L-脯胺酸衍生物之含銅催化劑對2-萘酚及其衍生物的不對稱氧化偶合反應

Abstract

本研究以L-脯胺酸作為起始物，設計並合成一個具有掌性中心的含氮二牙配位基((S)-2-Diphenylmethyl-1-pyrrolidinyl)methyl pyridine (DPPP)，藉由DPPP與Cu(OTf)2 於存有NaOMe 的甲醇溶液下反應，可得到一個二價銅錯合物[Cu2(DPPP)2(OH)2](OTf)2 (1)，並利用X-ray 繞射結構解析鑑定錯合物1 的幾何結構，為具有氫氧基架橋之雙核銅中心的分子結構，且每個銅金屬配位一個DPPP 配位基，形成平面四邊形的配位環境，兩個銅離子間的距離為2.937 Å 。以錯合物1 當作催化劑對3-羥基-2-萘甲酯進行氧化偶合反應，僅獲得少量的偶合產物。為了改進銅錯合物的催化能力，於是將DPPP 修飾為一個含氮三牙配位基(S)-N-phenyl-1-(pyridin-2-ylmethyl)pyrrolidine-2-carboxamide (HPPPC)，藉由HPPPC 與CuCl2 反應可成功地合成出二價銅錯合物Cu(HPPPC)Cl2 (2)與Cu(PPPC)Cl (3)，以X-ray 繞射結構解析兩者的幾何結構，可知錯合物2的配位環境為四方角錐體，而錯合物3 則為平面四邊形。使用PPPC- (10 mol%)與Cu(OTf)2 (10 mol%)當作催化劑，並加入有機鹼(10 mol%)，可進行2-萘酚的氧化偶合反應，產率可達81%，相同的催化劑亦可進行3-羥基-2-萘甲酯的氧化偶合反應，若是使用HPPPC 與Cu(OTf)2 當作催化劑並添加有機鹼，卻僅能進行2-萘酚的氧化偶合反應。

A bidentate chiral ligand, ((S)-2-Diphenylmethyl-1-pyrrolidinyl)methyl pyridine (DPPP) derived from L-proline, was designed and prepared. Reaction of Cu(OTf)2 with DPPP in MeOH in the presence of NaOMe gave a copper(II) complex, [Cu2(DPPP)2(OH)2](OTf)2 (1). The molecular structure of complex 1 determined by X-ray crystallography revealed a dinuclear copper core bridged by two hydroxide groups with a distance between the copper centers at 2.937 Å and each copper center coordinated with a DPPP ligand, forming a square planar geometry. Unfortunately, complex 1 can only catalyze the oxidative coupling reaction of methyl 3-hydroxy-2-naphthoate in low yield. In order to enhance the catalytic ability of the copper complexes, DPPP was modified to a tridentate ligand, (S)-N-phenyl-1-(pyridin-2-ylmethyl)pyrrolidine-2-carboxamide (HPPPC). Reaction of HPPPC with CuCl2 provided copper(II) complexes, Cu(HPPPC)Cl2 (2) and Cu(PPPC)Cl (3). Complexes 2 and 3 were determined by X-ray crystallography and their geometries were square pyramidal and square planar, respectively. When PPPC- (10 mol%) and Cu(OTf)2 (10 mol%) were used as a catalyst in presence of organic base (10 mol%), the oxidative coupling reaction for 2-naphthol was in 81% yield. The same oxidative coupling reaction for methyl 3-hydroxy-2-naphthoate can also be catalyzed by the same catalytic system. However, when HPPPC and Cu(OTf)2 were used as a catalyst in presence of organic base, the oxidative coupling reaction only occurred for 2-naphthol.