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. 2010 Feb 5;75(3):897-901.
doi: 10.1021/jo902333y.

A simple and mild synthesis of 1H-isochromenes and (Z)-1-alkylidene-1,3-dihydroisobenzofurans by the iodocyclization of 2-(1-alkynyl)benzylic alcohols

Raffaella Mancuso  1 , Saurabh Mehta, Bartolo Gabriele, Giuseppe Salerno, William S Jenks, Richard C Larock
Affiliations

A simple and mild synthesis of 1H-isochromenes and (Z)-1-alkylidene-1,3-dihydroisobenzofurans by the iodocyclization of 2-(1-alkynyl)benzylic alcohols

Raffaella Mancuso et al. J Org Chem. .

Abstract

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.

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Figures

Figure 1
Figure 1
X-ray Evidence for the Structural Assignment of 1-Alkylidene-1,3-dihydroisobenzofurans
Scheme 1
Scheme 1
Proposed Mechanistic Pathways for the Iodocyclization of 2-(1-Alkynyl)benzylic alcohols (1)
See this image and copyright information in PMC

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