Enolates kinetic, trapping with

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 first step requires a specific enol from an enone. Treatment with LDA achieves kinetic enolate rmation by removing one of the more acidic hydrogens immediately next to the carbonyl group. The other enolate would be the thermodynamic product. The lithium enolate is trapped with leiSiCl to give the silyl enol ether. 

Trialkylsilyl halides show a great propensity to react with the oxygen rather than the carbon of enolate anions. Stork showed that 0-alkylation allows enolates to be trapped as the trialkylsilyl enol ether, which is most useful for kinetic enolates in which a lithium enolate (such as the kinetic enolate derived from 2-methyl-cyclohexanone and LDA) is reacted with trimethylsilyl chloride to give an isolable intermediate, 112. jjig enolate is trapped with high efficiency, and conversion to the enolate is readily accomplished by treatment with methyllithium, which generates the kinetic enolate (113) and the volatile trimethylsilane (Me3SiH). This... 

English-Zimmerman fragmentation, vinylogons 31,147 Enimines s. Ketenimines Enisocyclics s. a. Enecyclo... Enolate anions, a-alkylation of ketones via - 31, 890 Enolates s. a. Ammonium enolates, Metal -kinetic, trapping with formaldehyde 29,894s31 Enol carbonates... 

Enolates prepared by the treatment of ketones with strong bases such as lithium diisopropylamide are trapped with trialkylchlorosilanes to give the kinetically controlled enol silyl ethers (eq (51)) [44]. 

Silylethenyl ketones undergo smooth Michael addition with Grignard reagents or alkyllithiums to give the enolates 178, which are then trapped with benzalde-hyde to afford the E- and Z-isomers of enones 179 after the Peterson reaction (Scheme 2.114) [307]. ( )-Alkenes become the major products when the condensation with benzaldehyde is carried out under thermodynamic control at room temperature in diethyl ether, while Z-isomers are more favored as kinetically controlled products at 78 °C in THF. 1-Silyl acrylates show reactivities similar to those of 1-silylethenyl ketones [308]. 

The ketone is added to a large excess of a strong base at low temperature, usually LDA in THF at -78 °C. The more acidic and less sterically hindered proton is removed in a kineti-cally controlled reaction. The equilibrium with a thermodynamically more stable enolate (generally the one which is more stabilized by substituents) is only reached very slowly (H.O. House, 1977), and the kinetic enolates may be trapped and isolated as silyl enol ethers (J.K. Rasmussen, 1977 H.O. House, 1969). If, on the other hand, a weak acid is added to the solution, e.g. an excess of the non-ionized ketone or a non-nucleophilic alcohol such as cert-butanol, then the tautomeric enolate is preferentially formed (stabilized mostly by hyperconjugation effects). The rate of approach to equilibrium is particularly slow with lithium as the counterion and much faster with potassium or sodium. 

Recently, we have demonstrated another sort of homogeneous sonocatalysis in the sonochemical oxidation of alkenes by O2. Upon sonication of alkenes under O2 in the presence of Mo(C0) , 1-enols and epoxides are formed in one to one ratios. Radical trapping and kinetic studies suggest a mechanism involving initial allylic C-H bond cleavage (caused by the cavitational collapse), and subsequent well-known autoxidation and epoxidation steps. The following scheme is consistent with our observations. In the case of alkene isomerization, it is the catalyst which is being sonochemical activated. In the case of alkene oxidation, however, it is the substrate which is activated. 

Trapping the kinetic enolate of a methyl ketone with diethyl phosphochloridate provides an enol phosphate, that can, in turn, be converted to an alkyne ... 

Pedersen350 showed that a,a-dimethylacetoacetic acid cannot enolize decarboxylates readily and thus concluded that the keto tautomers of /3-oxo acids are kinetically unstable. The enol intermediate formed in the decarboxylation of /3-oxo acids has been trapped by reaction with bromine3S1 and has also been detected spectrophotometrically in the decarboxylation of a,a-dimethyloxaloacetic acid,341 oxaloacetic acid352 and fluorooxaloacetic acid.342... 

For years most Michael reactions were carried out under protic conditions so that rapid proton transfer was possible. However, in the early 1970s several groups performed Michael reactions under aprotic conditions and these processes are now quite common. Early attempts at trapping a kinetic enolate in aprotic solvents with simple enones such as methyl vinyl ketone or an a. -unsaturated ester such as acrylate led to a scrambling of the enolate (using the Michael product as proton source).8 However, the introduction of an a-trialkylsilyl group in the enone (93 Scheme 10) permitted the trapping of kinetic... 

