Structural characterization of an enantiomerically pure amino acid imidazolide and direct formation of the beta-lactam nucleus from an alpha-amino acid.

Decomposition of a diazo beta-ketoamide derived from N-trityl serine imidazolide and N-protected acetanilides provides, instead of the expected 3-acyloxindole product, an enantiomerically pure (EP) beta-lactam. The amino acid stereocenter is incorporated, the second chiral center is induced, and trityl protection of the beta-lactam ring is realized for the first time. The desired 3-acyloxindole is obtained from oxindole and Tr-Ser(OBn)-imidazole, the X-ray of which provides the first structural determination of an EP amino acid imidazolide.

A Lewis acid-Lewis base bifunctional catalyst from a new mixed ligand.

Covalent attachment of quinine to a salen framework through a racemic linker gave a new mixed ligand in a 1:1 diastereomeric mixture, from which an active Lewis acid-Lewis base (LA*-LB*) bifunctional catalyst derived from Co(II) was discovered by the screening of metal complexes. The remarkable intramolecular bifunctional catalytic activity (1 mol % catalyst loading) of the new catalyst was demonstrated using a proof-of-principle reaction. [reaction: see text].

Carbanion stabilization by distal silyloxy groups. Origin of the high diastereoselectivity in the formation of quaternary centers with aryllead(IV) triacetate reagents.

Derivatives of methyl 5-hydroxy-2-oxo-1-cyclohexanecarboxylate react with aryllead(IV) reagents in high yield and with wide variation in diastereoselectivity. Ab initio calculations are consistent with a heretofore unrecognized attraction between the carbanionic center of the beta-ketoester intermediate and the distal OSiR(3) group. This attractive interaction stabilizes the silyl group in the axial conformation and leads to the excellent trans diastereoselection in the formation of quaternary centers. [reaction: see text]

Diazonamide support studies: stereoselective formation of the C10 chiral center in both the CDEFG and AEFG fragments.

The synthesis of both the AEFG macrolactam and the CDEFG bis-indole/tyrosine units found in the marine natural product diazonamide A is presented. Key to the success of the synthesis is the highly stereoselective direct C-arylation of an oxindole by an aryllead(IV) reagent derived from tyrosine.