Enolate anions trapping

The reductive carbomethoxylation procedure, resulting in formation of the desired trans ring fusion and introduction of carbomethoxy function at C4 is based on enolate anion trapping procedure of G. Stork, P. Rosen, N. Goldman, R. V. Coombs and J. Tsuji, J. Amer. Chem. Soc., 87, 275 (1965). 

Few a-ketosulphoxides 123 were prepared by trapping the enolate anions 124, which are generated by the Michael addition of Grignard reagents to easily available a, jS-unsaturated carbonyl compounds 125, with methanesulphinyl chloride174 (equation 65). 

Although unhindered enones and enoates work well, attempted 1,4-reduction of acrylonitrile afforded a-silylated product 9 (Scheme 5.4). Presumably this unexpected product results from a 1,4-reduction/a-anion trapping by the PhMe2SiCl present in solution. Curiously, there was no mention of any similar quenching of intermediate enolates on either carbon or oxygen when unsaturated ketones or esters were involved. 

Thiol anions normally add reversibly to uracil derivatives <1991T4361>, although stable adducts can be isolated when the intermediate enolate is trapped with an added electrophile <2006JHC1095>. Thus, the addition of lithium phenylthiolate to 5-fluoro-l,3-dimethyluracil 457 in the presence of benzaldehyde gave a 46% yield of the adduct 458 as a mixture of only two diastereomers <2006JHC1095>. 

A synthesis of this compound was devised by Ohmizu, Iwasaki and co-workers and featured a three-component tandem conjugate addition/enolate trapping as key step (Scheme 12.24) [82]. In this synthesis, the acyl anion equivalent cyanohydrin 165 was first treated with LDA and allowed to react with methyl crotonate 166. The resulting enolate was trapped with 2,3,5-trimethoxy benzylbromide 168 to afford crude intermediate 169, which was immediately deprotected in situ to afford ketone product 170. Both the ester and the ketone functionalities were then reduced at low temperature to afford the corresponding diol 171. Upon treatment with trifluoroacetic acid, the desired Friedel-Craft cyclization adduct 172 was obtained. The latter tricyclic compound was then further elaborated to the final target 164 through a short sequence of standard transformations. 

Addition of a silylating reagent such as Me3SiCl to the reaction mixture traps the enolate anions and produces two silyl enol ethers in a ratio which reflects the ratio of the enolate anions. Thus if 2-methylcyclohexanone is added to the hindered base LDA at -78 °C and the mixture stirred for 1 hour at -78 °C and quenched with MeySiCl, then the major product is the silyl enol ether derived from the kinetic enolate. In contrast, heating 2-methylcyclohexanone, triethylamine, and Me3SiCl at 130 °C for 90 hours... 

Annelation. Cleavage of l-(trimethylsilyloxy)-2-alkoxycarbonylcyclo-propanes (1) with KF-18-crown-6 generates y-oxo-a-ester enolate anions, which can be trapped by electrophiles. Trapping with a vinyl phosphonium salt results in [3 + 2] annelation to provide annelated cyclopentanones (2).1... 

Otherwise, cuprous iodide-catalyzed addition of methylmagnesium iodide to 2-cyclohexen-l-one in ether at 0 °C, followed by trapping of the resultant enolate anion 188 with cyclopropanecarboxaldehyde 189, afforded the two diastereomers of the cyclopropylcarbinol 190 a. Further transformation into the corresponding acetates 190b (acetic anhydride, pyridine), followed by treatment with l,5-diazabicyclo[4.3.0]-non-5-ene (DBN) in refluxing benzene, provided in 78 % yield, a mixture of the desired P-cyclopropyl enones 191 and 192, in a ratio of 13 1, Eq. (60) 127). 

An unsymmetrical ketone can form two different enolates. In some situations it is possible to distinguish between them by trapping the separate enolates as their silyl enol ethers. The anions may then be regenerated from the silyl enol ether in an aprotic solvent under non-equilibrating conditions using fluoride ion. The rapidly formed kinetic enol of 2-methylcyclohexanone may be trapped using lithium di-isopropylamide as the base (Scheme 3.77a). On the other hand, the thermodynamically more stable enol is trapped with a milder base such as triethylamine (Scheme 3.77b). ... 

The copper-mediated 1,4-addition of alkyl groups to a,P-unsaturated ketones affords regiochemically pure enolate anions (see also Section 7.5) which may be trapped at oxygen with silyl halides, acyl halides, or dialkylcarbonates to provide silyl enol ethers, enol acetates, or enol carbonates, respectively. These can be unmasked at a later stage by reaction with MeLi to regenerate the enolate for further elaboration. ... 

Lithium and potassium tri-sec-butylborohydride (L- and K-Selectride) selectively reduce the olefin of many a,g-unsaturated carbonyl compounds.79 The intermediate enolate anions may also be trapped by electrophiles, providing a regiospecific reductive alkylation of a,g-unsaturated carbonyl compounds. 

The radical generated by the reduction of an N-acyliminium ion pool can be trapped with an electron-deficient olefin, such as acrylate ester, which is known to be a good radical acceptor (Scheme 5.29). In the presence of a large excess amount of proton, a 1 1 adduct is obtained in good yield. A mechanism involving radical addition to the electron-deficient olefin followed by one-electron reduction to give the carbanion or enolate anion that is trapped by a proton has been suggested. 

---