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

• Published in: Chemistry – A European Journal
• Main Authors: Barluenga, José, Vázquez‐Villa, Henar, Merino, Isabel, Ballesteros, Alfredo, González, José M.
• Format: Article in Journal/Newspaper
• Language: English
• Published: Wiley 2006
• Subjects: IPY
• Online Access: http://dx.doi.org/10.1002/chem.200501505; https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fchem.200501505; https://onlinelibrary.wiley.com/doi/full/10.1002/chem.200501505

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‐1 H ‐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.