Preparation of enol acetates

Preparation of enamines, 409 Preparation of enol acetates, 411 Preparation of enol ethers, 409 Preparation of a-halo ketones, 267 Preparation of 3/3-hydroxyandrosta-5,15-dien-17-one, 302... 

Preparation of enol acetates. Barton et al. used perchloric acid as catalyst for... 

Preparation of enol acetates [1, 800, after citation of ref. 18] It has been shown in at least two cases that the perchloric acid catalyzed acetic anhydride enol acetylation is thermodynamically controlled.183 Thus the 3-keto-5/3-steroid, 17/3-acetoxy-50-androstane-3-one (1), on reaction with acetic anhydride-perchloric acid gives the two enol acetates (2) and (3) in the ratio 93.5 to 6.5. The calculated ratio derived from the relative stability of (2) and (3) is 96 4. If a mixture of 65% of (2)... 

The acetylation of amines with isopropenyl acetate appears to be a transition between the highly exothermic reactions of acyl halides and anhydrides with amines on the one hand and the reaction of amines with more conventional esters on the other. While this reagent is of particular value in the preparation of enol acetate, it has been used for the preparation of amides. One interesting aspect of its use is that acetone forms as a coproduct which may distill off as the reaction proceeds. Isopropenyl acetate and other isopropenyl esters may also be used to Y-acylate amides and imides. By the judicious selection of starting amides and isopropenyl esters, tertiary amides with three different acyl groups may be synthesized. This may very well be one of very few reaction systems which permits the synthesis of this rare group of tertiary amides. 

Acetylation of Other O, N, and C Centers. In addition to the preparation of enol acetates from ketones, isopropenyl acetate has also seen use in the acetylation of other O, N, and C centers. Hydroxy acetylation was first noted" as a simultaneous reaction... 

After succeeding in the asymmetric reductive acylation of ketones, we ventured to see if enol acetates can be used as acyl donors and precursors of ketones at the same time through deacylation and keto-enol tautomerization (Scheme 8). The overall reaction thus corresponds to the asymmetric reduction of enol acetate. For example, 1-phenylvinyl acetate was transformed to (f )-l-phenylethyl acetate by CALB and diruthenium complex 1 in the presence of 2,6-dimethyl-4-heptanol with 89% yield and 98% ee. Molecular hydrogen (1 atm) was almost equally effective for the transformation. A broad range of enol acetates were prepared from ketones and were successfully transformed into their corresponding (7 )-acetates under 1 atm H2 (Table 19). From unsymmetrical aliphatic ketones, enol acetates were obtained as the mixtures of regio- and geometrical isomers. Notably, however, the efficiency of the process was little affected by the isomeric composition of the enol acetates. 

Trialkylstannyl enolates can be prepared from enol acetates by reaction with trialkyltin alkoxides and are sufficiently reactive to add to aldehydes. Uncatalyzed addition of trialkylstannyl enolates to benzaldehyde shows anti stereoselectivity.31... 

Nitration of ketones or enol ethers provides a useful method for the preparation of a-nitro ketones. Direct nitration of ketones with HN03 suffers from the formation of a variety of oxidative by-products. Alternatively, the conversion of ketones into their enolates, enol acetates, or enol ethers, followed by nitration with conventional nitrating agents such as acyl nitrates, gives a-nitro ketones (see Ref. 79, a 1980 review). The nitration of enol acetates of alkylated cyclohexanones with concentrated nitric acid in acetic anhydride at 15-22 °C leads to mixtures of cis- and rrans-substituted 2-nitrocyclohexanones in 75-92% yield. 4-Monoalkylated acetoxy-cyclohexanes give mainly m-compounds, and 3-monoalkylated ones yield fra/w-compounds (Eq. 2.40).80... 

