Cycloalkanones coupling

Ketoesters 9 can be coupled to give enol ethers 10, which may for example be converted to cycloalkanones by hydrolysis. 

Cycloalkanones. The synthesis of cycloalkenes by intramolecular coupling of a diketone with a Ti(0) reagent (8, 483) has been extended to a cycloalkanone synthesis. Thus reaction of a keto ester with TiCli/LiAlHj in the presence of triethylamine results in cycloalkanones in moderate to high yield. ... 

The reductive coupling of carbonyl compounds with formation of C-C double bonds was developed in the early seventies and is now known as McMurry reaction [38, 39]. The active metal in these reactions is titanium in a low-valent oxidation state. The reactive Ti species is usually generated from Ti(IV) or Ti(III) substrates by reduction with Zn, a Zn-Cu couple, or lithium aluminum hydride. A broad variety of dicarbonyl compounds can be cyclized by means of this reaction, unfunctionalized cycloalkenes can be synthesized from diketones, enolethers from ketone-ester substrates, enamines from ketone-amide substrates [40-42], Cycloalkanones can be synthesized from external keto esters (X = OR ) by subsequent hydrolysis of the primary formed enol ethers (Scheme 9). 

Extension of the low-valent titanium dicarbonyl coupling reaction to ketoesters leads to cyclic enol ethers, and hydrolysis of these affords the corresponding cycloalkanones. This methodology has been applied to the synthesis of various natural products, as exemplified by the preparation of the highly unsaturated C(14) macrocyclic ketone shown below. 

A second new synthesis of exo-alkylidene-cycloalkanones involves coupling of the appropriate a-chloronitroalkane with an a-ethoxycarbonylcycloalkanone followed by chloride ion promoted de-ethoxycarbonylation and loss of nitrite ion (Scheme 74). ... 

Lessard, Spino, and coworkers developed the formation of iV-heterocycles from cycloalkanones using a photochemical ring contraction reaction coupled with a Beckmann rearrangement ring expansion." Their methodology is an impressive approach to transform disubstituted cycloalkanones into N-heterocycles of the same ring size tSchemp The... 

Acetals, toluenesulfonates, esters, and ethers The compatibility of these groups with the McMurry reaction is illustrated by the coupling products of substituted cycloalkanones, 23 [4] and 24 [39], and benzaldehydes, 25 and 26 [40, 41] (Figure 6.4). However, benzylidene acetals were found to be cleaved in a modified McMurry reaction (see Section 6.2.6). 

Intramolecular reductive coupling of cycloalkanones tethered to alkynoates in the presence of ( -propene)titanium gives hydroxy esters in a diastereoselective manner (Scheme 191). ... 

TABLE 56.13 Photochemical Coupling Reaction of Cycloalkanone at Room Temperature... 

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