Potassium enolates

It was claimed that the Z-form of the allylic acetate 430 was retained in homoallylic ketone 431 obtained by reaction with the potassium enolate of 3-vinylcyclopentanone (429), after treatment with triethylborane[282]. Usually this is not possible. The reaction of a (Z)-allylic chloride with an alkenylaluminum reagent to give 1,4-dienes proceeds with retention of the stereochemistry to a considerable extent when it is carried out at -70 C[283]. 

Stork and his colleagues, working with nonsteroidal compounds, have shown that only lithium enolates may be alkylated successfully in ammonia or tetrahydrofuran. The more basic sodium and potassium enolates undergo... 

Electrostatic interactions can guide alkylation under certain conditions. Examine the electrostatic potential map of the potassium enolate of ethyl acetoacetate. Is carbon or oxygen more electron rich Are electrostatic interactions likely to favor addition of oxygen or carbon Examine atomic charges and electrostatic potential maps for diethylsulfate, ethyl chloride, ethyl bromide and ethyl iodide, pay attention to the backside of the electrophilic carbon. Order the systems from most to least electron poor. Which reaction is most likely to be guided by electrostatics Least likely Can the experimental results be fully explained on this basis ... 

Electrostatic potential map of the potassium enolate of ethyl acetoacetate shows negatively-charged regions (in red) and positively-charged regions (in blue). 

Nitradon of the potassium enolates of cycloalkanones with pentyl n silyl enol ethers with nitroniiim tetraflnoroborate " provides a method for the preparadon of cydic ct-nitro ketones. Tnflnoroacetyl nitrate generated from tnflnoroacedc anhydnde and ammonium nitrate is a mild and effecdve nitradug reagent for enol acetates fEq. 2.411. ... 

At the end of this time the crystalline precipitate which had formed was filtered off with suction, washed with diethyl ether, and dried in a vacuum desiccator. The product comprised essentially the potassium enolate of ethyl fluoromalonaldehydate (alternative nomenclature, the potassium salt of fluoromalonaldehydic acid ethyl ester). 

A mixture of 103.6 grams (0.6 mol) of the freshly prepared potassium enolate of ethyl fluoromalonaldehydate, 83.4 grams (0.3 mol) of S-methylisothiouronium sulfate and 32.5 grams (0.6 mol) of sodium methoxide was refluxed with stirring in 1,500 ml of absolute methanol. At first the reactants dissolved to a great extent, but very shortly thereafter precipitation occurred. The reaction mixture was refluxed for 2 hours and at the end of this time was evaporated to dryness in vacuo. The residue was treated with 280 ml of water incomplete dissolution was observed. 

The highest enantioselectivities in the base-catalyzed Michael additions have so far been obtained using achiral bases complexed to chiral crown ethers. The addition of methyl 2,3-dihydro-l-oxo-1//-indene-2-carboxylate (1) to 3-buten-2-one using 4 mol% of a [l,T-binaphthalcnc]-2,2 -diol derived optically active crown ether 3 in combination with potassium AY/-butoxide as the base illustrates this successful method 259 260 It is assumed that the actual Michael donor is the potassium enolate complex of 1 and crown ether 3. 

We do not list the many hydrolyses of sodium or potassium enolates, and so on, found in Organic Syntheses. The hydrolysis of a Grignard reagent to give an alkane is found at OS II, 478 the reduction of a vinylic tin compound at OS VIII, 381 and the reduction of an alkynylsilane at OS VIII, 281. 

Fig. 1.3. Potassium enolate of methyl t-butyl ketone open circles are oxygen and small circles are potassium, (a) left panel shows only the enolate structures (b) right panel shows only the solvating THF molecules. The actual structure is the superposition of both panels. Reproduced from J. Am. Chem. Soc., 108, 462 (1986), by permission of the American Chemical Society.

Ester enolates are somewhat less stable than ketone enolates because of the potential for elimination of alkoxide. The sodium and potassium enolates are rather unstable, but Rathke and co-workers found that the lithium enolates can be generated at -78° C.69 Alkylations of simple esters require a strong base because relatively weak bases such as alkoxides promote condensation reactions (see Section 2.3.1). The successful formation of ester enolates typically involves an amide base, usually LDA or LiHDMS, at low temperature.70 The resulting enolates can be successfully alkylated with alkyl bromides or iodides. HMPA is sometimes added to accelerate the alkylation reaction. 

Alkylations of this type also proved to be sensitive to the cation. Good stereoselectivity (15 1) was observed for the lithium enolate, but the sodium and potassium enolates were much less selective.75 This probably reflects the weaker coordination of the latter metals. 

Diketones. Potassium enolates of some ketones can dimerize with incorporation of a methylene group from DMF to give 1,5-diketones. This novel reaction requires a rert-alkyl or phenyl group attached to the carbonyl group.2... 

Potassium enolates derived from the chiral Schiff bases obtained by reaction of racemic a-amino esters with 2-hydroxypinan-3-one undergo diastereoselective protonation, as evidenced by release of optically active a-amino esters on subsequent cleavage of the imine (Scheme 5). ... 

