Preparation of α-Aminobenzylphosphonic Acids with a Stereogenic Quaternary Carbon Atom via Microscopically Configurationally Stable α-Aminobenzyllithiums
Preparation of α-Aminobenzylphosphonic Acids with a Stereogenic Quaternary Carbon Atom via Microscopically Configurationally Stable α-Aminobenzyllithiums
复制标题
DOI：
10.1002/chem.200800475
复制
发表时间：
2008-01-01
影响因子：
4.3
通讯作者：
Hammerschmidt, Friedrich
中科院分区：
文献类型：
--
作者：
Kuliszewska, Edyta;Hanbauer, Martin;Hammerschmidt, Friedrich
1-苯基乙胺的对映体用氯代磷酸二乙酯/Et3N进行磷酸化，然后在氮原子上进行Boc保护(Boc=叔丁氧基)。这些磷酰胺通过使用sBuLi/N，‘N’-四甲基乙二胺(TMEDA)来金属化得到α-氨基苯基硫化物，其异构化为α-氨基膦酸酯，产率高达80%，并保留了碳原子上的构型。在Et2O中，中间的叔基有机硫在-78℃到0℃之间在显微镜下是稳定的。用沸腾的6M HCl或最好是Me3SiBr/(烯丙基)SiMe3解封受保护的α-氨基膦酸根，当Boc基团被二乙氧基膦取代时，α-氨基苄基锂中间体甚至在-78℃下也部分对映异构化并重排生成具有50%ee(ee=对映体过量)的α-氨基膦酸根。类似地，从1-(1-萘基)乙基-1-吲哚和1，2，3，4-四氢-1-萘胺或1-叠氮并-1，2，3，4-四氢-1，2，3，4-四氢萘的外消旋体和/或对映体中衍生的N-Boc保护的磷酰胺以较高的产率转化为氨基膦。以氨基甲酸奎宁为固定相的手性离子交换固定相上的高效液相色谱测定，解封后的α-氨基膦酸手性对映体过量(97-99%)。由1，2，3，4-四氢-1-萘胺衍生的外消旋Boc保护的二乙基磷酰胺与LiTMP/TMEDA(TMP=2，2，6，6-四甲基哌啶)反应生成1-羟乙基膦-苯胺酸盐。通过单晶X-射线结构分析确定了主异构体的构型。
The enantiomers of 1-phenyl-ethylamine were phosphorylated with diethyl 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 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 Et2O. The protected alpha-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 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-hydroxyethylphos-phonamidates resulted. The configuration of the main isomer was determined by means of a single-crystal X-ray structure analysis.