Enolates 2-methyl-2- -3-pentanone

Fig. 7.3. Crystal structures of some lithium etiolates of ketones. (A) Unsolvated hexameric enolate of methyl t-butyl ketone (B) tetrahydrofuran solvate of tetramer of enolate of methyl r-butyl ketone (C) tetrahydrofuran solvate of tetramer of enolate of cyclopentanone (D) dimeric enolate of 3,3-dimethyl-4-(r-butyldimethylsiloxy)-2-pentanone. (Structural diagrams are reproduced from Refs. 66-69.) by permission of the American Chemical Society and Verlag Helvetica Chimica Acta AG.

Still s synthesis of monensin (1) is based on the assembly and union of three advanced, optically active intermediates 2, 7, and 8. It was anticipated that substrate-stereocontrolled processes could secure vicinal stereochemical relationships and that the coupling of the above intermediates would establish remote stereorelationships. Scheme 3 describes Still s synthesis of the left wing of monensin, intermediate 2. This construction commences with an aldol reaction between the (Z) magnesium bromide enolate derived from 2-methyl-2-trimethylsilyloxy-3-pentanone (21) and benzyloxymethyl-protected (/ )-/ -hydroxyisobutyraldehyde (10).2° The use of intermediate 21 in aldol reactions was first reported by Heathcock21 and, in this particular application, a 5 1 mixture of syn aldol diastereoisomers is formed in favor of the desired aldol adduct 22 (85% yield). The action of lithium diisopropylamide (LDA) and magnesium(n) bromide on 21 affords a (Z) magnesium enolate that... 

In contrast to LDA, LiHMDS favors the Z-enolate.14 Certain other bases show a preference for formation of the Z-enolate. For example, lithium 2,4,6-trichloroanilide, lithium diphenylamide, and lithium trimethylsilylanilide show nearly complete Z-selectivity with 2-methyl-3-pentanone.15... 

The E.Z ratio can be modified by the precise conditions for formation of the enolate. For example, the E.Z ratio for 3-pentanone and 2-methyl-3-pentanone can be increased by use of a 1 1 lithium tetramethylpiperidide(LiTMP)-LiBr mixture for... 

Little steric differentiation is observed with either the lithium or boron enolates of 2-methyl-2-pentanone.102... 

A lower molecular weight methyl ketone and an olefin are isolated as products of this reaction. That the enol is formed as a primary product which rearranges to the ketone follows from its detection in the IR spectrum of gaseous 2-pentanone upon photolysis. 3 In addition to the ketone and olefinic products, one usually obtains varying amounts of cyclobutanols. 

A jy -diastereoselective aldol reaction based on titanium enolates from (A)-l-benzyloxy-2-methyl-3-pentanone was developed by Solsona et al. (Equation (12)).64 The titanium enolate of this chiral ketone afforded the corresponding syn-syn aldol adducts in high yields and diastereomeric ratios with a broad range of aldehydes. 

The is-boron enolates of some ketones can be preferentially obtained with the use of dialkylboron chlorides.17 The data in Table 2.3 pertaining to 3-pentanone and 2-methyl-3-pentanone illustrate this method. Use of boron triflates with a more hindered amine favors the Z-enolate. The contrasting stereoselectivity of the boron triflates and chlorides has been discussed in terms of reactant conformation and the stereoelectronic requirement for perpendicular alignment of the hydrogen being removed with the carbonyl group.18 The... 

The procedure reported here provides a convenient method for the a-hydroxylation of ketones which form enolates under the reaction conditions. The reaction has been applied successfully to a series of para-substituted acetophenones, 1-phenyl-1-propanone, 3-pentanone, cyclopentanone, cyclohexanone, cycloheptanone, cyclododecanone, 2-methyl cyclohexanone, 2-norbornanone and benzalacetone. In the case of a steroidal example it was shown that a carbon-carbon double bond and a secondary hydroxyl group are not oxidized. A primary amino function, as in the case of p-aminoacetophenone, is not affected.5 Similarly, a tertiary amino ketone such as tropinone undergoes the a-hydroxy at ion reaction.5... 

The reductive dehalogenation predominates in the photoinduced reactions of 32 with 3-pentanone, 2-methyl-3-pentanone, and 2,4-dimethyl-3-pentanone. Although, substitution is favored over reduction in all of the reactions of 32 with cyclic ketone enolates, a competing reduction is responsible for the lower yields observed with cyclopentanone and cyclohexanone compared to cyclooctanone (Scheme 10.59) [73]. 

