David B. Collum

Method of Continuous Variations: Applications of Job Plots to the Study of Molecular Associations in Organometallic Chemistry[**]

Applications of the method of continuous variations (MCV or the Method of Job) to problems of interest to organometallic chemists are described. MCV provides qualitative and quantitative insights into the stoichiometries underlying association of m molecules of A and n molecules of B to form A(m)B(n) . Applications to complex ensembles probe associations that form metal clusters and aggregates. Job plots in which reaction rates are monitored provide relative stoichiometries in rate-limiting transition structures. In a specialized variant, ligand- or solvent-dependent reaction rates are dissected into contributions in both the ground states and transition states, which affords insights into the full reaction coordinate from a single Job plot. Gaps in the literature are identified and critiqued.

Lithium Diisopropylamide-Mediated Ortholithiations: Lithium Chloride Catalysis

Ortholithiations of a range of arenes mediated by lithium diisopropylamide (LDA) in THF at -78 degrees C reveal substantial accelerations by as little as 0.5 mol % of LiCl (relative to LDA). Substrate dependencies suggest a specific range of reactivity within which the LiCl catalysis is optimal. Standard protocols with unpurified commercial samples of n-butyllithium to prepare LDA or commercially available LDA show marked batch-dependent rates--up to 100-fold--that could prove significant to the unwary practitioner. Other lithium salts elicit more modest accelerations. The mechanism is not discussed.

Kinetic cyanations of ketone enolates

Abstract Kinetic cyanations of ketone enolates using p-toluenesulfonyl cyanide provide efficient routes to β-ketonitriles.

Palladium-catalyzed stille couplings of aryl-, vinyl-, and alkyltrichlorostannanes in aqueous solution

Abstract Stille coupling of water-soluble aryl and vinyl halides with alkyl-, aryl-, and vinyltrichlorostannane derivatives (RSnCl 3 ) are effected in aqueous solution using a catalyst generated in situ from PdCl 2 and KOH both with and without added PhP( m -C 6 H 4 SO 3 Na) 2 . The yields are generally good to excellent, although some limitations of the protocol are described.

Reductions and radical cyclizations of aryl and alkyl bromides mediated by NaBH4 in aqueous base

Abstract Reductions and free radical cyclizations of alkyl- and aryl bromides are effected in aqueous base by NaBH 4 in conjunction with a base-soluble dialkyltin(IV) reagent and 4,4′-azobis(4-cyanovaleric acid) (ACVA). The aryl bromides reduce at lower rates under tin-free conditions using simply NaBH 4 -ACVA.

Regioselective Lithium Diisopropylamide-Mediated Ortholithiation of 1-Chloro-3-(trifluoromethyl)benzene: Role of Autocatalysis, Lithium Chloride Catalysis, and Reversibility

Ortholithiation of 1-chloro-3-(trifluoromethyl)benzene with lithium diisopropylamide (LDA) in tetrahydrofuran at -78 °C displays characteristics of reactions in which aggregation events are rate limiting. Metalation with lithium-chloride-free LDA involves a rate-limiting deaggregation via dimer-based transition structures. The post-rate-limiting proton transfers are suggested to involve highly solvated triple ions. Autocatalysis by the resulting aryllithiums or catalysis by traces (<100 ppm) of LiCl diverts the reaction through di- and trisolvated monomer-based pathways for metalation at the 2 and 6 positions, respectively. The regiochemistry is dictated by a combination of kinetically controlled metalations overlaid by an equilibration involving diisopropylamine that is shown to occur by the microscopic reverse of the monomer-based metalations.

Mercury(II)-mediated opening of cyclopropanes. Effects of proximate internal nucleophiles on stereo- and regioselectivity

Etude des effets de moities acide carboxylique et ester internes sur les regio- et stereoselectivites inherentes au clivage induit par le mercure(II) de cyclopropanes non actives. Bien que les cyclisations fournissent classiquement des lactones avec une forte stereoselectivite, des pertes surprenantes de selectivite sont occasionnellement observees

Lithium Hexamethyldisilazide-Mediated Enolizations: Influence of Triethylamine on E/Z Selectivities and Enolate Reactivities

Lithium hexamethyldisilazide (LiHMDS) in triethylamine (Et 3N)/toluene is shown to enolize acyclic ketones and esters rapidly and with high E/ Z selectivity. Mechanistic studies reveal a dimer-based mechanism consistent with previous studies of LiHMDS/Et 3N. E/ Z equilibration occurs when <2.0 equiv of LiHMDS are used. Studies of the aldol condensation and Ireland-Claisen rearrangement of the resulting Et 3N-solvated enolates show higher and often complementary diastereoselectivities when compared with analogous reactions in THF. The Et 3N-solvated enolates also display a marked (20-fold) acceleration of the Ireland-Claisen rearrangement with evidence of autocatalysis. A possible importance of amine-solvated enolates is discussed.

Substituent effects on the stereochemistry of substituted cyclohexanone dimethylhydrazone alkylations. An x-ray crystal structure of lithiated cyclohexanone dimethylhydrazone

Observation de hautes selectivites axiales dans les alkylations des hydrazones metalliques cyano-substituees, mais pas dans le cas de substitution alcoxycarbonyl

Lithium Phenolates Solvated by Tetrahydrofuran and 1,2-Dimethoxyethane: Structure Determination Using the Method of Continuous Variation

The method of continuous variation in conjunction with (6)Li NMR spectroscopy was used to characterize lithium phenolates solvated by tetrahydrofuran and 1,2-dimethoxyethane. The strategy relies on the formation of ensembles of homo- and heteroaggregated phenolates. The symmetries and concentration dependencies of the heteroaggregates attest to the aggregation numbers of the homoaggregates. The structurally diverse phenols afford substrate- and solvent-dependent combinations of lithium phenolate monomers, dimers, trimers, tetramers, and pentamers. We discuss the refinement of protocols for characterizing O-lithiated species. Computational studies examine further the substituent and solvent dependencies of aggregation.