Enolate anions, lactams, reaction with

An abnormal unidirectional Claisen reaction has been reported for the addition of deprotonated cyclohexyl [l- C]acetate (58) to the carbonyl group of the a-N-Boc-substituted lactone 59, providing hemiketal 60 (Figure 6.24). The competitive condensation of the enolate anion of 59 with 58 is probably hindered for steric reasons by the deprotonated A-Boc group or because of its negative charge. Subsequent catalytic reduction furnished a mixture of the A-Boc-amino diol 61 and its epimer. Deprotection of the desired epimer followed by base-catalyzed cyclization provided lactam 62, the key intermediate in the synthesis of [3- C]castanospermine 63. ... 

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... 

The [2 -I- 2] cycloaddition of ketenes and imines is an important route to the P-lactam ring (azetidinone), which is a crucial structural feature of the penicillin class of antibiotics. A number of theoretical treatments of this reaction indicate that in solution phase this is a two-step reaction, with the second step being rate determining. The stepwise nature of the reaction is accommodated by the relative stability of both charged moieties, an iminium cation and an enolate anion. 

The ylide from (97) reacted with llV-desmethyIdiazepam (35) in a one-pot reaction to give (98) in 50% yield (Equation (3)). This is a variation on the more usual reaction in which the lactam is converted into an enol phosphate, for example, by reaction with sodium hydride and dimorpholinophosphonic chloride, which is then reacted with the anion of dimethyl malonate <93JHC945>. 

Treatment of a-silyl esters with a base readily affords the corresponding enolates, which can be utilized for Peterson reactions (Scheme 2.70) [189-196]. LDA is the most widely used base for the deprotonation of a-silyl esters. The carbonyl compounds used in the above reactions are aldehydes, saturated and unsaturated ketones, amides, lactones, and lactams. The products, a,j8-unsaturated esters, are obtained as mixtures of the E- and Z-isomers in most cases. When another trimeth-ylsilyl group is present on the anionic carbon atom, the reactions of the carban-ion derived from the a,a-bis(trimethylsilyl) esters with ketones are unsuccessful, probably because of steric reasons, and result only in enolization [197]. 

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