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Mutual Kinetic Resolution of Racemic 3,4‐Dihydro‐3‐methyl‐2 H ‐[1,4]benzoxazines with Acyl Chlorides of Racemic O ‐Phenyllactic Acids and DFT Modelling of Transition States
Author(s) -
Korolyova Marina A.,
Vakarov Sergey A.,
Kozhevnikov Dmitry N.,
Gruzdev Dmitry A.,
Levit Galina L.,
Krasnov Victor P.
Publication year - 2018
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201800656
Subject(s) - chemistry , acylation , substituent , kinetic resolution , reagent , ring (chemistry) , selectivity , transition state , density functional theory , computational chemistry , medicinal chemistry , gibbs free energy , stereochemistry , organic chemistry , catalysis , enantioselective synthesis , thermodynamics , physics
The effect of the electronic nature of the para substituent on the aromatic ring of 2‐aryloxypropionyl chlorides on the stereochemical outcome of the acylation of 3,4‐dihydro‐3‐methyl‐2 H ‐[1,4]benzoxazine and its 7,8‐difluoro‐containing analogue has been studied. The geometries of the diastereoisomeric transition states and the corresponding Gibbs free enthalpies of activation were determined through DFT calculations at the COSMO‐CH 2 Cl 2 ‐B3LYP‐D3‐gCP/def2‐TZVP (or def2‐SVP)//B3LYP‐D3‐gCP/def2‐SVP level of theory. It has been found that a low‐cost quantum chemical calculation at a chosen level of theory describes well the quantitative dependence of the selectivity of acylation on the structures of the reagents. The obtained results indicate that aromatic interactions between the reagents play a significant role in the process of stereodifferentiation, ensuring high selectivity of the acylation of benzoxazines with 2‐aryloxyacyl chlorides.