Synlett 2015; 26(11): 1541-1544
DOI: 10.1055/s-0034-1380675
letter
© Georg Thieme Verlag Stuttgart · New York

Enantiopure 3-Amino-Substituted 1-Indanones, 1-Tetralones, and 1-Benzosuberones via Friedel–Crafts Cyclisation of ω-Aryl-β-benz­amido Acids

Stephen G. Davies*, Euan C. Goddard, Paul M. Roberts, Angela J. Russell, James E. Thomson
  • Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Mansfield Road, Oxford, OX1 3TA, UK   Email: steve.davies@chem.ox.ac.uk
Further Information

Publication History

Received: 06 March 2015

Accepted: 03 April 2015

Publication Date:
20 May 2015 (eFirst)

Dedicated to Peter Vollhardt on the occasion of his 69th birthday

Abstract

Conjugate addition of enantiopure lithium (R)-N-benzyl-N-(α-methylbenzyl)amide to a range of ω-aryl-α,β-unsaturated esters gives the corresponding ω-aryl-β-amino esters as single diastereoisomers in high yields. Friedel–Crafts cyclisation of the pendant carbonyl group onto the ω-aryl ring then gives a range of 3-amino-substituted 1-indanones, 1-tetralones, and 1-benzosuberones, representing an efficient and short protocol for the preparation of these benzo-fused carbocycles in enantiopure form.

 
  • References and Notes

    • 1a Davies SG, Price PD, Smith AD. Tetrahedron: Asymmetry 2005; 16: 2833
    • 1b Davies SG, Fletcher AM, Roberts PM, Thomson JE. Tetrahedron: Asymmetry 2012; 23: 1111

      For related examples, see:
    • 2a Horton WJ, Thompson G. J Am. Chem. Soc. 1954; 76: 1909
    • 2b Zymalkowski P, Dornhege E. Tetrahedron Lett. 1968; 55: 5743
    • 2c Rault S, Dallemange P, Robba M. Bull. Soc. Chim. Fr. 1987; 6: 1079
    • 2d Kimbara K, Katsumata Y, Saigo K. Chem. Lett. 2002; 266
  • 3 For the preparation of 4 and 22, see: Davies SG, Garrido NM, Kruchinin D, Ichihara O, Kotchie LJ, Price PD, Price Mortimer AJ, Russell AJ, Smith AD. Tetrahedron: Asymmetry 2006; 17: 1793

