This proposed research will develop the use of lithium dialkylamide mixed aggregates as reagents for the stereoselective synthesis of enolates. Lithium enolates are important reagents in the synthesis of carbon-carbon bonds, and are used extensively in the pr3eparation of medicinal compounds. Synthesis of chiral drugs often depends on the availability of stereoselective aldol condensations and other reactions of enolates the stereoselectivity of these reactions is often limited by the availability of pure diastereomeric enolates. The stereoselectivity of these reactions is often limited by the availability of pure diastereomeric enolates. Enolates are generally prepared by deprotonation of aldehydes, ketones, and esters, and the stereoselectivity of enolates. Enolates are generally prepared by deprotonat8ion of aldehydes, ketones, and esters, and the stereoselectivity of enolate format8ion is dependent on the structure of the base that is used. Lithium dialkylamide mixed aggregates with alkyllithiums and lithium halides will be tested as inexpensive and easily prepared reagents for this purpose. The enolization reactions will be performed by addition of the carbonyl compound to a solution of the lithium dialkylamide or its mixed aggregates. The enolate will be trapped as the trimethylsilyl enol ether and the E/Z ratio determined by gas chromatography. The enolization reactions will be performed with several carbonyl substrates to determine the effects of stereoelectronic factors and to predict the stereoselectivity of enolization of carbonyl compounds that are actually used in drug synthesis. Ab initio calculations will be used to determine the activation energies leading to the E and Z 4enolates. Deprotonation activation energies will be calculated for lithium dialkylamides and their alkylithium and lithium halide mixed aggregates. The calculations will be performed on a variety of aldehyde, ketone, and ester substrate to capture the behavior of a range of stereoelectronic effects.
| Pratt, Lawrence M; Truhlar, Donald G; Cramer, Christopher J et al. (2007) Aggregation of alkyllithiums in tetrahydrofuran. J Org Chem 72:2962-6 |
| Hota, S; Crooke, P S; Adams, A B et al. (2006) Optimal phasic tracheal gas insufflation timing: an experimental and mathematical analysis. Crit Care Med 34:1408-14 |
| Pan, Z; Zavalin, A; Ueda, A et al. (2005) Surface-enhanced Raman spectroscopy using silver-coated porous glass-ceramic substrates. Appl Spectrosc 59:782-6 |
| Pratt, Lawrence M; Mu, R (2004) Structure, bonding, and solvation of dilithiodiamines. J Org Chem 69:7519-24 |
| Pratt, Lawrence M; Newman, Anthony; Cyr, Jason St et al. (2003) Ketone enolization with lithium dialkylamides: the effects of structure, solvation, and mixed aggregates with excess butyllithium. J Org Chem 68:6387-91 |
