Enolates Friedel-Crafts acylation

Diels-Alder reaction, 493 El reaction, 391-392 ElcB reaction, 393 E2 reaction, 386 Edman degradation, 1032 electrophilic addition reaction, 147-148. 188-189 electrophilic aromatic substitution, 548-549 enamine formation, 713 enol formation, 843-844 ester hydrolysis, 809-811 ester reduction, 812 FAD reactions. 1134-1135 fat catabolism, 1133-1136 fat hydrolysis, 1130-1132 Fischer esterification reaction, 796 Friedel-Crafts acylation reaction, 557-558... 

Titanium-mediated intramolecular Friedel-Crafts acylation and alkylation are important methods for construction of fused-ring systems (Scheme 29).107 As well as aromatics, olefin units also react in the same way.108 Alkylation of electron-rich olefins such as enol ethers or silyl enol ethers proceeds effectively in the presence of TiCl4.109... 

Friedel-Crafts acylation of 4-bromoindole led to 67, which, after protection by N-tosylation to give 68, was treated with methylmagnesium bromide and afforded compound 66, which contains the welwistatin C3-C16 bond as well as its gem-dimethyl substituent at C(16). A Lewis-acid catalyzed displacement of the tertiary hydroxyl in 66 by a cyclohexanone silyl enol ether afforded intermediate 69, which was then deprotected and N-mclhylalcd to 70 (Scheme 13). 

Because this is an unusual Friedel-Crafts acylation, we think it worthwhile to draw a mechanism in the description of a synthesis. This is just such a situation as we described above. Another electrophilic substitution occurs when this ketone reacts with bromine via its enol (Chapter 21). 

Acylations of ketone enols with anhydrides are catalysed by Lewis acids such as BF3, This process will remind you of Friedel-Crafts acylation but a better analogy is perhaps the aldol reaction where metals such as lithium hold the reagents together so that reaction can occur around a six-membered ring. 

Three reactions, which were known from the literature to be catalyzed by Lewis acids were selected as test reactions. A, was the Reetz alkylation of silyl enol ethers with -butyl chloride for which titanium tetrachloride is known to be useful [52]. B, was the Diels-Alder reaction between furan and acetylenedicarboxylic ester for which aluminium trichloride is a good catalyst [53]. C, was a Friedel-Crafts acylation for which aluminium trichloride is the preferred catalyst [54]. The reactions are summarized in Scheme 6. 

A number of the reactions discussed above were used in a synthetic sequence. Friedel Crafts acylation of (98) gives (99) after isomerization of the diene geometry using sodium methoxide. Bromination of aTMS-enol ether, formed from (99), with DBA was nonstereospecific however, the isomers were readily separated (Scheme 159). The pure a-bromoketone is stereospecificaUy methylated and transformed into an epoxide. Lewis acid mediated isomerization of the epoxide affords an optically pure ketone (100). 

In the presence of a stoichiometric amount of SbCls, Friedel-Crafts acylation proceeds with acyl hahdes and acid anhydrides [47], SbCls also promotes the Fries rearrangement of phenyl acetates [48], The electrophilic acylation of fluoro-olefins with acetyl fluoride or benzoyl fluoride is promoted by SbFs in liquid SOy [49], The Friedel-Crafts acylation of benzene and electron-rich arenes is successfully catalyzed by SbCl5-AgClO4 [50], SbCl, Ar.BCl [51], SbCl5-LiClO4 [52], or CaCI, AgSbFg [53] (Scheme 14,19), Acyl chlorides, acid anhydrides, and acyl enolates are used as sources of acyl groups. 

Reactions of Enol Ethers and Esters.—When enol acetylation of a steroid 4-en-3-one with acetic anhydride is catalysed by perchloric acid (or boron trifluoride ), C-acetylation of the enol acetate (373) occurs on prolonged reaction. This step, probably involving acetyl perchlorate ior airs, is akin to Friedel-Crafts acylation of aromatic compounds. Both 6-acetylation and 2-acetyIation are known, although each is prevented by the presence of a methyl group at the site. The products can be of various enolic types (e.g. 374 and 375). 

Michael reaction of an oc,p-unsaturated ketone with a silyl enol ether (Scheme 26) and a Diels-Alder reaction of an oxazolidinone derivative with cy-clopentadiene (Scheme 27) also worked well using MC Sc(OTf)3. Moreover, a Friedel-Crafts acylation proceeded smoothly to produce an aromatic ketone in a good yield (Scheme 28). Friedel-Crafts alkylation and acylation reactions are fundamental and important processes in organic synthesis as well as in indus-... 

A further antimony derivative, namely, bis-(para-methoxyphenyl) boryl hexachloroantimonate [prepared in situ from antimony pentachlo-ride and bis-(para-methoxyphenyl)boryl chloride] can be utilized (25% mol) in the acylation of anisole and veratrole with acetone acyl enolates in 52%-88% yield. The major advantage of the method resides in the possibility of performing Friedel-Crafts acylation at room temperature in a reaction medium that can be kept almost neutral throughout the reaction, acetone being the only co-product. 

The reaction involves an intramolecular Friedel-Crafts acylation followed by halogenation of the intermediate dihydrothiepinone, probably via its enol form. 

Deprotonation. After iV,iV-diethyl-l-lithiovinylcarbamate, which is obtained by a deprotonation process (with r-BuLi as base), is converted into the organozinc reagent, it can be used to couple with aryl halides (e.g., bromides) and triflates in the presence of (dppf)PdClj to afford the enol carbamates of the acetophenones. The overall transformation can be considered an anionic equivalent of Friedel-Crafts acylation. ... 

Fluoroalkyl chromone derivatives can be obtained from the base catalysed reaetion between 2,2-dihydropolyfluoroalkanoates and phenols. Initial loss of HF allows Michael addition of the phenol and subsequent cyclisation of the enol ether yields the heterocycle. m-Substituted phenols give the expected mixture of 5- and 7-substituted chromones, whilst dihydroxy aromatic compounds give polycyclic materials (94JFC263). In a more conventional approach Z-3-(aryloxy)-polyfluoroalkenoic adds, derived from Michael addition of phenols to polyfluoro-2-alkynoic acids, undergo intramolecular Friedel-Crafts acylation to 2-polyfluoro-alkylchromones (94JFC25). 

Silyl-substituted allyl acetates react with Fc2(CO)9 under a CO atmosphere to give the corresponding ij -Fe(CO)4 complexes which are treated with a silyl enol ether in the presence of BF3 OEt2 to yield vinylsilanes 245 stereoselectively in moderate to good yields (equation 198). Allylstannane can also react undo- these conditions. The silyl-substituted butadiene complex of tricarbonyliron is treated with acetyl chloride in the presence of AICI3 at 0°C to give the Friedel-Crafts acylation products, dienone complexes, without desilylation -. ... 

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