Asymmetric synthesis of unusual fused tricyclic beta-lactam structures via aza-cycloadditions/ring closing metathesis.
Conveniently substituted bis-beta-lactams, pyrrolidinyl-beta-lactams, and piperidinyl-beta-lactams undergo ring-closing methatesis using Grubbs' carbene, Cl(2)(Cy(3)P)(2)Ru=CHPh, to give medium-sized rings fused to bis-2-azetidinone, pyrrolidinyl-2-azetidinone, or piperidinyl-2-azetidinone systems. The diolefinic cyclization precursors can be obtained from optically pure 4-oxoazetidine-2-carbaldehydes bearing an extra alkene tether at position 1 or 3 of the beta-lactam ring via [2 + 2] cycloaddition of imino 2-azetidinones, N-metalated azometine ylide [3 + 2] cycloaddition, and subsequent N-acylation of the pyrrolidinyl nitrogen atom, or through aza-Diels-Alder cycloaddition of 2-azetidinone-tethered imines. Under standard reaction conditions, the combination of cycloaddition reactions of 2-azetidinone-tethered imines with ring-closing methatesis offers an asymmetric entry to a variety of unusual fused tricyclic 2-azetidinones bearing two bridgehead nitrogen atoms.
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
Redondo
María C
MC
D001372:Aza Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D002625:Chemistry, Organic / Q000379:methods; D003500:Cyclization; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D007097:Imines / Q000737:chemistry*; D007202:Indicators and Reagents; D015394:Molecular Structure; D013237:Stereoisomerism; D047090:beta-Lactams / Q000138:chemical synthesis* / Q000737:chemistry
D001372:Aza Compounds; D006571:Heterocyclic Compounds; D007097:Imines; D007202:Indicators and Reagents; D047090:beta-Lactams