A Facile and Efficient Synthesis of Dihydroisobenzofuran Derivatives via Tandem Palladium‐Catalyzed Coupling, Propargyl‐Allenyl Rearrangement, [4+2] Cycloaddition and Aromatization Reaction

Abstract

A variety of dihydroisobenzofuran derivatives has been prepared in good yields via an interesting sequential reaction consisting of palladiumcatalyzed coupling, propargyl-allenyl rearrangement, [4 + 2] cycloaddition and aromatization. A double-coupling, rearrangement, [4 + 2] cycloaddition and aromatization process is also described for the synthesis of more complex and diverse structures.

Facile Synthesis of Polycyclic Fluorene Derivatives via a Palladium‐Catalyzed Coupling, Propargyl‐Allenyl Isomerization and Schmittel Cyclization Sequence

“…For examples, when 2f and 2g were employed to react with 3‐iodocyclohex‐2‐enone, the corresponding products 3f and 3h were obtained in 85% and 74% yields, respectively. Here it is worth noting that in either case we did not observe the formation of any Diels–Alder cycloadduct of the vinylallene intermediate with the alkene or alkyne moiety of R 4 ,5a,b indicating that the Schmittel cyclization of the presumed enyne‐allene intermediate such as B (Scheme ) proceeds preferentially rather than the Diels–Alder reaction. In addition to 3‐iodocyclohex‐2‐enone 1a and 1b , the reaction was also applicable to other electron‐deficient vinyl iodides such as 3‐iodobutenolides 1c and 1d , producing the corresponding products in good yields (entries 10–13).…”

“…pioneered the Sonogashira coupling‐isomerization reactions for the synthesis of a variety of useful compounds including chalcones, pyrazolines, pyrroles, fluorescent spirocycles, and some other pharmaceutically interesting heterocycles 4. Starting from electron‐deficient vinyl iodides and propargyl ethers, we previously established an interesting palladium‐catalyzed sequential reaction wherein the in situ generated vinylallene intermediate would undergo a Diels–Alder reaction under mild conditions, providing an efficient synthesis of structurally complex polycycles with 2,3‐dihydrofuran units5a and structurally diverse fused dihydroisobenzofuran derivatives 5b. Furthermore, our continuing study led us to an unexpected observation that the involved vinylallene intermediates can also be trapped by an intramolecular Alder‐ene reaction to produce some structurally interesting 2,3‐dihydrofurans, making these reactions an attractive diversity‐oriented approach to access a variety of useful skeletons 5c…”

Synthesis of Carbo- and Heterocycles via Coupling-Isomerization Reactions

“…By variation of the propargyl coupling partner to bispropargyl ethers 63, Huang and co-workers successfully achieved the synthesis of dihydroisobenzofuran derivatives 64 via a CIR-Diels-Alder-aromatization domino sequence (Scheme 26). 55 Likewise, bispropargyl ethers 63 without substituents at either alkynyl termini (R 2 = H) furnished pseudo-threecomponent products 65 by twofold Sonogashira couplings ( Figure 2). Interestingly, only the 3-aryl-substituted moiety participates in the isomerization step to give the propargyloxy allenyl key intermediate required for the Diels-Alder step.…”

Synthesis of Polycyclic Isoindoline Derivatives via Tandem Pd-Catalyzed Coupling, Propargyl–Allenyl Isomerization, [4 + 2] Cycloaddition and Aromatization Reaction

“…Müller et al pioneered the Sonogashira coupling/propargyl–allenyl isomerization reactions for the synthesis of a variety of useful compounds including chalcones, pyrazolines, pyrroles, fluorescent spirocycles, and some other pharmaceutically interesting heterocycles . In this aspect, we previously established a series of sequential reactions wherein an allene intermediate, generated in situ, would undergo cycloaddition reaction under mild conditions, providing an efficient synthesis of structurally complex polycycles with 2,3-dihydrofuran units, structurally diverse fused dihydroisobenzofuran derivatives, and other structurally complex polycycles . We anticipated that this protocol could be further extended to cyclic compounds in a broader dimension.…”