Ketones boron trifluoride complex

It was observed that the shift of the boron trifluoride adducts were all essentially similar, and no conclusions could be drawn a similar situation was found in our study of ketone-boron trifluoride complexes. 

A comparison has been made of carbonyl frequencies of cyclohexanones and their complexes with boron trifluoride. Spectra of the complexed ketones show disappearance of the free carbonyl absorption and replacement by a band at ca. 70 cm lower wavenumbers. This change is associated with a diminution of the force constant of the carbonyl bond. A u.v. spectroscopic study has also been made of cyclohexanone boron trifluoride complexes in CHjClj. For cyclohexanone a hypsochromic shift of the n ti band is noted on complexa-tion, as indicated by values of 287.3 nm, s = 17 for the free ketone and A 240.5 nm, e = 116 for the ketone boron trifluoride complex. Titanium tetrachloride also acts as a Lewis acid and forms complexes with ketones. However, the 50cm shift in the carbonyl frequency observed on complexation is taken as indicating that the oxygen-titanium bond is weaker than the oxygens boron bond. 

Notes. (1) Alternatively the reaction may be effected by adding the ketone and the acetic anhydride to 100 g (0.75 mol) of a 1 1 acetic acid-boron trifluoride complex (Section 4.2.5, p. 421). 

A mixture of an acid anhydride and a ketone is saturated with boron trifluoride this is followed by treatment with aqueous sodium acetate. The quantity of boron trifluoride absorbed usually amounts to 100 mol per cent, (based on total mola of ketone and anhydride). Catalytic amounts of the reagent do not give satisfactory results. This is in line with the observation that the p diketone is produced in the reaction mixture as the boron difluoride complex, some of which have been isolated. A reasonable mechanism of the reaction postulates the conversion of the anhydride into a carbonium ion, such as (I) the ketone into an enol type of complex, such as (II) followed by condensation of (I) and (II) to yield the boron difluoride complex of the p diketone (III) ... 

The solid appears to be a mixture of the complexes CH,COOH.BF, and 2CH COOH.BF,. The latter appears to be a liquid and is alone soluble in ethylene dichloride the former is a solid. The solid moiioocetic acid complex is obtained by saturating an ethylene dichloride solution of acetic acid with boron trifluoride, filtering and washing the precipitate with the solvent it is hygroscopic and should be protected from moisture. It may be used as required 0-75 mol is employed with 0-26 mol of ketone and 0 6 mol of anhydride. 

The 12-ketone is generally less reactive than 3-, 6- and 7-ketones but more reactive than the 11-ketone. 12-Ethylene ketals are readily prepared by the usual procedures and the 12-ketone can be selectively ketalized in the presence of a 20-ketone bearing a 17a-hydrogen or 17a-hydroxyl substituent [(81)- (82)]. ° The procedure of choice for this reaction utihzes ethylene glycol and boron trifluoride-ether complex at room temperature. 

The electron-rich thiophene ring system can be elaborated into complex, fused thiophenes by acid-mediated intramolecular annelation reactions. For example, treatment of alcohol 96 with trimethylsilyl triflate promoted a Friedel-Crafts acylation and subsequent dehydration giving benzo[b]thiophene 97, a potential analgesic <00JMC765>. Treatment of ketone 98 with p-toluenesulfonic acid resulted in the formation of fused benzo[b]thiophene 99 <00T8153>. Another variant involved the cyclization of epoxide 100 to fused benzo[f>]thiophene 101 mediated by boron trifluoride-etherate . 

In this procedure, the ketone is first converted to its enol acetate by reaction with acetic anhydride in the presence of a proton acid. Since this enol acetylation is performed under equilibrating conditions, the more stable enol acetate (usually the more highly substituted isomer) is produced. Acetylation of this enol acetate, catalyzed by the Lewis acid boron trifluoride, usually leads to the formation of the enol acetate of a /3-diketone which is cleaved by boron trifluoride to form acetyl fluoride and the borofluoride complex of the /3-diketone. Thus, this procedure offers a convenient and general synthetic route... 

The stoichiometric equivalents of halofluorides have been recently applied to transform alkylene dithioacetals into gcm-difluorides.70-71 Dithioacetals such as 1,3-dithiolanes and 1,3-dithianes arc readily obtained from the corresponding carbonyl compounds by the reaction with ethane-1,2-dithiol or propane-1,3-dithiol in the presence of the complexes boron trifluoride-bis(acetic acid) or boron trifluoride-diethyl ether. Using a two-step procedure, a range of aldehydes and ketones can be converted into gem-difluorides under mild conditions. 

