Enol Experimental Procedures

On the other hand, the method of Mukaiyama can be succesfully applied to silyl enol ethers of acetic and propionic acid derivatives. For example, perfect stereochemical control is attained in the reaction of silyl enol ether of 5-ethyl propanethioate with several aldehydes including aromatic, aliphatic and a,j5-unsaturated aldehydes, with syir.anti ratios of 100 0 and an ee >98%, provided that a polar solvent, such as propionitrile, and the "slow addition procedure " are used. Thus, a typical experimental procedure is as follows [32e] to a solution of tin(II) triflate (0.08 mmol, 20 mol%) in propionitrile (1 ml) was added (5)-l-methyl-2-[(iV-l-naphthylamino)methyl]pyrrolidine (97b. 0.088 mmol) in propionitrile (1 ml). The mixture was cooled at -78 °C, then a mixture of silyl enol ether of 5-ethyl propanethioate (99, 0.44 mmol) and an aldehyde (0.4 mmol) was slowly added to this solution over a period of 3 h, and the mixture stirred for a further 2 h. After work-up the aldol adduct was isolated as the corresponding trimethylsilyl ether. Most probably the catalytic cycle is that shown in Scheme 9.30. 

Experimental Procedure 4.2.10. Cycloaddition of an Acylcarbene Complex to an Enol Ether Ethyl 5-Ethoxy-2-trifluoromethyl-4,5-dihydro-3-furoate [1417]... 

Enolates lype Anions. The well-known Refoimatsky reaction allows the introduction of a functionalized two-carbon chain. Modified experimental procedures have now been proposed, such as the reaction of ethylbromoacetate with ketosugar 18 (Scheme 10) in the presence of zinc/silver graphite prepared from CgK, giving 19 in excellent yield [32],... 

In general, the experimental procedures for nucleophilic addition of organolithiums to aldehydes or ketones are straightforward [20]. Reduction via (3-hydride transfer and via ketyl formation is usually less troublesome in the case of organolithiums. On the other hand, a-deprotonation i.e., enolization of carbonyl compounds resulting from the high basicity of many organolithium compounds can be a real problem. 

Among the ethers of prolinol, (5)-2-methoxymethylpyrrolidinc [SMP, (S)-10] has found most applications. It is readily prepared from prolinol by the normal sodium hydride/iodo-methane technique9,13 (sec also Section 2.3. for O-alkylations of other amino alcohols) and is also commercially available. An improved synthesis from proline avoids the isolation of intermediates and gives the product (which is highly soluble in water) by continuous extraction14. SMP has been used as the lithium salt in deprotonation and elimination reactions (Section C.) and as an auxiliary for the formation of chiral amides with carboxylic acids, which in turn can undergo carbanionic reactions (Sections D.l.3.1.4., D.l. 1.1.2.. D.l. 1.1.3.1., in the latter experimental procedures for the formation of amides can be found). Other important derivatives are the enamines of SMP which are frequently used for further alkylation reactions via enolates (Sections D.l.1.2.2.. where experimental procedures for the formation of enamines are... 

Recently, the enolate method has emerged as a widely and frequently employed method in the synthesis for reasons like the easy access to the starting materials, simplicity and mildness of the experimental procedures, accurate predictability of the stereochemistry of the products and good to excellent realization of the stereoselection. This method can be further sub-divided into sub-topics like the simple enolate method [11], the Ireland silyl ketene acetal method, the chelated ester enolate method, imidate method, and the N,0- and N,S-acetal method. The present discussion will be restricted to simple enolate method as the remaining sub-topics are covered separately in this book. 

The dramatic acidifying effect of the carbonyl group is due to its inductive effect and its ability to delocalize and thereby stabilize the negative charge in the enolate ion, as reflected in 17 (Eq. 18.9), which is the resonance hybrid of the resonance structures 3a and 3b (Sec. 18.1). Because the pfC values of aldehydes and ketones fall in the range of water pK 15.7) and alcohols (pfC 15.5-18), it is possible to generate enolate ions using anions such as hydroxide or alkoxide (Eq. 18.3, B = HO and RO , respectively) these are the bases utilized in the experimental procedures of this section. 

