利用金雞納鹼衍生的一級胺催化劑進行有機不對稱催化反應來建構具有螺環骨架的環己酮衍生物

Abstract

本篇論文主要研究，利用不同的金雞納鹼衍生的催化劑分別進行有機不對稱的共價催化反應與非共價催化反應來建構環己酮衍生物。 第一部分，以 1,3-二茚酮烯類衍生物 50 與,-不飽和酮類 26 進行有機不對稱共價催化反應，建構具有高非鏡像與高鏡像選擇性的螺環骨架的環己酮衍生物 49；此反應可得大於 20:1 的非鏡像異構物比例，產率 61-99%，鏡像超越值 68-99%；且 1,3-二茚酮烯類衍生物 50 可分為 1,3-二茚酮 48 與醛類 36 與 26 進行三組分反應。

第二部分，經由 α,β-不飽和-1,3-雙酮 72 和 (E)-2-氰基-3-苯基丙烯酸乙酯 83 的有機不對稱非共價催化反應，建構具有四級碳的多取代環己酮衍生物 84；此反應得單一非鏡像異構物，產率為 59-98%，鏡像超越值可高達 86%；且起始物 72、83 可與聯胺試劑進行一鍋化反應生成具有吡唑的雙環產物 91。In my thiesis, the cinchona alkaloid derived organocatalysts were utilized for the synthesis of cyclohexanone derivatives via the covalent or non-covalent asymmetric organocatalysis. In the first part, an unprecedented chiral primary amine catalyzed enantioselective method is demonstrated for the synthesis of the thermodynamically less stable trans 2,6-disubstituted spiro cyclohexanones by using 2- alkylidene-1,3-indandiones 50 and α,β-unsaturatedketones 26 as starting material. Both the enantiomeric forms of the trans isomer could be obtained in high yields and excellent enantioselectivities using either of the pseudo enantiomers of the cinchona alkaloid-derived chiral catalyst. Also the 1,3-indandiones 48 and aldehydes 36 can instead of 2- alkylidene-1,3-indandiones 50 to do the three-component reaction.

In the second part, a series of novel cyclohexanone derivatives with a quaternary stereocenter were synthesized via organocatalytic asymmetric double Michael addition of α,β-unsaturated-1,3-diketones 72 to (E)-ethyl 3-aryl 2-cyanoacrylates 83 in high yields and good enantioselectivities along with excellent diastereoselectivity (dr >25:1). The substrates 72 and 83 were further allowed to react with hydrazine hydrate to furnish bicyclic products 91 by one operation.