Facile Access to 1,5-Benzodiazepines via Amine-Promoted (4+3) Annulations of δ-Acetoxy Allenoates with o-Diaminobenzenes 
under Mild Conditions

Yi-Fan Wang; Cheng-Yu He; Longlei Hou; Ping Tian; Guo-Qiang Lin; Xiaofeng Tong

doi:10.1055/s-0037-1609347

Synlett, Table of Contents

Synlett 2018; 29(09): 1176-1180
DOI: 10.1055/s-0037-1609347

letter

Facile Access to 1,5-Benzodiazepines via Amine-Promoted (4+3) Annulations of δ-Acetoxy Allenoates with o-Diaminobenzenes under Mild Conditions

Yi-Fan Wang

^aKey Laboratory for Advanced Materials and Institute of Fine Chemicals, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, P. R. of China Email: tongxf@ecust.edu.cn

,

Cheng-Yu He

^bKey Laboratory of Synthetic Chemistry of Natural Substances, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, P. R. of China Email: tianping@sioc.ac.cn

,

Longlei Hou

^aKey Laboratory for Advanced Materials and Institute of Fine Chemicals, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, P. R. of China Email: tongxf@ecust.edu.cn

,

Ping Tian *

^bKey Laboratory of Synthetic Chemistry of Natural Substances, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, P. R. of China Email: tianping@sioc.ac.cn

^cInnovation Research Institute of Traditional Chinese Medicine (IRI), Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, P. R. of China Email: tianping@shutcm.edu.cn

,

Guo-Qiang Lin

^bKey Laboratory of Synthetic Chemistry of Natural Substances, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, P. R. of China Email: tianping@sioc.ac.cn

^cInnovation Research Institute of Traditional Chinese Medicine (IRI), Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, P. R. of China Email: tianping@shutcm.edu.cn

,

Xiaofeng Tong*

^aKey Laboratory for Advanced Materials and Institute of Fine Chemicals, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, P. R. of China Email: tongxf@ecust.edu.cn

› Author Affiliations

Abstract

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Abstract

An amine-promoted (4+3) annulation of δ-acetoxy allenoate with o-diaminobenzene is reported, providing a facile access to 1,5-benzodiazepine. This method features wide reaction scope, mild conditions, and readily available starting materials. The cascade reaction involves aza-Michael addition of o-diaminobenzene to allenoate, elimination of acetate group, and subsequent 1,6-aza-Michael addition.