    • For the preparation of 5, see:
    • 4a Bunnage ME, Davies SG, Goodwin CJ. Synlett 1993; 731
    • 4b Bunnage ME, Davies SG, Goodwin CJ, Ichihara O. Tetrahedron 1994; 50: 3975
  • 5 Costello JF, Davies SG, Ichihara O. Tetrahedron: Asymmetry 1994; 5: 1999
  • 6 Crystallographic data (excluding structure factors) have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication number CCDC 1044396.
  • 7 For the preparation of 22 and 24, see: Davies SG, Mulvaney AW, Russell AJ, Smith AD. Tetrahedron: Asymmetry 2007; 18: 1554
    • 8a Coote SJ, Davies SG, Middlemiss D, Naylor A. J. Chem. Soc., Perkin Trans. 1 1989; 2223
    • 8b Coote SJ, Davies SG, Fletcher AM, Roberts PM, Thomson JE. Chem. Asian J. 2010; 5: 589
  • 9 General experimental procedure (ester hydrolysis/acid chloride formation/Friedel–Crafts cyclisation sequence). The requisite β-benzamido tert-butyl ester (1 mmol) was dissolved in TFA (2 mL) and the solution was stirred at r.t. for 30 min. After this time the TFA was removed in vacuo. The residue was co-evaporated with PhMe (3 × 4 mL), then dried under high vacuum. The residue was then dissolved in CH2Cl2 (2 mL) and one drop of DMF, then (COCl)2 (1.1 mmol) was added drop-wise. The resultant solution was stirred until cessation of effervescence, then cooled to 0 °C. AlCl3 (2.0 mmol) was added portion-wise, and the resultant solution was stirred for 16 h. The reaction was quenched with H2O (0.5 mL) and the resultant mixture was stirred for 10 min. The layers were separated and the aqueous layer was extracted with CH2Cl2 (3 × 5 mL). The combined organic layers were washed sequentially with 10% aq HCl (20 mL), sat. aq NaHCO3 (20 mL) and brine (20 mL), then dried (MgSO4), filtered and concentrated in vacuo.Data for 16: solid; mp 168–169 °C; [α]21 d +23.1 (c 1.1, CHCl3); IR: νmax 1679, 1642; 1H NMR (400 MHz, CDCl3): δ = 2.83 (1 H, dd, J = 16.9, 8.8 Hz), 3.05 (1 H, ddd, J = 16.9, 4.2, 0.9 Hz), 3.12 (1 H, dd, J = 16.1, 8.0 Hz), 3.43 (1 H, dd, J = 16.1, 4.5 Hz), 4.80–4.88 (1 H, m), 6.33 (1 H, d, J = 7.0 Hz), 7.27–7.72 (8 H, m), 8.05–8.08 (1 H, m); 13C NMR (100 MHz, CDCl3): δ = 35.7, 44.6, 46.0, 126.9, 127.2, 128.6, 129.6, 131.7, 132.1, 134.3, 140.6, 167.2, 195.7; HRMS (ESI+): m/z calcd for C17H16NO2 + ([M+H]+): 266.1181; found: 266.1185.Data for 17: oil; [α]22 d +19.8 (c 1.4, CHCl3); IR: νmax 1674, 1627; 1H NMR (400 MHz, CDCl3): δ = 1.74–1.82 (1 H, m), 2.46–2.55 (1 H, m), 2.83 (1 H, dd, J = 17.0, 1.6 Hz), 2.94 (1 H, dd, J = 14.0, 6.3 Hz), 3.18 (1 H, dt, J = 14.0, 4.2 Hz), 3.82 (1 H, ddd, J = 17.0, 11.9, 1.8 Hz), 4.57–4.66 (1 H, m), 6.80 (1 H, br s), 7.21–7.48 (5 H, m), 7.66–7.81 (3 H, m), 8.04 (1 H, d, J = 8.0 Hz); 13C NMR (100 MHz, CDCl3): δ = 31.1, 32.9, 45.7, 47.0, 123.3, 126.8, 127.1, 127.3, 129.1, 130.2, 131.6, 133.1, 134.2, 137.5, 138.5, 142.2, 167.9, 201.6; HRMS (ESI+): m/z calcd for C18H17NNaO2 + ([M+Na]+): 302.1156; found: 302.1151.Data for 30: solid; mp 80–81 °C; [α]23 d +4.6 (c 0.7, CHCl3); IR: νmax 1682; 1H NMR (400 MHz, CDCl3): δ = 2.58 (1 H, dd, J = 19.0, 3.3 Hz), 2.96 (1 H, dd, J = 19.0, 7.7 Hz), 3.88 (3 H, s), 5.86–5.90 (1 H, m), 6.78 (1 H, d, J = 8.3 Hz), 6.95 (1 H, dd, J = 8.6, 2.1 Hz), 7.08 (1 H, d, J = 2.1 Hz), 7.44–7.48 (2 H, m), 7.52–7.54 (1 H, m), 7.61 (1 H, d, J = 8.6 Hz), 7.84–7.86 (2 