Because the a-nitroketones are prepared by the acylation of nitroalkanes (see Section 5.2), by the oxidation of (3-nitro alcohols (Section 3.2.3), or by the nitration of enol acetates (Section 2.2.5), denitration of a-nitro ketones provides a useful method for the preparation of ketones (Scheme 7.10). A simple synthesis of cyclopentenone derivatives is shown in Eq. 7.66.76... 

Camell and co-workers have recently applied lipase-catalysed resolution to formally desymmetrize prochiral ketones that would not normally be considered as candidates for enzyme resolution, through enantioselective hydrolysis of the chemically prepared racemic enol acetate. " For example, an NK-2 antagonist was formally desymmetrized by this approach using Pseudomonas fluorescens hpase (PFL) (Scheme 1.40). By recychng the prochiral ketone product, up to 82 % yields of the desired (5)-enol acetate (99 % ee) could be realized. This method offers a mild alternative to methodologies such as base-catalysed asymmetric deprotonation, which requires low temperature, and biocatalytic Baeyer-Villiger oxidation, which is difficult to scale up. 

Pattenden and Teague have prepared tricyclic diol 684 which is epimeric to the naturally occurring A < -capnellene-8p,10a-diol (68S) Their strategy, which is summarized in Scheme LXXI, encompasses two critical cyclization steps. The first is the Lewis acid-catalyzed ring closure of enol acetate 686 and the second involves reductive closure of acetylenic ketone 687. It is of interest that the oxidation of 688 proved to be stereospecific. 

Formal replacement of hydrogen by fluorine takes place in the a-position of a ketone by treatment of enol acetates with triethylamine tris(hydrogen fluoride).51-55 The kinetically favored isomers are formed.51,55 Furthermore, benzylic positions bonded with an electron-withdrawing group (ketone, ester, nitrile, sulfonate) can be fluorinated electrochemically.51" 6-58 There are also various examples of the preparation of a-fluorosulfides front sulfides.51... 

Some of the reactions of PO3- parallel enzymatic reactions promoted by adenosine triphosphate (ATP). Pyruvate kinase catalyzes the equilibration of ATP and pyruvate with adenosine diphosphate (ADP) and phosphoenol pyruvate (11,12). In a formal sense, this reaction resembles the preparations of enol phosphate (eqs. 6 and 7). Cytidine triphosphate synthetase catalyzes the reaction of uridine triphosphate with ammonia to yield cytidine triphosphate (13). In a formal sense, this reaction resembles the replacement of the ester carbonyl group of ethyl acetate by the nitrogen of aniline (eq. 8). 

D. Cahard, P. Duhamel, Alkoxide-Mediated Preparation of Enolates from Silyl Enol Ethers and Enol Acetates - From Discovery to Synthetic Applications, Eur. J. Org. Chem. 2001, 1023-1031. 

The yields of enol acetates prepared by boiling the aldehydes with acetic anhydride and potassium acetate range from 40%-60%, and the a-bromo-aldehyde dimethyl acetals ate formed in about 80% yield. These products can be hydrolyzed with varying yields to the a-bromoaldehydes. A typical example is the synthesis of a-bromoheptaldehyde (40% over-all). ... 

Halo acetals have been prepared by the action of alcohol on halo ketones and halo aldehydes.An indirect application of this reaction consists in the halogenation of enol acetates with subsequent reaction of the brominated products with alcohols to give the halo acetals. ... 

Stereospecific aldol synthesis of / -hydroxy acids derived from R) + )-t-butyl-p tolysulfinyl acetate has been reported [25 Eq. (18)]. The t-BuMgBr was crucial to the enolate generation without racemization. Magnesium diisopropylamide was used in preparation of the acetate precursor. 

