2- Methylcyclopentanone, alkylation

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 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. 

TABLE 5. Regio- and enantioselective alkylation of 2-methylcyclopentanone (31a) and 2-methylcyclohexanone (31b) with an optically active Lewis acid... 

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.

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