Advances in the stereoselective synthesis of antifungal agents and ...

Chapter 2 642.3.1.2.2. Effect of Substitution in the Triarylphosphinemoiety on the Rate of Alcohol Activation.Hughes studied the effect of substitution in the triarylphosphine on therate of alcohol activation and found, as expected, that electron withdrawinggroups, such as chlorine in positions 2 or 4 increase the electrophilicity ofphosphorus. In table 2.1 the relative rates of formation of theoxyphosphonium intermediate A at 0 °C with substituted triarylphosphinesin CH 2 Cl 2 solution are summarized.SubstituentRelative Ratem - Cl 6200p - Cl 3600H 780m - Me 300p - Meo 1Table 2.1 :Effect of substituents on the rate of formation of the oxyphosphonium intermediateA.The strongly desactivating effect of the 4-MeO group suggests that asignificant dπ-pπ overlap may occur between the aryl ring and phosphorusas shown in figure 2.13.PhP - O + CH 3PhFigure 2.13: dπ-pπ overlap2.3.1.2.3. The SN2 Reaction.The final step of the Mitsunobu reaction is the SN2 reaction of theanion A- with the oxyphosphonium intermediate B. Generally the reactionproceeds with complete stereochemical inversion. However, for particularsubstrates, this general rule is not respected, indicating that an SN1component becomes relevant. Another side- and competitive reaction is theE1 elimination that in some cases can become the major reaction.