Gold-Free Aldol-Type Additions of α-Isothiocyanato Imides to Aldehydes

Key words

α-isothiocyanato imides - β-hydroxy-α-amino acids - thiourea catalyst

Significance

Seidel and co-workers report an organocatalytic diastereo- and enantioselective aldol addition of α-isothiocyanato imides to aldehydes. The reaction is catalyzed by bifunctional thiourea catalyst 1. A sterically demanding substitution on the imide is necessary for high diastereoselectivities and moreover for suppressing the formation of undesired product 2. The applicability was shown by preparing the protected β-hydroxy-α-amino acid 3 on a large scale and reducing the catalyst loading to 1 mol%.

Comment

A direct organocatalytic and highly ­diastereo- and enantioselective approach to protected syn-β-hydroxy-α-amino acids under mild conditions with low catalyst loadings is presented. The approach complements one of the first catalytic asymmetric aldol reactions by Ito and Hayashi (J. Am Chem. Soc. 1986, 108, 6405). So far, the majority of methods available to synthesize syn-β-hydroxy-α-amino acids rely on diastereoselective approaches, for example the use of chiral auxiliaries. A catalytic enantioselective approach to these compounds remains challenging. An expansion of this method to different imides would be desirable.