Reactions of aziridine-2-carboxylic acid derivatives with aldehydes and ketones

Optically active 2,2-dimethyl-1,3,4-triazabicyclo[4.1.0]heptan-5-one: synthesis, spontaneous resolution and absolute configuration

“…The simplest method for obtaining enantiopure materials is their spontaneous resolution by crystallisation, which may occur when the racemate is a conglomerate. 13,14 For the strained aziridine-2-carboxylic acid derivative 2,2-dimethyl-1,3,4-triazabicyclo[4.1.0]heptan-5-one 1 5 the non-centrosymmetric space group P2 1 was determined by X-ray structural analysis. 6 This means that compound 1 forms a conglomerate.…”

“…Indeed, on crystallisation (from CHCl 3 or acetone) of (±)-1 prepared by a known procedure, 5 crystalline samples showing (+) or (-) rotation were obtained. † In order to determine its absolute configuration compound 1 was synthesised from commercial (S)-Ser-OMe hydrochloride {[a] D 23 = 3.5° (c 5.0 MeOH)} (Scheme 1), eventually giving (S)-(-)-1.…”

“…Azy-OMe (S)-(-)-2 was prepared under Mitsunobu conditions 15 and was converted into (S)-(-)-1 by a known procedure, 5 the mp of (-)-2 is higher than that of its racemate: 135-136 °C and 126-127 °C, respectively. The rotation of (S)-(-)-1 in MeOH was found to decrease gradually from -87° to -68.1° (after 1.6 h), -65.7° (after 2.3 h), reaching a constant value of -59.8°a fter 24 h. According to 1 H NMR, the isomerisation of (S)-(-)-1 into isopropylidenehydrazide (S)-(-)-4 to reach equilibrium 1:4 » 2 (Scheme 2) is responsible for the observed mutarotation.…”

“…(±)-1: obtained by method described in ref. 5, mp 126-127 °C (acetone). 1 H NMR (CDCl 3 ) d: 1.29 (s, 3H, Me A ), 1.40 (s, 3H, Me B ), 2.13 (dd, 1H, H b , 3 J ab 5.9 Hz, 2 J bc 1.0 Hz), 2.25 (dd, 1H, H c , 3 J ac 3.0 Hz, 2 J bc 1.0 Hz), 2.65 (ddd, 1H, H a , 3 J ab 5.9 Hz, 3 J ac 3.0 Hz, 4 J ad 2.7 Hz), 3.94 (s, 1H, H e ), 6.82 (s, 1H, H d ).…”