BASE-INDUCED DIMERIZATION OF URETHANE-PROTECTED AMINO-ACID - N-CARBOXANHYDRIDES

tert-Butyloxycarbonyl-protected N-carboxanhydrides of amino acids dime rize in the presence of base in aprotic media to form 3,5-dialkyl-2,4- dioxo-1-pyrrolidine analogs. Depending on the nature of the base, diff erent ratios of isomers were obtained. The reaction with lithium bis(t rimethylsilyl)amide lead to one isomer only. After deprotection of the tert-butyloxycarbonyl groups and coupling of (benzyloxycarbonyl)valin e, a homogeneous product was obtained. Reduction with sodium borohydri de again gave a homogeneous product. Nuclear Overhauser enhancement sp ectroscopy and X-ray crystallography identified the stereochemistry in positions 3 and 5 of the pyrolidine as Z. When 1, 8-diazabicyclo[5.4. 0]undec-7-ene was used as the base, the condensation led to a 1:3 rati o of isomers. The major isomer was different from the one obtained wit h lithium bis(trimethylsilyl)amide. The (benzyloxycarbonyl)valine deri vative from this compound was obtained as a 1:1 mixture of isomers, le ading to the conclusion that this condensation product was an enantiom eric mixture of the E isomers. The pure Z isomer from the lithium bis( trimethylsilyl)amide reaction was converted to a mixture of Z and E is omers in a ratio of 1:3 when, treated with 1,8-diazabizycol[5.4.0]unde c-7-ene. The (benzyloxycarbonyl)valine derivative of the E isomer from this conversion was again a 1:1 mixture; therefore, the Z isomer obta ined with lithium bis(trimethylsilyl)amide was believed to have been a n enantiomeric mixture. Several other examples indicated that this rea ction occurred also with other tert-butyloxycarbonyl-protected N-carbo xy-anhydrides.