Cesium Carbonate Mediated Cyclization of Oxotryptamines with Allenoates: An Approach to Spiro[azepane-4,3′-indol]-2′(1′H)-ones

Abstract

A new method was developed for the synthesis of spiro[azepane-4,3′-indol]-2′(1′H)-ones in yields of up to 96% with a broad substrate scope by using oxotryptamines as dual-nucleophilic reagents to react with allenoates in the presence of cesium carbonate under mild conditions. In accord with previous works and a deprotonation-tracing experiment, a plausible reaction mechanism is proposed.

Key words

oxotryptamines - allenoates - spiro compounds - oxindoles - [4+3]-annulation

Publication History

Received: 13 April 2021

Accepted after revision: 11 May 2021

Accepted Manuscript online:
11 May 2021

Article published online:
02 June 2021

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• 14 Spiro[azepane-4,3′-indol]-2′(1′H)-ones 3aa–3am; General Procedure A dried 25 mL Schlenk tube was charged with the appropriate 3-(2-aminoethyl)indolin-2-one 2 (0.1 mmol, 1.0 equiv) and Cs₂CO₃ (0.2 mmol, 1.0 equiv), then evacuated and backfilled with argon three times. Allenoate 1 (0.24 mmol, 1.2 equiv) and anhyd MeCN (4.0 mL) were added under argon, and the mixture was stirred at 60 °C for 12 h. The mixture was then concentrated under reduced pressure and purified by flash chromatography [silica gel, PE–EtOAc (4:1)]. Ethyl {1′-Methyl-2′-oxo-1-tosyl-1,1′,2,2′,3,5-hexahydrospiro[azepine-4,3′-indol]-7-yl}acetate (3aa) White solid; yield: 90.0 mg (96%); mp 144–145 °C; R_f = 0.53 (PE–EtOAc, 2:1). IR (EtOH): 2932, 2249, 1707, 1610, 1493, 1344, 1156, 1085, 1026, 961, 910, 814 cm^–1. ¹H NMR (400 MHz, CDCl₃, TMS): δ = 7.83 (d, J = 8.4 Hz, 2 H), 7.57 (d, J = 7.4 Hz, 1 H), 7.35 (d, J = 8.0 Hz, 2 H), 7.27 (td, J = 7.7, 1.3 Hz, 1 H), 7.01 (td, J = 7.6, 1.1 Hz, 1 H), 6.84 (dd, J = 7.8, 0.9 Hz, 1 H), 5.60 (dd, J = 8.2, 6.0 Hz, 1 H), 4.21–4.05 (m, 3 H), 3.85 (d, J = 17.3 Hz, 1 H), 3.82–3.71 (m, 1 H), 3.40 (d, J = 17.4 Hz, 1 H), 3.16 (s, 3 H), 2.45 (s, 3 H), 2.29 (t, J = 11.6 Hz, 1 H), 2.20–2.10 (m, 1 H), 1.80 (dd, J = 14.2, 8.3 Hz, 1 H), 1.66 (d, J = 11.0 Hz, 1 H), 1.27 (t, J = 7.2 Hz, 3 H). ¹³C NMR (100 MHz, CDCl₃, TMS): δ = 179.3, 170.9, 143.5, 142.6, 137.8, 136.9, 132.2, 129.6, 127.9, 127.0, 126.3, 124.6, 122.2, 108.0, 60.7, 44.8, 43.8, 41.8, 35.7, 31.8, 26.0, 21.4 (d, J = 1.7 Hz), 14.0. HRMS (ESI): m/z [M + H]⁺ Calcd for C₂₅H₂₉N₂O₅S: 469.1792; found: 469.1799.