Asymmetric hydrogenation of N-sulfonylated-alpha-dehydroamino acids: toward the synthesis of an anthrax lethal factor inhibitor.
A novel and highly enantioselective Ru-catalyzed hydrogenation of N-sulfonylated-alpha-dehydroamino acids has been discovered and demonstrated in the synthesis of an anthrax lethal factor inhibitor (LFI). Herein, this methodology is used to prepare N-sulfonylated amino acids in up to 98% ee. This unprecedented hydrogenation uses a chiral Ru catalyst rather than Rh as typical for acylated dehydroamino acids and esters, and this work reports the first asymmetric hydrogenation of a tetrasubstituted dehydroamino acid derivative using a Ru catalyst. [reaction: see text]
Shultz
C Scott
CS
Department of Process Research and the Catalytic Reactions Discovery and Development Lab, Merck and Co Inc., P.O. Box 2000, Rahway, New Jersey 07065. scott_shultz@merck.com
Dreher
Spencer D
SD
Ikemoto
Norihiro
N
Williams
J Michael
JM
Grabowski
Edward J J
EJ
Krska
Shane W
SW
Sun
Yongkui
Y
Dormer
Peter G
PG
Dimichele
Lisa
L
D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000942:Antigens, Bacterial; D001408:Bacillus anthracis / Q000737:chemistry / Q000472:pathogenicity; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors*; D002384:Catalysis; D006865:Hydrogenation; D012428:Ruthenium / Q000737:chemistry*; D013237:Stereoisomerism
D000596:Amino Acids; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; C030325:anthrax toxin; D012428:Ruthenium