2- methylcyclopentanone, enolate

Identify the thermodynamie enolate for each system shown above (2-pentanone enolate A and B 2-methylcyclopentanone enolate A and B decalinone enolate A and B). Also, compare eleetrostatic potential maps for eaeh pair of enolates. What struetural and/or electronic features, if any, appear to dictate which enolate is favored ... 

Carbomethoxy-3-methylcyclopentanone enol methyl carbonate refluxed 24 hrs. in methanolic Na-methoxide -> dimethyl 3-methyladipate. Y 99%. This is the final step of a stereospecific synthesis of polysubst. alkanedioic esters and acids. F. e. s. R. G. and M. F. Salomon, J. Org. Chem. 40, 1488 (1975). 

The syn TS is favored by about 1 kcal/mol, owing to reduced eclipsing, as illustrated in Figure 1.4. An experimental study using the kinetic enolate of 3-(/-butyl)-2-methylcyclopentanone in an alkylation reaction with benzyl iodide gave an 85 15 preference for the predicted cis-2,5-dimethyl derivative. 

The regioselectivity of the enolization can be controlled in a similar way for cyclic ketones. Typical examples are the enolization of 2-methylcyclopentanone (6)5 and 2-methylcyclohex-anone (7)9, u. 

Electrostatic potential map for methylcyclopentanone lithium enolate A, shows negatively-charged regions (in red) and positively-charged regions (in blue). 

Unsymmetrical ketones can yield two different enolates, and in some cases the one that is the less stable thermodynamically is formed faster.148 Scheme 24 illustrates the example of 2-methylcyclopentanone. When this ketone is added slowly to excess f-butyllithium, the proton is removed preferentially from the less substituted carbon. If excess ketone is added, it can serve as a proton donor to allow equilibrium to be established, and nearly all the enolate is then the more highly substituted one.149 It may be possible in some cases to take advantage of such a selective formation of one of two possible enolates in synthesis. A more general procedure is to use a compound in which the desired position is activated... 

The rates for the methylation of cyclopentanone and for the proton abstraction from 2-methylcyclopentanone were significantly increased by a factor of 7500 and 5, respectively, when six equivalents of HMPA were added to the reaction. Using 31P, 7Li and 13C NMR spectroscopy, Suzuki and Noyori found that the tetrasolvated Dy dimer was exclusively generated from the tetrameric (T0,4) and dimeric (D0,4) tetrasolvated lithium amine-free enolate of cyclopentanone (0.16 M in THF, —100 °C, ratio 2/3)275. Kinetic analysis gave a first-order reaction in dimer and HMPA for the reaction with a modulation for free HMPA33, and a first-order reaction in dimer for deprotonation, independent of HMPA. Possible transition state structures for alkylation and proton abstraction are drawn in Scheme 85. 

Scheme 2 shows the results of two studies on the methylation of the lithium enolate of cyclopentanone (10), which was prepared by deprotonation of the ketone with trityllithium in DME or by cleavage of the 1-trimethylsiloxycyclopentene with methyllithium in THF. A signiEcant quantity of over-alkylation occurred when the enolate was treated with methyl iodide, particularly when DME was employed as the solvent at room temperature. Also, as indicated in Scheme 2, Noyori and coworkers showed that by adding 3 equiv. of HMPA to the enolate (10) and reducing the temperature at which the reaction was conducted, the yield of 2-methylcyclopentanone was greatly improved.

Posner investigated the addition of the larger naphthyl Grignard reagent (65) to enantiomerieally pure cyelopentanone sulfoxide (66). The reaetion proeeeded with excellent enantioselectivity to provide P-naphthyl-a-methylcyclopentanone sulfoxide (67) in 42% yield and >98% de after in situ methylation of the intermediate enolate anion (Scheme 4.34) [42]. 

When the thermodynamic enolate of 2-methylcyclopentanone reacts with benzophenone, the reaction is sluggish, but assume that the aldol product is formed. Draw this product. Will heating this product lead to the alkene product Now draw the product expected from the reaction of the kinetic enolate anion and benzophenone. Will heating this product lead to the alkene ... 

Deprotonation of an unsytnmetrical ketone such as 2-methylcyclopentanone may lead to two isomeric species, a more substituted and a less substituted enolate. The former, featuring the more substituted double bond, is more stable than the latter (Section 11-5). As in the elimination reaction of a haloalkane via the E2 mechanism (Section 7-7), the choice of base and reaction conditions determines which one is formed. For example, addition of 2-methylcyclopentanone to a cold solution of LDA in THF gives predominantly the less substituted, less stable enolate. The reason is that LDA is a bulky base and prefers to remove a hydrogen from the less-hindered a-carbon, generating the less stable anion, termed the kinetic enolate. Under these conditions, namely, the absence of a proton source and at low tanperatures, equilibration with the more stable enolate does not occur, and the kinetic enolate can be used as such in practical further transformations. 

When 2-methylcyclopentanone is treated with the bulky base hi-phenyhnethyllithium under the two sets of conditions shown, the two possible enolates are generated in differing ratios. Why is... 

Write the structures of the isomeric enols of 2-methylcyclopentanone and rank them in order of relative stability. 

Methylcyclopentanone gives a mixture of two enolates in a 94 6 ratio, (a) Write their structures and (b) assign their relative stabilities. 

Ketones were deprotonated with GaEta at higher temperatures [55]. Carbonyl addition or reduction by GaEta did not proceed, which was contrasted with the use of AlEta giving only a small amount of the enolate accompanied by considerable amounts of the byproducts. GaEta turned out to be a nonnucleophilic base for ketone enolization. The reaction of 2-methylcyclopentanone at 125 followed by reaction with benzoyl chloride predominantly gave a 5-benzoyl derivative, indicating that deprotonation occurred at a less hindered site (Scheme 7.29). The reaction... 

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