Acylation, Diastereoselective Alkylation, and Cleavage of an Oxazolidinone Chiral Auxiliary

• Published in: Journal of chemical education 2008-05, Vol.85 (5), p.695
• Main Authors: Smith, Thomas E, Richardson, David P, Truran, George A, Belecki, Katherine, Onishi, Megumi
• Format: Article
• Language: English
• ISSN: 0021-9584; 1938-1328
• DOI: 10.1021/ed085p695

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.