MECHANISMBoth cyclic and acyclic imides as well as hydrazoic acid (HN3) can be alkylated using the Mitsunobu reaction (see Mitsunobu, O. Synthesis 1981, 1). The reaction generally proceeds with complete inversion of stereochemistry at the alcohol reacting center.
100 mL 1-neck flask, stirbar, septum, N2
Dissolved 0.471 g of alcohol I
in 10 mL of dry THF. Stirred at rt. Added 0.459 g of DEAD followed by 0.695 g of Ph3
P and 0.390 g of phthalimide. After 16 h, TLC (10:90 EtOAc-hexanes, PMA) shows unreacted starting material at Rf 0.35 and product spot at Rf 0.51. Added an additional 0.088 g of phthalimide, 0.184 g of Ph3
P and 0.144 g of DEAD. After 5 h, the solvent was removed by rotary evaporation to give a viscous yellow oil. The product was isolated by flash chromatography on silica gel using 10:90 EtOAc-hexanes as eluant. The product was a clear, pale yellow oil.
1H NMR (CDCl3, 300 MHz) d 7.79 (dd, J = 5.5, 3.1 Hz, ArH), 7.67 (dd, J = 5.5, 3.1 Hz, ArH), 5.69 (m, H2), 5.01 (dd, J = 17.1, 1.4 Hz, trans H1), 4.91 (d, J = 11.0 Hz, cis H1), 4.26 (tt, J = 10.1, 5.3 Hz, H4), 2.78 (m, H3), 2.47 (m, H3), 2.07 (m, H5), 1.71 (m, H5), 1.19 (m, CH2s), 0.84 (bt, J = 6.8 Hz, CH3)