Organocatalytic Stereoisomerization versus Alkene Isomerization: Catalytic Asymmetric Synthesis of 1-Hydroxy-trans-2,5-diphenylphospholane 1-Oxide
Organocatalytic Stereoisomerization versus Alkene Isomerization: Catalytic Asymmetric Synthesis of 1-Hydroxy-trans-2,5-diphenylphospholane 1-Oxide
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有机催化立体异构化与烯烃异构化：1-羟基-反式-2,5-二苯基磷杂环戊烷 1-氧化物的催化不对称合成
DOI：
10.1055/s-0032-1316835
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
P. Naumov
中科院分区：
文献类型：
--
作者：
L. Hintermann;M. Schmitz;O. V. Maltsev;P. Naumov
研究了有机催化不对称立体异构化或烯烃异构化作为具有最小结构变化的原子经济反应的潜力。 1,4-二芳基丁-1,3-二烯与(二烷基氨基)二氯膦和三氯化铝的 McCormack 环加成反应得到内消旋-2,5-二芳基-1-(二烷基氨基)-1-氧代-2,5-二氢-1H-膦，其被认为是不对称异构化的合适底物 在双功能有机催化剂（金鸡纳生物碱、竹本催化剂）存在下，(1R,5R)-2,5-二芳基-1-(二烷基氨基)-1-氧代-4,5-二氢-1H-磷化合物的 ee 和定量收率高达 91%。研究了底物范围和催化机理。该反应涉及碱基夺取质子，但不存在初级氘 KIE。富集的(1R,5R)-1-(二乙氨基)-1-氧代-2,5-二苯基-4,5-二氢-1H-磷酯被水解为(5R)-1-羟基-1-氧代-2,5-二苯基-4,5-二氢-1H-磷酯，其在溶解金属条件下非对映选择性氢化，得到 (2R,5R)-1-羟基-1-氧代-2,5-二苯基磷杂环戊烷（菲奥德酸）优选 tomeso-1-羟基-1-氧代-2,5-二苯基磷杂环戊烷。 Fiaud’s酸是手性磷杂环戊烷合成的基础材料，通过镍催化的Wenkert芳基化、McCormack环加成、不对称二氢-1H-磷杂环戊烷异构化、水解和非对映选择性氢化，以噻吩为原料，通过五个步骤实现了Fiaud’s酸的不对称催化全合成。
The potential for an organocatalytic asymmetric stereoisomerization or alkene isomerization as atom-economic reaction with minimal structural change was investigated. The McCormack cycloaddition of 1,4-diarylbuta-1,3-dienes with (dialkylamino)dichlorophosphane and aluminum trichloride givesmeso-2,5-diaryl-1-(dialkylamino)-1-oxo-2,5-dihydro-1H-phospholes, which were identified as suitable substrates for asymmetric isomerization to (1R,5R)-2,5-diaryl-1-(dialkylamino)-1-oxo-4,5-dihydro-1H-phospholes in the presence of bifunctional organocatalysts (cinchona alkaloids, Takemoto catalyst) in up to 91% ee and quantitative yield. The substrate range and the mechanism of the catalysis were studied. The reaction involves proton abstraction by the base, but a primary deuterium KIE is absent. Enriched (1R,5R)-1-(diethylamino)-1-oxo-2,5-diphenyl-4,5-dihydro-1H-phosphole was hydrolyzed to (5R)-1-hydroxy-1-oxo-2,5-diphenyl-4,5-dihydro-1H-phosphole, which was hydrogenated diastereoselectively under dissolving metal conditions to give (2R,5R)-1-hydroxy-1-oxo-2,5-diphenylphospholane (Fiaud’s acid) in preference tomeso-1-hydroxy-1-oxo-2,5-diphenylphospholane. An asymmetric catalytic total synthesis of Fiaud’s acid, which is a building block for chiral phospholane synthesis, has been realized in five steps from thiophene, using nickel-catalyzed Wenkert arylation, McCormack cycloaddition, asymmetric dihydro-1H-phosphole isomerization, hydrolysis, and diastereoselective hydrogenation.