Palladium/Lewis Acid Catalyzed Desymmetrization of Fulvene-Derived Bicyclic Hydrazines: A Facile Synthesis of Substituted Alkylidene Cyclopentenes

Abstract

Desymmetrization of fulvene-derived bicyclic hydrazines by a palladium/Lewis acid catalyzed reaction with allyl and vinyl stannanes leading to the efficient synthesis of synthetically important alkylidene cyclopentenes is described.

Key words

fulvenes - bicyclic hydrazines - alkylidene cyclopentenes - organostannanes - Lewis acids

References and Notes

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19

Typical Procedure ( 3a): 2,3-Carbethoxy-7-diphenyl-methylene-2,3-diazabicyclo[2.2.1]hept-5-ene (1) (122 mg, 0.302 mmol), allyltributyltin (2; 50 mg, 0.151 mmol), were taken in a Wheaton vial, and dissolved in anhyd toluene
(4 mL). PPh₃ (20 mol%), Pd₂(dba)₃·CHCl₃ (5 mol%) were added to the reaction mixture followed by the addition of Sc(OTf)₃ (2 mol%). The reaction mixture was stirred at
60 °C for 10 h. Completion of the reaction was monitored by TLC and the reaction mixture was subjected to silica gel (100-200 mesh) column chromatography (EtOAc-hexane, 1:4) to afford the product 3a in 88% (59.3 mg) yield.
White solid; mp 136 °C; R _f 0.6 (EtOAc-hexane, 1:3). IR (neat): 3302, 3057, 2978, 1742, 1713, 1489, 1412, 1300, 1220, 1124, 751, 696 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 7.30-7.14 (m, 10 H), 6.34-6.31 (m, 1 H), 6.06 (d, 1 H, J = 3.9 Hz), 5.84-5.78 (m, 1 H), 5.56-5.46 (m, 1 H), 5.17-5.06 (m, 2 H), 4.15-4.11 (m, 2 H), 3.89-3.88 (m, 2 H), 3.31-3.18 (m, 1 H), 2.58-2.43 (m, 1 H), 2.30-2.20 (m, 1 H), 1.24 (t, 3 H, J = 6.9 Hz), 1.03 (t, 3 H, J = 6.6 Hz). ¹³C NMR (75 MHz, CDCl₃): δ = 155.3, 153.5, 140.7, 138.2, 136.5, 135.9, 132.2, 130.0, 129.7, 128.6, 128.0, 127.1, 117.4, 113.7, 62.1, 61.9, 49.4, 37.5, 30.6, 14.9, 14.5. MS (LR-FAB): m/z calcd for C₂₇H₃₀N₂O₄ (M + Na⁺): 469.54; found: 469.97.
Compound 3b: Brownish-yellow solid; mp 86 °C; R _f 0.5 (EtOAc-hexane, 1:3). IR (neat): 3302, 3065, 2980, 1744, 1716, 1594, 1489, 1443, 1413, 1382, 1303, 1267, 1219, 1171, 1026, 918, 756, 701 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 7.29-7.41 (m, 10 H), 6.37-6.35 (m, 1 H), 6.03-6.01 (m, 1 H), 5.54-5.51 (m, 1 H), 5.19-5.17 (m, 1 H), 5.09-5.06 (m, 2 H), 4.15-4.13 (m, 2 H), 3.89-3.87 (m, 2 H), 3.86-3.85 (m, 1 H), 1.25 (t, 3 H, J = 6.9 Hz), 1.03 (t, 3 H, J = 6.5 Hz). ¹³C NMR (75 MHz, CDCl₃): δ = 156.9, 155.0, 142.5, 141.6, 139.4, 138.9, 135.1, 134.3, 133.2, 130.1, 128.7, 127.3, 126.6, 123.1, 117.6, 67.1, 62.1, 53.7, 28.1, 14.6, 13.9. MS (LR-FAB): m/z calcd for C₂₆H₂₈N₂O₄ (M + Na⁺): 455.51; found: 455.75.