Characterization of â-Amino Ester Enolates as Hexamers via 6Li NMR Spectroscopy

As part of a program to prepare new antithrombotic agents, we discovered that unprotected â-amino esters can be exclusively C-alkylated. We sought to optimize this process by studying the structures and reactivities of â-amino ester enolates.1 Determining the aggregation state of an enolate, however, is especially difficult due to the high symmetry of the possible aggregatessmonomers, dimers, tetramers, and hexamerssand the spectroscopically opaque Li-O linkage.2 Herein we describe a spectroscopic method used to assign â-amino ester enolates (1) as hexamers in solution. To understand these studies we must briefly digress by describing the dynamic phenomena that are commonly observed for organo-lithium aggregates but may seem surprising to the nonspecialist.3 At the lowest attainable NMR probe temperatures (<-100 °C), fast processes including solvent exchange,4 conformational equi-libria,5 and chelate isomerizations6 can become observable on NM