| Abstract: | The extent of racemization under various circumstances is reported for the coupling of the N-protected model dipeptide Z-Gly-Phe to Val-OMe, mediated by N,N'-bis(2-oxo-3-oxazolidinyl)phosphinic chloride (BOC-Cl). BOP-Cl can be used for peptide syntheses either in a one-pot reaction or with preactivation. Maximum yields are obtained with 1.2 equiv. BOP-Cl and 1.2–1.5 equiv. amino-nucleophile and 2.2 equiv. mediatorial base in tetrahydrofuran, but the amount of stereomutation is only tolerable with the use of suppressors (4–6%). BOP-Cl/ HOBt (88% yield, 0% racemization) and BOP-Cl/imidazole (96% yield, 1.6% racemization) are the best choices in apolar solvents and HOBt is to be preferred in DMF (89% yield, 2.4% racemization). Most other additives, HOSu, NP, Pfp, ZnCl2, DMAP, etc., are not good suppressors. |
