利用一價銠金屬催化α-重氮-β,γ-不飽和酯類化合物與苯胺化合物進行高度鏡像及區域選擇之不對稱加成反應

Abstract

本篇論文論述利用一價銠金屬與掌性雙環[2.2.2]雙烯配基L1c、L1f形成錯合物後，催化環狀α-重氮-β,γ-不飽和酯類化合物11或是鏈狀α-重氮-β,γ-不飽和酯類化合物8，形成銠金屬碳烯(rhodium carbenoid)中間體，再使含氮親核試劑9進行具有位向選擇性的不對稱加成反應。反應成功地合成出一系列具有掌性中心之環狀γ-胺基α,β-不飽和酯類化合物12，產率為16–55%，鏡像超越值為26–91%；及鏈狀γ-胺基α,β-不飽和酯類化合物10，產率為9–60%，鏡像超越值為84–>99.5%。將具有掌性中心的γ胺基α,β-不飽和乙酯化合物10hb經由數步反應後，可合成出β位具有取代基的γ胺基酸-普瑞巴林衍生物101。

This thesis describes the regioselective and enantioselective of rhodium(I)-catalyzed asymmetric N-H insertion reaction of α-diazo β,γ-unsaturated esters 11, 8 with anilines 9. In presence of 3.0 mol % Rh (I)-catalyst in situ generated from [RhCl(C2H4)2]2 and chiral bicyclo [2.2.2] octadiene ligand L1c, L1f . The reaction was afforded enantiorich regid γ-amino α,β-unsaturated esters 12 in 16–55% yield with 26–91% ees and linear γ-amino α,β-unsaturated esters 10 in 9–60% yield with 84–>99.5% ees. Synthesis of pregabalin derivative 101 was performed to prove feasibility of this method.