Procedure:  15 mL 1-neck flask, stirbar, septum, N₂ inlet

                  Dissolved 0.090 g of I in 4.0 mL of dry CH₂Cl₂.  Stirred; cooled to -78 C.  Added 0.405 mL of a 1.0 M solution of BBr₃ in CH₂Cl₂ dropwise.  The reaction mixture was stirred as the bath was allowed to slowly warm to rt.  After 4 h, TLC showed product spot at Rf 0.15 (5:19 EtOAc-hexanes, UV).  The reaction mixture was then poured into sat. aq. NH₄Cl and extracted with CH₂Cl₂.  The organic layer was dried over MgSO₄, filtered and the solvent was removed by rotary evaporation.  The product was isolated by flash chromatography on silica gel using 10:90 EtOAc-hexanes.  The product was a clear, colorless oil which could be recrystallized from hexanes to give white crystals. 

 

mp 87 C

 

¹H NMR (CDCl₃, 400 MHz) d 7.26 (m, ArH), 4.98 (s, OH), 3.25 (m, H5), 3.00 (m, H8), 2.63 (ddd, J = 17.6, 11.2, 7.3 Hz, H8), 2.53 (s, ArCH₃), 2.39 (s, ArCH₃), 1.95-1.75 (m, H6, H7), 1.20 (d, J = 6.9 Hz, CH₃). 

 

notes

 

This particular reaction is the final step in the total synthesis of Cacalol (see This reaction is reported by Garofalo, A.W.; Litvak, J.; Wang, L.; Dubenko, L.G.; Cooper, R.; Bierer, D.E.  J. Org. Chem.  1999, 64, 3369).

 

The reaction has been shown to proceed as follows. 

 

With aryl alkyl ethers, BBr₃ selectively affords the alkylbromide and aromatic alcohol (see Benton, F.L.; Dillon, T.E.  J. Am. Chem. Soc.  1942, 64, 1128).   Other solvents such as benzene or pentane may be used and it has been suggested that low yields may be caused by poor turnover rates of the reagent and that stoichiometric amounts of BBr₃ may improve the deprotection (see McOmie, J.F.W.; Watts, M.L.; West, D.E.  Tetrahedron  1968, 24, 2289).  It may also be preferable to use additional BBr₃ for substrates containing potentially coordinating functional groups (COOH, NHR, etc.).