Table 1. Iodination of Alkanes Using tert-Butyl Hypoiodite at 40 °C
a Isolated yields, isomeric ratios determined by NMR. b A mixture of 1 equiv of Br2, 1 equiv of I2, and 2 equiv of t-BuONa was used, and only iodopentane
was formed. c No 4-iodoheptane was detected.
weak oxygen-iodine bond in 1 can be cleaved photochemi-
cally or thermally to afford the tert-butoxy radical 3. The
fragmentation of the tert-butoxy radical 3 into acetone and
a methyl radical is also known but this does not compete
with the fast abstraction of hydrogen atoms by 3 from
alkanes.14 We adopted the most simple protocol for the
generation of tert-butyl hypoiodite, the reaction between
sodium tert-butoxide and iodine.15 The generation of tert-
butyl hypoiodite is performed in an excess of the alkane
(concentration: 0.05-0.1 m). The alkane is then iodinated
under very mild reaction conditions at 40 °C for several
hours. The hydrogen-abstracting radical 3 or 4 is formed by
thermal decomposition of the precursor 1/2 at this temper-
ature. The alkyl radical then abstracts an iodine atom from
1/2 or recombines with an iodine radical to form the
iodoalkanes. Even extremely unreactive n-alkanes (5-7) can
be converted into the corresponding alkyl iodides and the
products can be separated from excess alkane and purified
by simple distillation. The yields obtained using this method
of an in situ generation of tert-butyl hypoiodite 1 are higher
than using other methods. When 1 is synthesized from tert-
butyl hypochlorite and HgI2, cyclohexane is iodinated in 51%
yield using 1,1,2-trichlorotrifluoroethane (Freon 113) as
solvent (iodination of toluene: 34%). These reactions were
only carried out on a 1 mmol scale under photochemical
conditions.6,11 By our method of in-situ generation of 1 we
obtain iodocyclohexane in 85% and benzyliodide in 50%
yield on a 20 mmol scale (Table 1, entries 6 and 8).16
Different metal alkoxides, such as sodium methoxide,
sodium ethoxide, potassium tert-butoxide, and sodium
(7) Barluenga, J.; F. Gonza´lez-Bobes, F.; Gonza´lez, J. M. Angew. Chem.
2002, 114, 2668; Angew. Chem., Int. Ed. 2002, 41, 2556.
(8) (a) Schreiner, P. R.; Lauenstein, O.; Butova, E. D.; Fokin, A. A.
Angew. Chem. 1999, 111, 2956; Angew. Chem., Int. Ed. 1999, 38, 2786.
(b) Lauenstein, O.; Fokin, A. A.; Schreiner, P. R. Org. Lett. 2000, 2, 2001.
(c) Fokin, A. A.; Lauenstein, O.; Gunchenko, P. A.; Schreiner, P. R. J.
Am. Chem. Soc. 2001, 123, 1842. (d) Schreiner, P. R.; Lauenstein, O.;
Butova, E. D.; Gunchenko, P. A.; Kolomitsin, I. V.; Wittkopp, A.; Feder,
G.; Fokin, A. A. Chem. Eur. J. 2001, 7, 4996. (e) Kimura, T.; Fujita, M.;
Sohmiya, H.; Ando, T. Ultrason. Sonochem. 2002, 9, 205.
(9) Akhrem, I.; Orlinkov, A.; Vitt, S.; Chistyakov, A. Tetrahedron Lett.
2002, 43, 1333.
(10) Liguori, L.; Bjørsvik, H.-R.; Bravo, A.; Fontana, F.; Minisci, F.
Chem. Commun. 1997, 1501.
(11) Tanner, D. D.; Gidley, G. C.; Das, N.; Rowe, J. E.; Potter, A. J.
Am. Chem. Soc. 1984, 106, 5261.
(12) Hartung, J.; Gottwald, T.; Spehar, K. Synthesis 2002, 1469.
(13) Amey, R. L.; Martin, J. C. J. Am. Chem. Soc. 1979, 101, 3060.
(14) (a) Batt, L.; Hisham, M. W. M.; Mackay, M. Int. J. Chem. Kinet.
1989, 21, 535. (b) Fittschen, C.; Hippler, H.; Viskolcz, B. Phys. Chem.
Chem. Phys. 2000, 2, 1677.
(16) Representative Procedure. Iodocyclohexane 9a: Iodine (5.08 g,
20 mmol) was dissolved in cyclohexane (220 mL, 2 mol), and sodium tert-
butoxide (1.92 g, 20 mmol) was added. The suspension was stirred at 40
°C for 15 h. The mixture was washed with 0.2% aq Na2S2O3 (60 mL) and
dried over MgSO4. The solvent was removed under reduced pressure and
the residue distilled to yield iodocyclohexane 9a (3.55 g, 84%) as a colorless
liquid. All reaction products were identified by GC/MS and NMR analysis
and were found to be identical to published data.
(15) Akhtar, M.; Barton, D. H. R. J. Am. Chem. Soc. 1964, 86, 1528.
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Org. Lett., Vol. 5, No. 24, 2003