Ortholithiation and reaction with (-)-menthyl p-toluenesulfinate introduces a sulfoxide substituent ortho to the stereogenic Ar-CO axis of an aromatic amide. The sulfoxide exerts a powerful conformational bias on the axis, such that after rapid equilibration at ambient temperature essentially only one of two diastereoisomeric Ar-CO atropisomers is populated. Sulfoxide-lithium exchange by treatment with t-BuLi regenerates the ortholithiated amide in an enantiomerically pure and conformationally stable form. Rapid electrophilic trapping of the organolithium therefore generates highly enantiomerically enriched atropisomeric tertiary aromatic amides. The overall process, involving temporary substitution of lithium to sulfoxide to lithium, amounts to a dynamic resolution under thermodynamic control.

Heterocyclic amines (HAs) are potent mutagens that form at high temperatures in cooked, protein-rich food. Due to their frequent intake, these compounds are considered a risk factor for human cancer. Cooking conditions and eating habits strongly influence the level of HA exposure. Thus, it is difficult to assess the intake of HAs in a large population. Food-frequency questionnaires (FFQs), designed to provide data on parameters that affect HA formation, were used to survey a small population (459 persons) from Barcelona (NE Spain). Subsequently, the most-consumed food items named were cooked according to the preferences of the population surveyed and analyzed for HAs using SPE and LC-MS/MS. In the population studied, the estimated intake via consumption of 13 meat dishes was 285.6 ng of mutagenic HAs per capita and day. PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) was the HA to which the population was most exposed, mainly from fried chicken and griddled beef. When the co-mutagens norharman and harman are included, the mean daily intake of HAs rises to 475.6 ng per capita and day. A novel putative DMIP regioisomer was detected in the cooked meats, which was analyzed in the present study by multistage MS

Atropisomeric aromatic amides bearing 2-sulfanyl groups are oxidised by m-CPBA to the corresponding sulfoxides apparently with very high diastereoselectivity. NMR studies and oxidations of chiral benzamides however indicate that the kinetic selectivity of the oxidation is in fact relatively poor, and that the final diastereoisomeric ratio (typically >99:1) is under thermodynamic control, with relatively unhindered Ar-CO rotation readily converting the less stable to the more stable product diastereoisomer. Molecular mechanics indicates that the thermodynamic diastereoselectivity results principally from electrostatic repulsion between the C=O and S-O dipoles.

The orientation of a tertiary amide group adjacent to an aromatic ring may be governed by the stereochemistry of an adjacent chiral substituent. With a chiral substituent in both ortho positions, matched/mismatched pairs of isomers result. Evidence for matched stereochemistry is provided by the clean NMR spectra of single conformers, while mismatching gives poor or unexpected selectivities in the formation of chiral substituents, or mixtures of amide conformers. Attempts to use the match-mismatch effect to select for racemic pairs of enantiomeric substituents, and hence develop a "racemate-sequestering" reagent, are described, along with the use of "matching" to scavenge a single enantiomer of a diamine from material of incomplete enantiomeric purity.

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