Palladium-Catalyzed Novel Cycloisomerization: An Unprecedented Domino Oxidative Cyclization towards Substituted Carbocycles

Abstract

Efficient Pd-catalyzed cyclization of homoallylated β-bromo-vinylalcohols via a domino process to carbocycle derivatives in presence of different bases is reported. An unexpected and novel palladium-mediated Heck-type intramolecular oxidative ­cyclization of 1-bromohexa-1-ene-5-yn-3-ol derivatives is also ­described.

Key words

Heck reaction - palladacycles - tandem reactions - oxidation - isomerization

References

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7

General Procedure for the Palladium-Catalyzed Cyclization. The appropriate homoallylated or propargylated β-bromo-vinylalcohols, Pd(OAc)₂ (10 mol%), PPh₃ (0.25 equiv), base (1 equiv)[HCOONa (1 equiv) for propargylated compound only] and DMF (6-8 mL) were placed in a two-neck round-bottom flask. After degassing with N₂ the mixture was heated to 70 °C for 4 h. After cooling, the reaction mixture was diluted with cold H₂O and extracted with Et₂O (4 × 25 mL), and dried (Na₂SO₄). The solvent was evaporated, and the product was isolated by column chromatography (PE-EtOAc 9:1).

8

General Procedure for Propargylation.
A mixture of β-bromo vinylaldehyde (1 mmol), propargyl bromide (1.3 mmol), indium metal (SRL, India) (1.2 mmol), NaI (3 mmol) in DMF (4-5 mL) was stirred at 0 °C until completion of the reaction (checked by TLC). The reaction mixture was quenched with aq NH₄Cl solution diluted with H₂O and extracted with Et₂O (3 × 25 mL). The solvent was removed at r.t. under vacuum.

11

Spectral Data of Representative Compounds.
7-Methoxy-9-methylene-8,9-dihydro-7 H -cyclopenta[ a ]acenaphthylene (II): ¹H NMR (200 MHz, C₆D₆): δ = 3.01-3.16 (m, 2 H), 3.20 (s, 3 H), 4.48 (dd, 1 H, J = 2.87 Hz, J = 2.96 Hz), 5.02 (br s, 1 H), 5.49 (br s, 1 H), 7.20-7.31 (m, 3 H), 7.45-7.60 (m, 3 H). Anal Calcd for C₁₇H₁₄O: C, 87.15; H, 6.02. Found: C, 88.25; H, 5.92. 3-Methyl-3,4,5,6,7,8-hexahydro-2 H -azulen-1-one ( 3d): IR (CHCl₃): ν_max = 1685 cm^-1. ¹H NMR (200 MHz, CDCl₃): δ = 1.15 (d, 3 H, J = 6.96 Hz), 1.42-1.67 (m, 6 H), 1.73-1.83 (m, 4 H), 2.26-2.58 (m, 2 H), 2.67-2.7 (m, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 18.98, 23,09, 26.33, 26.50, 31.13, 31.42, 37.04, 43.13, 141.72, 181.02, 208.11. MS (EI, 70 eV): m/z = 164 [M⁺]. Anal Calcd for C₁₁H₁₆O: C, 80.44; H, 9.82. Found: C, 80.65; H, 9.62.
10-Methyl-9,10-dihydro-8 H -fluoranthen-7-one ( 6b):
IR (CHCl₃): ν_max = 1660 cm^-1. ¹H NMR (200 MHz, CDCl₃): δ = 1.55 (d, 3 H, J = 7.12 Hz), 2.06-2.09 (m, 1 H), 2.39-2.78 (m, 3 H), 3.39-3.45 (m, 1 H), 7.53 (m, 2 H), 7.79 (d, 1 H, J = 8.20 Hz), 7.92-7.98 (m, 2 H), 8.26 (d, 1 H, J = 6.79 Hz). ¹³C NMR (75 MHz, CDCl₃): δ = 20.38, 29.19, 31.32, 35.68, 126.11, 126.21, 126.96, 127.54, 128.41, 128.66, 130.86, 136.81, 161.66, 196.89. MS (EI, 70 eV): m/z = 234 [M⁺]. Anal Calcd for C₁₇H₁₄O: C, 87.15; H, 6.02. Found: C, 86.92; H, 5.93.