The Reaction of o‐Alkynylarene and Heteroarene Carboxaldehyde Derivatives with Iodonium Ions and Nucleophiles: A Versatile and Regioselective Synthesis of 1H‐Isochromene, Naphthalene, Indole, Benzofuran, and Benzothiophene Compounds

Abstract

The reaction of o-alkynylbenzaldehydes 1 with different alcohols, silylated nucleophiles 5, electron-rich arenes 10, and heteroarenes 12 in the presence of the reagent IPy(2)BF(4), at room temperature, gave functionalized 4-iodo-1H-isochromenes 2, 6, 11, and 13 in a regioselective manner. When alkynes 16 and alkenes 19 and 20 were used as nucleophiles, a regioselective benzannulation reaction took place to form 1-iodonaphthalenes 17 and 1-naphthyl ketones 18, respectively. Moreover, the latter process has been adapted to accomplish the synthesis of indole, benzofuran, and benzothiophene derivatives (23, 27, and 28, respectively). The three patterns of reactivity observed for the o-alkynylbenzaldehyde derivatives with IPy(2)BF(4) stem from a common iodinated isobenzopyrylium ion intermediate, A, that evolves in a different way depending on the nucleophile present in the reaction medium. A mechanism is proposed and the different reaction pathways observed as a function of the type of nucleophile are discussed. Furthermore, the reaction of the o-hexynylbenzaldehyde 1 b with styrene was monitored by NMR spectroscopy. Compound III, a resting state for the common intermediate in the absence of acid, has been isolated. Its evolution in acid media has been also tested, thereby providing support to the proposed mechanism.

Highly Selective Electrophile‐Induced Cascade Reactions between o‐Alkynylbenzaldehydes and Styrene Oxides Leading to the Formation of 1‐Naphthyl Ketones

“…[11a] (4) Electrophile-mediated reactions have been reported to give 1-naphthyl ketones of type 14; [11][12][13] however, the present method produces only regioisomers of type 3 ( Figure 3). …”

“…[10] The subsequent paper from the same research group applied this strategy [ for the synthesis of indoles and benzofurans. [11] Pioneering work from the laboratory of Larock revealed that simple molecular iodine can equally be used to synthesize naphthalenes from alkynals and alkenes/alkynes. [12] It should be noted that all these processes are complimentary to the metal-catalyzed process.…”

Six‐Membered Rings with One Oxygen: Pyrylium Ion, Related Systems and Benzo‐Derivatives

“…Finally, aromatization by elimination of HI gives the indoles 110. This proposal is supported by detailed mechanistic and spectroscopic studies that allowed the isolation of analogues of the cationic intermediates 111 and 112 [54].…”

Five‐Membered Heterocycles: Benzofuran and Related Systems

“…Synthesis of different types of substituted benzoheterocycles under metal-free protocols have been developed. The combination of o-alkynylbenzaldehyde derivatives, iodonium ions and alkenes was demonstrated to effectively produce the corresponding benzofurans [66]. The rapid access to benzofurans with interesting di-and tri-substitution patterns and featuring the 2,3-unsubstituted ring motif has been established (Scheme 7.36).…”