H, m); 13C NMR (100 MHz, CDCl3): δ = 45.1, 47.7, 55.9, 109.0, 117.4, 125.1, 127.1, 128.7, 131.9, 133.5, 137.4, 157.1, 166.0, 167.4, 201.7; HRMS (ESI+): m/z calcd for C17H16NO3 + ([M+H]+): 282.1130; found: 282.1130.Data for 31: solid; mp 83–85 °C; [α]23 d +6.9 (c 0.5, CHCl3); IR: νmax 1682; 1H NMR (400 MHz, CDCl3): δ = 2.56 (1 H, dd, J = 19.0, 3.3 Hz), 3.20 (1 H, dd, J = 19.0, 7.7 Hz), 3.84 (3 H, s), 5.82 (1 H, td, J = 8.1, 3.3 Hz), 6.89 (1 H, dd, J = 8.5, 2.2 Hz), 7.04 (1 H, d, J = 2.2 Hz), 7.09 (1 H, d, J = 8.5 Hz), 7.41–7.44 (2 H, m), 7.56–7.58 (2 H, m), 7.85 (2 H, d, J = 7.4 Hz); 13C NMR (100 MHz, CDCl3): δ = 44.9, 47.6, 55.9, 109.0, 117.4, 124.9, 127.1, 128.7, 129.8, 131.9, 133.7, 157.1, 165.9, 167.5, 201.9; HRMS (ESI+): m/z calcd for C17H15NNaO3 + ([M+Na]+): 304.0944; found: 304.0937.Data for 32: solid; mp 80–83 °C; [α]23 d +10.6 (c 1.0, CHCl3); IR: νmax 1682; 1H NMR (400 MHz, CDCl3): δ = 2.79 (1 H, dd, J = 16.9, 8.3 Hz), 2.97 (1 H, dd, J = 16.9, 4.1 Hz), 3.09 (1 H, dd, J = 15.9, 7.5 Hz), 3.28 (1 H, dd, J = 15.9, 6.1 Hz), 3.88 (3 H, s), 4.80–4.88 (1 H, m), 6.20 (1 H, d, J = 7.2 Hz), 6.76 (1 H, app s), 6.90 (1 H, dd, J = 8.8, 1.9 Hz), 7.23–7.52 (4 H, m), 7.70 (2 H, d, J = 8.1 Hz); 13C NMR (100 MHz, CDCl3): δ = 31.9, 44.9, 46.2, 55.6, 112.6, 126.8, 128.3, 130.4, 131.6, 131.7, 132.8, 141.4, 142.7, 164.3, 166.4, 195.1; HRMS (ESI+): m/z calcd for C18H17NNaO3 + ([M+Na]+): 318.1101; found: 318.1092.Data for 33: solid; mp 84–85 °C; [α]22 d +2.4 (c 1.2, CHCl3); IR: νmax 1682; 1H NMR (400 MHz, CDCl3): δ = 2.77 (1 H, dd, J = 16.8, 8.1 Hz), 2.96 (1 H, dd, J = 16.8, 4.6 Hz), 3.07 (1 H, dd, J = 15.4, 6.5 Hz), 3.25 (1 H, dd, J = 15.4, 3.1 Hz), 3.86 (3 H, s), 4.78–4.85 (1 H, m), 6.40 (1 H, d, J = 7.5 Hz), 7.41–7.57 (5 H, m), 7.82 (2 H, d, J = 7.2 Hz); 13C NMR (100 MHz, CDCl3): δ = 31.3, 42.4, 46.7, 55.9, 109.9, 122.6, 124.0, 126.8, 128.4, 131.6, 133.8, 134.9, 146.2, 161.2, 166.7, 195.0; HRMS (ESI+): m/z calcd for C18H17NNaO3 + ([M+Na]+): 318.1106; found: 318.1105.Data for 36: solid; mp 79–81 °C; [α]23 d +5.7 (c 0.5, CHCl3); IR: νmax 1682; 1H NMR (400 MHz, CDCl3): δ = 2.63 (1 H, dd, J = 19.3, 3.1 Hz), 3.36 (1 H, dd, J = 19.3, 7.4 Hz), 3.86 (3 H, s), 5.86 (1 H, td, J = 7.8, 3.0 Hz), 6.51 (1 H, d, J = 8.0 Hz), 7.20 (1 H, d, J = 2.5 Hz), 7.26 (1 H, dd, J = 8.5, 2.5 Hz), 7.45 (2 H, t, J = 7.7 Hz), 7.54 (1 H, t, J = 7.3 Hz), 7.58 (1 H, d, J = 8.5 Hz), 7.80 (2 H, d, J = 7.5 Hz); 13C NMR (100 MHz, CDCl3): δ = 45.8, 47.5, 55.7, 104.8, 124.7, 126.9, 127.0, 128.7, 131.9, 133.7, 138.3, 146.4, 160.9, 166.8, 203.2; HRMS (ESI+): m/z calcd for C17H15NNaO3 + ([M+Na]+): 304.0944; found: 304.0934.Data for 37: solid; mp 86–87 °C; [α]22 d +7.2 (c 0.3, CHCl3); IR: νmax 1682; 1H NMR (400 MHz, CDCl3): δ = 2.78 (1 H, dd, J = 16.8, 9.3 Hz), 2.97 (1 H, dd, J = 16.8, 3.7 Hz), 3.02 (1 H, dd, J = 15.9, 8.5 Hz), 3.29 (1 H, dd, J = 16.8, 4.1 Hz), 3.79 (3 H, s), 4.70–4.79 (1 H, m), 6.78 (1 H, d, J = 7.6 Hz), 7.09 (1 H, dd, J = 8.4, 2.8 Hz), 7.17 (1 H, d, J = 8.4 Hz), 7.33–7.37 (2 H, m), 7.43–7.45 (1 H, m), 7.46 (1 H, d, J = 2.8 Hz), 7.71 (2 H, d, J = 7.3 Hz); 13C NMR (100 MHz, CDCl3): δ = 34.9, 44.4, 46.2, 55.5, 109.2, 122.5, 127.1, 128.6, 130.7, 131.7, 132.8, 133.3, 134.1, 158.8, 167.4, 196.0; HRMS (ESI+):m/z calcd for C18H18NO3 + ([M+H]+): 296.1287; found: 296.1286.