Zhang et al. [52] used iodine to catalyze the hetero-Diels-Alder reaction of pentafluorobenzylidineaniline (CgF5CH=NAr) with enol ethers to afford the corresponding tetrahydroquinoline derivatives 23 and 24 as a mixture of cis/trans stereoisomers. Mild and neutral reaction conditions, facile experimental procedure and the use of iodine made this method attractive for practical synthesis of many fluorinated tetrahydroquinoline derivatives (Scheme 10.18). 

Typical Experimental Procedures for Generation of Titanium Enolates... 

Typical Experimental Procedure for Crossed Aldol Reaction via Boron Enolate (Eq. (7)) [6a]... 

The acidity constants of protonated ketones, pA %, are needed to determine the free energy of reaction associated with the rate constants ArG° = 2.3RT(pKe + pK ). Most ketones are very weak bases, pAT < 0, so that the acidity constant K b cannot be determined from the pi I rate profile in the range 1 < PH <13 (see Equation (11) and Fig. 3). The acidity constants of a few simple ketones were determined in highly concentrated acid solutions.19 Also, carbon protonation of the enols of carboxylates listed in Table 1 (entries cyclopentadienyl 1-carboxylate to phenylcyanoacetate) give the neutral carboxylic acids, the carbon acidities of which are known and are listed in the column headed pA . As can be seen from Fig. 10, the observed rate constants k, k for carbon protonation of these enols (8 data points marked by the symbol in Fig. 10) accurately follow the overall relationship that is defined mostly by the data points for k, and k f. We can thus reverse the process by assuming that the Marcus relationship determined above holds for the protonation of enols and use the experimental rate constants to estimate the acidity constants A e of ketones via the fitted Marcus relation, Equation (19). This procedure indicates, for example, that protonated 2,4-cyclohexadienone is less acidic than simple oxygen-protonated ketones, pA = —1.3. 

The reactions of the lithium enolate of diethyl 2-[(diphenylmethylene)amino]malonate with several alkynyliodonium triflates are rare examples of enolate alkynylations with iodonium species other than the ethynyl(phenyl)- and (phenylethynyl)phenyliodonium ions (equation 125)16. Two experimental protocols were followed, i.e. addition of the enolates to the iodonium salts and vice versa, the former procedure giving higher yields of alkynylmalonates. As with other enolate alkynylations, these reactions are thought to involve alkylidenecarbene intermediates. It has been proposed, however, that the carbenes rearrange with migration of the diethyl 2-[(diphenyl) amino] malonate anion 16. 

Finally, concordant results have been obtained from a kinetic study of the iodination of acetophenone and acetone at very low iodine concentration (Verny-Doussin, 1979). The procedure used is similar to that followed for the determination of equilibrium constants for enol formation by the kinetic-halogenation method, i.e. second-order rate constants were measured under conditions such that halogen additions to enol and enolate are rate-limiting (43). Under these conditions, the experimental kn-values can be expressed by... 

The preparation of dialkyl 1-alkynylphosphonates by an appropriate P-elimination procedure was first recorded in 1957, when it was reported that the action of EtONa on diethyl 2-[3-(diethoxyphosphinyl)propenyl] phosphate in refluxing EtOH leads to diethyl 1-propynylphosphonate in 69% yield (Scheme 1.13). The experimental conditions are crucial, and it has been shown that successful elimination of phosphate takes place to the exclusion of the ethanolysis reaction only at elevated temperature. At room temperature, diethyl 2-[3-(diethoxyphosphinyl)propenyl] phosphate is reported to undergo competing ethanolysis to triethyl phosphate and diethyl 2-oxo-propylphosphonate. Because of the drastic reaction conditions required for the subsequent conversion to 1-alkynylphosphonates, this method was rarely used and remained underdeveloped for a sigiuficant period of time. Fortunately, many efforts have been made to discover bases that might cause elimination of the phosphate from the enol without also bringing about isomerization or hydrolysis. The development of a variety of milder alternative methods has led to the much more widespread adoption of this elimination sequence. ... 

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