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Synlett 2016; 27(04): 575-580
DOI: 10.1055/s-0035-1560507
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© Georg Thieme Verlag Stuttgart · New York

Catalytic Asymmetric Cascade Dearomatization of Tryptamines with Indol-3-ylmethanols: Diastereo- and Enantioselective Synthesis of Structurally Complex Indole Derivatives

Fei Jiang
a   Jiangsu Key Laboratory of Green Synthetic for Functional Materials, School of Chemistry and Chemical Engineering, Jiangsu Normal University, Xuzhou 221116, P. R. of China
,
Yu-Chen Zhang
a   Jiangsu Key Laboratory of Green Synthetic for Functional Materials, School of Chemistry and Chemical Engineering, Jiangsu Normal University, Xuzhou 221116, P. R. of China
,
Xue Yang
a   Jiangsu Key Laboratory of Green Synthetic for Functional Materials, School of Chemistry and Chemical Engineering, Jiangsu Normal University, Xuzhou 221116, P. R. of China
,
Qiu-Ning Zhu
a   Jiangsu Key Laboratory of Green Synthetic for Functional Materials, School of Chemistry and Chemical Engineering, Jiangsu Normal University, Xuzhou 221116, P. R. of China
,
Feng Shi*
a   Jiangsu Key Laboratory of Green Synthetic for Functional Materials, School of Chemistry and Chemical Engineering, Jiangsu Normal University, Xuzhou 221116, P. R. of China
b   Jiangsu Province Key Laboratory of Fine Petrochemical Engineering, Changzhou University, Changzhou 213164, P. R. of China   Email: fshi@jsnu.edu.cn
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Publication History

Received: 23 August 2015

Accepted after revision: 28 September 2015

Publication Date:
21 October 2015 (online)

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Abstract

A chiral phosphoric acid-catalyzed asymmetric cascade dearomatization reaction of tryptamines with indol-3-ylmethanols has been established. This not only realized the first catalytic asymmetric cascade substitution of indol-3-ylmethanols, but also provided an efficient and stereoselective method (99% yield, >95:5 dr, 95:5 er) for constructing complex pyrroloindoline-based skeletons with three contiguous stereogenic centers, two of which were all-carbon quaternary centers.

Key words

dearomatization - asymmetric catalysis - tryptamines - indoles - cascade reactions - organocatalysis

Supporting Information

    Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0035-1560507.
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  • References

