Protonation-assisted conjugate addition of axially chiral enolates: asymmetric synthesis of multisubstituted β-lactams from α-amino acids.
β-Lactams with contiguous tetra- and trisubstituted carbon centers were prepared in a highly enantioselective manner through 4-exo-trig cyclization of axially chiral enolates generated from readily available α-amino acids. Use of a weak base (metal carbonate) in a protic solvent (EtOH) is the key to the smooth production of β-lactams. Use of the weak base is expected to generate the axially chiral enolates in a very low concentration, which undergo intramolecular conjugate addition without suffering intermolecular side reactions. Highly strained β-lactam enolates thus formed through reversible intramolecular conjugate addition (4-exo-trig cyclization) of axially chiral enolates undergo prompt protonation by EtOH in the reaction media (not during the work-up procedure) to give β-lactams in up to 97% ee.
Institute for Chemical Research, Kyoto University, Uji 611-0011, Japan.
Tomoyuki
T
Yoshimura
Masatoshi
M
Takuwa
Keisuke
K
Tomohara
Makoto
M
Uyama
Kazuhiro
K
Hayashi
Pan
P
Yang
Ryuichi
R
Hyakutake
Takahiro
T
Sasamori
Norihiro
N
Tokitoh
Takeo
T
Kawabata
D000596:Amino Acids / Q000737:chemistry*; D002264:Carboxylic Acids; D002384:Catalysis; D003500:Cyclization; D006865:Hydrogenation; D015394:Molecular Structure; D012997:Solvents; D013237:Stereoisomerism; D047090:beta-Lactams / Q000138:chemical synthesis* / Q000737:chemistry
D000596:Amino Acids; D002264:Carboxylic Acids; D012997:Solvents; D047090:beta-Lactams