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Synlett 2006(2): 215-218  
DOI: 10.1055/s-2005-923586
LETTER
© Georg Thieme Verlag Stuttgart · New York

A Convenient Method for in situ Generation of I2 Using CuSO4/NaI and Its Applications to the Deprotection of Acetals, Etherifications and ­Iodolactonizations

Aaron D. Bailey, Steven M. Cherney, Peter W. Anzalone, Erin D. Anderson, Justin J. Ernat, Ram S. Mohan*
Department of Chemistry, Illinois Wesleyan University, Bloomington, Illinois 61701, USA
Fax: +1(309)5563864; e-Mail: rmohan@iwu.edu;
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Publication History

Received 28 September 2005
Publication Date:
23 December 2005 (online)

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Abstract

A convenient method for the in situ generation of I2 using CuSO4/NaI has been developed. The applications of this method to the deprotection of acetals, etherifications and iodolactonizations have been demonstrated. The use of toxic and corrosive molecular iodine is avoided.

Key words

acetals - chemoselectivity - ethers - lactones - iodine

5

In the deprotection of acetals using molecular I2 in acetone (ref. 4), the formation of iodoacetone or disappearance of I2 color was not reported.

6

Typical Procedure for Acetal Deprotection.
A solution of vanillin acetate dimethyl acetal (0.424 g, 1.76 mmol), and NaI (0.159 g, 1.06 mmol, 0.6 equiv) in dry acetone (9.0 mL) was stirred at r.t. under N2 as anhyd CuSO4 (0.169 g, 1.06 mmol, 0.6 equiv) was added. The reaction progress was followed by 1H NMR spectroscopy. After 3 h 25 min, the mixture was suction filtered using a fritted glass funnel and the solids were washed with acetone (5 mL). Then, H2O (25 mL) was added to the filtrate and most of the acetone was removed on a rotary evaporator. The residue was then extracted with Et2O (2 × 20 mL) and the organic layer was then washed with aq 10% Na2S2O3 (10 mL), sat. NaCl (10 mL) and dried (Na2SO4). The organic layer was concentrated on a rotary evaporator to yield 0.268 g (78%) of vanillin acetate as a white solid that was found to be at least 98% pure.

9

Although solid copper waste is produced in this method, the solids are collected by suction filtration and hence easily contained. No toxic aqueous waste stream is generated.

10

Typical Procedure for Iodolactonization.
5-Hexenoic acid (0.140 g, 1.23 mmol) was stirred in H2O (17 mL) at r.t. as solid NaHCO3 (0.206 g, 2.46 mmol, 2 equiv), NaI (0.731 g, 4.91 mmol, 4.0 equiv) and anhyd CuSO4 (0.769 g, 4.91 mmol, 4 equiv) were added sequentially. After 40 min, the mixture was suction filtered. Then, aq 10% Na2S2O3 (25 mL) was added to the filtrate, which was then extracted with Et2O (3 × 10 mL). The combined organic layers were washed with sat. NaCl (25 mL) and dried (Na2SO4). The solvent was removed on a rotary evaporator to yield 0.248 g (84%) of the product as a pale yellow liquid that was determined to be >96% pure by 1H NMR and 13C NMR analysis.