Synthesis of Phthalides and 3,4-Dihydroisocoumarins Using the Palladium-Catalyzed Intramolecular Benzannulation Strategy

Abstract

A novel method for the synthesis of phthalides and 3,4-dihydroisocoumarins via the palladium-catalyzed intramolecular benzannulation of bis-enyne and enyne-diyne systems is described. Various kinds of substituted phthalides 9 and 17 and 3,4-dihydroisocoumarins 19 were synthesized from 8, 16, and 18, respectively, in moderate to excellent yields. The benzannulation reaction proceeded chemoselectively to give the corresponding fused ring compounds A without the formation of the regioisomeric products B (eq 6). Furthermore, this methodology was applied to the synthesis of biologically active 3-n-butylphthalide 23.

Transition-Metal-Catalyzed Reactions in Heterocyclic Synthesis

“…126 The reaction proceeds through formation of the palladacycle 148 followed by reductive elimination of palladium Gilbertson and DeBoef demonstrated that the [4 + 2 + 2]-cycloaddition of the yne-dienes 149 with the alkyne 150 took place in the presence of rhodium and silver catalysts to give the eight-membered trienes 151 in good yields (Scheme 51). 127 Evans et al reported that [4 + 2 + 2]-cycloaddition of 1,6-enynes 152 with 1,3-butadiene proceeded in the presence of catalytic amounts of Rh(PPh 3 ) 3 Cl and AgOTf and the corresponding 1,4-cyclooctadienes 153 were obtained in good to high yields (Scheme 52).…”

Development of Efficient Catalytic Arylation of Aldehydes with Thioether-Imidazolinium Carbene Ligands

“…[57][58][59][60] Because of their significance, various methods for the synthesis of 3-arylphthalides have been reported. However, not many transition metal-catalyzed synthetic reactions for 3-arylphthalides have been developed, [61][62][63][64][65] although catalytic methods could be highly efficient processes. In particular, there were only a few reports on the synthesis of 3-arylphthalides using transition metal-catalyzed 1,2-addition as key reaction, [66][67][68][69] and more catalytically active and practically advantageous processes have been desirable.…”

Development of New Cycloaddition Reactions Based on the Unique Reactivity of Unsaturated Hydrocarbons

“…This reaction has been applied to the synthesis of 8, one of the phthalides, some of which are known as biologically active natural products (Chart 6). 17) We also carried out this reaction in fluorous biphasic system in the presence of perfluoro-tagged palladium catalyst (Chart 7). The benzannulation proceeded when we carried out the reaction of 9 in a mixture of heptane and hexafluoropropene trimer.…”