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

                  Dissolved 13.171 g of I in 200 mL of dry THF.  Stirred; cooled to -78 C.  Added 105 mL of 0.5 M KHMDS in toluene.  After 2 h, 7.0 mL of bromoacetate IV was added and the reaction mixture was stirred overnight as the bath warmed to rt.  After 16 h, TLC (10:90 EtOAc-hexanes, UV) showed product spot at Rf 0.31.  The reaction mixture was quenched with sat. aq. NH₄Cl and 1.0 M HCl was added to lower the pH to ~5.  The mixture was extracted with EtOAc.  The organic layer was dried over MgSO₄, filtered and the solvent was removed by rotary evaporation.  Flash chromatography of the residue on silica gel using 10:90 EtOAc-hexanes as eluant gave a yellow oil which was triturated with cold hexanes to afford the product as a white solid.  HPLC analysis indicated a diastereomeric product ratio of >95:5. 

 

¹H NMR (CDCl₃, 300 MHz) d 7.36-7.26 (m, ArH, 5H), 4.64 (m, oxazolidinone CH, 1H), 4.25 (m, NCOCH, 1H), 4.15 (d, J = 4.9 Hz, ArCH₂, 2H), 3.33 (dd, J = 13.2, 2.7 Hz, COCH₂, 1H), 2.73 (dd, J = 15.4, 9.9 Hz, oxazolidinone CH₂, 2H), 2.48 (dd, J = 16.5, 4.4 Hz, COCH₂, 1H), 1.63-1.28 (m, CH₂CHMe₂, 3H), 1.42 (s, CO₂C(CH₃)₃, 9H), 0.93 (d, J = 5.5 Hz, C(CH₃)₂, 3H), 0.91 (d, J = 6.0 Hz, C(CH₃)₂, 3H). 

 

notes

 

Two things are important to the stereochemical outcome of this reaction.  First, allylic strain in the developing transition state strongly favors formation of the Z-enolate. 

 

Second, attack of the nucleophile from the re face is blocked by the benzyl group of the oxazolidinone due to the chelated intermediate.  Addition to the si face is then strongly preferred. 

 

Sodium hexamethyldisilazide and lithium hexamethyldisilazide can be substituted for KHMDS as was first reported (see Beckett, R.P.; Crimmin, M.J.; Davis, M.H.; Spavaold, Z.  Synlett  1993, 137).