α-Selective Allylation of Isatin Imines Using Metallic Barium

Abstract

The Barbier-type allylation of isatin imines with allylic chlorides was achieved by using metallic barium as the promoter. Various α-allylated 3-amino-2-oxindoles were synthesized from the corresponding allylic chlorides and isatin imines. The double-bond geometry of allylic chlorides was retained throughout the reaction. An arylic bromide or iodide functionality of the products was robust to metalation under the optimum reaction conditions.

Key words

allylation - allylic chlorides - 3-amino-2-oxindoles - barium - imines

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• 12 Typical Experimental Procedure for α-Selective Allylation: Synthesis of 1-Benzyl-3-[(4-bromophenyl)amino]-3-(3-methylbut-2-en-1-yl)indolin-2-one (3aa, Table 1, Entry 6; Table 4, Entry 8; Table 5, Entry 1) Freshly cut barium (small pieces, 137.3 mg, 1.0 mmol) was placed in a Schlenk tube (50 mL) under an argon atmosphere and covered with dry THF (1 mL). The mixture was ultrasonicated for 30 min, and THF was removed through a cannula under an argon stream. The resulting barium pieces were vigorously stirred under reduced pressure until they were pulverized. Then, a solution of prenyl chloride (2a, 0.112 mL, 1.0 mmol) and isatin imine 1a (97.8 mg, 0.25 mmol) in THF (4 mL) was added to the resulting barium powder at room temperature under an argon atmosphere. After being heated to 70 °C, the mixture was stirred for 12 h at this temperature and concentrated in vacuo after filtration through a Celite pad. The residual crude product was purified by column chromatography on silica gel (hexane–EtOAc, 9:1) to afford 3-prenylated 3-amino-2-oxindole 3aa; mp 136–137 °C. The chemical yield (86%) was determined by ¹H NMR spectroscopy using 1,4-bis(trimethylsilyl)benzene as the internal standard. Spectral Data of the Product ¹H NMR (400 MHz, CDCl₃): δ = 7.19–7.31 (m, 7 H, ArH), 6.98–7.04 (m, 3 H, ArH), 6.78 (d, 1 H, J = 7.9 Hz, ArH), 6.05–6.08 (m, 2 H, ArH), 5.05 (tt, 1 H, J = 1.1, 5.7 Hz, CH), 4.96 (d, 1 H, J = 15.4 Hz, one H of CH₂), 4.87 (d, 1 H, J = 15.4 Hz, one H of CH₂), 4.40 (br, 1 H, NH), 2.62–2.73 (m, 2 H, CH₂), 1.67 (s, 3 H, CH₃), 1.57 (s, 3 H, CH₃). ¹³C NMR (100 MHz, CDCl₃): δ = 177.5, 144.3, 141.9, 138.1, 135.6, 131.7 (2 C), 129.5, 129.0, 128.7 (2 C), 127.7, 127.6 (2 C), 123.8, 122.9, 117.0 (2 C), 115.4, 111.1, 109.6, 64.4, 44.1, 39.0, 26.0, 18.1. IR (neat): 3328, 2917, 1700, 1592, 1486, 1369, 1320, 812, 754, 731 cm^–1. ESI-MS: m/z calcd for [C₂₆H₂₅ON₂BrNa]⁺ [M + Na]⁺: 483.1042; found: 483.1036