Key words

1,5-benzodiazepine - annulation - allenoate - diaminobenzene - catalyst-free

Full Text

References

References and Notes

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10 CCDC 1816325 contains the supplementary crystallographic data for 3ga. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.
11 Acetoxy Allenoates 1 and o-Diaminobenzenes 2 To a 10 mL vial were added o-diaminobenzene 2 (0.2 mmol, 1.0 equiv), DIPEA (0.24 mmol, 1.2 equiv), and toluene (2 mL), followed by the slow addition of a solution of δ-acetoxy allenoate 1 (0.24 mmol,1.2 equiv) in toluene (2 mL). The solution was stirred for 12 h at room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography using petroleum ether and ethyl acetate (30:1 to 15:1 v/v) as the eluent to give the corresponding annulations product 3. Ethyl (Z)-2-{4-(4-Isopropylphenyl)-1,3,4,5-tetrahydro-2H-benzo[b][1,4]diazepin-2-ylidene}acetate (3da) Yellow solid, 86% yield; mp 70–72 °C. ¹H NMR (400 MHz, CDCl₃): δ = 10.26 (s, 1 H), 7.26 (d, J = 8.2 Hz, 2 H), 7.20 (d, J = 8.2 Hz, 2 H), 6.99–6.93 (m, 2 H), 6.92–6.85 (m, 1 H), 6.76–6.72 (m, 1 H), 4.79 (dd, J = 9.6, 3.8 Hz, 1 H), 4.64 (s, 1 H), 4.23–4.06 (m, 2 H), 3.66 (br s, 1 H),2.90 (hept, J = 6.9 Hz, 1 H), 2.72 (dd, J = 13.8, 9.6 Hz, 1 H), 2.49 (ddd, J = 13.8, 3.8, 1.3 Hz, 1 H), 1.34–1.17 (m, 9 H). ¹³C NMR (100 MHz, CDCl₃): δ = 170.28, 158.84, 148.67, 142.39, 137.83, 129.65, 126.80, 125.98, 124.91, 122.48, 121.35, 120.70, 83.95, 64.84, 58.79, 40.39, 33.76, 23.94, 23.91, 14.53. IR (KBr): 3853, 3336, 2960, 2929, 2870, 1734, 1654, 1616, 1560, 1540, 1507, 1480, 1437, 1364, 1286, 1266, 1246, 1157, 1117, 1095, 1051, 829 cm^–1. HRMS (ESI): m/z calcd for C₂₂H₂₇N₂O₂ ⁺: 351.2067; found: 351.2067 [M + H]⁺. Ethyl (Z)-2-{4-(4-Cyanophenyl)-1,3,4,5-tetrahydro-2H-benzo[b][1,4]diazepin-2-ylidene}acetate (3ha) Yellow solid, 72% yield; mp 60–62 °C. ¹H NMR (400 MHz, CDCl₃): δ = 10.16 (s, 1 H), 7.66–7.60 (m, 2 H), 7.55–7.50 (m, 2 H), 7.03–6.92 (m, 3 H), 6.83–6.79 (m, 1 H), 5.00–4.92 (m, 1 H), 4.43 (s, 1 H), 4.21–4.04 (m, 2 H), 3.73 (s, 1 H), 2.73 (dd, J = 13.8, 4.7 Hz, 1 H), 2.49 (dd, J = 13.9, 7.0 Hz, 1 H), 1.26 (t, J = 7.1 Hz, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 169.98, 157.03, 149.30, 137.66, 132.43, 130.48, 127.12, 125.09, 122.49, 122.38, 120.97, 118.63, 111.61, 85.04, 64.57, 58.93, 39.37, 14.44. IR (neat): 3629, 3567, 3343, 3057, 2980, 2931, 2228, 1734, 1653, 1616, 1559, 1541, 1501, 1437, 1405, 1364, 1284, 1267, 1233, 1159, 1118, 1095, 1048, 833 cm^–1. HRMS (ESI): m/z calcd for C₂₀H₂₀N₃O₂ ⁺: 334.1550; found: 334.1550 [M + H]⁺. Ethyl (Z)-2-{4-Methyl-1,3,4,5-tetrahydro-2H-benzo[b][1,4]diazepin-2-ylidene}acetate (3pa) Yellow liquid, 82% yield. ¹H NMR (400 MHz, CDCl₃): δ = 10.13 (s, 1 H), 6.91–6.75 (m, 3 H), 6.71–6.64 (m, 1 H), 4.61 (s, 1 H), 4.08 (q, J = 7.1 Hz, 2 H), 3.88–3.76 (m, 1 H), 3.17 (br s, 1 H), 2.40 (dd, J = 13.8, 4.4 Hz, 1 H), 2.15 (dd, J = 13.8, 7.0 Hz, 1 H), 1.26–1.17 (m, 6 H).¹³C NMR (100 MHz, CDCl₃): δ = 170.11, 159.16, 137.87, 130.34, 124.67, 122.27, 121.67, 120.90, 84.25, 58.79, 55.83, 39.31, 23.40, 14.54. IR (neat): 3347, 2973, 2927, 1648, 1616, 1588, 1498, 1447, 1364, 1307, 1274, 1232, 1159, 1115, 1095, 1044, 916, 784 cm^–1. HRMS (ESI): m/z calcd for C₁₄H₁₉N₂O₂ ⁺: 247.1441; found: 247.1440 [M + H]⁺. Ethyl (Z)-2-{4-Benzyl-1,3,4,5-tetrahydro-2H-benzo[b][1,4]diazepin-2-ylidene}acetate (3qa) Yellow solid, 85% yield; mp 106–108 °C. ¹H NMR (400 MHz, CDCl₃): δ = 10.13 (s, 1 H),7.31–7.12 (m, 5 H), 6.89–6.75 (m, 3 H), 6.63–6.56 (m, 1 H), 4.64 (s, 1 H),4.16–4.00 (m, 2 H),3.94–3.82 (m, 1 H), 3.23 (br s, 1 H), 2.82–2.67 (m, 2 H), 2.42 (dd, J = 13.7, 4.7 Hz, 1 H), 2.23 (dd, J = 13.8, 7.2 Hz, 1 H), 1.21 (t, J = 7.1 