Facile Synthesis of Spirooxindole‐Cyclohexenes via Phosphine‐Catalyzed [4 + 2] Annulation of α‐Substituted Allenoates

Abstract

A phosphine‐catalyzed [4 + 2] annulation of α‐substituted allenoate with exocyclic alkene moiety of oxindoles or indan‐1,3‐diones has been developed. Thus, under the catalysis of PPh3 (20 mol%), a series of spirooxindole‐ or spiroindan‐1,3‐dione‐cyclohexenes have been obtained in moderate to excellent yields and regioselectivity from the annulations of α‐methyl allenoates with 3‐methyleneoxindoles or 2‐methyleneindan‐1,3‐diones. This method offers an easy access to structurally novel spirocyclohexenes.

Phosphine Organocatalysis

“…He, Chen, et al explored the phosphine-catalyzed [4 + 2] annulations of α -substituted allenoates with oxindoles and indan-1,3-diones presenting exocyclic alkene moieties (Scheme 323). 395 With 20 mol % of PPh 3 as the catalyst, they examined the scope of the [4 + 2] annulations of the allenoates with isatin-derived alkenes or indan-1,3-dione-derived alkenes in toluene at 80 °C, obtaining a series of spirooxindole- or spiroindan-1,3-dione-cyclohexenes in moderate to excellent yields and regioselectivity.…”

“…He, Chen et al explored the phosphine-catalyzed [4 + 2] annulations of α-substituted allenoates with oxindoles and indan-1,3-diones presenting exocyclic alkene moieties (Scheme 323). 395 nate and arylidenemalononitriles mediated by the amino acidbased chiral phosphine P74 (Scheme 325). 397 tert-Butyl vinylidenesuccinate was used to enhance the diastereoselectivities.…”

Organophosphine-Catalyzed [4C+X] Annulations

“…Although Lu’s group have reported the highly enantioselective [4+2] annulation reactions of β’-alkoxy carbonyl and β′-electron-poor aryl substituted allenoates with isatylidenemalononitrile for the synthesis of functionalized chiral 3-spirocyclohexene-2-oxindoles in 2012, reactivities of the simple, non-substituted α-methyl allenoates 4 were not examined. In 2017, Chen, He and co-workers investigated the [4+2] annulations of 2-methyl-2,3-butadienoates 4 with isatylidenemalononitrile 60 ( Scheme 20 ) [ 58 ], and found that the expected spiroannulation could proceed smoothly to deliver two separable regioisomers 61 and 62 derived from γ- and β′-addition, respectively, when conducting the reaction at 80 °C with the use of PPh 3 as the catalyst. Regioselectivities were unsatisfactory in most cases except for halogen-substituted N -Ac isatin-derived alkenes (R = Ac, 61 : 62 = 5:95).…”