oxindoles

“…Almost at the same time, Franz reported similar reactions using catalyst 147 or 148 (Scheme ) 100. Interestingly, they found that the same configuration of spiro oxindolone product was obtained for both the ( S )‐ 147 and ( R )‐ 148 , indicating that the substitution on the binaphthyl system directs the sense of enantioselection.…”

Isatin derivatives in reactions with phosphorus(III–V) compounds

“…136 Substituted isatins were used in Michael reaction for the synthesis of compounds 124, using chiral sterically congested phosphoric acids, such as compound 125, for improving the enantioselectivity of the reaction (Scheme 62 …”

Microwave‐Assisted One‐Pot [3+2] Cycloaddition of Azomethine Ylides and 3‐Alkenyl Oxindoles: A Facile Approach to Pyrrolidine‐Fused Bis‐Spirooxindoles

“…Pyrrolidinyl spirooxindole constitutes an important class of spirooxindoles, especially in naturally occurring alkaloids such as cyanogramide (Figure ), spirotryprostatin A and B, pteropodine, elacomine, horsifoline and gelsemine which possess a wide range of biological activities like antimicrobial, anticancer, antifungal, etc . Inspired by the biological significance of these spirocyclic heterocyclic motifs,– versatile synthetic strategies have been directed towards the synthesis of this class of molecules employing 1,3‐dipolar cycloadditions,– Morita‐Baylis‐Hillman reaction,– Pictet‐spengler reaction and so forth. Among them, the most successful method is 1,3‐dipolar cycloaddition reaction of azomethine ylide with various substituted dipolarophiles to construct spiro[pyrrolidin‐2,3′‐oxindoles] scaffold –…”