By means of a systematic approach, several green solvent candidates were tested for their feasibility to replace the reprotoxic dimethylformamide (DMF) as a solvent used in solid-phase peptide synthesis (SPPS). According to the results presented in this paper, it is clear that N-butylpyrrolidinone (NBP) is the best green solvent candidate to replace DMF in SPPS.

A number of N-acryloyl-, N-crotonoyl-, N-(3,3,3-trifluorocrotonoyl)-, N-cinnamoyl-, and N-(3-nitroacryloyl)-4-isopropyl-or -4-phenyl-oxazolidin-2-ones with geminal diphenyl substitution, i.e., 7 -15, have been prepared and used for conjugate additions of organocuprate reagents (Me, i Pr, Ph, 4-MeOPh) in the b-carbonyl ( Table 2) and in the a-carbonyl position (NO 2 -derivative 11 in Scheme 3). The yields and diastereoselectivities are compared with previously tested enoyl-oxazolidinones ( Table 2). Highest diastereoselectivities (> 90%) are always observed with the 4-Ph derivatives (Hruby effect). Nitroacryloyl-oxazolidinones and a corresponding phenylmenthol ester undergo less diastereoselective additions (Scheme 3). A 3-(1-methylethyl)-5,5-diphenyloxazolidin-2-one (DIOZ)-derived Li 2 -enolatenitronate was also tested for a-carbonyl alkylation (Scheme 4). The X-ray crystal structures of three acryloyl-oxazolidinones and of four adducts are described (Tables 1 and 3), and they serve for configurational assignments and description of the stereochemical courses of the additions and alkylation. Possible applications of the nitro compounds for the preparation of b 2 -amino acids are discussed (Scheme 2).