One-pot synthesis of metalated pyridines from two acetylenes, a nitrile, and a titanium(II) alkoxide

Ryoichi Tanaka; Akio Yuza; Yuko Watai; Daisuke Suzuki; Yuuki Takayama; Fumie Sato; Hirokazu Urabe

doi:10.1021/ja050261e

One-pot synthesis of metalated pyridines from two acetylenes, a nitrile, and a titanium(II) alkoxide

J Am Chem Soc. 2005 Jun 1;127(21):7774-80. doi: 10.1021/ja050261e.

Authors

Ryoichi Tanaka¹, Akio Yuza, Yuko Watai, Daisuke Suzuki, Yuuki Takayama, Fumie Sato, Hirokazu Urabe

Affiliation

¹ 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.

PMID: 15913367
DOI: 10.1021/ja050261e

Abstract

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.