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 AmBn. 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.

Review: 107 refs.

The results of a combination of 6Li and 13C NMR spectroscopic and computational studies of oxazolidinone-based lithium enolates—Evans enolates—in tetrahydrofuran (THF) solution revealed a mixture of dimers, tetramers, and oligomers (possibly ladders). The distribution depended on the structure of the oxazolidinone auxiliary, substituent on the enolate, and THF concentration (in THF/toluene mixtures). The unsolvated tetrameric form contained a D2d-symmetric core structure, whereas the dimers were determined experimentally and computationally to be trisolvates with several isomeric forms.

Aldol additions to isobutyraldehyde and cyclohexanone with lithium enolates derived from acylated oxazolidinones (Evans enolates) are described. Previously characterized trisolvated dimeric enolates undergo rapid addition to isobutyraldehyde to give a 12:1 syn:syn selectivity in high yield along with small amounts of one anti isomer. The efficacy of the addition depends critically on aging effects and the reaction quench. Unsolvated tetrameric enolates that form on warming the solutions are unreactive toward isobutyraldehyde and undergo retroaldol reaction under forcing conditions. Additions to cyclohexanone are relatively slow but form a single isomeric adduct in >80% yield. The ketone-derived aldolates are robust. All attempts to control stereoselectivity by controlling aggregation failed. Rate studies of addition to cyclohexanone trace the lack of aggregation-dependent selectivities to a monomer-based mechanism. The synthetic implications and possible utility of lithium enolates in Evans aldol additions are discussed.

Building on structural and mechanistic studies of lithiated enolates derived from acylated oxazolidinones (Evans enolates) and chiral lithiated amino alkoxides, we found that amino alkoxides amplify the enantioselectivity of aldol additions. The pairing of enantiomeric series affords matched and mismatched stereoselectivities. The structures of mixed tetramers showing 2:2 and 3:1 (alkoxide-rich) stoichiometries are determined spectroscopically. Rate and computational studies provide a viable mechanistic and stereochemical model based on the direct reaction of the 3:1 mixed tetramers, but they raise unanswered questions for the 2:2 mixed aggregates.