Tanaka Ryoichi, Yuza Akio, Watai Yuko, Suzuki Daisuke, Takayama Yuuki, Sato Fumie, Urabe Hirokazu
Department of Biological Information, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259-B-59 Nagatsuta-cho, Midori-ku, Yokohama, Kanagawa 226-8501, Japan.
J Am Chem Soc. 2005 Jun 1;127(21):7774-80. doi: 10.1021/ja050261e.
Four-component coupling process involving two acetylenes, a nitrile, and a divalent titanium alkoxide reagent, Ti(O-i-Pr)(4)/2i-PrMgCl, directly yielded titanated pyridines in a highly selective manner. The reaction can be classified into four categories: (i) a combination of an internal acetylene, a terminal acetylene, sulfonylnitrile, and the titanium reagent to yield alpha-titanated pyridines, (ii) a combination of an internal acetylene, a (sulfonylamino)acetylene, a nitrile, and the titanium reagent to yield alternative alpha-titanated pyridines, (iii) a combination of an internal acetylene, a (sulfonylamino)acetylene, a nitrile, and the titanium reagent to yield titanated aminopyridines, and (iv) a combination of an acetylenic amide, a terminal acetylene, a nitrile, and the titanium reagent to yield pyridineamides with their side chain titanated. Some of these reactions enabled virtually completely regioselective coupling of two different, unsymmetrical acetylenes and a nitrile to form a single pyridine. Synthetic applications of these reactions have been illustrated in the preparation of optically active pyridines and medicinally useful compounds.
涉及两个乙炔、一个腈和二价钛醇盐试剂Ti(O-i-Pr)(4)/2i-PrMgCl的四组分偶联过程以高度选择性的方式直接生成了钛代吡啶。该反应可分为四类：(i) 一个内乙炔、一个端乙炔、磺酰腈和钛试剂的组合，生成α-钛代吡啶；(ii) 一个内乙炔、一个（磺酰氨基）乙炔、一个腈和钛试剂的组合，生成另一种α-钛代吡啶；(iii) 一个内乙炔、一个（磺酰氨基）乙炔、一个腈和钛试剂的组合，生成钛代氨基吡啶；(iv) 一个炔酰胺、一个端乙炔、一个腈和钛试剂的组合，生成侧链被钛化的吡啶酰胺。其中一些反应能够实现两种不同的、不对称的乙炔和一个腈几乎完全区域选择性地偶联以形成单一吡啶。这些反应的合成应用已在光学活性吡啶和药用化合物的制备中得到了说明。
