ABAM, a model for bioaccumulation of POPs in birds: validation for adult herring gulls and their eggs in Lake Ontario.

An Avian BioAccumulation Model (ABAM) of persistent organic pollutant (POP) uptake and elimination in adult life-stage of birds was validated by simulation of concentrations of DDE, dieldrin, mirex, and HCB in herring gull eggs in Lake Ontario for the years 1985, 1990, and 1992. These chemicals represented a range of whole-body half-lives of 82-265 days in the gull. Dietary intake of POPs by a female gull was simulated by a dynamic bioenergetics model which included dependence on temperature, photoperiod, egg production, and feeding chicks. Concentrations in the two main prey fish of the gull in Lake Ontario were used for POP exposure. Clearance from the female was based on a two compartment toxicokinetic model. Egg concentrations were estimated from egg/whole body female concentration ratios. Simulated concentrations were compared to measured concentrations in gull eggs from 4 different colonies in the northern part of Lake Ontario. Simulations using a diet of 81% fish and 19% uncontaminated food resulted in the best fit with least variance among predicted and measured data. The mean ratio of predicted to measured concentrations in eggs was 1.0 +/- 0.27 among chemicals, years, and colonies for this exposure scenario. This result was in excellent agreement with field assessments of herring gull diet composition in Lake Ontario of 80-82% fish. The ability to perform accurate a priorisimulations for the range of test conditions employed in the validation constituted a rigorous test of the soundness of the model's structure and parameterization. With species-specific adjustments, ABAM can be regarded as a general model for lipophilic POPs bioaccumulation in birds.

Asymmetric hydroformylation of vinyl acetate: application in the synthesis of optically active isoxazolines and imidazoles.

(R)- and (S)-2-(Acetyloxy)-propanal were prepared [93.8% ee, 102 b/l for (R), 96.9% ee, 149 b/l for (S)] via asymmetric hydroformylation of vinyl acetate on a 150-180 g scale and were used as the starting materials in the synthesis of chiral isoxazoline and imidazole derivatives which proceeded without racemization of the chiral center.

Highly active, regioselective, and enantioselective hydroformylation with Rh catalysts ligated by Bis-3,4-diazaphospholanes.

Azines made by the reaction of hydrazine with ortho-formylbenzoic acid react with 1,2-diphosphinobenzene and either succinyl chloride or phthaloyl chloride in ca. 30% yield to give rac-bis-3,4-diazaphospholanes bearing benzoic acid groups in the 2 and 5 positions. Condensation of the benzoic acid functionalities with enantiomerically pure amines affords diastereomeric benzoamides which can be separated by flash chromatography. Application of the resolved bis-3,4-diazaphosholanes to Rh-catalyzed enantioselective hydroformylation of styrene, allyl cyanide, and vinyl acetate under mild pressures (20-500 psig of CO/H2) and temperatures (40-120 degrees C) reveals high activities and selectivities for all three substrates. At 60 degrees C and 500 psig syn gas, the best ligand provides outstanding regio- and enantioselectivities (styrene, 89% ee, b:l = 30:1; allyl cyanide, 87% ee, b:l = 4.8:1; vinyl acetate, 95% ee, b:l = 40:1) while achieving turnover frequencies of ca. 3000 h-1.

Solid-phase synthesis of chiral 3,4-diazaphospholanes and their application to catalytic asymmetric allylic alkylation.

Functionalized chiral diazaphospholanes ligate to a variety of transition metals, yielding chiral, catalytically active, metal complexes. Previous work has established that amino acid derivatization of the carboxyl groups of (R,R)-N,N'-phthaloyl-2,3-(2-carboxyphenyl)-phenyl-3,4-diazaphospholane (1) yields phosphines that are excellent ligands for palladium-catalyzed asymmetric allylic alkylation reactions. Alanine functionalization is particularly effective for allylic alkylation of 1,3-dimethylallyl acetate. Standard Merrifield resins and amino acid coupling methods are used to synthesize the bead-attached phosphine having the topology bead-linker-LAla-(R,R)-1-LAla-OMe, as a 1:1 mixture of linkage isomers. Use of this supported phosphine in Pd-catalyzed asymmetric allylic alkylation yields 92% enantiomeric excess, matching prior solution-phase results. A 20-member collection of amino acid-functionalized phosphines on beads with the topology bead-linker-AA(2)-AA(1)-1-AA(1)-AA(2) was synthesized by using parallel solid-state methods and screened for efficacy in allylic alkylation. Resulting enantioselectivities indicate that the AA(1) position has the strongest effect on the reaction. Catalyst activities can vary widely with the nature of the phosphine ligand and the reaction conditions. Meaningful analysis of intrinsic catalytic activities awaits identification of the structure and abundance of the active catalyst.

Resolved chiral 3,4-diazaphospholanes and their application to catalytic asymmetric allylic alkylation.

One-pot condensation of PhPH2, phthaloyl chloride, and the azine of 2-carboxybenzaldehyde (1) results in the new phosphine, rac-N,N'-phthaloyl-2,3-(2-carboxyphenyl)-phenyl-3,4-diazaphospholane (rac-2), in 88% yield. Resolution via selective crystallization of the diastereomeric alpha-methylbenzylamine salts followed by coupling with amino acids and other amines provides rapid access to new collections of chiral phosphines (3). Pd-catalyzed alkylation of 1,3-dimethylallyl acetate and 1,3-diphenylallyl acetate at room temperature in the presence of 3 exhibits enantioselectivities as high as 92% ee and 97% ee, respectively, with strong sensitivity to the nature of the amino acid appendages. The presence of PF6- salts profoundly affects both the yield and the selectivity of catalytic allylic alkylation.