Ruthenium-catalyzed activation of DNA-binding compounds in aqueous buffers and in cellular environments.

The reactivity of the dihydrides MH 2 Cl 2 (P i Pr 3 ) 2 (M = Os (1), Ru (2)) toward allenes has been studied. Complex 1 reacts with 2 equiv of 3-methyl-1,2-butadiene and 1-methyl-1-(trimethylsilyl)allene to give 1 equiv of olefin and the π-allene derivatives OsCl 2 (η 2 -CH 2 dCdCRMe)(P i Pr 3 ) 2 (R = Me (3), Me 3 Si (4)). The X-ray structure of 4 proves the coordination to the metal center of the carbon-carbon double bond of the allene with the lowest steric hindrance. In toluene, complexes 3 and 4 are unstable and evolve into the hydride-alkenylcarbyne derivatives OsHCl 2 (tCCHdCRMe)(P i Pr 3 ) 2 (R = Me (5), Me 3 Si ( 6)). DFT calculations on the model compound OsCl 2 (η 2 -CH 2 dCdCMe 2 )(PMe 3 ) 2 (3t) suggest that the π-allene to hydride-alkenylcarbyne transformation involves the migration of both hydrogen atoms of the CH 2 group of the allene. The first of them occurs between the terminal and central carbon atoms and takes place throught the metal center. The second one is a 1,2-hydrogen shift from the allene terminal carbon to osmium. The reactions of the ruthenium complex 2 with the previously mentioned allenes give olefins and RuCl 2 (η 2 -CH 2 dCdCRMe)(P i Pr 3 ) 2 (R = Me (7), Me 3 Si ( 8)), which in dichloromethane and in the presence of allene afford the disubstituted vinylidene complexes RuCl 2 (dCdCRMe)(P i Pr 3 ) 2 (R = Me (9), Me 3 Si ( 10)). The structure of 10 in the solid state has been determined by X-ray diffraction analysis. DFT calculations show that the formation of 9 and 10 can be rationalized in terms of the initial isomerization of 7 and 8 to alkenylcarbene species, which subsequently undergo metathesis reactions with a second allene molecule.

Readily accessible hex-5-ynylidenecyclopropane derivatives cycloisomerize to bicyclic five-membered carbocycles upon heating with catalytic amounts of a palladium complex.

A new method for the generation of oxidopyrylium zwitterions has been developed that allows for its use in the [5 + 2] cycloaddition of substrates incorporating thermally unstable functionalities, providing for the synthesis of previously inaccessible precursors to tiglianes, daphnanes, and ingenanes.Phorbol (1), daphnane (2), and ingenane (3) derivatives, long recognized as highly potent tumor promoters, have recently found use in numerous other studies ranging from cell differentiation and AIDS virus expression to the biochemical basis of learning.2,3 The effects caused by these compounds are attributed in most cases to an anomalous activation of one or more isozymes of the protein kinase C family.2 3"4 In order to develop an understanding of the structural requirements for this activation process and to obtain information about the physiological role of these isozymes, access to specifically modified derivatives of the above families is required.5 Recently, we reported two syntheses of phorbol.6®"® We describe herein a new advance in this area involving a novel 4-methoxy-3-oxidopyrylium-alkene cycloaddition (Scheme I). This process allows for the facile synthesis of previously inaccessible BC ring precursors of phorbol derivatives and serves more generally to broaden the utility of oxidopyrylium cycloadditions in [5C + 2C] approaches to complex sevenmembered rings.The motivation for this study derived from the view that cycloadduct 4 by virtue of its C-ring unsaturation would serve as a versatile precursor to the tigliane, daphnane, and(1) Postdoctoral Fellow of the Ministerio de Educación y Ciencia (Spain), 1989-1990. (2) (a) Naturally Occurring Phorbol Esters; Evans, F. J., Ed.

The selective functionalization of C(sp3)−H bonds using transition‐metal catalysis is among the more attractive transformations of modern synthetic chemistry. In addition to its inherent atom economy, such reactions open unconventional retrosynthetic pathways that can streamline synthetic processes. However, the activation of intrinsically inert C(sp3)−H bonds, and the selection among very similar C−H bonds, represent highly challenging goals. In recent years there has been notable progress tackling these issues, especially with regard to the development of intermolecular reactions entailing the formation of C−C and C−heteroatom bonds. Conversely, the assembly of cyclic products from simple acyclic precursors using metal‐catalyzed C(sp3)−H bond activations has been less explored. Only recently has the number of reports on such annulations started to grow. Herein we give an overview of some of the more relevant advances in this exciting topic.