Intramolecular acylation has been used frequently. Houben-Hoesch cyclization of 1 -/ -cyanoethylpyrrole (2a) gives l-oxo-2,3-dihydropyrrolizine (3a).9-17 Difficulties occur because polymerization of the nitrile (2a) can be a side reaction. Addition of boron trifluoride [3a (33%)]11 or its ethyl ether complex [3a (60-80%)]15 has been recommended. Treatment of nitrile 2a with a molten aluminum chloride-potassium chloride-sodium chloride mixture yields 70% of ketone 3a but the experimental conditions are highly critical.13 A reproducible procedure that is based mainly on Clemo s specification9,10 gave 22% of ketone 3a.17 Purification of 3a should be carried out in an efficient fume hood because it appears to induce analgesia.1 ... 

The acylating reagent may be an acid chloride or an acid anhydride. Symmetrical ketones (—CH2 R = R2) yield only a single regioisomer. Thus acetone or cyclohexanone may be acylated with acetic anhydride in the presence of boron trifluoride-etherate to pentane-2,4-dione and 2-acetylcyclohexanone respectively (Expt 5.102). Both diketones are present in the reaction mixture as boron difluoride complexes [(10) and (11) respectively], from which they may be released by treatment with sodium acetate. Pentane-2,4-dione is appreciably water soluble and is isolated by means of its characteristic copper complex (12). 

Imidazole-containing compounds have been utilized as reagents for various synthetic transformations. A convenient access to substituted allyl enol carbonates was established through the reaction of ketone enolates with the complex of allyl l//-imidazole-l-carboxylates 74 and boron trifluoride etherate <07JOC9372>. Relatively mild and highly efficient Cul-catalyzed /V-arylation procedures for imidazoles with aryl and heteroaryl bromides or chlorides have been developed in the presence of ligands 75 and cesium carbonate <07JOC2737>. a, -Unsaturated 2-acyl imidazoles 76 are an alternative and practical class of dienophiles for the DNA-based catalytic asymmetric Diels-Alder reaction in... 

A selection of A//p gp values has already been given in Table 2-4 in Section 2.2.6. This new Lewis basicity scale is more comprehensive and seems to be more reliable than the donor number scale. Analogously, a Lewis basicity scale for 88 carbonyl compounds (esters, carbonates, aldehydes, ketones, amides, ureas, carbamates) has been derived from their standard molar enthalpies of complexation with gaseous boron trifluoride in dichloromethane solution [143]. The corresponding Aff Q gp values range from 33 kJ mol for di-t-butyl ketone to 135 kJ mol for 3-diethylamino-5,5-dimethyl-cyclohexen-2-one. 

In the case of the tricyclic epoxides la-c the outcome of the reaction depends on the ring size. The formation of 2 and 3 was explained by the following mechanism. Cleavage of the epoxide ring with boron trifluoride diethyl ether complex gives the zwitterionic intermediate 4. Subsequent transfer of fluoride anion to the cationic center C2 leads to fluoroborate 5 (path a), which is hydrolyzed to yield 2. Spiro ketone 3 is obtained by a 1,2-alkyl shift in 4 (path b). 

Treatment of a, -epoxy sulfoxides with tw O equivalents of potassium hydrogen fluoride/ boron trifluoride-diethyl ether complex reagent in chloroform at room temperature gives a-fluoro ketones in moderate to good yield together with some rearranged products.There are no other examples of the use of this reagent. 

Perfluoroalkyllithium reagents react with electrophiles such as aldehydes, ketones, silicon and tin halides, alkyl halides, carbonates, esters, boron trifluoride-imine complexes, and sulfur dioxide. ... 

The aldol reactions of these complexes were first observed by Corey in the presence of Lewis acid such as boron trifluoride for ketones and tin chlorides for aldehydes (Scheme 3.8). 

Anions formed from group 6 and manganese Fischer carbene complexes undergo aldol condensations with aldehydes and ketones. Allylic carbenes exclusively react in the y position with aldehydes affording dienyl-substituted carbenes. For alkoxy-substituted carbenes, the presence of an excess Lewis acid see Lewis Acids Bases), such as boron trifluoride etherate, titanium tetrachloride, or tin tetrachloride is required for the reaction to proceed in reasonable yield. The initial aldol product can be isolated without elimination (Scheme 12). ... 

