Additions Leading to a-Substituted Amino Acids

The addition of halogen to acylaminoacrylic esters with subsequent loss of hydrogen halide to form p-halo-a-acylamino-acrylic esters has been the subject of numerous reports 198, 274, 330, 376). p-Bromo-a-acylamino-acrylic ester is also obtainable by rearrangement of N-bromo-a-acylamino-acrylic ester (378). Further reaction of the P-halo-a-acyl-aminoacrylic esters with bromine or N-bromosuccinimide and subsequent treatment with alcohol affords P,P-dihalo-a-alkoxy-a-acylaminopro-pionic acid esters 274, 379), important intermediates for biomimetic P-lactam syntheses (275). 

Kinetically controlled addition of hydrogen halide to acylaminoacrylic ester leads to a-halo-a-acylamino-propionic acid ester (76), which gradually rearranges in the reaction solution into the p-halo-derivative 236, 241, 301). The a-halo compound can be captured with mercaptans, alcohols or water, forming the appropriate a-substituted a-acylamino-propionic acid esters (77) 197,199). 

Alkoxymercuration of acylaminoacrylic acids followed by NaBILi-reduction affords a-alkoxy-a-acylaminopropionic acids 139). 

Amides can be added to acylaminoacrylic ester even without acid catalysis to form the a,a-diacylaminopropionic acid ester 150, 364). An analogous addition has been described in the reaction of N-acyl-dehydro-proline with acetamide 136) (see Section IV. A. 6). Analogous intramolecular additions, leading to the formation of five- and six-membered rings, proceed even under basic catalysis (see Section VI. A. 2.4). 

Finally, the first step in the acid hydrolysis of an acylenamino acid to acylamide and a-keto acid is the electrophilic addition of a proton. 

---