title: Preparation of alpha-aminobenzylphosphonic acids with a stereogenic quaternary carbon atom via microscopically configurationally stable alpha-aminobenzyllithiums.
abstract: The enantiomers of 1-phenylethylamine were phosphorylated with diethyl chlorophosphate/Et(3)N 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 alpha-aminobenzyllithiums that isomerised to alpha-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 degrees C in Et(2)O. The protected alpha-aminophosphonates were deblocked by using boiling 6 M HCl or preferably Me(3)SiBr/(allyl)SiMe(3). When the Boc group was replaced by the diethoxyphosphinyl group, the alpha-aminobenzyllithium intermediate partially enantiomerised even at -78 degrees C and rearranged to yield an alpha-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 alpha-aminophosphonic acids of excellent enantiomeric excess (97-99 %), as determined by means of HPLC on a chiral ion-exchange stationary phase based on quinine carbamate. When racemic Boc-protected diethyl phosphoramidate derived from 1,2,3,4-tetrahydro-1-naphthylamine was metalated with LiTMP/TMEDA (TMP=2,2,6,6-tetramethylpiperidine), 1-hydroxyethylphosphonamidates resulted. The configuration of the main isomer was determined by means of a single-crystal X-ray structure analysis.
authors.affiliation: Department of Organic Chemistry, University of Vienna, Währingerstrasse 38, Vienna, Austria.
authors.forename: Edyta
authors.initials: E
authors.lastname: Kuliszewska
authors.forename: Martin
authors.initials: M
authors.lastname: Hanbauer
authors.forename: Friedrich
authors.initials: F
authors.lastname: Hammerschmidt
mesh_terms: D002244:Carbon / Q000737:chemistry*; D018020:Lithium Compounds / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D063065:Organophosphonates / Q000138:chemical synthesis* / Q000737:chemistry; D013055:Spectrophotometry, Infrared
chemical_list: D018020:Lithium Compounds; D063065:Organophosphonates; D002244:Carbon