  • 1 These two authors contributed equally to the work.
  • 4 Menozzi C, Dalko PI, Cossy J. Chem. Commun. 2006; 4638
  • 11 3′-(2,3,8,8a-Tetrahydropyrrolo[2,3-b]indol-3a(1H)-yl)-1′,3′-dihydro-1H,2′H-2,3′-biindol-2′-ones 3; General Procedure CH2Cl2 (4 mL) was added to the mixture of the appropriate indol-3-ylmethanol 1 (0.1 mmol), tryptamine 2 (0.2 mmol), catalyst 4a (0.01 mmol), and 5 Å MS (100 mg). The mixture was stirred at 0 °C for 12 h then filtered to remove the MS. The solid powder was washed with EtOAc, and the organic phase was concentrated under the reduced pressure to give a residue that was purified by flash column chromatography (silica gel previously flushed with 10% Et3N–PE).
  • 12 tert-Butyl 3a-(1′-Benzyl-2′-oxo-1′,2′-dihydro-1H,3′H-2,3′-biindol-3′-yl)-3,3a,8,8a-tetrahydropyrrolo[2,3-b]indole-1(2H)-carboxylate (3aa) White solid, yield: 89% (88:12 dr); mp 152–154 °C; [α]D 20 +390.9 (c 0.1, acetone). IR (KBr): 3321, 3055, 2971, 1700, 1609, 1456, 1364, 1341, 1168, 1011, 741, 687 cm–1. 1H NMR (400 MHz, CDCl3): δ = 8.32 (s, 1 H), 8.11 (s, 1 H), 7.60 (d, J = 7.6 Hz, 1 H), 7.47 (d, J = 8.0 Hz, 1 H), 7.42–7.27 (m, 7 H), 7.24–7.04 (m, 5 H), 7.03–6.91 (m, 3 H), 6.88 (d, J = 2.4 Hz, 1 H), 4.99 (d, J = 1.6 Hz, 2 H), 4.37 (s, 1 H), 3.15–2.80 (m, 2 H), 2.49 (t, J = 7.2 Hz, 2 H), 1.42 (s, 9 H). 13C NMR (100 MHz, CDCl3): δ = 176.2, 155.8, 141.9, 137.0, 135.6, 134.7, 132.3, 131.7, 129.5, 129.4, 128.8, 128.7, 127.9, 127.8, 125.6, 125.2, 123.9, 123.0, 122.8, 121.9, 121.7, 120.4, 119.4, 119.2, 114.1, 111.5, 110.8, 110.2, 109.6, 53.3, 44.4, 28.5. HRMS (ESI): m/z [M – H]+ calcd for C38H35N4O3: 595.2709; found: 595.2707. Chiral HPLC: Daicel Chirapak IC [hexane–i-PrOH (70:30), flow rate: 1.0 mL/min; T = 30 °C, 254 nm]: tR  = 5.293 (major), 6.280 (minor); er: 90:10. tert-Butyl 3a-(1′-Methyl-2′-oxo-1′,2′-dihydro-1H,3′H-2,3′-biindol-3′-yl)-3,3a,8,8a-tetrahydropyrrolo[2,3-b]indole-1(2H)-carboxylate (3da) White solid; yield: 83% (>95:5 dr); mp 173–175 °C; [α]D 20 +112.0 (c 0.7, acetone). IR (KBr): 3322, 3055, 2928, 2360, 2341, 1705, 1609, 1457, 1366, 1170, 742, 696, 541 cm–1. 1H NMR (400 MHz, CDCl3): δ = 8.51 (s, 1 H), 8.15 (s, 1 H), 7.58 (d, J = 7.6 Hz, 1 H), 7.48 (d, J = 8.0 Hz, 1 H), 7.40–7.28 (m, 3 H), 7.20–7.09 (m, 3 H), 7.09–7.02 (m, 2 H), 6.98 (t, J = 8.0 Hz, 2 H), 6.84 (d, J = 2.4 Hz, 1 H), 4.61 (s, 1 H), 3.30 (s, 3 H), 3.14–2.95 (m, 2 H), 2.63–2.46 (m, 2 H), 1.43 (s, 9 H). 13C NMR (100 MHz, CDCl3): δ = 176.3, 155.9, 142.7, 137.1, 134.7, 132.2, 131.9, 129.4, 128.8, 125.6, 125.1, 124.0, 123.1, 122.6, 121.8, 121.5, 120.2, 119.4, 119.1, 113.7, 111.5, 110.9, 110.0, 108.8, 53.3, 40.6, 28.5, 26.7, 24.9. HRMS (ESI): m/z [M + Na]+ calcd for C32H32N4NaO3: 543.2372; found: 543.2374. Chiral HPLC: Daicel Chirapak IC [hexane–i-PrOH (70:30), flow rate: 1.0 mL/min; T = 30 °C, 254 nm]: tR  = 6.963 (major), 13.767 (minor); er: 87:13. tert-Butyl 3a-(1′-Benzyl-5′-methyl-2′-oxo-1′,2′-dihydro-1H,3′H-2,3′-biindol-3′-yl)-3,3a,8,8a-tetrahydropyrrolo[2,3-b]indole-1(2H)-carboxylate (3fa) White solid; yield: 43% (>95:5 dr); mp 210–212 °C; [α]D 20 +133.2 (c 0.4, acetone). IR (KBr): 3347, 2974, 2926, 2359, 2341, 1699, 1456, 1088, 880, 742 cm–1. 1H NMR (400 MHz, CDCl3): δ = 8.39 (s, 1 H), 8.10 (s, 1 H), 7.61 (d, J = 7.6 Hz, 1 H), 7.46 (d, J = 8.0 Hz, 1 H), 7.38–7.27 (m, 6 H), 7.16 (d, J = 8.4 Hz, 4 H), 7.09–7.04 (m, 2 H), 6.99 (t, J = 7.6 Hz, 1 H), 6.88–6.82 (m, 2 H), 4.96 (s, 2 H), 4.43 (s, 1 H), 3.14–2.85 (m, 2 H), 2.51 (t, J = 7.2 Hz, 2 H), 2.24 (s, 3 H), 1.43 (s, 9 H). 13C NMR (100 MHz, CDCl3): δ = 176.2, 155.9, 139.5, 137.0, 135.8, 134.7, 132.6, 132.3, 131.9, 129.0, 128.8, 127.9, 127.8, 125.9, 125.6, 124.0, 122.7, 121.8, 121.7, 120.3, 119.4, 119.2, 114.2, 111.5, 110.8, 110.1, 109.4, 53.4, 44.4, 40.5, 28.5, 24.9, 21.1. HRMS (ESI): m/z [M + Na]+ calcd for C39H38N4NaO3: 633.2842; found: 633.2849. Chiral HPLC: Daicel Chirapak IC [hexane–i-PrOH (70:30), flow rate: 1.0 mL/min; T = 30 °C, 254 nm]: tR  = 5.387 (major), 6.747 (minor); er: 90:10. tert-Butyl 3a-(1′-Benzyl-6-bromo-2′-oxo-1′,2′-dihydro-1H,3′H-2,3′-biindol-3′-yl)-3,3a,8,8a-tetrahydropyrrolo[2,3-b]indole-1(2H)-carboxylate (3la) White solid; yield: 40% (>95:5 dr); mp 103–105 °C; [α]D 20 +65.3 (c 0.3, acetone). IR (KBr): 3420, 2923, 2852, 2360, 2341, 1716, 1684, 1169, 1105, 939, 742, 698 cm–1. 1H NMR (400 MHz, CDCl3): δ = 8.59 (s, 1 H), 8.05 (s, 1 H), 7.59 (d, J = 7.6 Hz, 1 H), 7.48 (s, 1 H), 7.38–7.26 (m, 8 H), 7.18–7.11 (m, 2 H), 7.07 (d, J = 1.6 Hz, 1 H), 7.06–7.03 (m, 1 H), 7.03–6.94 (m, 2 H), 6.79 (d, J = 2.8 Hz, 1 H), 4.96 (s, 2 H), 4.41 (s, 1 H), 3.11–2.85 (m, 2 H), 2.50 (t, J = 7.2 Hz, 2 H), 1.43 (s, 9 H). 13C NMR (100 MHz, CDCl3): δ = 176.2, 155.9, 141.8, 137.9, 135.5, 134.7, 132.0, 131.4, 129.3, 128.9, 128.0, 127.8, 125.1, 124.5, 124.5, 123.6, 123.2, 122.8, 122.0, 119.6, 119.2, 116.4, 114.5, 114.3, 110.9, 110.3, 109.7, 53.2, 44.4, 28.5. HRMS (ESI): m/z [M + Na]+ calcd for C38H35BrN4NaO3: 697.1791; found: 697.1826. Chiral HPLC: Daicel Chirapak IC [hexane–i-PrOH (70:30), flow rate: 1.0 mL/min; T = 30 °C, 254 nm]: tR  = 13.320 (major), 41.177 (minor); er: 95:5