Novel extension of Meyers' methodology: stereoselective construction of axially chiral 7,5-fused bicyclic lactams.
A novel extension of Meyer's lactamization is reported for the preparation of seven-membered ring lactams 1a-d incorporating a biaryl unit. The required keto-esters 2a-c were readily accessible via the Suzuki coupling reaction. A borylation-Suzuki coupling (BSC) sequence was successfully developed for the high-yielding preparation of keto-ester 2d. Cyclization of the resulting keto-esters 2a-d or keto-acids 5a,c,d in the presence of (R)-phenylglycinol afforded the desired lactams 1a-d in high yields (72-93%) and excellent diastereoselectivities (>95%). This methodology provides a facile stereoselective access to new axially chiral bridged biaryls.
Penhoat
Maël
M
Laboratoire de Chimie Organique Fine et Hétérocyclique Associé au CNRS, IRCOF-INSA, Rue Tesnières B.P 08, F-76131 Mont Saint Aignan Cédex, France.
Levacher
Vincent
V
Dupas
Georges
G
D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D003500:Cyclization; D007769:Lactams / Q000138:chemical synthesis* / Q000737:chemistry; D008024:Ligands; D008956:Models, Chemical; D015394:Molecular Structure; D013237:Stereoisomerism; D013997:Time Factors
D007769:Lactams; D008024:Ligands