Aziridines. 59. Regioselectivity in nucleophilic Ring Opening of 2-Methylaziridines. Lag of bond making as model for the abnormal opening

Abstract

The regioselectivity ratio RS = normal: abnormal opening of activated 2‐methylaziridines 2 by nucleophiles is found to range from 0.10 to unmeasurable large (only normal opening = substitution at CH2 by strongly basic carbanions). RS is assumed to result from SN2 variants differing in the degree to which bond breaking is ahead of bond making including perhaps synchronous SN2. Bond breaking will be more ahead for the N‐CMe bond. High nucleophilic power pushes bond making toward a synchronous process resulting in great RS. The decrease in RS with acyl activation relative to sulfonyl activation is in accord with a flattening of the nitrogen pyramid (planarization effect). The planarization effect is retained in acidic medium by O‐protonation: Rs 0.10–0.14 for methanolysis as compared to RS 0.43 for N‐protonated sulfonylaziridine 2h. AM1 calculations support the planarization hypothesis. – No indication for SET with trityl anion was found.

The Dinosyl Group: A Powerful Activator for the Regioselective Alcoholysis of Aziridines

“…ported. [15,21,25,33] Addressing this, we were striving for easily accessible N-activated aziridines that are reactive enough to undergo regioselective alcoholysis without any additional activation. N-Ts-Aziridines were considered as an obvious starting point, although ring cleavage with weak nucleophiles like alcohols in general still requires additional activation.…”

“…While sufficiently activated aziridines undergo ring cleavage with a variety of strong nucleophiles [16,20] easily, weak nucleophiles like alcohols generally require either the application of the corresponding alkoxide [15,[21][22][23][24][25] or, more frequently, the use of Lewis acids as catalysts. [26][27][28][29][30][31][32] Only few sporadically mentioned examples of uncatalyzed alcoholysis (MeOH, EtOH) of aziridines are re-3126 hindered position.…”

“…NTs-Aziridines exhibit relatively high reactivity towards ring cleavage and they do not undergo side reactions at the activating group, which is observed with N-acyl-or carbamatetype aziridines. [15,16] In our research towards new synthetic ligands for the polyamine binding site of the NMDA receptor [17][18][19] we encountered difficulties in the synthesis of compound B, intended as a prototype for a combinatorial library of compounds with general structure A (Figure 1). …”

Nucleophilic ring opening of aziridines

“…Alcoholic NRO of 43a (Scheme 9) strongly prefers the primary carbon [37]. R = Et provides 95% of 44, no other product is detectable.…”

“…The red THF solution of Trcan be titrated with a THF solution of 30a, the instant discoloration indicating a very fast reaction. Elevated temperatures may bring about a conversion [37]. Analogously, 78 is obtained as sole product from 43a and the Grignard reagent [37].…”