Methyl ketone enolates

Carbohydrate-derived methyl ketone enolates show absolutely no induced diastereosclcctivity with respect to aldehydes see ... 

Methyl ketone enolates are hydroxylated by MoOPH, but the products tend to undergo condensation with the starting enolate, resulting in poor yields. Methyl ketone hydroxylation has been described by Moriarty, using c6H5I=0/CH30H-°He.a... 

It is also generally true that the greater the number of contributing resonance forms, the greater will be the resonance stabilization. For this reason die enolate of a yS -diketone has much more resonance stabilization than die enolate of a simple ketone (three resonance forms versus two). The electrons are delocalized over five atoms in the former versus three atoms in the latter. In addition, the electron density on the carbon atom is less in the diketone enolate than in a simple methyl ketone enolate. 

Methyl ketone enolates bearing a /1-heteroatom substituent have been designed to effect highly 1,5-diastereoselective additions to aldehyde electrophiles and used to achieve double-stereodifferentiating aldol reactions.30... 

Some /J-heteroatom substituted a,/J-unsaturated acyl silanes react with methyl ketone enolates in a stepwise stereoselective cyclopentannelation process, formally a [3 + 2] annelation, which may proceed through aldol reaction followed by Brook rearrangement and cyclization (Scheme 111)223. 

Ab initio through-space/bond interaction analysis was applied to 3 + 2-anulation based on Brook rearrangement using /i-phcnylthioacryloylsilanes with alkyl methyl ketone enolates (Scheme 103).150 The major product has the large substituents on the same side of the five-membered ring. Orbital interactions related to the carbanion... 

On the other hand, with heterosubstituted chiral aldehydes, the product distribution for the reaction with methyl ketone enolates is strongly influenced by the nature of the metal, the nature of the heteroatom and its position within the molecule. A chair-like transition state explained the formation of the Felkin adduct, while a boat-like transition state was invoked for the formation of the anti-Felkin adduct. However, this assumption was recently challenged by Roush and coworkers using deuterated pinacolone lithium enolate565. Performing a set of aldolizations with chiral and non chiral aldehydes led these authors to show that the isomeric purity of the enolate correlates almost perfectly with the ratio and pattern of deuterium labeling in the 2,3-an/t-aldol formed consistent with a highly favoured chair-like transition state (Scheme 115). 

Denmark, S. E., Stavenger, R. A., Wong, K.-T. Lewis Base-Catalyzed, Asymmetric Aldol Additions of Methyl Ketone Enolates. J. Org. Chem. 1998, 63, 918-919. 

Same measures of stereocontrol had previously been observed in approaches to pyrethroid acids involving intramolecular enolate alkylation. As outlined in Figure 3, workers at Sumitomo have investigated the cyclization of a methyl ketone enolate (5). They obtained a 9 1 ratio of cis trans products upon ring closure initiated by sodium hydroxide. The methyl ketone was subsequently converted to the corresponding carboxylic acid via the haloform reaction. 

Figure 3. Stereoselection in the cyclization of the methyl ketone enolate...

For the addition of acetate and methyl ketone enolates (one new stereocenter), a number of approaches have been taken to induce enantioselectivity (review [69]) one of these methods will be mentioned in the succeeding section, along with the propionate and ethyl ketone additions. In the open transition structures of Figure... 

Denmark SE, Stavenger RA, Wong K-T (1998) Lewis base-catalyzed, asymmetric aldol additions of methyl ketone enolates. J Org Chem 63 918-919... 

Methylenetitanocene complex 70, generated from the dimethyltitanacyclobu-tane 69 reacts vith acid chlorides and anhydrides [67]. Ho vever, as acid chloride is more reactive to vards 70 than ester, the succinic acid monoester monochloride 71 is converted indo aldol 73 via methyl ketone enolate 72 vith high selectivity (Scheme 12.47) [67b[. 

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