Palladium(0)-catalyzed Ring Expansion Reactions of Hydroxy Methoxyallenylisoindolinones via Inter- and Intramolecular Carbopalladation Using Aryl and Vinyl Halides

Abstract

Palladium(0)-catalyzed one-atom ring expansion of various hydroxy methoxyallenylisoindolinones 2 proceeded in the presence of aryl and vinyl halides to give the corresponding isoquinolinediones 3 in various yields. Tandem intramolecular carbopalladation-heterocyclic ring expansion reaction of compound 5 was also achieved to give a tetracyclic compound 6.

Key words

allene - heterocycle - palladium - ring expansion - tandem reaction

References

• 1 Hesse M. Ring Enlargement in Organic Chemistry   VCH Publishers, Inc.; New York: 1991. 
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4

Typical Experimental Procedure for Synthesis of a Hydroxy Methoxyallenylisoindolinone 2 (R = Me): A solution of methoxyallene (1.14 g, 16.27 mmol) in anhyd THF (17 mL) was treated with 1.61 M n-butyllithium in
n-hexane (8.44 mL, 13.59 mmol) under N₂ atmosphere at
-30 °C and stirred for 10 min. Then the solution was added to a THF (20 mL) solution of N-methylphthalimide 1 (R = Me) (2.19 g, 13.59 mmol) at -78 °C. After being stirred at -78 °C for 10 min, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was washed with brine, dried over MgSO₄, and filtered. The filtrate was evaporated in vacuo to afford the crude product, which was purified by column chromatography on silica gel to give compound 2 (R = Me) (2.09 g, 67%) as yellow powder.

5

Typical Experimental Procedure for the intermolecular Ring Expansion Reaction: A mixture of N-methyl-3-hydroxy-3-(1-methoxypropadienyl)isoindolin-1-one(2) (R = Me) (0.10 g, 0.43 mmol), Pd(PPh₃)₄ (0.05 g, 0.043 mmol), K₂CO₃ (0.18 g, 1.30 mmol), and 4-iodotoluene (0.38 g, 1.74 mmol) in anhyd THF (8.6 mL) was refluxed under N₂ atmosphere for 48 h. The reaction mixture was quenched with sat. NH₄Cl and extracted with EtOAc. The organic layer was washed with brine, dried over MgSO₄, and filtered. The filtrate was evaporated in vacuo to afford the crude product, which was purified by column chromatography on silica gel with hexane-EtOAc (8:1) to give N-methyl-3-methoxy-3-[1-(p-methylphenyl)ether-2,3-dihydroisoquinoline]-1,4-dione 3 (R = Me, R′ = p-MePh) (0.104 g, 77%) as a pale yellow oil.

6

X-ray data for 4: C₁₉H₁₅NO₃, MW = 305.33, yellow prismatic crystal, monoclinic, space group P2₁/c (#14), a = 7.836(1) Å, b = 26.084(5) Å, c = 7.770(1) Å, V = 1477.7(4) ų, β = 111.50(1)°, Z = 4, R = 0.067, Rw = 0.130.