Aggregation and Solvation of Chiral N,P‐Amide Ligands in Coordinating Solvents: A Computational and NMR Spectroscopic Study

Abstract

Scheme 1. Lithium ligand libraries from amino acids.

Chiral Lithium Amides: Tuning Asymmetric Synthesis on the Basis of Structural Parameters

“…Adding THF to the Et 2 O solution did not affect the initial structures with the exception of the Et 2 O‐THF swap. A further study carried out with 2 b 4b (R 2 =Bn, Figure , left) in Et 2 O led to the same dimeric structural arrangement . Finally, as with the 2 b 2 series, decreasing the steric bulk of the achiral substituent R 1 (R 1 =Me instead of i ‐Pr) favors the formation of ladder‐type homodimers as with 2 b 4d and 2 b 4e in THF (Figure , right).…”

“…Series 2 b 4 : The group of Hilmersson has also been interested in CLAs 2 b 4 (Figure ) bearing a chelating phosphine. NMR investigations have been run to clarify the structures of these amides and related mixed aggregates …”

Computational Perspectives on Organolithiums

“…A pragmatic solution to the overestimation of calculated entropies was recently employed by Rönnholm and coworkers in a study on equilibrium constants of a set of lithium aminophosphines. By rescaling the calculated entropy uniformly for all systems studied by about 25% down to 1.5 kcal mol −1 , a satisfactory agreement between NMR measurements and calculated values was obtained [71].…”

“…For example, the modeling of THF and DEE by the smaller ligand DME has been questioned several times, mainly by Pratt and Mu [70]. Recent studies using DME as a model for THF in the calculation of lithium amide dimers and transition states (TSs) for enantioselective aldehyde alkylation with chiral lithium amides using dispersion-corrected DFT could, on the other hand, only show small relative effects due to the choice of solvent (1-3 kJ mol −1 ) [71,72]. The use of the smaller solvent in those studies was a pre-requisite to be able to calculate a large number of structures covered.…”

“…Structure determination of a large set of chiral lithium amides in different solvents using a combination of advanced NMR techniques and computational chemistry have additionally been advanced by research groups of Hilmersson [50,61,71,[114][115][116], Davidsson [59,62,116], Maddaluno [117], and Nudelman [118].…”