Intramolecular Cycloaddition in Cyclohexa-2,4-dienone and Photochemical Reactions: An Efficient Route to Azatriquinane and Azasterpurane Frameworks

Abstract

A novel, efficient and stereoselective entry to azatriquinane and azasterpurane frameworks from simple aromatic precursor, is described. The methodology involves in situ generation of cyclohexa-2,4-dienones containing a tether and intramolecular π4s+π2s cycloaddition that leads to a bicyclo[2.2.2]octenone-annulated five-membered ring that contains nitrogen. Further manipulation of the resulting adduct followed by photochemical sigmatropic shifts readily furnished the azatriquinane and azasterpurane frameworks.

Key words

cyclohexa-2,4-dienone - cycloaddition - oxa-di-π-methane rearrangement - 1,3-acyl shift photochemistry

References and Notes

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13

All the compounds gave satisfactory spectral and analytical data. Data for adduct 13: mp 159-161 °C. IR: 1733 cm^-1. ¹H NMR (300 MHz, CDCl₃): d = 7.70-7.74 (m, 2 H), 7.31-7.37 (m, 2 H), 5.20-5.24 (br m, 1 H, b-H of b,g-enone moiety), 3.60-3.68 (m merged with part of an AB system, J _AB = 10.6 Hz, 2 H), 3.52 (part of an AB system, J _AB = 10.6 Hz, 1 H), 3.14 (part of an AB system, J _AB = 6.0 Hz, 1 H), 2.85-2.92 (m merged with another signal, 1 H), 2.84 (part of an AB system, J _AB = 6.0 Hz, 1 H), 2.45 (s, 3 H, Me), 2.12-2.34 (m, 3 H), 1.87 (d, J = 1.5 Hz, 3 H, Me), 1.26 (ddd, J ₁ = 12.1 Hz, J ₂ = 5.1 Hz, J ₃ = 1.8 Hz, 1 H). ¹³C NMR (75 MHz, CDCl₃): d = 200.9 (CO), 146.4, 143.8, 133.9, 129.8, 127.3, 121.6, 58.8, 56.6, 52.0, 51.8, 49.2, 44.6, 41.5, 24.8, 21.5, 20.2. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₉H₂₂SNO₄: 360.1270; found: 360.1274.

14

Data of the compound 15: mp 164-166 °C. IR: 1723 cm^-1. ¹H NMR (400 MHz, CDCl₃): d = 7.73 (d, J = 8.0 Hz, 2 H), 7.34 (d, J = 8.0 Hz, 2 H), 5.00 (br m, 1 H, b-H of b,g-enone moiety), 3.60-3.64 (m, 2 H), 3.44 (d, J = 10.3 Hz, 1 H), 2.71-2.79 (m, 2 H), 2.44 (s, 3 H), 1.83-2.18 (m, 4 H), 1.79 (d, J = 1.8 Hz, 3 H), 1.16-1.21 (m of dd, J ₁ = 12.5 Hz, J ₂ = 5.8 Hz, 1 H). ¹³C NMR (100 MHz, CDCl₃): d = 207.6 (CO), 148.7, 143.6, 134.3, 129.9, 127.5, 120.2, 59.3, 52.4, 49.6, 40.6, 38.9, 37.9, 28.0, 21.7, 19.8. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₈H₂₁SNO₃: 332.1320; found: 332.1306. Crystal data: C₁₈H₂₁NO₃S, M = 331.42, crystal size = 0.23 × 0.18 × 0.15 mm, monoclinic, P2_1/n, Z = 4, a = 11.4521(8), b = 10.5769(7), c = 13.7991(9) Å, λ = 0.71073 Å, a = 90.000 β = 103.366(6)°, V = 1626.18(19) ų, D _calcd = 1.354 mg/m³, T = 150 (2) K, F(000) = 704. Reflections collected/unique = 9895/1761, [R(int) = 0.0581], final R indices [I > 2σ(I)], R1 = 0.0581, wR2 = 0.1019, R indices (all data), R ₁ = 0.1126, wR ₂ = 0.1161. The complete crystal data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif quoting the CCDC number 677807.

17

Data for compound 18: IR: 1726 cm^-1. ¹H NMR (400 MHz, CDCl₃): d = 7.61 (d, J = 8.0 Hz, 2 H, ArH), 7.29 (d, J = 8.0 Hz, 2 H), 3.22-3.27 (m, 2 H), 2.94 (superimposed dd, J ₁ = 9.0 Hz, 1 H), 2.78 (d, J = 9.7 Hz, 1 H), 2.64 (dd, J ₁ = 9.7 Hz, J ₂ = 5.2 Hz, 1 H), 2.50 (dd, J ₁ = 18.3 Hz, J ₂ = 10.0 Hz, 1 H), 2.27-2.46 (s merged with a m, 4 H), 1.86-1.89 (m, 1 H), 1.69-1.80 (m, 2 H), 1.34 (s, 3 H), 1.18-1.21 (br m, 1 H). ¹³C NMR (100 MHz, CDCl₃): d = 213.9, 144.2, 131.5, 129.9, 128.2, 53.1, 48.7, 48.6, 46.7, 46.0, 45.5, 45.4, 45.2, 41.8, 21.7, 13.5. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₈H₂₁SNO₃: 332.1320; found: 332.1309.

18

Data for compound 19: mp 132-134 °C. IR: 1772 cm^-1. ¹H NMR (400 MHz, CDCl₃): d = 7.72 (d, J = 8.0 Hz, 2 H), 7.34 (d, J = 8.0 Hz, 2 H), 5.29 (br s, 1 H), 4.06 (m of d, J = 14.3 Hz, 1 H), 3.89 (superimposed dd, J ₁ = J ₂ = 8.0 Hz, 1 H), 3.74 (m of d, J = 14.3 Hz, 1 H), 2.95 (dd, J ₁ = 17.7 Hz, J ₂ = 9.1 Hz, 1 H), 2.67-2.74 (m, 2 H), 2.50-2.58 (m, 1 H), 2.44 (s, 3 H, Me), 2.34-2.42 (m, 1 H), 2.00 (ddd, J ₁ = 12.3 Hz, J ₂ = 6.1 Hz, J ₃ = 2.4 Hz, 1 H), 1.22 (s, 3 H), 1.00-1.07 (m, 1 H). ¹³C NMR (100 MHz, CDCl₃): d = 208.8, 143.8, 139.8, 133.4, 129.9, 127.8, 118.7, 63.1, 53.7, 51.4, 46.1, 33.9, 30.8, 23.8, 21.7, 20.3. HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₈H₂₁SNO₃Na: 354.1140; found: 354.1143.