Diastereoselective acylation of 3,4-dihydro-3-methyl-2H-[1,4]benzoxazines with 2-phenoxy carbonyl chlorides

作者：Vakarov Sergey A; Gruzdev Dmitry A; Sadretdinova Liliya Sh; Chulakov Evgeny N; Pervova Marina G; Ezhikova Marina A; Kodess Mikhail I; Levit Galina L^*; Krasnov Victor P

来源：Tetrahedron: Asymmetry , 2015, 26(5-6): 312-319.

DOI：10.1016/j.tetasy.2015.02.004

In the search for novel efficient chiral resolving agents, we have studied the diastereoselective acylation of 3,4-dihydro-3-methyl-2H-[1,4]benzoxazine and 7,8-difluoro-3,4-dihydro-3-methyl-2H-[1,4]benzoxazine with acyl chlorides of 2-phenoxy carboxylic acids (2-phenoxypropionic, 2-phenoxyisovaleric, and 2-phenoxy-3-phenylpropionic) in toluene and dichloromethane at different temperatures. HPLC analysis of the acylation products showed the predominant formation of (R*,S*)-diastereoisomeric amides in all cases. It was found that acylation with the studied acyl chlorides was highly stereoselective; 2-phenoxy-isovaleryl chloride demonstrated the highest stereoselectivity (selectivity factors up to 499). A model for the diastereoisomeric transition states in the interaction between racemic amine and acyl chloride is proposed.

• 出版日期2015-3-28