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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
Author(s) -
Barluenga José,
VázquezVilla Henar,
Merino Isabel,
Ballesteros Alfredo,
González José M.
Publication year - 2006
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200501505
Subject(s) - nucleophile , chemistry , regioselectivity , benzofuran , indole test , benzothiophene , medicinal chemistry , reactivity (psychology) , reagent , reaction mechanism , stereochemistry , organic chemistry , catalysis , thiophene , medicine , alternative medicine , pathology
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.