Stereospecific Synthesis of (2S,4S,6S)-2-Amino-4,6-Dihydroxypimelic Acid

The Lewis acid catalyzed stereoselective carbonyl−ene-reaction between (2S,5S)-1-benzoyl-2-tert-butyl-3-methyl-5-(2-propenyl)imidazolidin-4-one (2) and anhydrous butyl glyoxylate was investigated with the aim to obtain highly functionalized amino acids. This reaction is assumed to proceed in a nonsynchronous fashion, giving rise to competing reactions within the time interval between the C−C bond formation and the proton migration step. Thus, a hypothesized dipolar intermediate could undergo two reaction pathways: besides conventional ene product 3, two further products 4 and 5 are obtained via nucleophilic attack involving two different neighboring carbamoyl groups. Acidic hydrolysis of both products afforded title compound 1. The absolute configuration of the two newly formed chiral centers was assigned by NMR measurements of lactone 4 and its rigid derivative 7. By varying the temperature (−20° to 25 °C) and the type of Lewis acid (SnCl4, FeCl3) the reaction can be directed to give either of the possible reaction products. A plausible reaction mechanism is proposed.