Development and Synthetic Application of Metalative Reppe Reaction

这项研究开发了新的Reppe反应方式，从三种不同的不对称乙苯中得到单一的芳香族化合物作为钛酸酯形式。或者，用腈取代上面的一两个乙炔(S)，我们也发展了氮杂-雷佩反应，生成金属化的吡啶或吡咯作为单一的异构体。此外，通过这些新反应还合成了一些具有生物活性或重要药用价值的化合物。因此，1)由乙烯酯、末端乙炔、二价钛醇盐试剂(Ti(O-i-Pr)_4/2i-PrMgCl(1))和炔丙基溴化物合成了单一异构体的苯基钛化合物。该反应用于首次合成环蝶菌素A和高效合成抗癌药物普拉米星的芳香族部分。2)以乙酰酰胺、末端乙炔、钛试剂1和磺酰基腈为原料合成了α-吡啶基钛化合物。将该反应应用于抗过敏物质苯环七氢吡啶的合成。3)由乙酰胺、末端乙炔、钛试剂1和腈合成了单一的吡啶甲醛异构体。4)以乙炔、腈、钛试剂1和磺酰乙炔为原料合成了α-吡啶基钛化合物。以旋光性腈为起始反应，我们得到了一种旋光活性的环硫唑霉素吡啶单元的高效制备。5)以乙炔、(磺酰氨基)乙炔、钛试剂1和腈为原料合成了氨基吡啶类化合物。6)从不对称的乙炔、钛试剂1和两种不同的氰化物中得到了单一的吡咯甲醛异构体。

This research has developed new styles of the Reppe reaction, which afford single aromatic compounds as a titanated form from three different, unsymmetrical acetylenes. Alternatively, replacing one or two acetylene(s) above with nitriles, we also developed an aza-Reppe reaction, producing metalated pyridines or pyrroles as a single isomer. Moreover, some biologically active compounds or medicinally important compounds were prepared by these new reactions. Thus, 1)benzyltitanium compounds were obtained as a single isomer from acetylenic esters, terminal acetylenes, a divalent titanium alkoxide reagent (Ti(O-i-Pr)_4/2 i-PrMgCl (1)), and propargyl bromides. This reaction was applied to the first synthesis of alcyopterosin A and an efficient synthesis of an aromatic moiety of an anti-cancer agent, pradimicin. 2)α-Pyridyltitanium compounds were obtained as a single isomer from acetylenic amides, terminal acetylenes, the titanium reagent 1, and a sulfonylnitrile. This reaction was applied to the synthesis of an antiallergic substance, benzocycloheptapyridine. 3)Pyridinecarbaldehydes were obtained as a single isomer from acetylenic amides, terminal acetylenes, the titanium reagent 1, and nitriles. 4)α-Pyridyltitanium compounds were obtained as a single isomer from acetylenes, nitriles, the titanium reagent 1, and a sulfonylacetylene. Starting this reaction with optically active nitriles, we attained an efficient preparation of an optically active pyridine unit of cyclothiazomycin. 5)Aminopyridines were obtained as a single isomer from acetylenes, (sulfonylamino)acetylenes, the titanium reagent 1, and nitriles. 6)Pyrrolecarbaldehydes were obtained as a single isomer from unsymmetrical acetylenes, the titanium reagent 1, and two different nitriles.