A simple and mild synthesis of 1H-isochromenes and (Z)-1-alkylidene-1,3-dihydroisobenzofurans by the iodocyclization of 2-(1-alkynyl)benzylic alcohols.
A variety of iodo-substituted isochromenes, dihydroisobenzofurans, and pyranopyridines are readily prepared in good to excellent yields under mild conditions by the iodocyclization of readily available 2-(1-alkynyl)benzylic alcohols or 2-(1-alkynyl)-3-(hydroxymethyl)pyridines. Reactions are carried out in MeCN at 25 degrees C with 3 equiv of I(2) as the iodine source and NaHCO(3) (3 equiv) as the base. The regiochemical outcome of the reaction strongly depends on the substitution pattern of the starting material. In particular, the 5-exo-dig cyclization mode, leading to dihydroisobenzofurans, is observed in the case of substrates bearing a tertiary alcoholic group, owing to the gem-dialkyl effect, while the 6-endo-dig cyclization mode, leading to isochromene or pyranopyridines, is the usually preferred pathway in the case of substrates bearing a primary or secondary alcoholic group.
Mancuso
Raffaella
R
Dipartimento di Chimica, Università della Calabria, 87036 Arcavacata di Rende (CS), Italy.
Mehta
Saurabh
S
Gabriele
Bartolo
B
Salerno
Giuseppe
G
Jenks
William S
WS
Larock
Richard C
RC
D000466:Alkadienes / Q000138:chemical synthesis* / Q000737:chemistry; D001572:Benzofurans / Q000138:chemical synthesis* / Q000737:chemistry; D001578:Benzopyrans / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D003500:Cyclization; D007455:Iodine / Q000737:chemistry*; D015394:Molecular Structure; D013237:Stereoisomerism
D000466:Alkadienes; D001572:Benzofurans; D001578:Benzopyrans; D007455:Iodine