Regio- and Stereoselective Synthesis of Dispiro-bisoxindoles via [3+2] Annulation Involving Nitroisatylidene as a Vinylogous Michael Donor

Abstract

A cascade [3+2] annulation, involving a γ-selective vinylogous Michael addition of nitroalkylideneoxindoles to various electron deficient alkenes followed by an intramolecular Michael addition, provides access to dispiro-bis-oxindoles and spirooxindoles. Up to four contiguous chiral centers, including two quaternary spirocenters, are generated in this high-yield regio-and diastereoselective transformation that also provides a convenient entry into conformationally constrained γ-amino acid derivatives.S pirocyclic oxindole belongs to one of the leading and most diverse classes of frameworks present in numerous natural products, 1 for instance, prosurugatoxin I, 2 neosurugatoxin II, 3 surugatoxin aglycone III, 4 citrinalin A and B IV, 5 and cyclopiamine A and B V (Figure 1). 6,7 These spiro compounds

Supported l-tryptophan on Fe3O4@SiO2 as an efficient and magnetically separable catalyst for one-pot construction of spiro[indene-2,2′-naphthalene]-4′-carbonitrile derivatives

“…13,14 Furthermore, vinylogous Michael addition was reported as a key step in the preparation of many spiro compounds. 15–17 …”

Enantioselective Desymmetrization of Curcumins with 3‐Olefinic Oxindoles for the Synthesis of Spirocyclohexanoneoxindoles

“…order to avoid any self-disproportionation of enantiomers (SDE) during column chromatography. [26] Ethyl (1S,2S,6R,Z)-3-((E)-1-hydroxy-3-(4-methoxyphenyl)-allylidene)-6-(4-methoxyphenyl)-1'-methyl-2',4dioxospiro[cyclohexane-1,3'-indoline]-2-carboxylate (3 a): Yellowish solid; Yield 48 mg, 84 %; dr > 95 : 5; R f = 0.5 (25 % EtOAc in petroleum ether); mp 183-185 °C; IR (KBr, cm À 1 ) 3451 (br, s), 1726 (s), 1703 (vs), 1612 (s), 1602 (s); 1 H NMR (500 MHz, CDCl 3 ) δ 1.14 (t, J = 7.1 Hz, 3H), 2.86 (dd,J = 19.2,6.5 Hz,1H),3.05 (s,3H),3.56 (dd,J = 19.2,11.9 Hz,1H),3.64 (s,3H),3.78 (s,1H),3.81 (s,3H), 4.05 (dq, J = 10.9, 7.1 Hz, 1H), 4.26 (dq, J = 10.9, 7.1 Hz, 1H), 4.39 (dd, J = 11.9, 6.5 Hz, 1H), 6.54 (d,J = 8.6 Hz,2H),6.57 (d,J = 8.1 Hz,1H),6.84 (overlapped d,J = 8.5 Hz,2H),6.86 (overlapped d,J = 15.3 Hz,1H),6.90 (d,J = 8.6 Hz, 2H), 6.95 (t, J = 8.1 Hz, 1H), 7.14 (overlapped d, J = 8.1 Hz, 1H), 7.15 (overlapped t, J = 8.1 Hz, 1H), 7.44 (d, J = 8.5 Hz, 2H), 7.68 (d,J = 15.3 Hz,1H),17.39 (s,1H); Confirmed by 1 H-1 H COSY experiment; 13 C{H} NMR (125 MHz, CDCl 3 ) 14. 2, 26.1, 37.4, 40.1, 47.2, 51.7, 55.2, 55.5, 61.3, 103.7, 108.4, 113.3, 114.5, 116.9, 122.1, 124.3, 128.1, 128.6, 128.8, 129.6, 130.0, 130.9, 142.2, 143.2, 158.5, 161.5, 172.7, 176.2, 180.6, 194.…”

“…Although comparable yields and diastereoselectivities were maintained in toluene and CH 3 CN, the product was racemic (entries 2-3), and in THF only poor conversion was observed (entry 4). Subsequently, several cinchona-based thiourea and squaramide catalysts C2-C11 were screened in various solvents (entries [5][6][7][8][9][10][11][12][13][14][15][16][17][18]. The reaction in the presence of quininethiourea C2 furnished 3 a in low yield (38 %) with excellent ee (90 %, entry 5).…”

“…All the 1 H-1 H connectivities were confirmed by COSY experiment. The characteristic signals in 13 C NMR for the cyclohexane ring appeared at δ 52.0 (spirocarbon), 47.8 (methine carbon α to ester), 40.4 (benzylic methine), 37.3 (methylene carbon) 103.6 (exocyclic double bond carbon α to carbonyl), and 195.5 (carbonyl). Lactam carbonyl, ester carbonyl and enolic OH carbon appear at, respectively, δ 172.…”

“…Various approaches include [4+2] cycloadditions, [9] cascade double‐Michael reactions, [10] and other miscellaneous methods [11] . Recently, we and others have reported a racemic synthesis of spiro‐oxindoles via Hauser‐Kraus annulation [12] and formal [3+2] annulation reactions [13] …”