P(NMe₂)₃-mediated reductive [1+4] annulation of isatins with enones: a facile synthesis of spirooxindole-dihydrofurans

Abstract

A novel P(NMe2)3-mediated reductive [1+4] annulation reaction between isatins and enones has been developed, providing the facile synthesis of spirooxindole-dihydrofurans. This reaction unveils the first practical approach to construct five-membered cyclic motifs via a Kukhtin-Ramirez adduct involved [1+4] annulation mode.

A Phosphorus(III)‐Mediated (4+1)‐Cycloaddition of 1,2‐Dicarbonyls and Aza‐o‐Quinone Methides to Access 2,3‐Dihydroindoles

“…For this study, we chose to utilize a Kukhtin–Ramirez ‐like redox neutral condensation to exploit the biphilic nature of oxyphosphonium enolates as C 1 subunits . Recent work by Radosevich , He , and our own group have demonstrated the versatility of this approach in providing direct access to C−C and C−X bonds …”

Unusual Formal [1+4] Annulation through Tandem P(NMe2)3‐Mediated Cyclopropanation/Base‐Catalyzed Cyclopropane Rearrangement: Facile Syntheses of Cyclopentenimines and Cyclopentenones

“…The in situ-generated Kukhtin-Ramirez adduct from 4a and P(NMe 2 ) 3 acts as the basic catalyst. [11][12][13] On the basis of the above mechanistic investigations and closely related reports from our group and others, [7][8][9] ap roposed mechanism to account for the formation of 3 or 6 is depicted in Scheme4.P resumably,t he reaction is initiated by formation of the Kukhtin-Ramirez adduct A from isatin 1 or a-keto ester 4 and P(NMe 2 ) 3 . [5] Through its dipolar form B, the Kukhtin-Ramirez adduct subsequentlye ngages in aM ichael addition to diene 2,a ffording the intermediate C,w hich then undergoes as terically favored intramolecular substitutionv ia its allylic carbanion form C1 to give the vinylcyclopropane intermediate 5.…”

“…[8] Aside from [1+ +2] annulation reactions, we also demonstrated that Kukhtin-Ramirez adducts can undergo [1+ +4] annulation with enones,a ffording af acile synthesis of dihydrofurans (Scheme 1b). [9] These annulation reactions originate from the characteristic reactivity of Kukhtin-Ramirez adducts as 1,1-dipoles and presumably proceed through aM ichael addition-intramolecular substitution sequence.…”

“…Intrigued by the attractive annulation reactivity of Kukhtin-Ramirez adductsa s1 ,1-dipoles [7][8][9] and also motivated by the fact that 1,1-dicyano-1,3-dienes are effective substrates in [1+ +4] annulation reactions with 1,1-dipoles, [4c-f] our furthere xtension of the protocol to 1,1-dicyano-1,3-dienes disclosed an unusualf ormal [1+ +4] annulation. It affords af acile synthesis of cyclopentenimines in au nique manner,i nw hich one cyano group together with three olefinicc arbon atoms of the dienes was incorporated into the cyclopentene motif (Scheme 1c).…”

“…[5] Through its dipolar form B, the Kukhtin-Ramirez adduct subsequentlye ngages in aM ichael addition to diene 2,a ffording the intermediate C,w hich then undergoes as terically favored intramolecular substitutionv ia its allylic carbanion form C1 to give the vinylcyclopropane intermediate 5. [8,9] Due to the acidity of the hydrogen at the gcarbon of the dicyanoalkene moiety, [14] the intermediate 5 is deprotonated by the in situ-generated Kukhtin-Ramirez adduct B, [12] leadingt ot he formation of carbanion D.S ubsequent ring opening of D affords intermediate E, [15] which undergoes an intramolecular nucleophilic additiono ft he carbanion to the cyano group, furnishing intermediate F.F inally, F undergoes protonation to give the product 3 or 6.…”