Lithium diisopropylamide, reaction with lactams

When 2-lithio-2-(trimethylsilyl)-l,3-dithiane,9 formed by deprotonation of 9 with an alkyllithium base, is combined with iodide 8, the desired carbon-carbon bond forming reaction takes place smoothly and gives intermediate 7 in 70-80% yield (Scheme 2). Treatment of 7 with lithium diisopropylamide (LDA) results in the formation of a lactam enolate which is subsequently employed in an intermolecular aldol condensation with acetaldehyde (6). The union of intermediates 6 and 7 in this manner provides a 1 1 mixture of diastereomeric trans aldol adducts 16 and 17, epimeric at C-8, in 97 % total yield. Although stereochemical assignments could be made for both aldol isomers, the development of an alternative, more stereoselective route for the synthesis of the desired aldol adduct (16) was pursued. Thus, enolization of /Mactam 7 with LDA, as before, followed by acylation of the lactam enolate carbon atom with A-acetylimidazole, provides intermediate 18 in 82% yield. Alternatively, intermediate 18 could be prepared in 88% yield, through oxidation of the 1 1 mixture of diastereomeric aldol adducts 16 and 17 with trifluoroacetic anhydride (TFAA) in... 

The lithium diisopropylamide solution prepared above is transferred dropwise, via a cannula, into the bicyclic lactam solution. The dry ice/acetone bath is replaced by an ice-water bath, where the reaction mixture is kept for 40 min to complete formation of the lithium enolate. The reaction mixture is cooled again (30 min) with a dry ice/acetone bath. Freshly distilled ethyl iodide (25.8 g, 13.4 mL, 165.4 mmol) (Note 9) is added slowly, via syringe, to the mixture and stirring is continued for 55 min in a... 

In 2001, Sierra and coworkers have reported that ethyl 3-ferrocenylpropanoate reacting with an excess of lithium diisopropylamide (LDA) afforded an enolate that condensed with imine the resulting reaction mixture contained the expected 2-azetidinone as a cisltrans mixture (3 1), and the unexpected 3-hydroxy p-lactam [136]. The ferrocene moiety was linked to the p-lactam ring at the C-3 position, (Scheme 51). 

These compounds can be alkylated twice at the 6-position in a stereocontrolled fashion (eq 2). Treatment of the unsubstimted bicyclic lactam with Lithium Diisopropylamide and reaction of the enolate anion with an alkyl halide affords the monosubstimted product The epimeric mixture is treated again with LDA and a second alkyl halide to give the dialkylated bicyclic lactam. The... 

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