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Synlett 2012; 23(11): 1667-1669
DOI: 10.1055/s-0031-1291155
DOI: 10.1055/s-0031-1291155
letter
An Acid-Catalysed Hydroamination Approach to Isoindolines
Further Information
Publication History
Received: 16 March 2012
Accepted: 12 April 2012
Publication Date:
11 June 2012 (online)

Abstract
Acid-catalysed intramolecular hydroaminations of 2-alkenylarylethylamine derivatives lead smoothly to isoindolines via benzylic carbenium ion generation.
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References
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- 5 Henderson, L.; Knight, D. W.; Williams, A. C. Tetrahedron Lett. 2012, submitted
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- 7 Preparation of Isoindolines 10b–d; Typical Procedures: 1-(4-Chlorobenzyl)-2-tosylisoindoline (10b)� i) (E)-N-[2-(4-Chlorostyryl)benzyl]-4-methylbenzene-sulfonamide 9b (95 mg, 0.238 mmol, 1.0 equiv) was dissolved in dry dichloromethane (10 ml), to which was added TfOH (0.20 ml, 0.119 mmol, 0.5 equiv). The resulting solution was heated to 40 °C for 24 h, then cooled to room temperature and quenched using saturated aqueous K2CO3. The quenched solution was then separated and the aqueous layer was extracted with dichloromethane (3 x 10 ml). The combined organic layers were dried over K2CO3, filtered through a plug of silica gel and the filtrates and washings evaporated to give the isoindole 10b as a yellow oil (77 mg, yield: 81%).�ii) (E)-N-[2-(4-Chlorostyryl)benzyl]-4-methylbenzene-sulfonamide 9b (106 mg, 0.267 mmol, 1.0 equiv) was dissolved in dichloromethane (10 ml), to which was added concentrated sulfuric acid (2 drops). The resulting suspension was stirred at 40 °C for 48 h, then cooled to room temperature and quenched with saturated aqueous K2CO3. The quenched solution was then separated and the aqueous layer was extracted with dichloromethane (3 x 10 ml). The combined organic layers were dried over K2CO3, filtered through a plug of silica gel and the filtrates and washings evaporated to give the isoindole 10b as a yellow oil (74 mg, yield: 70%).�The two samples showed identical spectroscopic and analytical data. IR (film): 3277, 3062, 3028, 2923, 2855, 1598, 1448, 1274, 815, 750, 658 cm–1. 1H NMR (400 MHz, CDCl3) δ = 7.75–7.52 (m, 4 H, 2 × Ts CH and 2 × Ar CH), 7.35–6.88 (m, 8 H, 2 × Ts CH and 6 × Ar CH), 5.31 (d, 1 H, J = 15.4 Hz, CHaHbN), 4.59 (d, 1 H, J = 15.4 Hz, CHaHbN), 4.11 (t, 1 H, J = 6.2 Hz, CHN), 2.98 (app. br s, 2 H, CH2), 2.28 (s, 3 H, Ts CH3). 13C NMR (400 MHz, CDCl3) δ = 143.2 (C), 139.8 (C), 137.0 (C), 132.6 (C), 132.4 (C), 132.2 (C), 129.6 (ArCH), 129.5 (2 × TsCH), 128.6 (ArCH), 128.5 (ArCH), 128.4 (ArCH), 127.4 (ArCH), 127.2 (ArCH), 127.1 (2 × TsCH), 126.5 (ArCH), 125.9 (ArCH), 54.7 (CHN), 44.0 (CH2N), 32.3 (CH2), 21.6 (TsCH3). HRMS (APCI): m/z calcd. for C22H21ClNO2S [M + H]+ = 398.0982 (Cl35); found 398.0983 (Cl35)�
- 8 AlHadi, A.; Knight, D. W. unpublished observations
For recent reviews of alkene hydroamination, see: