Alkenals, acylation reactions

It has been suggested that the kinetic preference for formation of (3,y-unsaturated ketones results from an intramolecular deprotonation, as shown in the mechanism above.51 The carbonyl-ene and alkene acylation reactions have several similarities. Both reactions occur most effectively in intramolecular circumstances and provide a useful method for ring closure. Although both reactions appear to occur through highly polarized TSs, there is a strong tendency toward specificity in the proton abstraction step. This specificity and other similarities in the reaction are consistent with a cyclic formulation of the mechanism. 

Intermodular Alkylation by Carbocations. The formation of carbon-carbon bonds by electrophilic attack on the ir system is a very important reaction in aromatic chemistry, with both Friedel-Crafts alkylation and acylation following this pattern. These reactions are discussed in Chapter 11. There also are useful reactions in which carbon-carbon bond formation results from electrophilic attack by a carbocation on an alkene. The reaction of a carbocation with an alkene to form a new carbon-carbon bond is both kinetically accessible and thermodynamically favorable. 

Boger and Mathvink [134] recently reported the generation of acyl radicals from phenyl selenoesters and their participation in macrocyclization through free-radical alkene addition reactions. As shown in Scheme 73, the 16-membered macrocycle 222 was obtained from phenyl selenoester 221 in 68% yield. 

Ionic liquids can be used as replacements for many volatile conventional solvents in chemical processes see Table A-14 in the Appendix. Because of their extraordinary properties, room temperature ionic liquids have already found application as solvents for many synthetic and catalytic reactions, for example nucleophilic substitution reactions [899], Diels-Alder cycloaddition reactions [900, 901], Friedel-Crafts alkylation and acylation reactions [902, 903], as well as palladium-catalyzed Heck vinylations of haloarenes [904]. They are also solvents of choice for homogeneous transition metal complex catalyzed hydrogenation, isomerization, and hydroformylation [905], as well as dimerization and oligomerization reactions of alkenes [906, 907]. The ions of liquid salts are often poorly coordinating, which prevents deactivation of the catalysts. 

If a group, such as (C(0)0CH2CH2CH2CH=CH2), was used, the olefin was conforma-tionally constrained to bind perpendicular to the Pd—C bond and insertion-cyclization did not occur. Alkene insertion reactions into metal-acyl bonds usually occur more rapidly than insertions into metal-alkyl bonds. 

The carbonium ion may also be formed from an alkene or alcohol. The carbonium ion formed from any of these starting materials is particularly prone to rearrangement reactions. These are called Wagner-Meerwein rearrangements, and severely limit the synthetic utility of this reaction to form simple alkyl substituted aromatic compounds. The tendency to rearrange may be reduced if the acyl derivative is used instead. This modification is called the Friedel-Crafts acylation reaction, and it has the further advantage that normally only monoacylation occurs, instead of the polyalkylation that happens using the simple Friedel-Crafts reaction. 

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. 

Intermolecular ketyl alkene coupling reactions have been incorporated into a cascade that ultimately affords medium sized rings [58]. Specifically, chloroalkyl ketones react with acrylates, whereupon chloroalkyl lactones are formed in situ. Photolysis of these intermediates in the presence of excess Sml2 initiates an intramolecular nucleophilic acyl substitution reaction between the halide and the lactone, creating the medium-sized ring (Eq. 50). 

The photochemical addition of alkenes to the pyrrole ring of indole to give cyclobutane products was first reported by Julian and Foster in 1973 [43], They found that both electron-rich and electron-poor alkenes add to indole, but only if an acyl group is present on the indole nitrogen atom. With monosubstituted alkenes the reaction was regioselective and, with the exception of vinyl acetate, the exo stereoisomer was produced as either the major or the only product (Scheme 15). A mechanism involving the indole triplet excited state was suggested, based on the observation that the reaction could be sensitized by acetophenone and quenched by naphthalene. 

---