THERMAL REORGANIZATION AND CYCLOADDITION REACTIONS OF A CHIRAL, NON-RACEMIC AZIRIDINONE (ALPHA-LACTAM) AND ABINITIO CALCULATIONS OF THE C2H3NO ENERGY HYPERSURFACE

The thermal reorganization of the racemic (1 a) and the non-racemic aziridinone (R)-la (92% e.e.) is studied in solution in the temperature range of 100-140-degrees-C. Besides traces of the imine 8, which is the product of a direct [2 + 1] cycloreversion of la, the aldehyde 2a and the isocyanide 4a 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)-Sa (5-10%), which is obtained when neat 1 a is heated in the presence of 4a. The configuration of (E)-Sa 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-degrees-C, while racemization of (R)-1a is observed with k [(R)-1a --> (S)-l al = 8.1 . 10(-6) s-1. The formal [3 + 1] cycloaddition of tert-butyl isocyanide (4 a) to (R)-l a produces (E,R*)-5a of unknown absolute configuration and a low enantiomeric excess (ca. 10%). The product (ER*)-5a is not racemized under the reaction conditions. The results are interpreted in terms of a nucleophilic attack of the isocyanide 4a to C-3 of (R)-l 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 (ER)-5a. - Dimethylformamide reacts with (R)-l a at temperatures as low as 80-100-degrees-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-NMe2) bond. In the reaction of (R)-1a with dimethylformamide, the oxazolidinones (2R,5S)- and (2S,5S)-15 (85-90% e.e.) are formed which are hydrolyzed to the known alpha-hydroxyamide (S)-16. Hence, the configuration at C-5 of both cis- and trans-15 is (S), and the [3 + 2] cycloaddition of (R)-l a to dimethylformamide involves inversion at C-3 of (R)-l a. This result strongly suggests a nucleophilic attack of dimethylformamide to (R)-l 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 C1 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.