Diethyl phosphorocyanidate adds to a,/J-unsaturated aldehydes or ketones in the presence of lithium cyanide in a 1,2-fashion28. Boron trifluoride-diethyl ether complex catalyzed rearrangement of these allylic phosphates shows high E selectivity (>85 15) for the adducts derived from aldehydes and Z selectivity (>90 10) for ketone adducts. The selectivity of the rearrangement can be explained by assuming a chairlike transition state, in which the sterically more demanding x-substituent occupies the quasi-equatorial position. The steric requirement decreases in the order of R1 > CN > H. Thus, the cyano substituent occupies the quasi-equatorial position in the aldehyde-derived adduct (R1 = H), but the quasi-axial position in the ketone-derived adduct (R1 = CH3, C6H5). 

Acid-catalysed rearrangements of highly alkylated ketones have been reported outside the steroid field [2go], but only one such steroid reaction seems to be known. It occurred when the 5j3-methyl-A nor-B-homo-6-ketone (i) was allowed to react with boron trifluoride, giving the normal 5 5-methyi-cholestan-4-one (3 [2gi], The initial ketone-BFg complex (i) may rearrange via the epoxide (2), although alternative bond-migration sequences can be formulated with the same end result. 

The isolation of the initial aldol products from the condensation of the enolates of carbene complexes and carbonyl compounds is possible if the carbonyl compound is pretreated with a Lewis acid. As indicated in equation (9), the scope of the aldol reaction can also be extended to ketones and enolizable aldehydes by this procedure. The condensations with ketones were most successful when boron trifluoride etherate was employed, and for aldehydes, the Lewis acid of choice is titanium tetrachloride. The carbonyl compound is pretreated with a stoichiometric amount of the Lewis acid and to this is added a solution of the anion generated from the caibene complex. An excess of the carbonyl-Lewis acid complex (2-10 equiv.) is employed however, above 2 equiv. only small improvements in the overall yield are realized. 

Substituted quinazolines 49 are conveniently prepared by the action of formamide on 2-aminophenyl alkyl, aryl, and arylalkyl ketones 48 in the presence of boron trifluoride diethyl ether complex as catalyst.This variation gives good yields and cleaner products than the method- in which formic acid is used as catalyst. 

Miscellaneous.—The 2-hydroxymethylene-ketone (310) forms a reasonably stable crystalline mesomeric complex (311) by reaction with boron trifluoride. Reaction of the complex with methyl-lithium, followed by acid, gave the 2-ethylidene-ketone (312), though in low yield. 

Low temperature (-50 C) H and F NMR spectra of a- or -substituted ketones, esters and nitriles complexed to boron trifluoride showed that boron coordinates preferentially at the most basic and least-hindered base when more than one coordination site is present in the ligand. Ordinarily a relative measure of chemical shifts for each type of complex would be derived from the spectra of a number of model complexes. For example, F chemical shifts for BF3 complexes of ketones (acetone), esters (methyl acetate), nitriles (acetonitrile) and ethers (diethyl ether) were measured as 149 p.p.m., 150 p.p.m., 144 p.p.m. and 156 p.p.m., respectively. Inspection of the resonance frequency and relative intensities of each peak would then reveal Ae types and ratios of the complexes present in solution. 

The solid monoacelie acid complex (hygroscopic) can be made by saturating an ethylene chloride solution of acetic acid with boron trifluoride, Altering, and washing the precipitate with more solvent the liquid diacetic acid complex remains in solution. The solid complex is recommended for the acetylation of a ketone, such as cyclohexanone. Thus acetic acid is stirred in an ice bath and boron trifluoride... 

But-3-enyltrimethylsilanes undergo cyclodesilylation to give cyclopropanes 7 on reaction with acid chlorides activated by a Lewis acid. Titanium(IV) chloride was found to be the most effective activator of the Lewis acids studied. No reaction was observed for boron trifluoride-diethyl ether complex, zinc(II) chloride and iron(III) chloride. A variety of aliphatic, aromatic and alkenoyl chlorides were successfully utilized affording the corresponding cyclo-propylmethyl ketones in fairly good yields. It has been verified that the j8-chloro ketones 9 are secondary reaction products derived from the cyclopropyl ketones 7. The formation of these chloro ketones can be avoided by performing the reaction at low temperature. 

Reaction of 58 (R = H) with a vinyl ketone in the presence of boron trifluoride-diethyl ether complex yielded cycloadducts, e.g. 62, in poor yields only. Further limitations were shown with deactivated, more hindered enones. In this case, the only isolated product was 4-acetyl-dispiro[2.1.2.3]decan-9-one (61, 28%), apparently generated via [4 + 2] cycloaddition of the (2-trimethylsiloxypropylidene)cyclopropane with itself. 

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