139585-72-1Relevant articles and documents
Thermal Reorganization and Cycloaddition Reactions of a Chiral, Non-Racemic Aziridinone (α-Lactam) and Ab Initio Calculations of the C2H3NO Energy Hypersurface
Quast, Helmut,Leybach, Holger,Wuerthwein, Ernst-Ulrich
, p. 1249 - 1262 (2007/10/02)
The thermal reorganization of the racemic (1a) and the non-racemic aziridinone (R)-1a (92percent e.e.) is studied in solution in the temperature range of 100-140 deg C.Besides traces of the imine 8, which is the product of a direct cycloreversion of 1a, the aldehyde 2a and the isocyanide 4a are formed in almost quantitative yield.A small fraction of the latter rearranges to the nitrile 3 or adds to unchanged 1a to afford the iminoazetidinone (E)-5a (5-10percent), which is obtained when neat 1a is heated in the presence of 4a.The configuration of (E)-5a is based on nuclear Overhauser experiments.The disappearance of 1a follows a first-order rate law with k = 44 * 10-6 s-1 at 130 deg C, while racemization of (R)-1a is observed with k (S)-1a> = 8.1 * 10-6 s-1.The formal cycloaddition of tert-butyl isocyanide (4a) to (R)-1a produces (E,R*)-5a of unknown absolute configuration and a low enantiomeric excess (ca.10percent).The product (E,R*)-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)-1a resulting in an acyclic nitrilium type zwitterion (R)-21 which, to a large extent racemizes via the ketene imine 22 before ring-closure to the final product (E,R)-5a. - Dimethylformamide reacts with (R)-1a at temperatures as low as 80-100 deg 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)-1a with dimethylformamide, the oxazolidinones (2R,5S)- and (2S,5S)-15 (85-90percent 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 cycloaddition of (R)-1a to dimethylformamide involves inversion at C-3 of (R)-1a.This result strongly suggests a nucleophilic attack of dimethylformamide to (R)-1a 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 mol1-).Energy-rich zwitter-ionic transition states (E)- and (Z)-32 (Erel = 281.9 and 234.6 kJ mol-1) are found 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 conta...
