Procedure:  500 mL 1-neck flask, stirbar, septum, N₂ inlet

                  Dissolved 4.078 g of acid I in 150 mL of dry THF.  Stirred; cooled to 0 C.  Slowly added 85 mL of 1.0 M borane in THF.  Vigorous bubbling was observed.  After addition, the bath was removed and the reaction mixture was allowed to warm to rt.  After 45 min, TLC (50:50 EtOAc-hexanes, I₂) showed product spot at Rf 0.29.  The reaction mixture was carefully quenched with 50 mL of water, concentrated by rotary evaporation to ~75 mL and extracted with EtOAc.  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 Et₂O as eluant.  The product was a clear, colorless oil. 

 

¹H NMR (CDCl₃, 300 MHz) d 3.70 (t, J = 6.0 Hz, CH₂OH, 2H), 2.91 (m, CH₂s, 4H), 2.77 (m, CH₂, 2H), 2.05 (m, CH₂, 2H), 1.85 (m, CH₂, 2H), 1.65-1.54 (m, CH₂s, 4H).

 

notes

 

The first step in the reaction has been established to be the formation of a triacyloxyborane formed by the addition of three equivalents of acid to one equivalent of borane (see a) Brown, H.C.; Heim, P.; Yoon, N.M.  J. Am Chem. Soc.  1970, 92, 1637.  b) Yoon, N.M.; Pak, C.S.; Brown, H.C.; Krishnamurthy, S.; Stocky, T.P.  J. Org. Chem.  1973, 38, 2786). 

 

Two additional equivalents of borane are required to complete the reduction of the acid to the trialkoxyboroxine.  Upon hydrolysis with water the alcohol is liberated along with the formation of trihydroxyborane. 

 

Carboxylic acids can be selectively reduced with borane in the presence of many other functional groups such as alkyl and aryl nitro, sulfone, sulfide, disulfide, tosyl, and alkyl and aryl halides.  The rate of reduction is not infuenced by bulky groups alpha to the carboxyl group, however, electron withdrawing substituents in this position will tend to decrease rates.