Thermische Reorganisation und Cycloadditionen eines chiralen, nicht‐racemischen Aziridinons (α‐Lactams) sowie ab‐initio‐Berechnungen zur C2H3NO‐Energie‐Hyperfläche

Abstract

Thermal Reorganization and Cycloaddition Reactions of a Chiral, Non‐Racemic Aziridinone (α‐Lactam) and Ab Initio Calculations of the C2H3NO Energy Hypersurface[1]The thermal reorganization of the racemic (1 a) and the non‐racemic aziridinone (R)‐1 a (92% e.e.) is studied in solution in the temperature range of 100–140 °C. Besides traces of the imine 8, which is the product of a direct [2 + 1] cycloreversion of 1 a, the aldehyde 2 a and the isocyanide 4 a are formed in almost quantitative yield. A small fraction of the latter rear‐ranges to the nitrile 3 or adds to unchanged 1 a to afford the iminoazetidinone (E)‐5 a (5–10%), which is obtained when neat 1 a is heated in the presence of 4 a. The configuration of (E)‐5 a is based on nuclear Overhauser experiments. The disappearance of 1 a follows a first‐order rate law with k = 44 ° 10‐6 s‐1 at 130°C, while racemization of (R)‐1 a is observed with k [(R)‐1 a] = 8.1 · 10‐6 s‐1. The formal [3 + 1] cycloaddition of tert‐butyl isocyanide (4 a) to (R)‐1 a produces (E, R*)‐5 a of unknown absolute configuration and a low enantiomeric excess (ca. 10%). The product (E, R*)‐5 a is not racemized under the reaction conditions. The results are interpreted in terms of a nucleophilic attack of the isocyanide 4 a to C‐3 of (R)‐1 a resulting in an acyclic nitrilium type zwitterion (R)‐21 which, to a large extend, racemizes via the ketene imine 22 before ring‐closure to the final product (E,R)‐5 a. – Dimethylformamide reacts with (R)‐1 a at temperatures as low as 80–100 °C to give the diastereomeric oxazolidin‐5‐ones cis‐and trans‐15. The former is formed first and subsequently isomerizes to trans‐15. The configuration of cis‐ and trans‐15 is based on nuclear Overhauser experiments. The proton signals of the dimethylamino group of both cis‐ and trans‐15 are temperature‐dependent and split into two singlets of equal intensity at Tc = 271 and 250 K as a result of the retardation of two processes, viz. the N inversion and the rotation around the (C–NMe2) bond. In the reaction of (R)‐1 a with dimethylformamide, the oxazolidinones (2R,5S)‐ and (2S,5S)‐15 (85–90% e.e.) are formed which are hydrolyzed to the known α‐hydroxyamide (S)‐16. Hence, the configuration at C‐5 of both cis‐ and trans‐15 is (S), and the [3 + 2] cycloaddition of (R)‐1 a to dimethylformamide involves inversion at C‐3 of (R)‐1 a. This result strongly suggests a nucleophilic attack of dimethylformamide to (R)‐1 a rather than trapping of an acyclic aziridinone isomer. – In order to rationalize the observed reactions and reactivities, we performed high‐level calculations on the parent aziridinone 29 and its cyclic (30, 31) and acyclic (32–35) isomers as well. Among the three‐membered rings, 29 (MP2/6‐31G*//6–31G*, Erel = 0.00 kJ mol‐1) is lowest in energy, followed by the iminooxiranes (E)‐ and (Z)‐31 (Erel = 30.8 and 26.0 kJ mol‐1) and the methyleneoxaziridine 30 (Erel = 195.6 kJ mol‐1). Energy‐rich zwitter‐ionic transition states (E)‐ and (Z)‐32 (Erel = 281.9 and 234.6 kJ mol‐1) are found with the RHF method. The UHF method is used for open‐shell species. Thus, UHF/6–31G*//6–31G* optimizations result in the planar triplet states 33 having very low relative energies, but high spin contamination. UMP2/6‐31G* single‐point calculations of these triplets result in unrealistic, high relative energies. Complete UHF singlet geometry optimizations lead to the local minimum structure 35 of C1 symmetry (Erel = 34.9 kJ mol‐1). At the highest computational level employed (UMP4SDTQ/6–31 + G*//6–31G*), a relative energy of 178.8 kJ mol‐1 is obtained for 35. An activation energy of (170 ° 25) kJ mol‐1 is estimated for the ring opening of the parent aziridinone 29 involving species with high diradical character.