The nitration of enol acetates with acetyl nitrate is a regiospecific electrophilic addition to the 3-carbon of the enol acetate, followed by a hydrolytic conversion of the intermediate to the a-nitro ketone. With enol acetates of substituted cyclohexanones the stereochemistry is kinetically established. So, 1-acetoxy-4-methylcyclohexene (22) yields the thermodynamically less stable rrans-4-methyl-2-nitrocylo-hexanone (24) in greater proportion cis. trans = 40 60) (equation 8). This mixture can be equilibrated in favor of the thermodynamically more stable cis diastereomer (23) (cis. trans = 85 15). Nitration of 1-ace-toxy-3-methylcyclohexene (25) leads to frans-3-methyl-2-nitrocyclohexanone (26), which is also the thermodynamically more stable isomer (equation 9). No stereoselection occurs in the kinetically controlled nitration with acetyl nitrate of l-acetoxy-5-methylcyclohexene (27 equation 10), but the 1 1 mixture of the 5-methyl-2-nitrocyclohexanones can be equilibrated in favor of the trcms diastereomer (28) (cis trans = 10 90). 2-Alkyl-2-nitrocyclohexanones cannot be prepared in acceptable yields by nitration of the corresponding enol acetates with acetyl nitrate. 

Several procedures have been developed for the preparation of a-arylselenocarbonyl compounds including phenylselenenylation of enol acetates, enol ethers and lithium and copper enolates. Oxi-... 

Alternatively these compounds are prepared by the treatment of enol acetates with trialkylalkoxystannanes or addition of alkoxystannanes to ketenes (eq (132)) [127]. The ratio of O- and C-enolates is dependent on the substituents on enol acetates. 

The standard Ireland conditions for the ester enolate rearrangement (lithium diisopropylamine, tetrahydrofuran) give a retro-Michael addition product in this ease. However, silyl ketene acetal 15 is successfully obtained by the silyl triflate/triethylamine protocol539 for the preparation of ketene acetals which proceeds via a silyladon and then deprotonation mechanism560-563. 

Acetals of a-bromo aldehydes are obtainable from <%,/ -dibromoalkyl acetates by an analogous procedure in which these esters are prepared from enol acetates and bromine and are then converted into acetals by means of alcohols.939 A simple synthesis of <%-keto aldehydes is to treat a-brominated phenacyl phenyl ethers with alkoxides or phenoxides.940 This method is particularly useful for the preparation of aryl acetals because it avoids the side reactions that can complicate reactions between phenols and aldehydes in an acidic medium. 

OL-Iodo ketones, a-lodo ketones are usually prepared by reaction of enol acetates with NIS. A new method involves reaction of an alkene with silver chromate and iodine in the presence of pyridine. The actual reagent is presumably a mixed anhydride of hypoiodous acid and chromic acid. Dichloromethane is the most useful solvent. ... 

This reaction was first reported by Bedoukian in 1944. It is a reaction for preparing Qf-brominated ketones or aldehydes via a sequential process, including the formation of enol acetate, the addition of bromine to enol acetate, and the acidic hydrolysis of the resulting intermediate addition. ... 

Two synthetically in iortant variants of the Ferrier carbocyclization reaction have been reported. One is a rearrangement of enol acetate 24 (Scheme 12.7). Reaction of 24 with a stoichiometric amount of Hg salt afforded an organomercurial intermediate 25, which was then treated with NaCl to induce the cyclization affording inosose derivatives 26a and 26b with good stereoselectivity. As biologically inportant myo-inositol derivatives, such as d-myo-inositol phosphates, are optically active, the enol-acetate version of the Ferrier carbocyclization would be effective for the preparation of enantiomerically pure inositol derivatives. 

The Ferrier carbocyclization reaction of an enol-acetate substrate gives an a,p-dihydroxy-cyclohexanol derivative (see Schemes 12.7 and 12.81. This transformation would be effective for the chiral synthesis of inositol derivatives. A retrosynthetic plan for the marine natural product tetrodotoxin 88 based on the enol-acetate version of Ferrier carbocyclization is shown in Scheme 12.22. Tetrodotoxin 88 was planned to be synthesized from lactone 89, the precursor of which would be highly functionalized cyclohexane 90. Cyclohexane 90 was envisioned to arise from cyclohexanone 91. For the preparation of 91, Ferrier carbocyclization of enol acetate 92 would be a suitable transformation. d-Glucose derivative 93 possessing an exo-methylene at C-3 would serve as a promising precursor of 92. 

