Synthesis of nonracemic dimethyl α-(hydroxyfarnesyl)phosphonates via oxidation of dimethyl farnesylphosphonate with (camphorsulfonyl)oxaziridines
Synthesis of nonracemic dimethyl α-(hydroxyfarnesyl)phosphonates via oxidation of dimethyl farnesylphosphonate with (camphorsulfonyl)oxaziridines
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DOI：
10.1021/jo980984z
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发表时间：
1999-01-22
影响因子：
3.6
通讯作者：
Wiemer, DF
中科院分区：
文献类型：
--
作者：
Cermak, DM;Du, YM;Wiemer, DF
探索了非外消旋α-（羟基法呢基）膦酸二甲酯及其母体膦酸的几种合成策略。通过外消旋α-羟基膦酸酯与（S）-（+）-O-甲基扁桃酸的酯化反应制备的非对映异构体衍生物是可能的，并且这些非对映异构体可以根据文献先例指定为绝对立体化学;然而，水解为α-羟基膦酸伴随着广泛的异构化。将非外消旋的亚磷酰胺加入法呢醛中也得到非外消旋的物质，但水解还是有问题。用非外消旋的（邻磺酰基）氧氮杂环丙烷氧化法呢基膦酸二甲酯阴离子被证明是区域选择性和立体选择性地形成α-羟基膦酸酯。通过将氧化产物转化为它们的（S）-（+）-O-甲基扁桃酸酯衍生物，建立了类似于70%ee的对映体过量。虽然这些甲酯的水解伴随着广泛的外消旋，这两种对映异构体的α-（羟基法呢基）膦酸得到低ee通过这种策略。
Several strategies for synthesis of nonracemic dimethyl alpha-(hydroxyfarnesyl)phosphonate and the parent phosphonic acid have been explored. Separation of diastereomeric derivatives prepared by esterification of racemic a-hydroxy phosphonate with (S)-(+)-O-methylmandelic acid was possible, and these diastereomers could be assigned absolute stereochemistry on the basis of literature precedent; However, hydrolysis to the alpha-hydroxy phosphonic acid was accompanied by extensive isomerization. Addition of a nonracemic phosphonamidite to farnesal also gave nonracemic material, but again hydrolysis was problematic. Oxidation of dimethyl farnesylphosphonate anion with nonracemic (camphorsulfonyl)oxaziridines was shown to be regio- and stereoselective for formation of the a-hydroxy phosphonate. Enantiomeric excess of similar to 70% ee was established by conversion of the oxidation products to their (S)-(+)-O-methylmandelate derivatives. Although hydrolysis of these methyl esters was accompanied by extensive racemization, both enantiomers of alpha-(hydroxyfarnesyl)phosphonic acid were obtained in low ee by this strategy.