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Asymmetric Synthesis of Unusual Fused Tricyclic β-Lactam Structures via Aza-Cycloadditions/Ring Closing Metathesis

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journal contribution
posted on 18.01.2003, 00:00 by Benito Alcaide, Pedro Almendros, Jose M. Alonso, María C. Redondo
Conveniently substituted bis-β-lactams, pyrrolidinyl-β-lactams, and piperidinyl-β-lactams undergo ring-closing methatesis using Grubbs' carbene, Cl2(Cy3P)2Ru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 β-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.