Synthesis of optically pure highly functionalized gamma-lactams via 2-azetidinone-tethered iminophosphoranes.
A synthesis of optically pure densely functionalized gamma-lactams starting from 2-azetidinone-tethered iminophosphoranes has been developed. Full chirality transfer has been accomplished from the enantiomerically pure 2-azetidinones. The addition of lithium acetylides to 4-oxoazetidine-2-carbaldehydes at -78 degrees C smoothly yielded propargylic alcohols with excellent diastereoselectivities. Propargylic alcohols were converted to mesylates, which by exposure to sodium azide afforded the corresponding azides. Treatment of beta-lactams bearing an azido side chain with triphenylphosphine (TPP) gave lambda(5)-phosphazenes (iminophosphoranes, phosphine imines), which were not isolated. The sodium methoxide promoted reaction of the phosphazene beta-lactams smoothly provided gamma-lactams, through a N1-C2 bond breakage process on the four-membered lactam with concomitant ring expansion, followed by hydrolysis.
Alcaide
Benito
B
Departamento de Química Orgánica I, Facultad de Química, Universidad Complutense, 28040 Madrid. Spain. alcaideb@quim.ucm.es
Almendros
Pedro
P
Alonso
Jose M
JM
D001384:Azetidines / Q000737:chemistry*; D007097:Imines / Q000737:chemistry; D007769:Lactams / Q000138:chemical synthesis* / Q000737:chemistry; D010753:Phosphoranes / Q000737:chemistry*; D013237:Stereoisomerism
C116379:2-azetidinone; D001384:Azetidines; D007097:Imines; D007769:Lactams; D010753:Phosphoranes