Enantioselective Total Synthesis of (-)-trans-Dendrochrysine via a Ring-Rearrangement Metathesis Approach

Abstract

The enantioselective total synthesis of the dipyrrolidine alkaloid (-)-trans-dendrochrysine was accomplished in 18 steps starting from tropone. The key step was a ring-rearrangement ­metathesis for the construction of the bisheterocyclic skeleton of the natural product in a single step.

Key words

total synthesis - olefin metathesis - ruthenium - hetero­cycles - alkaloids

References and Notes

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19

(-)-trans-Dendrochrysine: R _f 0.30 (SiO₂, hexanes-CH₂Cl₂-Et₂NH, 10:4:1); [α]_D ²⁰ -9.2° (c = 0.25, CHCl₃). ¹H NMR (500 MHz, CDCl₃, 323 K): δ = 1.19-2.16 (m, 8 H), 2.34 (s, 3 H), 2.39-2.65 (m, 3 H), 2.69-2.89 (m, 2 H), 2.98-3.11 (m, 1 H), 3.31 (ddd, J = 3.2, 9.0, 16.7 Hz, 1 H), 3.60-3.75 (m, 2 H), 4.49-4.68 (m, 1 H), 6.72 (d, J = 15.5 Hz, 1 H), 7.35-7.42 (m, 3 H), 7.51-7.56 (m, 2 H), 7.69 (d, J = 15.5 Hz, 1 H). ¹³C NMR (125 MHz, CDCl₃, 353 K): δ = 22.3, 24.1 (br), 29.5, 31.4, 40.3, 45.5 (br), 46.9 (br), 47.8 (br), 53.9 (br), 56.6, 62.2, 119.4, 127.7, 128.7, 129.4, 135.7 (C_q), 141.8, 164.8 (C_q), 207.5 (C_q). IR (ATR): 2957 (m), 2927 (m), 2875 (m), 2852 (m), 2780 (m), 1708 (m), 1650 (s), 1605 (s), 1577 (m), 1497 (m), 1450 (m), 1415 (s), 1375 (m), 1347 (m), 1306 (m), 1259 (m), 1201 (m), 1185 (m), 764 (m) cm^-1. MS (EI, 70 eV): m/z (%) = 340 [M⁺] (26), 279 (25), 278 (43), 277 (100), 209 (10), 201 (16), 199 (11), 183 (10), 167 (28), 150 (10), 149 (80), 140 (51), 131 (51), 126 (10), 124 (10), 103 (22), 98 (20), 97 (23), 85 (10), 84 (85), 83 (12). HRMS: m/z calcd for C₂₁H₂₈N₂O₂: 340.2151; found: 340.2155.