The demand for new chemicals spanning the fields of health care to materials science combined with the pressure to produce these substances in an environmentally benign fashion pose great challenges to the synthetic chemical community. The maximization of synthetic efficiency by the conversion of simple building blocks into complex targets remains a fundamental goal. In this context, ruthenium complexes catalyze a number of non-metathesis conversions and allow the rapid assembly of complex molecules with high selectivity and atom economy. These complexes often exhibit unusual reactivity. Careful consideration of the mechanistic underpinnings of the transformations can lead to the design of new reactions and the discovery of new reactivity.

A wide variety of diynols containing tertiary, secondary, and primary propargylic alcohols undergo a cycloisomerization reaction to form dienones and dienals in the presence of a catalytic amount of [CpRu(CH(3)CN)(3)]PF(6). The formation of five- and six-membered rings is possible using this methodology. Secondary diynols react to form single geometrical isomeric dienones and -als. Primary diynols undergo a cycloisomerization as well as a hydrative cyclization process. The utility of primary diynol cycloisomerization is demonstrated in a synthesis of (+)-alpha-kainic acid.

[reaction: see text] The chemoselectivity of the ruthenium-catalyzed hydrative diyne cylization is explored in an expeditious synthesis of the tricyclic alkaloids cylindricine C, D, and E.

The cycloisomerization of diyne-ols catalyzed by [CpRu(CH3CN)3]PF6 to 2-vinyl-1-acylcycloalkenes proceeds via a ruthenacyclopentadiene involving initial ionization of the tertiary or secondary alcohol, followed by readdition. In the case of primary alcohols, a competing pathway wherein water first adds would appear to occur. The feasibility of this proposed minor pathway was tested in the reaction of diynes in the presence of water. Quite excitingly, cyclization comcommittant with addition of water to form 1-acylcycloalkenes occurs. This proves to be general process to form five- and six-membered rings. Interestingly, hydrative cyclization of Z-5-decen-2,8-diyne to 1-acetyl-2-ethyl-cyclohexa-1,4-diene occurs without isomerization of the double bonds. Furthermore, the epoxide of the same substrate cyclizes without opening of the strained epoxide. Unsymmetrically substituted diynes cyclize with remarkable chemoselectivity wherein water attacks the less hindered alkynes. beta-branching of any kind gives only a single product. Remarkably, even competing methyl versus ethyl still effects a 2.5:1 selectivity in favoring water addition to the methyl-bearing alkyne. Alcohols can replace water and provide enol ethers. Strong mechanistic evidence suggests two reaction manifolds indeed operate, depending upon the presence of propargyl alcohols and the degree of substitution on the hydroxyl-bearing carbon.

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Metal-catalyzed dimerizations of terminal alkynes have been extensively explored with numerous different metals. [1][2][3] Typically, the products are enynes derived from tail-to-tail or head-to-tail

CpRu(NCCH3)3+PF6- catalyzes the cycloisomerization of diyne-ols to alpha,beta,gamma,delta-unsaturated aldehydes and ketones in good-to-excellent yields. 1-Hydroxy-2,7-diynes and 1-hydroxy-2,8-diynes can be utilized to form highly functionalized five- and six-membered rings, respectively. Tertiary as well as secondary propargyl alcohols are cycloisomerized to a single isomeric product. A wide variety of tether substitution can be tolerated. Even totally unsubstituted tethers can be employed, as geminal disubstituents are not required for cyclization. Additional hydroxyl substituents at an alternative "internal" propargylic position are eliminated during the reaction-a feature that leads to a convenient cyclopentadiene synthesis. Furthermore, 3-hydroxy-1,6-diynes also can be cyclized to form cross-conjugated aldehydes.

A novel route to the neuroexcitatory amino acid, kainic acid, is developed. The key concept derives from a ruthenium-catalyzed cycloisomerization of a tethered alkyne-propargyl alcohol to form a cyclic 2-vinyl-1-acyl compound. A single stereocenter introduced by an asymmetric reduction of a ketone sets the stage for all the other stereocenters. A novel 1,6-addition of silyl cuprate serves to install a hydroxyl group at the diene termines. [reaction: see text]