The potassium enolate prepared from atrolactic acid derivative II undergoes aldol reaction to give 12 in a highly stereoselective manner. Successive acid treatment gives syn-amino acid 13 in good yield (7). 

Snider and colleagues have developed the sequential ene reaction/thia-[2,3]-Wittig reaction which provide appropriately functionalized product 152 at allylic position on simple alkene 150 in two steps involving intermediate 151 (equation 87) . Thia-[2,3]-Wittig rearrangement was often utilized as a key step of natural product synthesis. Masaki and colleagues have demonstrated that the potassium enolate thia-[2,3]-rearrangement of aUyl sulfide 153 to 154 is useful for the synthesis of terpenoid diol component 155 of the pheromonal secretion of the queen butterfly (equation 88) . 

Hydroxy and 0x0 groups and other O-linked groups. Treatment of the potassium enolate of the pyrrolo-benzazepine and benzoxepine ketones 68 with the A7,A7-diethylcarbamyl chloride gives carbamates 69 (Scheme 14, Section 2.1.1.5 (2002JMC4276)). A similar modification has been reported for a benzopyrro-lo[l,2]thiazepine (1997EJM241). 

Spirocyclic oxindole 60 was synthesized by [3,3]-sigmatropic rearrangement of the Af-phenyl-O-acylhydroxamic acid 58 (equation 19). The potassium enolate formed by treatment of 58 with potassium hexamethyldisilazide at low temperature rearranged to 59, which easily cyclized to the spirocyclic oxindole 60. Spirooxindoles were previously synthesized by Wolff and Taddei. The spirooxindole 60 was formed in 51% yield from cyclohexanecarboxylic acid after heating the preformed lithium salts of phenyl hydrazide 61 to 205-210 °C. 

THF and DME are slightly polar solvents which are moderately good cation solvators. Coordination to the metal cation involves the oxygen lone pairs. These solvents, because of their lower dielectric constants, are less effective at separating ion pairs and higher aggregates than are the polar aprotic solvents. The crystal structures of the lithium and potassium enolates of methyl /-butyl ketone have been determined by X-ray crystal-... 

Fig. 1.2. Potassium enolate of methyl /-butyl ketone large cirlces = oxygen, small circles = potassium, (a) Left-hand plot shows only methyl /-butyl ketone residues, (b) Right-hand plot shows only the solvating THF molecules. The crystal is a composite of these two structures. (Reproduced with permission from Ref. 44. Copyright 1986 American Chemical Society.)...

This procedure for the acetylation of methyl alkyl ketones to form /3-diketones is a modification5 of an earlier procedure, which used boron trifluoride gas as the catalyst.6 3-n-Butyl-2,4-pentanedione has also been prepared by the acetylation of 2-heptanone catalyzed with boron trifluoride gas,7 by the thermal rearrangement of the enol acetate of 2-heptanone,7 and by the alkylation of the potassium enolate of 2,4-pentanedione with n-butyl bromide.8... 

Reaction of o-iodobenzenesulfonamide 265 with the potassium enolate of ketones 266 in liquid ammonia under photochemical conditions affords 1,2-benzothiazine 1,1-dioxides 267 in excellent yield (Scheme 37) <2005JOC9147>. While a variety of other ketone substrates have been investigated for this reaction, those containing /3-hydrogens afford significant amounts of benzenesulfonamide by dehalogenation of the starting material 265. 

A typical example is alkylation of the steroid ester 11. Treatment of 1 with LDA in tetrahydrofuran at —78 °C for 1 hour followed by addition of 4-bromo-2-methyl-2-butene in the presence of HMPA at —78 °C to —20 °C furnished an 87 13 mixture of the monoalkylated esters 3a and 3b. The potassium enolate 2 (KHMDS, THF, —78 °C, 1 h) has been hydroxylated with an oxaziridine reagent in 70% yield to give a 3 1 mixture of a-hydroxy derivatives. 

The reaction of potassium dienoxy borates with A-fluorobis(phenylsulfonyl)amine (la) gives y-fluoro enones in good yield. The potassium dienoxy borates are prepared by treating potassium enolates derived from unsaturated ketones with 2-phenyl-1,3,2-benzodioxaborole. This methodology offers a convenient alternative to the traditional fluorination of dienol acetates, ethers, or enamines.145 An example is given by the formation of 13.145... 

Polymer-supported reagent. HMPT supported on a polystyrene-type resin is a catalyst for SN2 reactions5-7 and for reduction of ketones by NaBIi4.7 It also has a marked effect on the alkylation of ethyl acetoacetate with diethyl sulfate. In the presence of solid HMPT the enolales undergo 60 70% O-alkylation. In the absence of HMPT, the lithium enolate does not react and the sodium and potassium enolates undergo C-alkylation (90-100%). There is some difference in the effect of solid and liquid I1MPT The solid HMPT increases the reactivity of the K. enolate more than the liquid form, whereas the reverse is true with the Li enolate.8... 

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