Update of the Imine-Anion-Mediated Smiles Rearrangement: Application to Migration of Electron-Neutral/Rich Aromatic Groups

Abstract

We have revisited the imine-anion-mediated Smiles rearrangement for the synthesis of ortho-hydroxyphenyl arylketimines. Detailed examinations revealed that migration of various aromatic groups, previously considered to be unsuited to S_NAr-type reactions, such as electron-rich or sterically hindered aromatic groups, can be accomplished by introducing bulky 9-anthryllithium as a nucleophile. Among the aromatic groups examined, naphthyl groups (1- and 2-naphthyl groups) exhibited an excellent performance, and their migration ability was well illustrated by the reaction with less bulky nucleophiles.

Key words

imines - Smiles rearrangement - S_NAr reaction - nitriles - nucleophilic addition

Publication History

Received: 09 November 2023

Accepted after revision: 29 November 2023

Accepted Manuscript online:
29 November 2023

Article published online:
04 January 2024

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• 12 To the best of our knowledge, this is the first example showing the reactivity difference between a 1-naphthyl group and a 2-naphthyl group. No clear difference in the migration abilities of 1-naphthyl and 2-naphthyl groups is found in the report by the Clayden group.^11a
• 13 Synthesis of Ketimines by the Imine-Anion-Mediated Smiles Rearrangement: General Procedure A 1.60 M solution of BuLi in hexane (0.28 mmol, 1.40 equiv) was added to a solution of the appropriate aryl bromide (0.30 mmol, 1.50 equiv.) in THF (1.0 mL) at –78 °C, and the mixture was stirred for 15 min at –78 °C. A solution of the appropriate benzonitrile (0.20 mmol) in THF (2.0 mL) was then added and then the solution was gradually allowed to warm to r.t. When the reaction was complete, it was stopped by adding H₂O. The crude products were extracted with EtOAc (×3), and the combined organic extracts were washed with brine, dried (Na₂SO₄), and concentrated in vacuo. The residue was purified by column chromatography. 2-[(E)-9-Anthryl(phenylimino)methyl]phenol (4a) Purified by column chromatography [silica gel, hexane–EtOAc (30:1)] to give a yellow solid; yield: 73.5 mg (quant); mp 261–263 °C. IR (neat): 3049, 1604, 1567, 1482, 1449, 1355, 1298, 1264, 1247, 1224, 1197, 1168, 930 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 14.85 (s, 1 H), 8.43 (s, 1 H), 8.02–7.91 (m, 2 H), 7.88–7.74 (m, 2 H), 7.51–7.26 (m, 5 H), 7.16 (d, J = 7.8 Hz, 1 H), 6.88–6.60 (m, 5 H), 6.57–6.40 (m, 2 H). ¹³C NMR (75 MHz, CDCl₃): δ = 172.6, 162.1, 146.6, 133.4, 132.0, 130.6, 129.1, 128.7, 128.6, 128.5, 128.0, 126.8, 125.7, 125.5, 124.8, 120.7, 120.5, 118.5, 117.9. Anal. Calcd for C₂₇H₁₉NO: C, 86.84; H, 5.13; N, 3.75. Found: C, 86.70; H, 5.41; N, 3.58. 2-[(E)-1-Naphthyl(phenylimino)methyl]phenol (4b) Purified by column chromatography [silica gel, hexane–EtOAc (20:1)] to give a yellow solid; yield: 40.7 mg (60%); mp 129–131 °C. IR (neat): 3059, 2927, 2854, 1602, 1593, 1593, 1566, 1484, 1451, 1399, 1306, 1248, 1195, 1148, 1119, 1072, 1036 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 14.70 (s, 1 H), 7.80 (d, J = 7.8 Hz, 2 H), 7.68 (d, J = 7.8 Hz, 1 H), 7.47–7.27 (m, 4 H), 7.23 (d, J = 7.2 Hz, 1 H), 7.11 (d, J = 8.1 Hz, 1 H), 7.01–6.92 (m, 2 H), 6.87–6.71 (m, 4 H), 6.57 (ddd, J = 8.1, 8.1, 0.9 Hz, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 173.0, 162.1, 146.8, 133.2, 132.9, 132.2, 132.2, 130.9, 129.2, 128.4, 128.2, 126.9, 126.7, 126.3, 125.7, 124.8, 124.7, 121.4, 120.3, 118.2, 117.9. Anal. Calcd for C₂₃H₁₇NO: C, 85.42; H, 5.30; N, 4.33. Found: C, 85.15; H, 5.07; N, 4.59. 2-[(E)-9-Anthryl(1-naphthylimino)methyl]phenol (11a) Purified by column chromatography [silica gel, hexane–EtOAc (30:1)] to give a yellow solid; yield: 87.4 mg (92%); mp 268–269 °C. IR (KBr): 3054, 2925, 2851, 1599, 1569, 1520, 1496, 1447, 1391, 1354, 1293, 1262, 1226, 1152, 1122, 1081 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 15.17 (s, 1 H), 8.50 (d, J = 8.1 Hz, 1 H), 8.41 (s, 1 H), 7.93 (d, J = 8.4 Hz, 2 H), 7.86 (d, J = 8.7 Hz, 2 H), 7.62 (d, J = 8.4 Hz, 1 H), 7.55 (dd, J = 7.2, 7.2 Hz, 1 H), 7.44 (d, J = 7.2 Hz, 1 H), 7.42–7.20 (m, 7 H), 6.67 (dd, J = 8.1, 8.1 Hz, 1 H), 6.62–6.49 (m, 2 H), 6.42 (d, J = 7.2 Hz, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 173.0, 162.3, 142.5, 133.5, 133.5, 132.1, 130.6, 129.5, 128.7, 128.5, 128.4, 127.8, 127.6, 126.8, 126.1, 125.6, 125.4, 124.8, 123.3, 121.0, 118.6, 118.1, 115.1. Anal. Calcd for C₃₁H₂₁NO: C, 87.92; H, 5.00; N, 3.31. Found: C, 87.70; H, 5.14; N, 3.52. 2-[(E)-9-Anthryl(2-naphthylimino)methyl]phenol (12a) Purified by column chromatography [silica gel, hexane–EtOAc (30:1)] to give a yellow solid; yield: 77.3 mg (86%); mp 227–229 °C. IR (neat): 3054, 2968, 1743, 1596, 1562, 1491, 1445, 1356, 1294, 1262, 1226, 1205, 1163, 1150, 1123 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 14.91 (s, 1 H), 8.39 (s, 1 H), 7.96–7.85 (m, 4 H), 7.49–7.11 (m, 12 H), 6.88 (dd, J = 8.7, 2.1 Hz, 1 H), 6.59–6.46 (m, 2 H). ¹³C NMR (75 MHz, CDCl₃): δ = 172.8, 162.2, 144.2, 133.5, 133.0, 132.0, 130.9, 130.6, 129.2, 128.8, 128.6, 127.9, 127.5, 127.3, 126.9, 125.9, 125.6, 125.5, 125.0, 120.9, 120.6, 118.6, 118.2, 118.0. Anal. Calcd for C₃₁H₂₁NO: C, 87.92; H, 5.00; N, 3.31. Found: C, 88.11; H, 5.28; N, 3.19. For characterization data for the other new compounds, see the Supporting Information.