Enol acyl, formation iodide

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... 

Methyl ketones. The Tebbe reagent (1) reacts with acyl chlorides to form methyl ketones in 35-65% yield (equation I). That an intermediate titanium enolate may be involved is indicated because addition of methyl iodide before aqueous work-up results in formation of an ethyl ketone. 

Unbranched and substituted alkyl carbamates, such as 146 or 147 [62,88] do not cause any problems in the deprotonation step. Deuteration (with CH3OD or dissolved CH3CO2D), methoxycarbonylation (gaseous CO2, followed by diazomethane after work-up or methyl chloroformate), alkylation with methyl iodide, substitution with trialkylsilyl chlorides, trialkyltin chlorides and even tri-methyllead bromide, addition onto aldehydes and ketones, and acylation with acid chlorides or esters, all proceed without difficulties. Although a ketone is formed in the latter reactions, which is at least 15 orders of magnitude thermodynamically more acidic than the alkyl carbamate we never observed enolate formation, racemization or epimerization - with one exception it occurred to some extent after formylation with formate esters [79]. 

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