Thermische Reorganisation und Cycloadditionen eines chiralen, nicht‐racemischen Aziridinons (α‐Lactams) sowie ab‐initio‐Berechnungen zur C 2 H 3 NO‐Energie‐Hyperfläche

Thermal Reorganization and Cycloaddition Reactions of a Chiral, Non‐Racemic Aziridinone (α‐Lactam) and Ab Initio Calculations of the C 2 H 3 NO 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 T c = 271 and 250 K as a result of the retardation of two processes, viz. the N inversion and the rotation around the (C–NMe 2 ) 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 * , E rel = 0.00 kJ mol ‐1 ) is lowest in energy, followed by the iminooxiranes ( E )‐ and ( Z )‐ 31 ( E rel = 30.8 and 26.0 kJ mol ‐1 ) and the methyleneoxaziridine 30 ( E rel = 195.6 kJ mol ‐1 ). Energy‐rich zwitter‐ionic transition states ( E )‐ and ( Z )‐ 32 ( E rel = 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 C 1 symmetry ( E rel = 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.