Hz, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 170.08, 158.92, 137.89, 137.57, 130.94, 129.27, 128.74, 126.70, 124.69, 122.15, 121.95, 121.33, 84.32, 62.01, 58.80, 43.31, 37.26, 14.52. IR (neat): 3386, 1618, 1588, 1505, 1404, 1365, 1332, 1285, 1262, 1225, 1158, 1123, 1095, 1065, 1039, 1004, 790 cm^–1. HRMS (ESI): m/z calcd for C₂₀H₂₃N₂O₂ ⁺: 323.1754; found: 323.1757 [M + H]⁺. Ethyl (Z)-2-{1,3,4,5-Tetrahydro-2H-benzo[b][1,4]diazepin-2-ylidene}acetate (3ra) Yellow solid, 45% yield; mp 56–58 °C. ¹H NMR (400 MHz, CDCl₃): δ = 10.22 (s, 1 H), 6.88–6.79 (m, 2 H), 6.76–6.70 (m, 1 H), 6.67–6.59 (m, 1 H), 4.61 (s, 1 H), 4.08 (q, J = 7.1 Hz, 2 H), 3.60–3.52 (m, 2 H), 3.13 (br s, 1 H), 2.49–2.41 (m, 2 H), 1.21 (t, J = 7.1 Hz, 3 H).¹³C NMR (100 MHz, CDCl₃): δ = 170.34, 160.98, 138.16, 128.87, 124.60, 122.64, 120.60, 119.79, 83.32, 58.81, 48.70, 33.76, 14.55. IR (neat): 3386, 1618, 1588, 1505, 1404, 1365, 1332, 1285, 1262, 1225, 1158, 1123, 1095, 1065, 1039, 1004, 790 cm^–1. HRMS (ESI): m/z calcd for C₁₃H₁₇N₂O₂ ⁺: 233.1285; found: 233.1284 [M + H]⁺. Ethyl (Z)-2-{7,8-Dimethyl-4-phenyl-1,3,4,5-tetrahydro-2H-benzo[b][1,4]diazepin-2-ylidene}acetate (3ab) Yellow solid, 70% yield; mp 100–102 °C. ¹H NMR (400 MHz, CDCl₃): δ = 10.18 (s, 1 H), 7.41–7.22 (m, 5 H), 6.76 (s, 1 H), 6.55 (s, 1 H), 4.80 (dd, J = 9.2, 4.0 Hz, 1 H), 4.58 (s, 1 H), 4.23–4.05 (m, 2 H), 3.56 (br s, 1 H), 2.67 (dd, J = 13.7, 9.2 Hz, 1 H), 2.50 (ddd, J = 13.7, 4.0, 1.1 Hz, 1 H), 2.17 (s, 6 H), 1.27 (t, J = 7.1 Hz, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 170.29, 158.92, 145.05, 135.43, 133.22, 129.69, 128.73, 127.83, 127.41, 126.05, 123.53, 121.90, 83.54, 65.16, 58.73, 40.37, 19.10, 18.74, 14.55. IR (KBr): 3376, 3276, 3064, 2973, 2906, 2888, 2859, 1654, 1609, 1513, 1482, 1451, 1428, 1365, 1310, 1281, 1242, 1199, 1160, 1129, 1094, 1048, 988, 950, 897 cm^–1. HRMS (ESI): m/z calcd for C₂₁H₂₅N₂O₂ ⁺: 337.1911; found: 337.1910 [M + H]⁺. Ethyl (Z)-2-{7,8-Dibromo-4-phenyl-1,3,4,5-tetrahydro-2H-benzo[b][1,4]diazepin-2-ylidene}acetate (3ae) Yellow solid, 34% yield; mp 60–62 °C. ¹H NMR (400 MHz, CDCl₃): δ = 10.17 (s, 1 H), 7.35–7.16 (m, 5 H), 7.13 (s, 1 H), 6.94 (s, 1 H), 4.72 (dd, J = 9.1, 3.6 Hz, 1 H), 4.57 (s, 1 H), 4.16–3.99 (m, 2 H), 3.69 (br s, 1 H), 2.62 (dd, J = 14.0, 9.1 Hz, 1 H), 2.48 (dd, J = 14.0, 3.7 Hz, 1 H), 1.20 (t, J = 7.1 Hz, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 170.23, 157.97, 143.54, 137.84, 131.84, 130.32, 128.03, 125.10, 122.55, 122.08, 121.74, 121.01, 84.72, 64.57, 58.98, 39.93, 14.61. IR (neat): 3420, 3132, 1717, 1653, 1617, 1559, 1540, 1507, 1490, 1457, 1404, 1300, 1239, 1160, 1066, 1010, 700 cm^–1. HRMS (ESI): m/z calcd for C₁₉H₁₉ Br₂N₂O₂ ⁺: 464.9808; found: 464.9806 [M + H]⁺. Ethyl (Z)-2-{4-Phenyl-1,3,4,5-tetrahydro-2H-naphtho[2,3-b][1,4]diazepin-2-ylidene}acetate (3af) Yellow solid, 51% yield; mp 65–67 °C. ¹H NMR (400 MHz, CDCl₃): δ = 10.43 (s, 1 H), 7.71–7.59 (m, 2 H), 7.45–7.23 (m, 8 H), 7.16 (s, 1 H), 4.85 (dd, J = 9.1, 4.6 Hz, 1 H), 4.67 (s, 1 H), 4.25–4.11 (m, 2 H), 3.96 (s, 1 H), 2.70 (dd, J = 13.8, 9.1 Hz, 1 H), 2.60 (dd, J = 13.8, 4.6 Hz, 1 H), 1.30 (t, J = 7.1 Hz, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 170.24, 158.02, 144.63, 137.89, 132.05, 131.81, 129.99, 128.83, 128.00, 126.73, 126.15, 125.77, 125.25, 124.32, 119.10, 116.58, 85.17, 64.80, 59.00, 39.54, 14.54. IR (KBr): 3629, 3619, 3600, 3587, 3567, 3546, 3528, 3503, 3355, 3056, 2977, 2926, 1734, 1717, 1684, 1654, 1616, 1576, 1559, 1541, 1522, 1507, 1490, 1474, 1457, 1437, 1364, 1286, 1248, 1185, 1156, 1096, 1047, 872, 788 cm^–1. HRMS (ESI). m/z calcd for C₂₃H₂₃N₂O₂ ⁺: 359.1754; found: 359.1753 [M + H]⁺.

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