1.2- diketone-TiCl

Silyl enol ethers can be dimerized to symmetrical 1,4-diketones by treatment with Ag20 in dimethyl sulfoxide or certain other polar aprotic solvents.465 The reaction has been performed with R2, R-1 = hydrogen or alkyl, though best yields are obtained when R2 = R1 = H. In certain cases, unsymmetrical 1,4-diketones have been prepared by using a mixture of two silyl enol ethers. Other reagents that have been used to achieve either symmetrical or cross-coupled products are iodosobenzene-BFy-EtiO.466 ceric ammonium nitrate,467 and lead tetraacetate.m If R1 = OR (in which case the substrate is a ketene silyl acetal), dimerization with TiCL, leads to a dialkyl succinate (32, R1 = OR).4 9... 

Monooximes of a-diketones have found applicability in the synthesis of 2-aminopyrazine 1-oxides by condensation with a-aminonitriles, and this reaction was used by White and coworkers in an approach to the synthesis of Cypridina etioluciferamine (Scheme 66 R = 3-indoloyl) (73T3761). In this instance, the use of TiCL as a catalyst was essential, since the carbonyl group in 3-acylindoles is normally deactivated and the required amine/carbonyl condensation is unpractically slow. Under normal circumstances the carbonyl group in simple alkyl-substituted monoximes of a-diketones is the more reactive site and the reaction is rapid, requiring no catalysis (69LA(726)loo). 

A solution of 2-methyl-l-(trimethylsilyloxy)cyclohex-l-ene (10 mmol) in dichloromethane (8 ml) was added dropwise over 15 min with stirring to acetyl chloride (10 mmol) and TiCL (10 mmol) in dichloromethane (15 ml) at —78 °C. After 1 h at -78 °C, the reaction mixture was allowed to warm to ambient temperature over 2h. It was then diluted with ether (20ml), and poured into saturated sodium hydrogen carbonate solution (50 ml). Normal work-up, followed by chromatography on silica gel, gave the y3-diketone (9.1 mmol, 91%). 

Later, p-acetoxy-substituted cyclic enones 87 with various ring sizes were also examined for intramolecular Stetter cyclization. Under the optimized Stetter conditions (1.0 equiv. of thiazolium salt 88 and 1.2 equiv. of EtsN in EtOH under reflux), bicyclic enedione 89 could be synthesized effectively (Scheme 4.27), but the yields mainly depended on the size of the ring in the substrate 87." Increasing the substrate ring size led to improved yields of 89. Cycloheptenone and cyclooctenone derivatives 87c,d afforded the desired enediones 89c,d in 80% yields. To reduce the conjugated C-C double bond, McMurry s procedure" using TiCls as a reductant was employed to give diketones 90 in excellent yields. 

Simple ketones and 1,3-diketones give conjugate addition in acidic solution as shown in Equation 7.22 [39], Here, too, the silyl enol ethers and TiCl may be used (Eq. 7.23) [40]. 

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