Efficient Entry to Diversely Functionalized Spirocyclic Oxindoles from Isatins through Carbonyl-Addition/Cyclization Reaction Sequences

Abstract

A novel approach to diversely functionalized spirocyclic oxindoles has been developed by using different metal-mediated carbonyl-addition/cyclization reaction sequences. Spirocyclization precursors, 2-indolinone-tethered homoallylic alcohols, (buta-1,3-dien-2-yl)methanols, and alpha-allenols have been obtained by regioselective addition of stabilized organoindium reagents to isatins in aqueous environment. Ruthenium-, silver-, and palladium-catalyzed reactions of the above unsaturated alcohol derivatives provided oxaspiro oxindoles.

Synthesis of 2-phenyl indoxyls

“…Our investigation began with the synthesis of several N-alkyl-2-phenyl indole derivatives (Scheme 2). The hydrolysis precursors were prepared in 2-3 steps from commercially available indoles via sequential N-alkylation and oxidation with Pb(OAc) 4 . 12 Alkylation of 2-phenyl indole 4 with cyclopropylmethyl bromide was followed by acetoxylation to give ester 5a.…”

“…1 As such, the synthesis of indoles 2 and indole analogs, such as indoxyl 3 and oxindole, 4 have received considerable attention from synthetic organic chemists. A number of different routes to 2-phenylindoxyls have been reported, including the addition of phenyl Grignard reagents to isatin 5 and alkyl grignard reagents to 2-phenyl-3H-indol-3-ones.…”

Computational Studies and Energies for the Dioxa-Pentaazaheptacyclo-Hentriaconta-Octaen-One through Density Functional Theory and Natural Bond Orbital

“…The interesting structural array and the highly pronounced pharmacological activity displayed by the class of spirooxindole compounds have made them attractive synthetic compounds [13][14][15][16]. Azaspiro derivatives are well-known [17][18][19], but the preparation of the corresponding oxa analogues has evolved at a relatively slow pace [20].…”

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Abstract:In this paper, the molecular structure and electronic properties of 2, 18,19,20,20.01,8.03,7.09,14.024,11,13,17(31),18,24,26, were calculated by the B3LYP density functional model using 6-31G, 6-311G, 6-311++G and 6-311++G(d,p) basis sets. B3LYP calculation results indicated some selected bond length and bond angle values for this molecule.

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Silver and platinum-catalysed addition of O–H and N–H bonds to allenes

“…Spirocyclic dihydrofuran derivatives have been synthesised using similar conditions with stoichiometric amounts of silver. The reaction has been applied by Alcaide, Almendros et al for the synthesis of spirocyclic oxindoles (Scheme 5a), 7 and spirocyclic 2-azetidinones (Scheme 5b).…”