Coupling of acetylene, nitrile, and a titanium reagent, Ti(O-i-Pr)(4)/2 i-PrMgCl, generated new azatitanacyclopentadienes in a highly regioselective manner. Their subsequent reaction with sulfonylacetylene afforded pyridyltitanium compounds, which, upon reaction with electrophiles, gave substituted pyridines virtually as a single isomer. When optically active nitriles were used in this reaction, chiral pyridines were obtained without loss of the enantiopurity. Alternatively, the azatitanacyclopentadiene prepared from an unsymmetrical acetylene reacted with an aldehyde or another nitrile to give furans or pyrroles having four different substituents again in a regioselective manner.

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.

Reactions of organo-metal compoundsO 0350 Facile Preparation of Various Heteroaromatic Compounds via Azatitanacyclopentadiene Intermediates. -Polysubstituted pyridines, furans, and pyrrolecarboxaldehydes are available. The reaction is highly regioselective. Starting from chiral nitriles, convenient synthesis of optically active pyridines is possible. -(SUZUKI, D.; NOBE, Y.; WATAI, Y.; TANAKA, R.; TAKAYAMA, Y.; SATO*, F.; URABE, H.; J. Am. Chem. Soc. 127 (2005) 20, 7474-7479; Dep. Biomol. Eng., Fac. Biosci. Biotechnol., Tokyo Inst. Technol., Midori, Yokohama 226, Japan; Eng.) -Jannicke 40-075

Alkoxide. -(TANAKA, R.; YUZA, A.; WATAI, Y.; SUZUKI, D.; TAKAYAMA, Y.; SATO*, F.; URABE*, H.; J. Am. Chem. Soc. 127 (2005) 21, p7774-p7780; Dep. Biomol. Eng., Fac. Biosci. Biotechnol., Tokyo Inst. Technol., Midori, Yokohama 226, Japan; Eng.) -Mischke 42-156

Alkoxide. -After quenching with electrophilic agents, a wide range of pyridine derivatives is obtained in good yields. The coupling is determined by the presence or absence of leaving groups in the acetylene or nitrile substrates. Good regioselectivities are achieved in the case of unsymmetrical acetylenes (to be continued). -(TANAKA, R.; YUZA, A.; WATAI, Y.; SUZUKI, D.; TAKAYAMA, Y.; SATO*, F.; URABE*, H.; J. Am. Chem. Soc. 127 (2005) 21, 7774-7780; Dep. Biomol. Eng., Fac. Biosci. Biotechnol., Tokyo Inst. Technol., Midori, Yokohama 226, Japan; Eng.) -Mischke 42-155