Acylation, Diastereoselective Alkylation, and Cleavage of an Oxazolidinone Chiral Auxiliary
A Multistep Asymmetric Synthesis Experiment for Advanced Undergraduates
Thomas E. Smith, David P. Richardson, George A. Truran, Katherine Belecki, and Megumi Onishi
Department of Chemistry, Williams College, Williamstown, MA 01267
An introduction to the concepts and experimental techniques of diastereoselective synthesis using a chiral auxiliary is described. The 4-benzyl-2-oxazolidinone chiral auxiliary developed by Evans is acylated with propionic anhydride under mild conditions using DMAP as an acyl transfer catalyst. Deprotonation with NaN(TMS)2 at -78 °C leads to a rigidly chelated enolate that is alkylated by allyl iodide preferentially from the least hindered diastereoface with 98:2 selectivity. Chromatographic purification followed by hydrolytic cleavage of the auxiliary using LiOH/H2O2 gives 2-methyl-4-pentenoic acid in high enantiomeric purity. This exercise gives students the opportunity to gain proficiency with the techniques of modern organic synthesis, including the manipulation of moisture-sensitive reagents, low temperature reactions, column chromatography, TLC, and NMR analysis. The experiment also provides a context for the discussion of important reaction mechanisms, such as acylation and enolate alkylation, and serves to reinforce the critical conceptual distinction between absolute and relative stereochemical control.
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