Titanium reagents, coupling with

Another well-known transformation of carbonyl derivatives is their conversion to pinacols (1,2-diols) via an initial one-electron reduction with highly active metals (such as sodium, magnesium, aluminum, samarium iodide, cerium(III)/ I2, yttrium, low-valent titanium reagents (McMurry coupling), etc.), amines, and electron-rich olefins and aromatics as one-electron donors (D).43 Ketyl formation is rapidly followed by dimerization44 (equation 22). 

An interesting deoxygenation of ketones takes place on treatment with low valence state titanium. Reagents prepared by treatment of titanium trichloride in tetrahydrofuran with lithium aluminum hydride [205], with potassium [206], with magnesium [207], or in dimethoxyethane with lithium [206] or zinc-copper couple [206,209] convert ketones to alkenes formed by coupling of the ketone carbon skeleton at the carbonyl carbon. Diisopropyl ketone thus gave tetraisopropylethylene (yield 37%) [206], and cyclic and aromatic ketones afforded much better yields of symmetrical or mixed coupled products [206,207,209]. The formation of the alkene may be preceded by pinacol coupling. In some cases a pinacol was actually isolated and reduced by low valence state titanium to the alkene [206] (p. 118). 

Table 2 Asymmetric pinacol coupling reactions of benzaldehyde with titanium reagents... 

Oxo esters undergo an intramolecular dicarbonyl coupling reaction on treatment with a low-valent titanium reagent to form a ketone. This was used in the synthesis of (Z)-7,l0,10-trimethyl-bicyclo[7.2.0]undec-6-en-2-one (4) from ethyl ( )-6-methyl-7-(4,4-dimethyl-2-oxocyclobutyl)-hept-5-enoate,108 Interestingly, the configuration of the isolated C -C double bond in the isolated product is sensitive to the reaction conditions. 

Corey Danheiscr Chandrasekaran /. Org. Chem. 1976, 41. 260 Pons Zahra Saniclli Tetrahedron Lett. 1981, 22, 3965. For some other titanium-containing reagents, see Clcrici Porta J. Org. Chem. 1985,50. 76 Handa Inanaga Tetrahedron Lett. 1987, 28. 5717. For a review of such coupling with Ti and V halides, see Lai Org. Prep. Proced. Int. 1980, 12. 363-391. 

Preparation Essentially this reaction involves the preparation of a low-valent titanium reagent that then couples carbonyl groups, including esters to aldehydes/ketones. Generally, TiCLt is reduced with some reducing agent (LiAIH4, Zn, Mg). 

The bifunctional cyclopropane 156 was also prepared by modified Simmons-Smith cyclopropanation 85) of 2-trimethylsilyl-2-propen-l-ol 157 84) followed by oxidation of the cyclopropylcarbinol 158 with activated manganese dioxide 88 >, in 72% overall yield, Eq. (50) 86,89). Coupling of the aldehyde 156 with 2,6-dimethylcyclohexenone 159 90) induced by the low valent titanium reagent from TiCl3 and zinc-copper couple (or lithium metal) provided the silylated cyclopropyldiene 160, in 50-60% yield, Eq. (51) 89 91>. 

Several ADAM (alkenyidiarylmethane) II non-nucleoside reverse transcriptase inhibitors were prepared by M. Cushman and co-workers. The McMurry reaction was the key transformation that enabled the coupling of the diaryl ketone with a variety of aldehydes in good yield. The commercially available TiCU-THF (2 1) and zinc dust was used to prepare the low-valent titanium reagent in refluxing THF. To this suspension was added the diaryl ketone and the aldehyde successively. 

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