a
Department of Synthetic and Biological Chemistry, Centre of Biomedical Research (CBMR), SGPGIMS Campus, Lucknow-226014, India
› Author AffiliationsThis work was supported by research funding to J.S. by SERB (CRG/2020/000381) and CSIR-EMR-II (02(0395)/21/EMR-II). B.S. thanks CSIR for a fellowship. T.S.B. is a DST-INSPIRE fellow.
A dearomative [3+2]-cycloaddition reaction of oxindole-embedded azaoxyallyl cations with indoles at the C3 position has been developed. The use of this new class of azaoxyallyl cation species in the reaction permits access to more-elaborate hexahydropyrrolo[2,3-b]indole moieties that contain a spiro-oxindole ring. The transformation displays a broad substrate scope and good regio- and stereoselectivity for the cycloaddition step. Several observations suggested that this class of azaoxyallyl cations can display a different reactivity pattern from those of commonly employed azaoxyallyl cation systems.
8 The reaction between 1-methyl-1H-indole and the α,α-dimethylazaoxyallyl cation afforded a C2-functionalized indole exclusively through a Friedel–Craft-type reaction. See ref. 3a.
9[3+2]-Cycloaddition: General ProcedureEt3N (1.5 equiv) was added to a solution of the appropriate indole derivative 1 (1.0 equiv) and α-halohydroxamate (oxindole) 2 (1.5 equiv) in PhCF3 (0.1 M) under argon. The mixture was stirred at rt until the starting material was consumed (TLC; ~60–90 min). The solvent was then removed under the reduced pressure, and the crude product was purified by column chromatography (silica gel, EtOAc–hexane).1′-(Benzyloxy)-1,3a′,8′-trimethyl-1′,3a′,8′,8a′-tetrahydro-2′H-spiro[indole-3,3′-pyrrolo[2,3-b]indole]-2,2′(1H)-dione (3)Prepared by the general procedure from 1,3-dimethyl-1H-indole (1b; 0.02 g, 0.137 mmol) and α-chlorohydroxamate 2a (0.067 g, 0.205 mmol), and purified by chromatography [silica gel, EtOAc–hexanes (1:4)] as a white foam; yield: 0.055 g (91%; dr 4.5:1); Rf = 0.4 (EtOAc–hexanes, 1:4).1H NMR (400 MHz, CDCl3): δ = 7.59 (d, J = 6.5 Hz, 2 H), 7.45–7.39 (m, 3 H), 7.33 (app t, J = 7.5 Hz, 1 H), 7.13 (app t, J = 7.4 Hz, 1 H), 6.96 (app t, J = 7.5 Hz, 1 H), 6.88 (d, J = 7.8 Hz, 1 H), 6.81 (d, J = 7.4 Hz, 1 H), 6.55 (app t, J = 7.4 Hz, 1 H), 6.44 (app t, J = 7.9 Hz, 2 H), 5.13 (d, J = 10.0 Hz, 1 H), 5.11 (d, J = 12.0 Hz, 1 H), 5.05 (s, 1 H), 3.28 (s, 3 H), 3.03 (s, 3 H), 1.31 (s, 3 H). 13C{1H} NMR (100 MHz, CDCl3): δ = 173.8, 165.1, 148.9, 145.4, 135.1, 130.2, 130.1, 129.6, 129.3, 129.1, 128.7, 128.6, 126.6, 124.7, 122.2, 117.4, 108.3, 107.0, 85.1, 77.5, 62.7, 52.3, 33.5, 26.8, 22.3. HRMS (ESI-TOF): m/z [M + H]+ calcd for C27H26N3O3: 440.1974; found: 440.1970.1-Benzyl-1′-(benzyloxy)-5-methoxy-3a′,8′-dimethyl-1′,3a′,8′,8a′-tetrahydro-2′H-spiro[indole-3,3′-pyrrolo[2,3-b]indole]-2,2′(1H)-dione (4)Prepared by the general procedure from 1,3-dimethyl-1H-indole (1b; 0.02 g, 0.137 mmol) and α-chlorohydroxamate 2b (0.089 g, 0.205 mmol), and purified by chromatography [silica gel, EtOAc–hexanes (1:4)] as a white foam; yield: 0.073 g (92%; dr 6:1); Rf = 0.4 (EtOAc–hexanes, 1:4).1H NMR (400 MHz, CDCl3): δ = 7.61 (d, 2 H), 7.46–7.40 (m, 3 H), 7.36–7.33 (m, 4 H), 7.30–7.28 (m, 1 H), 7.14 (app t, J = 7.6 Hz, 1 H), 6.75 (dd, J = 8.6, 2.5 Hz, 1 H), 6.64 (d, J = 8.6 Hz, 1 H), 6.56 (app t, J = 7.4 Hz, 1 H), 6.48 (app t, J = 7.1 Hz, 2 H), 6.41 (d, J = 2.5 Hz, 1 H), 5.20–5.13 (m, 3 H), 5.08 (s, 1 H), 4.79 (d, J = 15.8 Hz, 1 H), 3.57 (s, 3 H), 3.05 (s, 3 H), 1.39 (s, 3 H). 13C{1H} NMR (100 MHz, CDCl3): δ = 173.6, 165.2, 155.3, 149.0, 137.9, 135.6, 135.1, 130.1, 129.9, 129.5, 129.2, 129.0, 128.8, 127.8, 127.2, 126.8, 125.8, 117.3, 115.8, 114.6, 109.8, 107.1, 85.2, 77.5, 63.0, 55.7, 52.4, 44.4, 33.6, 22.6. HRMS (ESI-TOF): m/z [M + H]+ calcd for C34H32N3O4: 546.2393; found: 546.2391
For compound 16, we determined the relative orientation of the spiro oxindole carbonyl and the C–H bond at the ring fusion from the 3JC1,H3 value. The experimental value of 3JC1,H3 was ~3.0 Hz, which suggested a syn orientation between the indicated C–H bond and the carbonyl group (see Supporting Information for details). Based on reactive similarities, the relative orientation of this C–H bond and spiro-oxindole carbonyl is shown in Scheme [1]. A similar exercise is performed to determine the anomeric configurations of Kdo glycosides; for selected references, see:
10a
Zhang Z,
Xu Z,
Liu X,
Luo S,
Li T.
Org. Lett. 2021; 23: 6090
12 CCDC 2182551 contains the supplementary crystallographic data for compound 20. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures
