Synlett 2018; 29(05): 603-608
DOI: 10.1055/s-0036-1591838
letter
© Georg Thieme Verlag Stuttgart · New York

Enantioselective Construction and Transformations of Poly­functionalized 3,4-Dihydro-2H-thiopyrano[2,3-b]quinolines

Jia-Wen Zhang
Department of Chemistry and Life Science, Zhejiang Normal University, Jinhua 321004, P. R. of China   Email: xiejw@zjnu.cn
,
Li-Si-Han Yu
Department of Chemistry and Life Science, Zhejiang Normal University, Jinhua 321004, P. R. of China   Email: xiejw@zjnu.cn
,
Jian-Lian Dong
Department of Chemistry and Life Science, Zhejiang Normal University, Jinhua 321004, P. R. of China   Email: xiejw@zjnu.cn
,
Qi-Chao Sun
Department of Chemistry and Life Science, Zhejiang Normal University, Jinhua 321004, P. R. of China   Email: xiejw@zjnu.cn
,
Department of Chemistry and Life Science, Zhejiang Normal University, Jinhua 321004, P. R. of China   Email: xiejw@zjnu.cn
› Author Affiliations
We are grateful for financial support from the National Natural Science Foundation of China (21272214).
Further Information

Publication History

Received: 18 September 2017

Accepted after revision: 29 October 2017

Publication Date:
11 December 2017 (eFirst)

Abstract

We developed an enantioselective organocascade Michael/Henry reaction in the presence of a bifunctional organocatalyst to construct chiral polyfunctionalized 3,4-dihydro-2H-thiopyrano[2,3-b]quinolines. The resulting optically active products with three contiguous stereocenters, one quaternary and two tertiary, were obtained in moderate to good yields and with good to excellent enantioselectivities. Remarkably, the resulting products were readily converted into polyfunctionalized optically active furo[2′,3′:4,5]thiopyrano[2,3-b]quinoline, 3,4-dihydro-2H-thiopyrano[2,3-b]quinoline 1-oxide and 2,3-dihydro-4H-thiopyrano[2,3-b]quinolin-4-one derivatives.

Supporting Information

 
  • References and Notes


    • For selected examples of the Michael/Henry reaction
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  • 9 (2R,3R,4R)-3-Bromo-3-nitro-2-phenyl-3,4-dihydro-2H-thiopyrano[2,3-b]quinolin-4-ol (3aa): Typical Procedure A mixture of 2-mercaptoquinoline-3-carbaldehyde (1a; 19.0 mg 0.10 mmol), α-bromonitroalkene 2a (27 mg, 0.12 mmol), and catalyst C2 (9.0 mg, 0.02 mmol) in CHCl3 (2 mL) was stirred at –30 °C for 16 h. The product was then purified directly by flash chromatography (silica gel, 15% EtOAc–PE) to give a white solid; yield: 30 mg (78%, 95% ee); mp 193–194 °C; [α]D 25 +33.21 (c 0.5, THF). HPLC: Chiralpak OD column (15% i-PrOH–hexane, 1 mL/min); t major = 21.89 min, t minor = 13.16 min. 1H NMR (600 MHz, DMSO-d 6): δ = 8.42 (s, 1 H), 8.05 (d, J = 8.0 Hz, 1 H), 7.88 (d, J = 8.4 Hz, 1 H), 7.77 (t, J = 7.3 Hz, 1 H), 7.57 (dd, J = 9.7, 3.8 Hz, 3 H), 7.47 (dt, J = 19.06, 6.6 Hz, 4 H), 6.24 (s, 1 H), 6.03 (d, J = 7.3 Hz, 1 H). 13C NMR (151 MHz, DMSO-d 6): δ = 156.6, 146.9, 134.8, 132.1, 131.5, 131.2, 130.6, 130.0, 129.4, 128.7, 127.3, 126.6, 125.7, 110.8, 75.2, 51.1. ESI-HRMS: m/z [M + H]+ calcd for C18H14BrN2O3S: 416.9903; found: 416.9903.
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  • 12 (3aS,4R,11bR)-2-Amino-3a-nitro-4-phenyl-3a,11b-dihydro-4H-furo[2',3':4,5]thiopyrano[2,3-b]quinoline-3-carbonitrile (4aa): Typical Procedure A mixture of 3aa (42 mg, 0.10 mmol), malononitrile (20 mg, 0.30 mmol), and DBU (0.10 mmol) in THF (1 mL) was stirred at r.t. for 2 d. The product was directly purified by flash chromatography (silica gel, 10% EtOAc–PE) to give a white solid; yield: 27 mg (67%, >99% ee); mp 213–215 °C; [α]D 25 +16.37 (c 0.5, THF). HPLC: Chiralpak OD column (15% i-PrOH–hexanes, 1 mL/min); t major = 22.07 min, t minor = 28.92 min. 1H NMR (400 MHz, DMSO-d 6): δ = 8.43 (s, 1 H), 7.99 (dd, J = 8.2, 1.4 Hz, 1 H), 7.88–7.83 (m, 1 H), 7.76 (ddd, J = 8.4, 6.8, 1.5 Hz, 1 H), 7.68–7.62 (m, 2 H), 7.56 (ddd, J = 8.1, 6.8, 1.3 Hz, 1 H), 7.45–7.34 (m, 3 H), 6.72 (d, J = 5.7 Hz, 1 H), 6.15 (dd, J = 11.4, 2.5 Hz, 1 H), 5.54–5.45 (m, 2 H). 13C NMR (151 MHz, DMSO-d 6): δ = 156.3, 147.1, 141.3, 134.8, 131.9, 131.0, 130.0, 129.6, 129.1, 128.1, 127.3, 126.5, 126.5, 125.9, 125.9, 112.6, 110.8, 91.9, 75.2, 70.5, 45.7. ESI-HRMS: m/z [M + H]+ calcd for C21H15N4O3S: 403.0865; found: 403.0854
  • 13 (2R,3R,4R)-3-Bromo-3-nitro-2-phenyl-3,4-dihydro-2H-thiopyrano[2,3-b]quinolin-4-ol 1-oxide (6aa); Typical Procedure A mixture of 3aa (42 mg, 0.10 mmol), and m-CPBA (26 mg, 0.15 mmol) in THF (1 mL) was stirred at 0 °C for 5 h. The product was purified directly by flash chromatography (silica gel 1% MeOH–CH2Cl2) to give a white solid; yield: 37 mg (84%, 99% ee); mp 206–208 °C; [α]D 25 +93.71 (c 0.5, THF). HPLC: Chiralpak OD column (15% i-PrOH–hexane, 1 mL/min); t major = 20.68 min, t minor = 12.46 min. 1H NMR (600 MHz, DMSO-d 6): δ = 8.68 (s, 1 H), 8.26 (d, J = 7.8 Hz, 1 H), 8.21 (d, J = 8.3 Hz, 1 H), 7.97 (qd, J = 7.3, 3.8 Hz, 1 H), 7.85–7.81 (m, 1 H), 7.77 (s, 1 H), 7.72–7.69 (m, 2 H), 7.54 (dd, J = 3.8, 2.6 Hz, 3 H), 6.43 (s, 1 H), 6.19 (s, 1 H). 13C NMR (151 MHz, DMSO-d 6): δ = 158.8, 147.0, 137.0, 132.4, 132.1, 130.6, 130.5, 130.3, 129.7, 129.3, 129.0, 128.9, 128.3, 106.8, 75.3, 68.8. ESI-HRMS: m/z [M + H]+ calcd for C18H14BrN2O4S: 432.9852; found: 432.9854.