Acylative kinetic resolution of racemic amines using N-phthaloyl-(S)-amino acyl chlorides

Synthesis of functionalised β-keto amides by aminoacylation/domino fragmentation of β-enamino amides

“…Thus, the α-C-acylated intermediates 3a–j ( Table 1 ) and 4 ( Table 2 ) were obtained in good yields and excellent chiral integrity (er 3c – f ≥ 99:1). The phthaloyl-protected compounds 3k and 3l were obtained in low yields by the mixed carbonic anhydride method and after screening various alternative coupling reagents (mixed pivalic anhydrides, T3P, DCC, DIC, CDI) we were able to improve the yields of 3k , l to 77% and 60%, respectively, only by using the corresponding N -phthaloyl amino acid chlorides [ 35 – 36 ] as acylating reagents. The increased yield however came at the expense of chiral integrity, with nearly full racemisation.…”

Mutual Kinetic Resolution of Racemic 3,4‐Dihydro‐3‐methyl‐2H‐[1,4]benzoxazines with Acyl Chlorides of Racemic O‐Phenyllactic Acids and DFT Modelling of Transition States

“…Racemic 3‐methylbenzoxazines 1a and 1b and individual ( S ) enantiomers ( ee ≥ 97 %) were obtained as described previously. [5b], The acylating agents 2a – c were prepared starting from the corresponding acids upon treatment with an excess of oxalyl chloride (3 equiv. ).…”

“…GC analyses of amides 3a – c and 4a – c were performed by using a Shimadzu GC‐2010 instrument with a ZB‐5 capillary column (30 m × 0.25 mm × 0.25 µm). Racemic 3,4‐dihydro‐3‐methyl‐2 H ‐[1,4]benzoxazine ( 1a ), 7,8‐difluoro‐3,4‐dihydro‐3‐methyl‐2 H ‐[1,4]benzoxazine ( 1b ),[9a] their ( S )‐ enantiomers ( S )‐ 1a and ( S )‐ 1b [5b],[9b, c] and the racemic acids 5a ,[10b] 5b [10c] and 5c [10a] were prepared according to previously reported procedures. Acyl chloride 2a and amides ( R *, S* )‐ 3a and ( R *, S* )‐ 4a have been described earlier.…”

“…In recent years we have studied the acylative KR of racemic heterocyclic amines with enantiopure acyl chlorides, the derivatives of amino acids and 2‐arylpropionic and 2‐phenoxy acids . One of the goals of these studies was to establish the dependence of the stereochemical outcome of acylation on the reagent structures and reaction conditions in order to improve the efficiency of KR.…”

2-Arylpropionyl chlorides in kinetic resolution of racemic 3-methyl-2,3-dihydro-4H-[1,4]benzoxazines

“…Such an approach, which allows one to obtain individual enantiomers of chiral heterocyclic amines in high enough yields, is being successfully developed in our research group during last years. [20][21][22][23][24][25] It is known 26-29 that 2 arylpropionic acid derivatives can be used for the KR of racemic amines and alcohols. (S) Naproxen ((2S) 2 (6 methoxynaphth 2 yl)pro pionic acid) acyl chloride was for the first time used for the KR of racemic heterocyclic amines, 20,21 including 7,8 difluoro 3 methyl 2,3 dihydro 4H [1,4]benzoxazine (1) and 3 methyl 2,3 dihydro 4H [1,4]benzoxazine (2).…”