Methylcarbapenem intermediate stereoselective synthesis

The same author [63] reported the synthesis of 1 (3-methylcarbapenem intermediates such as 111 (Scheme 16), employing chiral imines prepared from (S)-methyl 3-hydroxy-2-methylpropionaldehyde and p-anisidine or DAM-NH2. The reaction of diketene 98 with these imines in the presence of imidazole produced a diastereomeric mixture of P-lactams 107 and 108 in a variable ratio. These authors found that the best results in terms of chemical yield and stereoselectivity could be obtained when the [2 + 2] cycloaddition reaction was performed on imines derived from DAM-NH2 toluene as solvent and using 4-methylimidazole instead of imidazole. Under these conditions the P-lactam 108b was obtained in 49% yield and the ratio of isomers 107b/108b was 1 15. 

Considerable efforts have been devoted to the stereoselective introduction of a /(-methyl function in intermediates for the synthesis of 1 jS-methylcarbapenems. While the trimethylsilyl trifluoromethanesulfonate catalyzed reaction of a 4-acetoxyazetidinone derivative with ketene acetals shows no selectivity, ketene thioacetals lead to stereoselective formation of the a-methyl isomer108. The zirconium enolate, however, shows high /(-methyl selectivity. 

P-Lactams. Diketene can function as an equivalent to acetylketene, CH3C0CH=C=0, to provide 3-acetyl-p-lactams by [2 + 2]cycloaddition with imines.1 A stereoselective cycloaddition of this type can furnish a useful precursor (2) to lp-methylcarbapenems. Thus reaction of diketene with the chiral imine 1, prepared in a few steps from the readily available methyl (S)-3-hydroxy-2-meth-ylpropionate (Aldrich), can provide the desired 3,4-frpreviously developed for synthesis of the antibacterial carbapenem 4. 

Intramolecular acid- or rhodium [II]-cataIysed carbene nitrogen-hydrogen insertion from iodonium ylide intermediates was used in an efficient synthesis of 1-/1-methylcarbapenems the cyclization products had different stereoselectivity, depending on the catalyst [11] ... 

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