Synthesis of Novel Phosphonoacetates Bearing a Stereogenic Phosphorous Atom and Application to Asymmetric HWE Reaction

在“新型含立体磷原子膦酰乙酸酯的合成及其在不对称HWE反应中的应用”的研究过程中，我们合成了新型的β-立体膦酰乙酸酯。我们还开发了一些新的反应，如不对称Horner-Wadsworth-Emmons（HWE）反应和去共轭酯化反应，以双（2，2，2-三氟乙基）膦酰基乙酸甲酯（一种Z-选择性HWE试剂）为原料，在三乙胺或DBU存在下，与各种醇进行醇解反应，制备了外消旋膦酰基乙酸酯。这些外消旋膦酰基乙酸酯的一些在一个高度有效的方式进行的PL催化动力学拆分，得到新的P-立体膦酰基乙酸酯。一个非对映选择性的HWE反应的P-立体膦酰基乙酸轴承（-）-薄荷醇作为手性助剂提供了相应的四取代烯烃在84%de。此外，我们证明了一种新的非对映选择性HWE反应的合成四取代烯烃的手性轴。以Sn（OSO_2CF_3）_2和N-乙基哌啶为催化剂，研究了不对称4-甲基环己酮与一种新的含O-苄基异曼酰胺的HWE试剂的不对称HWE反应。另一方面，2-环己基乙酸在4-（吡咯烷-1-基）吡啶催化下，以1-乙基-3-（3-二甲氨基丙基）碳二亚胺盐酸盐为偶联试剂进行解偶联酯化反应，得到2-（环己-1-烯基）乙酸异丙酯。而4-（吡咯烷-1-基）吡啶催化下与1，3-二环己基碳二亚胺的酯化反应不发生解偶联反应，得到2-亚环己基乙酸异丙酯，

In the course of studies on "Synthesis of Novel Phosphonoacetates Bearing a Stereogenic Phosphorous Atom and Application to Asymmetric HWE Reaction", we have synthesized novel P-stereogenic phosphonoacetates. We have also developed several new reactions, such as asymmetric Horner-Wadsworth-Emmons (HWE) reactions and deconjugative esterification.Racemic phosphonoacetates were readily prepared from methyl bis(2,2,2-trifluoroethyl)phosphonoacetate, a Z-selective HWE reagent, by alcoholysis with various alcohols in the presence of triethylamine or DBU. PLE-catalyzed kinetic resolution of some of these racemic phosphonoacetates proceeded in a highly effective manner to give the novel P-stereogenic phosphonoacetates. A diastereoselective HWE reaction of a P-stereogenic phosphonoacetate bearing (-)-menthol as a chiral auxiliary afforded the corresponding tetrasubstituted olefin in 84% de.In addition, we demonstrated a novel diastereoselective HWE reaction for the synthesis of tetrasubstituted alkenes with an axis of chirality. An asymmetric HWE reaction of a-symmetric 4-methylcyclohexanone and a novel HWE reagent bearing 0-benzylisoman.nide was investigated by employing Sn(OSO_2CF_3)_2 and N-ethylpiperidine. As a result, a-methyl-a,β-unsaturated ester, a tetrasubstituted alkene with an axis of chirality, was obtained in > 99% de.On the other hand, 4-(pyrrolidin-1-yl)pyridine-catalyzed deconjugative esterification of 2-cyclohexylidineacetic acids afforded isopropyl 2-(cyclohex-1-enyl)acetate by employing 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride as a coupling reagent. Whereas, 4-(pyrrolidin-1-yl)pyridine-catalyzed esterification with 1,3-dicyclohexylcarbodiimide was not accompanied by deconjugation and gave isopropy 2-cyclohexylideneacetate,