| |
[摘要]：The enantiomers of 1-phenyl-ethylamine were phosphorylated with di-Et chlorophosphate/Et3N and then Boc-protected (Boc = tert-butoxycarbonyl) at the nitrogen atom. These phosphoramidates were metalated by using sBuLi/N,N,N',N'-tetramethylethylenediamine (TMEDA) to give a-aminobenzyllithiums that isomerized to a-aminophosphonates in yields of up to 80% with retention of the configuration at the carbon atom. The intermediate tertiary organolithiums were found to be microscopically configurationally stable from -78 to 0癈 in Et2O. The protected a-aminophosphonates were deblocked by using boiling 6M HCl or preferably Me3SiBr/(allyl)SiMe3. When the Boc group was replaced by the diethoxy-phosphinyl group, the a-aminobenzyl- lithium intermediate partially enantiomerized even at -78癈 and rearranged to yield an a-aminophosphonate with 50% ee (ee = enantiomeric excess). Similarly, N-Boc-protected phosphoramidates derived from racemates and/or enantiomers of 1-(1-naphthyl)ethyl-, 1-indanyl- and 1,2,3,4-tetrahydro-1-naphthylamine or 1-azidoindan- and 1-azido-1,2,3,4-tetrahydronaphthalene were converted to aminophosphonates in good yields. Deblocking gave a-aminophosphonic acids of excellent enantiomeric excess (97-99%), as detd. by means of HPLC on a chiral ion-exchange stationary phase based on quinine carbamate. When racemic Boc-protected di-Et phosphoramidate derived from 1,2,3,4-tetrahydro-1-naphthylamine was metalated with LiTMP/TMEDA (TMP = 2,2,6,6-tetraethylpiperidine), 1-hydroxyethylphosphonamidates resulted. The configuration of the main isomer was detd. by means of a single-crystal X-ray structure anal. |
|
