銠金屬(I)/掌性雙烯配體催化芳基硼酸至4-酮基丁烯醯胺化合物行不對稱1,4加成反應

Abstract

本論文敘述以2莫耳百分比的一價銠金屬 (Rh) 與掌性雙烯配位基(chiral- diene ligand) 所形成的金屬錯合物，在最佳化條件下(24 °C，乙醇為溶劑，KHF2(aq)為添加劑)，催化芳基硼酸進行不對稱1,4-加成反應至(E)-1-嗎啉基-4-芳基丁烯-1,4-二酮 (16a)。可得一系列具有掌性中心的2-芳基-4-酮基丁醯胺產物，其產率最高可至99%，鏡像超越值最高也可達99.5%。 在合成應用上，以加成產物 18a作為起始物合成出α位置上為掌性四級碳中心的內酯46。此反應過程經由以NaBH4進行還原反應； 2) 酸性條件下環化成內酯，得其非鏡像異構物比例為2比1的一對非鏡像異構物45a及45b ; 3) 烷化步驟中合成出具有掌性四級碳中心的內酯46及其鏡像異構物ent-46。

This thesis describes the preparation of chiral 2,4-diaryl-4-oxobutanamindes from asymmetric conjugate addition reaction of various arylboronic acids to (E)-1-morpholino-4-arylbut-2-ene-1,4-dione 16. In the presence of 2 mol% of chiral rhodium catalyst comprising of [RhCl(C2H4)2]2 and chiral diene ligand 12e, the catalytic reaction proceeds in a high diastereoselective fashion to provide the corresponding adducts 18 with a C2-stereogenic center in up to 99% yield and >99.5% ee in EtOH using KHF2(aq) as an additive. In the synthetic application, compound 18a was transformed into enantiomeric isomers bearing a quaternary chiral center at the α–position of lactone compound 46. The sequence of the transformation involves 1) reduction of compound 18a with NaBH4; 2) the resulting diastereomeric isomers, with an approximate ratio of 2:1, were subjected to acid-catalyzed translactonization to yield 45a and 45b, respectively; 3) respective treatment of compound 45a and 45b with LDA at −78 °C and followed by MeI offered lactone 46 and its enantiomer ent-46.