Diastereoselective and enantiospecific synthesis of γ-substituted α,β-unsaturated nitriles from O-protected allylic cyanohydrins
Diastereoselective and enantiospecific synthesis of γ-substituted α,β-unsaturated nitriles from O-protected allylic cyanohydrins
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DOI：
10.1021/jo060239j
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发表时间：
2006-05-12
影响因子：
3.6
通讯作者：
Sansano, JM
中科院分区：
文献类型：
--
作者：
Baeza, A;Casas, J;Sansano, JM
γ-官能化的α,β-不饱和腈是通过钯或铱催化的与不同亲核试剂的亲核烯丙基取代反应，由α,β-不饱和醛衍生的对映体富集的氰醇-O-磷酸酯和碳酸酯以非对映选择性和对映专一性制备的。描述了二苄胺、苄胺、叠氮化钠、NaOAc、四正丁基乙酸铵（TBAA）、苯酚和N-羟基琥珀酰亚胺的相应钠盐以及亲碳核试剂丙二酸二甲酯钠的适当反应条件。衍生自巴豆醛、(E)-己-2-烯醛、辛-2-烯醛、2-甲基丁-2-烯醛和肉桂醛的不同取代的O-保护氰醇，例如碳酸酯和磷酸酯，被用作烯丙基底物。发生取代时，(E)-γ-官能化腈的构型完全保留，而Z-异构体的构型发生反转。一般来说，氰醇-O-磷酸盐是获得最高 E-非对映选择性的首选材料。当使用脂肪族化合物和肉桂醛衍生物时，二苄胺是在钯或铱催化剂存在下合成 γ-氮化 α,β-不饱和腈的最佳亲核试剂（高达 98% dr）。对于 γ-氧化 α,β-不饱和腈钠或 TBAA 的合成，选择试剂以避免高达 76% dr 的差向异构化。最后，与丙二酸钠的 Tsuji-Trost 反应仅在钯催化下才能进行，反应率高达 70% dr。
gamma-Functionalized alpha,beta-unsaturated nitriles are prepared diastereoselectively and enantiospecifically from enantioenriched cyanohydrin-O-phosphates and carbonates derived from alpha,beta-unsaturated aldehydes, either by palladium or iridium-catalyzed nucleophilic allylic substitution reactions with different nucleophiles. Appropriate reaction conditions for dibenzylamine, benzylamine, sodium azide, NaOAc, tetra-n-butylammonium acetate (TBAA), the corresponding sodium salts of phenol and N-hydroxysuccinimide and the carbonucleophile sodium dimethyl malonate are described. Different substituted O-protected cyanohydrins, such as carbonates and phosphates, derived from crotonaldehyde, (E)-hex-2-enal, oct-2-enal, 2-methylbut-2-enal, and cinnamaldehyde are used as allylic substrates. The substitution takes place with total retention of the configuration for the (E)-gamma-functionalized nitriles and with inversion of the configuration for the Z-isomers. In general, cyanohydrin-O-phosphates are the materials of choice to get the highest E-diastereoselectivity. Dibenzylamine is the best nucleophile for the synthesis of gamma-nitrogenated alpha,beta-unsaturated nitriles in the presence of either palladium or iridium catalysts when aliphatic compounds and cinnamaldehyde derivative are used (up to 98% dr). For the synthesis of gamma-oxygenated alpha,beta-unsaturated nitriles sodium or TBAA the reagents are selected to avoid epimerizations in up to 76% dr. Finally, the Tsuji-Trost reaction with sodium malonate works only under palladium catalysis in up to 70% dr.