TS Z-chair A). On the other hand, the Zi-enolates of 3-pentanone and methyl propanoate gave products slightly favoring a yyn-diastereomer. 

In the absence of chelation, comparison of the destabilizing syw-pentane interactions recently encouraged Evans and coworkers to use the Comforth model to justify the exalted 3,4-anti selectivity observed for a series of chiral a-oxygenated aldehydes reacting with the Z(O) boron and lithium enolates of 2-methyl-3-pentanone (Scheme 117)568. Comple-mentarily, the corresponding E(O) isomers showed, as expected, a striking difference in their 2,3-selectivities, while the 3,4 anti-selectivity was lowered in both cases a finding inconsistent with the PFA model. 

Stereoselective aldol condensation. Heathcock and Buse have previously employed 2-methyl-2-trimethylsiloxy-3-pentanone (1) in a highly stereoselective route to 3-hydroxy-2-methylcarboxylic acids (8, 295). Aldol condensation of the lithium enolate derived from 1 with a chiral aldehyde yields ery//iro-aldols, which are cleaved with periodic acid to -hydroxy carboxylic acids. However, when 1 is condensed with a chiral aldehyde such as 2, two eryt/iro-products (3 and 4) are produced. Heathcock and co-workers now report that the 1,2-diastereoselectivity of these aldol condensations can be enhanced by use of the ketone 5. Reaction of racemic 5 with racemic aldehyde 2 furnishes a single (racemic) adduct 6. 

Cp 2La CH(SiMe3)2 reacts with 3-pentanone to form the solvated enolate, Cp 2La —O—C(Et)=CHMe Et2CO (equation 9a), while with acetone it forms a chelate (equation 9b) after intramolecular aldol condensation. The reaction of the precursor bistrimethylsi-lyhnethyl organometallic with hydroxyketone, preformed from the pentanone, yields the enolate ketone solvate. This difference between acetone and 3-pentanone presumably reflects the difference in strain in the condensation product because the ethyl groups in 3-pentanone are rather much bigger than the methyl groups in acetone. 

Access to key materials for synthesis in this group has been possible for some years by reaction of acrolein with 2-methyl-3-pentanone in presence of p-toluenesulfonic acid, distilling off the water formed during the reaction, and leading to 2,6,6-trimethyl-2-cyclohexenone (690). Alternatively, 2-methyl-3-pentanone reacts with methyl acrylate in the presence of base (sodium methoxide/ methanol in xylene) to give 92% of the diketone 691 (probably as the enol). ... 

In one of the first such examples, the lithium enolate of (S)-3-methyl-2-pentanone was allowed to react with several aldehydes in the case of propanal, the two products are formed in 15% diastereomeric excess, favoring (179 equation 115). The di- -butylboron enolate of this ketone has been studied and found to give (179) and (180) in a ratio of 63 37 in CH2CI2 and 64 36 in pentane. ... 

There are many cases when formation of an enolate anion from a ketones is accompanied by formation of ( ) and (Z) isomers. Treatment of 2-methyl-3-pentanone with LDA (THF, -78°C), for example, gave a 60 40 mixture of the (Z) and (E) enolates (24 and 25) Subsequent reaction of 24 and 25 with a carbonyl... 

The procedure reported here provides a convenient method for the a-hydroxylation of ketones which form enolates under the reaction conditions. The reaction has been applied successfully to a series of para-substituted acetophenones, 1-phenyl-1-propanone, 3-pentanone, cyclopentanone, cyclohexanone, cycloheptanone, cyclododecannne, 2-methyl cyclohexanone, 2-... 

Diacetone alcohol [123-42-2] (4-hydroxy-4-methyl-2-pentanone) is an almost odorless ketone alcohol that is weakly acidic as a result of rearrangement to the enol form. It is miscible with water and organic solvents except aliphatic hydrocarbons. It acts as a good solvent for cellulose esters and ethers, alcohol-soluble resins, castor oil, and plasticizers. Poly(vinyl acetate) and chlorinated rubber are partially dissolved or swollen. Polystyrene, poly(vinyl chloride), vinyl chloride copolymers, dam-ar resins, resin esters, rubber, bitumen, mineral oils, ketone resins, and maleate resins are insoluble. Diacetone alcohol is used as a high boiler in stoving enamels to improve flow and gloss. 

The carbon-carbon bond cleavage step in a retro-aldol reaction involves, under basic conditions, a leaving group that is an enolate, or under acidic conditions, an enol. Write a mechanism for the retro-aldol reaction of 4-hydroxy-4-methyl-2-pentanone under basic conditions (shown above). 

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