Mutual kinetic resolution of 3-methyl-3,4-dihydro-2H-1,4-benzoxazines and 2-alkoxyacyl chlorides

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

“…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 …”

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

“…Very recently Vakarov and co-workers studied stereoselective acylation of racemic heterocylic amines and racemic 2-alkoxyacychloride. 19 For example, racemic amine (RS)-28 was treated with racemic acylchloride (RS)-29 in toluene for 6 h, which gave the major diastereoisomeric product (RS)-30 with high selectivity (>96 : 4 dr) and isolated in 85% yield (Scheme 8). Acylation of the analogues system were also extensively studied.…”

Multigram‐scale HPLC enantioseparation as a rescue pathway for circumventing racemization problem during enantioselective synthesis of ethyl 3,4‐dihydro‐2H‐1,4‐benzoxazine‐2‐carboxylate

“…In 2005, an overview of different strategies to provide racemic 1,4-benzoxazine analogs has been published, 22 but only few reports brought up procedures to obtain enantiomerically pure analogs. These procedures use metal [23][24][25][26][27] or phase transfer 28 catalyzed asymmetric reactions, kinetic resolution with enzyme 29,30 or chiral resolving agents, [31][32][33] stereoselective aryl addition, 34 asymmetric baker's yeast reduction, 35 and chiral 1,2-cyclic sulfamidates nucleophilic cleavage. 36 It is interesting to note that, while our targeted scaffold 1 is a key synthon for the design of promising therapeutic drugs (Figure 1), its synthesis and characterizations (optical rotation and electronic circular dichroism [ECD]) as enantiomers were never described in the literature.…”