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Preparation of α‐Aminobenzylphosphonic Acids with a Stereogenic Quaternary Carbon Atom via Microscopically Configurationally Stable α‐Aminobenzyllithiums
Author(s) -
Kuliszewska Edyta,
Hanbauer Martin,
Hammerschmidt Friedrich
Publication year - 2008
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200800475
Subject(s) - stereocenter , chemistry , enantiomer , medicinal chemistry , asymmetric carbon , stereochemistry , organic chemistry , enantioselective synthesis , optically active , catalysis
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 s BuLi/ N , N , N′ , N′ ‐tetramethylethylenediamine (TMEDA) to give α‐aminobenzyllithiums that isomerised to α‐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 °C in Et 2 O. The protected α‐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 α‐aminobenzyllithium intermediate partially enantiomerised even at −78 °C and rearranged to yield an α‐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 α‐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.