Stereoinversion in the diastereoselective acylation of benzoxazine derivatives with 2-aryloxypropionyl chlorides

Kinetic Resolution of Racemic 2‐Aryloxy Propionyl Chlorides Using Enantiopure (S)‐3,4‐Dihydro‐3‐methyl‐2H‐[1,4]benzoxazines

“…In this case, the products of acylation were enriched with (3 R *,2’ R *)‐diastereoisomers of amides 4 g and 5 g , the selectivity of this process being low (Table , entries 13 and 14: s =9 and 16). We have previously observed this phenomenon when acylation of amines 1 a,b was carried out in dichloromethane at −20 °C …”

“…The selectivity factor is the ratio of the rate constants of individual enantiomers ( s = k fast/ k slow) . We used an approach based on the interaction of racemic reagents, as previously described . In this case, the ratio of the diastereoisomeric amides formed is equal to the selectivity factor; moreover, ratio of the starting reagents, their concentration and the reaction duration do not affect the stereochemical outcome of the process, and therefore, the s value can be determined quite accurately …”

“…We have previously found that the interaction of amines 1 a and 1 b with 2‐(1‐naphthyloxy)propionyl chloride 3 g leads to the predominant formation of (3 R *,2’ R* )‐amides 4 g and 5 g , respectively; while acylation of these amines with 2‐(4‐nitrophenyloxy)propionyl chloride 3 f leads to the (3 S *,2’ R *)‐diastereoisomers of amides 4,5 f as the major products …”

“…We have previously studied acylative KR of racemic heterocyclic amines with chiral acid derivatives . We have also performed the DFT‐based simulation of the transition states in the acylation of 3‐methylbenzoxazines 1 a,b (Figure ) with 2‐aryloxy acyl chlorides and suggested an explanation of the observed stereoselectivity . At the same time, the task of preparation of individual enantiomers of 2‐arylroxy acids as a result of KR with enantiopure amines was not posed.…”

Mutual kinetic resolution: probing enantiorecognition phenomena and screening for kinetic resolution with racemic reagents

“…Acylation of the analogues system were also extensively studied. 20,21 Mutual kinetic resolution as a screening method for kinetic and parallel kinetic resolutions Mutual kinetic resolution can be a key initial evaluation method to assess the level of the enantiorecognition of the reagents. The levels of enantiorecognition are quantified by the stereoselectivity factor E, 5 which is determined from the product distribution using 1 H NMR spectroscopic analysis (i.e., ratio of the major diastereoisomeric product to the minor diastereoisomeric product).…”