A mixture of epoxides 483 obtained on oxidation of 482 with dimethyldioxirane, when exposed to ferric chloride provided, as the kinetically controlled product, the a-aldehyde 484, which without purification was reduced to the a-alcohol 485. The exclusive formation of 484 is believed to occur via the benzyl cation 486, generated by Lewis-acid opening of the oxirane ring, suffering a stereospecific kinetic 1,2-hydride shift The amino alcohol 487 obtained after sequential removal of O-benzyl and N-tosyl groups from 485, on treatment with triphenylphosphine and iodine in the presence of imidazole furnished the tetracyclic base 488, which was oxidised to the ketone 489. Trapping of the kinetically generated enolate of 489 as the silylether, followed by palladium diacetate oxidation yielded the enone 490. The derived... 

Mukaiyama found that Lewis acids can induce silyl enol ethers to attack carbonyl compounds, producing aldol-like products.22 The reaction proceeds usually at -78 °C without selfcondensation and other Lewis acids such as TiCl4 or SnCI4 are commonly used. The requisite silyl enol ether 27 was prepared by treatment of ketone 13 with lithium hexamethyl disilazide (LiHMDS) and trapping the kinetic enolate with chlorotrimethylsilane. When the silyl enol ether 27 was mixed with aldehyde 14 in the presence of BF3-OEt2 a condensation occurred via transition state 28 to produce the product 29 with loss of chlorotrimethylsilane. The induced stereochemistry in Mukaiyama reactions using methylketones and a, -chiral aldehydes as substrates... 

Making the Diels-Alder disconnection by drawing the mechanism of the reverse reaction 31a gives a new enol ether 32 and a quinone 33. The enol ether 32 is a derivative of the simple enone 34 and can be made by trapping the kinetic enolate with a suitable silyl group. 

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... 

Together with syntheses of 2-amino-8,9-dihydrothiazolo[4,5-/ - and [4,5-/ isoquinoline and 2-amino-4,5-dihydrothiazolo[5,4-7j]isoquinoline based upon an a-bromoketone/thiourea condensation similar to that described above, a direct thiazole ring annelation method for an N-protected octahydroquinolin-5-one has been developed. This involves the trapping of a kinetic enolate with TMS—Cl followed by regioselective bromination (NBS) and condensation with thio-... 

The geometry of the enolate intermediate was investigated by trapping experiments. When 23 (93% ee) was treated with potassium hydride and acetic anhydride in the presence of 18-crown-6, E-enol acetate 25 (59%) and its Z-isomer 26 (6%) were obtained together with the recovery of 23 (27%). The ee of the recovered 23 was unchanged. These observations indicate that the -enolate is the major intermediate under conditions of kinetic control. HPLC analysis of 25 with a chiral stationary phase indicated the existence of a pair of enantiomers (Figure 3.3a). Rapid interconversion between... 

Alternative reaction pathways exploring different synthetic possibilities have been studied. For instance, electron-rich dihydroazines also react with isocyanides in the presence of an electrophile, generating reactive iminium species that can then be trapped by the isocyanide. In this case, coordination of the electrophile with the isocyanide must be kinetically bypassed or reversible, to enable productive processes. Examples of this chemistry include the hydro-, halo- and seleno-carba-moylation of the DHPs 270, as well as analogous reactions of cyclic enol ethers (Scheme 42a) [223, 224]. p-Toluenesulfonic acid (as proton source), bromine and phenylselenyl chloride have reacted as electrophilic inputs, with DHPs and isocyanides to prepare the corresponding a-carbamoyl-(3-substituted tetrahydro-pyridines 272-274 (Scheme 42b). Wanner has recently, implemented a related and useful process that exploits M-silyl DHPs (275) to promote interesting MCRs. These substrates are reacted with a carboxylic acid and an isocyanide in an Ugi-Reissert-type reaction, that forms the polysubstituted tetrahydropyridines 276 with good diasteroselectivity (Scheme 42c) [225]. The mechanism involves initial protiodesilylation to form the dihydropyridinum salt S, which is then attacked by the isocyanide, en route to the final adducts. 

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