5‐(Pyrrolidine‐2‐yl)tetrazole: Rationale for the Increased Reactivity of the Tetrazole Analogue of Proline in Organocatalyzed Aldol Reactions

Abstract 5‐[(2 S )‐Pyrrolidine‐2‐yl]‐1 H ‐tetrazole ( 1 ), i. e. the tetrazolic acid analogue of proline, has been found to be significant more reactive than L ‐proline ( 2 ) in various organocatalyzed reactions. In the organocatalyzed direct asymmetric aldol reaction, acetone was reacted with aromatic and aliphatic aldehydes to afford the resulting β‐hydroxy ketones in good yields and moderate to high enantiomeric excesses. The increased reactivity of 1 , as compared to 2 , has been rationalized through a combined computational and NMR spectroscopic study. It was found that catalyst 2 was almost completely engaged in oxazolidinone formation with the aldehyde whereas 1 did not take part in such parasitic equilibrium. This finding, together with the improved solubility of the tetrazole analogue, is proposed to account for the observed reactivity. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)