Development and Synthetic Application of Metalative Reppe Reaction

本研究开发了一种新型的Reppe反应，将三种不同的不对称乙炔作为钛化形式生成单一芳香化合物。或者，用腈取代上面的一个或两个乙炔，我们也开发了aza-Reppe反应，产生金属化吡啶或吡咯作为单个异构体。此外，这些新反应还制备了一些具有生物活性或药用价值的化合物。因此，由乙炔酯、末端乙炔、二价钛醇氧试剂（Ti（O-i-Pr)_4/2 i-PrMgCl(1)）和丙炔溴作为单一异构体得到1）苄基钛化合物。这一反应被应用于第一次合成紫光色素A，并有效地合成了抗癌剂普拉地米星的芳香部分。2)α-吡啶基钛化合物是由乙炔酰胺、末端乙炔、钛试剂1和磺酰基腈组成的单一异构体。该反应用于合成抗过敏物质苯并环七吡啶。3)由乙炔酰胺、末端乙炔、钛试剂1和腈作为单一异构体得到吡啶乙醛。4)α-吡啶基钛化合物是由乙炔、腈、钛试剂1和磺酰基乙炔组成的单一异构体。从旋光性腈开始反应，我们得到了环噻唑霉素旋光性吡啶单元的有效制备。5)由乙炔、（磺胺）乙炔、钛试剂1和腈作为单一异构体得到氨基吡啶。6)由不对称乙炔、钛试剂1和两种不同的腈作为单一异构体得到了吡啶乙醛。

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.