And acylation of alkenes

The scope of Friedel-Crafts chemistry has been expanded beyond aromatic systems to nonaromatic systems, such as alkenes and alkynes and the mechanistic details have been investigated. The Friedel-Crafts alkylation and acylation of alkenes provide access to a variety of organic systems (eq 9). The acylation of alkynes provides access to cyclopentenone derivatives (eq 10). In addition, one can use this chemistry to access indenyl systems and vinyl chlorides. AllyUc suHones can undergo allylation chemistry (eq 11). ... 

A variety of other reaction conditions have been examined for acylation of alkenes by acyl chlorides. With the use of Lewis acid catalysts, reaction typically occurs to give both enones and jS-halo ketones.7 The latter reaction has been most synthetically useful in intramolecular cyclizations. The following reactions are illustrative. 

A formal asymmetric nucleophilic addition to carbonyl compounds is achieved by Trost and his co-workers in the allylic alkylation of acylals of alkenals. An excellent enantioselectivity is observed in this alkylation. The starting acylals are easily prepared by the Lewis-acid catalyzed addition of acid anhydrides to aldehydes, by use of Trost s ligand 118 (Scheme 13), where various carbon-centered nucleophiles are available (Scheme l4),101,101a-10lc Asymmetric synthesis of some natural products is achieved according to this procedure. 

Of the acylation of aliphatics, the acylation of alkenes pioneered by Nenitzescu was mainly explored, because the resulting unsaturated ketones are intermediates in synthesis. This acylation of alkenes, however, has its difficulties. First, the product unsaturated ketones, which are reactive compounds themselves, can undergo various further transformations, such as addition, elimination, and isomerization, often resulting in complex product mixtures. The acylation of alkenes, therefore, is less selective and often yields products other than expected by a simple substitution of one of the vinylic hydrogens. 

The acylation of alkenes with trifluoroacetic anhydride having only weak elec-trophilicity was reported to give a,p-unsaturated ketones in 19-49% yields.117 118 The reaction requires the use of the Me2S—BF3 complex as catalyst and takes place only with alkenes that readily form stable carbocations. Alkenes were also electrolyzed in CH2C12 solution of Et4NCl as the electrolyte at —5 to — 10°C in the... 

In the acylation of alkenes with acetyl chloride120 or acetic anhydride120,121 over zeolites (HX, HY, H-mordenite, H-ZSM-5, H-Beta) usually complex product mixtures including isomeric unsaturated ketones, chloroketones, and acetates were obtained. Zeolite HY proved to be the most active catalyst under mild experimental conditions (25-60°C).120,121... 

An interesting example of an indirect acylation of alkenes is the reaction of small olefins (ethylene, propylene, isobutylene) over H-ZSM-5 in the presence of CO at 23°C to give unsaturated ketones.122 In this case the acylium ion is formed in situ from the alkene and CO in the pores of the zeolite at ambient temperature ... 

Hydro acylation of alkenes was achieved in the presence of Wilkinson s catalyst and microwave irradiation under solvent-free conditions. As an example, benzaldehyde was reacted with dec- 1-ene to give 1-phenylundecan- 1-one in 83%yield within 30 min. Both domestic microwave ovens and single-mode reactors have been used for this reaction. The presence of an amine such as 2-amino-3-picoline or aniline and a carboxylic acid is crucial for the success of the reaction, showing that the formation of an imine plays an important role as an intermediate in the mechanism of this reaction29. 

Acylation of alkenes. Friedel-Crafts acylation (AlCl,) of alkenes suffers from lack of selectivity and low yields. The reaction is markedly improved by use of CHdj-Zn/Cu (3, 255) as catalyst. No cyclopropanation is observed. 

Acylation of alkenes and alkynes. Dienes and alkynes can be acylated under phase-transfer conditions by carbon monoxide and methyl iodide in the presence of -catalytic amounts of Co2(CO)s. The reaction with alkynes results in a 4-hydroxy-2-butenolide the probable mechanism is shown in equation (I). 

Friedel-Crafts acylation of alkenes (Daizens-Nenitzescu reaction ) with unsaturated acylium ions generated from acid halides and Lewis acids constitutes a general synthesis of divinyl ketones. 

In chapter 16 we shall discover that vinyl-copper reagents can be prepared with stereochemical control over double bond geometry and acylated directly with acid chlorides. We shall also meet vinyl silanes and see how they too can be acylated with acid chlorides. In this chapter we shall consider only the acylation of alkenes themselves with acid chlorides, that is the aliphatic Friedel-Crafts reaction.15 The normal Friedel-Crafts reaction 66 combines an aromatic compound with an acid chloride and a Lewis acid to give a cation 67 which loses a proton to give an aryl ketone 68. 

Protection of the primary and acylation of the secondary alcohol prepares the way for an Ireland-Claisen rearrangement. The E-enolate is produced and the [3,3] sigmatropic rearrangement transmits the chirality across the alkene to set up two new centres. The mechanism of the Ireland-Claisen rearrangement is described above 94 and occurs suprafacially across the backbone of the molecule through a chair-like transition state. We hope you agree both with the relative stereochemistry of the new centres and the E stereochemistry of the new alkene. 

Significant advances resulting from the use of aluminosilicate solids were made during the last few years [3-6] and the first industrial application of zeolites in large scale Friedel-Crafts acylations was reported very recently [7]. However, most of the efforts devoted so far focused on the acylation of aromatic compounds. To the best of our knowledge, recourse to heterogeneous aluminosilicate catalysts for the acylation of alkenes has not yet been reported. Conventional methods for alkene acylation [8] involve the use of Br0nsted or Lewis acids such as sulfuric acid [9], boron trifluoride [10], zinc chloride [11], or... 

By comparison with the reactions with aromatic substrates, the absence of the driving force of rearo-matization by proton loss in electrophilic acylations of alkenes leads to competition between alternative pathways for the carbocation intermediate. In particular, capture of halide to form 3-halo ketones can become dominant. Hence, the aliphatic Friedel-Crafts acylation reaction need not necessarily result in substitution of an acyl residue for a hydrogen atom in an alkene, nor in the formation of unsaturated ketones. Indeed, within this broader scope, acylations of alkynes and some classes of alkanes can be synthetically useful. 

With anhydrides, aluminum chloride reacts to form the acid chloride complex. Zinc chloride is more commonly used with acid anhydrides, although this is restricted practically to acetic and other simple anhydrides that can be used as the reaction solvent. This nevertheless remains a useful reagent for acylations, giving predominantly nonconjugated products. Active zinc compounds prepared from a zinc-copper couple and alkyl halides also promote the acylation of alkenes by acyl chlorides at room temperature. ... 

The acylation of alkenes gives rise to unsaturated ketones, which themselves may be further acylated under the same reaction conditions. This is particularly the case with the nonconjugated products that often are formed preferentially. The diacyl derivatives readily cyclize to form pyrylium salts when this can be accommodated, and the sequence represents one of the best strategies for the formation of pyrylium salts symmetrically substituted at the 2- and 6-positions. Friedel-Crafts acylation as a route to pyrylium salts has been reviewed, and compared with other synthetic strategies. ... 

Aromatic, aliphatic and heterocyclic acid chlorides all give high yields of ketones, [1,4] addition not being observed with a,3-unsaturated acid chlorides. This leads to a potentially very useful synthesis of divinyl ketones since, in contrast to Lewis acid catalyzed acylations of alkenes, under the neutral reaction conditions for the acylation of alkenylstannanes, cyclizations to cyclopentenones do not occur. 

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