Abstract
Inversion of secondary alcohols by the SN2 reaction of a cesium carboxylate with a secondary sulfonate in DMF has been widely used in synthesis.1,2 Because removal of DMF can be difficult, alternate procedures using benzene or toluene as the solvent with 0.5 equiv of 18-crown-6 to solubilize potassium and cesium carboxylates have also been extensively used.3 During our synthesis of dysiherbaine,4 we found that that the SN2 reaction of CsOAc (5 equiv) with crude nitrobenzenesulfonate 1 proceeded cleanly in toluene at reflux for 12 h to give 75−85% of 2 without the use of 18-crown-6.4 Surprisingly, no reaction occurred under the same conditions with pure 1. Since 1 was prepared from the alcohol with nitrobenzenesulfonyl chloride, Et3N, and DMAP in CH2Cl2, we suspected that residual DMAP present in crude 1 was necessary for the SN2 reaction with CsOAc in toluene at reflux. This was confirmed by heating a suspension of CsOAc (5 equiv) in a toluene solution of pure nosylate 1 (0.13 M) and DMAP (0.1 equiv) at reflux for 8 h to give 85% of acetate 2.