Cyclic ketones, formation intramolecular acylation

O. R. 1-9, C. R. Hauser and B. E. Hudson, Jr., The Acctoacetic Ester Condensation and Related Reactions lV-4, S. M. McElvain, The Acyloins 11-4, W. S. Johnson, The Formation of Cyclic Ketones by Intramolecular Acylation VIII-2, D. A. Shirley, The Synthesis of Ketones from Acid Chlorides and Organometallic Compounds of Magnesium, Zinc, and Cadmium. ... 

The Formation of Cyclic Ketones by Intramolecular Acylation William S. Johnson... 

When a 2-alkylbenzo[b]thiophene undergoes Friedel-Crafts acylation with A1C13-cinnamoyl chloride, the resulting 3-ketone cyclizes spontaneously into the 4-position with loss of benzene to give the cyclic ketone 124.515 With 2-bromobenzo[b]thiophene, a similar reaction gives a mixture of 124 [R = Cl (sic)] and the 2-Br, 3-COCH2CHPh2 substituted benzo[f>]thiophene derivative with 2-methoxybenzo[h]thiophene, the ether is demethylated to give 124(R = OH).516 The formation of other cyclic ketones by intramolecular cyclization of carboxylic acids will be considered in Section IV,M. 

The acyl-alkv biradical obtained by ring-opening of a cyclic ketone is able lo undergo intramolecular disproportionation in one of two ways. A hydrogen atom may be transferred to the acyl radical from the position adjacent to the alkyl group, and this produces an unsaturated aldehyde (4.21). Alternatively, a hydrogen may be transferred to the alkyl radical from the position adjacent to the acyl group, and this results in the formation of a ketene (4.22). Many ketenes are labile, and the use of a nucleophilic solvent or addend. 

Such reactions are particularly well suited to intramolecular dehydrative acylations for the formation of cyclic ketones. One advantage of this procedure is the fact that acid chloride need not be preformed, a process that often causes problems wiA unsaturated acids. Polyphosphoric acid is again the most commonly used reagent for the necessary dehydration and cyclization. 

Olah, G. A., Mathew, T., Famia, M., and Prakash, G. K. S. 1999. Nafion-H catalysed intramolecular Friedel-Crafts acylation formation of cyclic ketones and related heterocycles. Synlett 1067-1068. 

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. 

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