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Either trans- or cis-haloalkylation is possible through a three-component coupling [Eq. (1)]. The cis-bromoruthenation of an alkyne by lithium bromide and [CpRu(CH(3)CN)(3)]PF(6), catalyzed by SnBr(4), gives (Z)-vinyl bromides with high chemoselectivity. The degree of control over the sterochemistry raises intriguing mechanistic questions as well as offering practical synthetic utility.

A new strategy for the synthesis of 2,3-disubstituted cyclopentenones emerges from two key reactionsthe ruthenium-catalyzed three-component coupling of an equivalent of HBr, an alkyne, and a vinyl ketone and the Ni−Cr Barbier type reaction. As a result, these important structures are readily accessed from an alkyne and a vinyl ketone (which derive directly from carboxylic acids). Syntheses of tetrahydrodicranenone B and rosaprostol illustrate the new strategy.

A two component coupling of an allene and an activated olefin to form 1,3-dienes has been developed. The requisite allenes are synthesized either from terminal alkynes by a one carbon homologation using copper(I) iodide, paraformaldehyde, and diisopropylamine, via an ortho ester-Claisen rearrangement from a propargylic alcohol, or via a Wittig type reaction on a ketene generated in situ from an acid chloride. Mono- through tetrasubstituted allenes could be synthesized by these methods. Either cyclopentadienylruthenium(II) cyclooctadiene chloride or cyclopentadienylruthenium(II) trisacetonitrile hexafluorophosphate catalyze the addition reaction. When the former catalyst is employed, an alkyne activator is added to help generate the active catalyst. Through systematic optimization studies, a range of conditions was examined. The optimal conditions consisted of the use of cerium(III) trichloride heptahydrate as a cocatalyst in dimethylformamide as a solvent at 60 °C. The reaction was found to be chemoselect...

The ruthenium-catalyzed three-component coupling of an alkyne, an enone, and halide ion to form E- or Z-vinyl halides has been investigated. Through systematic optimization experiments, the conditions effecting the olefin selectivity were examined. In general, more polar solvents such as DMF favored the formation of the E-isomer, and less polar solvents such as acetone favored formation of the Z-isomer. The optimized conditions for the formation of E-vinyl chlorides were found to be the use of cyclopentadienyl ruthenium (II) cyclooctadiene chloride, stannic chloride pentahydrate as a cocatalyst, and for a chloride source, either ammonium chloride in DMF/water mixtures or tetramethylammonium chloride in DMF. A range of several other ruthenium (II) catalysts was also shown to be effective. A wide variety of vinyl chlorides could be formed under these conditions. Substrates with tethered alcohols or ketones either five or six carbons from the alkyne portion gave instead diketone or cyclohexenone products. Fo...

Catalyzed by ruthenium trisacetonitrile hexafluorophosphate 4, the Alder-ene type reaction of alkenes and internal alkynes provides an effective way to synthesize trisubstituted alkenes. Unlike most typical olefination protocols, this reaction is atom economical, and affords trisubstituted alkenes with defined olefin geometry. The regioselectivity can be explained invoking a steric argument based on the proposed mechanism. The first C-C bond formation generally involves sterically less hindered carbons of the alkenes and alkynes. Modest to very high regioselectivity can be achieved depending on the steric difference of the two substituents of alkynes.

Pyrimidine methyl anilines as potent and selective mGlu2 potentiators are described. Findings from the structure-activity-relationship investigations are discussed.

Exclusive Z-selectivity in the Ru-catalyzed bromoalkylation of alkynes with vinyl ketones is observed with aryl and other tertiary substituted acetylenic substrates, a feature that has led to an efficient synthesis of a COX-2 inhibitor. © 2000 Elsevier Science Ltd. All rights reserved. In previous papers, we reported the ruthenium-catalyzed haloalkylation of acetylenes could occur with either a cis 1 or trans 2 geometry to form Z-1 or E-1, respectively, as outlined in Scheme 1. 3 The competition of the conversion of 2 to 3 compared to the conversion of 4 to 5 determines the geometric selectivity. Our interest in employing the Z-bromoalkenes (Z-1, XBr) in a cyclopentenone synthesis 4 stimulated the need to enhance the Z-selectivity of the bromoalkylation process. Examination of 3 and 5 suggests that the steric interactions between