ORGN 272 |
| N-tert-Butoxycarbonyl (Boc)-N-methoxymethyl-α-amino acid derivatives undergo asymmetric α-alkylation in up to 93% ee by treatment with potassium hexamethyldisilazide (KHMDS) followed by alkyl halide without the aid of external chiral sources (memory of chirality). A chiral nonracemic enolate with C-N axial chirality is proposed as the crucial intermediate whose racemization barrier is 16.0 kcal/mol and the corresponding half-life is 22 h at –78 °C. This protocol was applied to intramolecular alkylation of α-amino acid derivatives. We report here an enantiodivergent asymmetric cyclization of N-Boc-N-ω-bromoalkyl-α-amino acid derivatives. With KHMDS in DMF, cyclization proceeds with retention of configuration in up to 98% ee, while inversion of configuration was observed with lithium 2,2,6,6-tetramethylpiperidide (LTMP) in THF in up to 91% ee. Thus, both enantiomers of cyclic amino acids with a tetrasubstituted carbon center were prepared in high enantiomeric purity from readily available L-α-amino acids.
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Asymmetric Syntheis of α-Amino Acids: Novel Developments and Future Directions
1:00 PM-5:40 PM, Monday, March 26, 2007 McCormick Place Lakeside -- Room E350, Level 3, Oral
Division of Organic Chemistry |
