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​Iodocyclization of phenyl allyl carbamates; ​Cyclic carbamates

SyntheticPage 299
DOI: 10.1039/SP299
Submitted Sep 04, 2008, published Sep 05, 2008
Mohammed Abid (abid@bwh.harvard.edu)
A contribution from Xudong Huang Group, BWH & Harvard Medical School


			Reaction Scheme: ​Iodocyclization of phenyl allyl carbamates

Chemicals Used

N-allylaniline, sodium hydride, benzyl chloroformate, iodine, tetrahydrofuran, methanol, ethyl acetate, hexane, dichloromethane and sodium sulfate. All the chemicals were purchased from Aldrich as used with any purification.

Procedure

NaH (360 mg, 15 mmol) was placed in a two neck RB flask under nitrogen along with 20 mL of THF. The mixture was cooled to 0oC using an ice bath, N-allylaniline (500 mg, 3.75 mmol) was added dropwise to the above mixture and stirred for 1h. Benzyl chloroformate (704 mg, 4.12 mmol) was added carefully and after complete addition the reaction mixture was warmed to RT and stirred for 4h. The reaction mixture was cooled to 0oC and MeOH (10 mL) added drop-wise. The solvents were evaporated under reduced pressure and residue was extracted in EtOAc, washed three times with water. The organic layer was dried over sodium sulfate and concentrated to give the crude Step I product as a pink oil (600 mg, 2.25 mmol, which was then dissolved in 25 mL of dichloromethane. Iodine crystals (1.7 g, 6.75 mmol) were dissolved in dichloromethane then added dropwise to the above mixture and stirred at RT for 24h. The reaction mixture was transferred to a separating funnel, the organic layer washed with sat. sodium thiosulfate (2 x 50 mL), water (2 x 50 mL) then dried over sodium sulfate and concentrated in vacuo. The crude mixture was subjected to column chromatography (10% EtOAc in hexane) to give the pure product as pale yellow solid (531 mg, 78%).

Author's Comments

The first step can also be performed using benzyl phenylcarbamate and allylbromide under similar reaction conditions.

Data

m.p. 82-84 deg oC, 1H NMR (300.12 MHz, CDCl3) 3.34 (dd, 1H, J = 8.40, 8.10 Hz), 3.43 (dd, 1H, J = 4.50, 3.60 Hz), 3.76 (dd, 1H, J = 6.00, 6.00 Hz), 4.14 (t, 1H, J = 9.0 Hz), 4.69 (m, 1H), 7.52(m, 2H), 7.37(m, 2H), 7.15(m, 1H). 13C NMR(75.46 MHz, CDCl3) 6.26, 50.81, 71.0, 118.2, 124.2, 129.0, 137.6, 153.9, MS(m/z)-303.12

Lead Reference

M. Wang, L. X. Gao, W. P. Mai, A. X. Xia, F. Wang, S. B. Zhang, J. Org. Chem. 2004, 69, 2874 -2876.

Other References

1. V. Blot, V. Reboul, P. Metzner, J. Org. Chem. 2004, 69, 1196 -1201. 2. S. P. Chavan, A. K. Sharma, Tetrahedron Lett. 2001, 42, 4923-4924.

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Keywords: iodine, nucleophilic, carbamates

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