A mixture of cis- and truns-1-methoxycyclododecenes was prepared in 98% yield from cyclododecanone by a modification of Claison s method of ketal formation. Amberlyst-15 is a superior catalyst for the preparation of enol ethers and acetals. 

The preparation of enol esters in a regio- and stereo-specific manner is important, as they are particularly valuable synthetic intermediates. A room-temperature reaction of vinylmercurials, mercury carboxylates, and a catalytic amount of palladium acetate provides a novel and convenient stereospecific route to a variety of enol carboxylates. ... 

It is readily prepared by the action of metallic sodium on dry ethyl acetate. The reaction, which occurs only in the presence of a trace of ethanol, is complex, but may be considered (in effect) as a condensation of two molecules of ethyl acetate under the influence of sodium ethoxide, the sodium derivative of the enol form being thus obtained. Clearly, only a trace of ethanol is thus initially... 

The majority of preparative methods which have been used for obtaining cyclopropane derivatives involve carbene addition to an olefmic bond, if acetylenes are used in the reaction, cyclopropenes are obtained. Heteroatom-substituted or vinyl cydopropanes come from alkenyl bromides or enol acetates (A. de Meijere, 1979 E. J. Corey, 1975 B E. Wenkert, 1970 A). The carbenes needed for cyclopropane syntheses can be obtained in situ by a-elimination of hydrogen halides with strong bases (R. Kdstcr, 1971 E.J. Corey, 1975 B), by copper catalyzed decomposition of diazo compounds (E. Wenkert, 1970 A S.D. Burke, 1979 N.J. Turro, 1966), or by reductive elimination of iodine from gem-diiodides (J. Nishimura, 1969 D. Wen-disch, 1971 J.M. Denis, 1972 H.E. Simmons, 1973 C. Girard, 1974),... 

The isoflavone 406 is prepared by the indirect a-phenylation of a ketone by reaction of phenylmercury(II) chloride with the enol acetate 405, prepared from 4-chromanone[371]. A simple synthesis of pterocarpin (409) has been achieved based on the oxypalladation of the oriho-mercurated phenol derivative 408 with the cyclic alkene 407[372,373]. 

Preparation of o,/3-Unsaturated Carbonyl Compounds by the Reactions of Silyl Enol Ethers and Enol Acetates with Ally Carbonates... 

Another preparative method for the enone 554 is the reaction of the enol acetate 553 with allyl methyl carbonate using a bimetallic catalyst of Pd and Tin methoxide[354,358]. The enone formation is competitive with the allylation reaction (see Section 2.4.1). MeCN as a solvent and a low Pd to ligand ratio favor enone formation. Two regioisomeric steroidal dienones, 558 and 559, are prepared regioselectively from the respective dienol acetates 556 and 557 formed from the steroidal a, /3-unsaturated ketone 555. Enone formation from both silyl enol ethers and enol acetates proceeds via 7r-allylpalladium enolates as common intermediates. 

Owing to the instability of a-halogenoaldehydes it is occasionally preferable to use more stable derivatives, such as enol acetate prepared according to Bedoukian s method (204) and a-bromoacetals (4, 8, 10, 16, 22, 67, 101, 426). An advantage is said to be in the yield however, this appears to be slight. The derivatives react in the same sense as the aldehydes themselves, that is, the acetal group as the more polarized reacts first and enters the C-4 position. It is likely that the condensation and cyclization occur by direct displacement of alkoxide ions. Ethyl-a,/3-dihalogeno ethers (159, 164, 177, 248) have also been used in place of the free aldehydes in condensation with thioamides. 

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