Low-valent titanium reagent

The synthesis of soluble PPV derivatives (82), via McMurry-type coupling of solubilized aromatic dialdehydes in the presence of low-valent titanium reagents, was described by Schliiter et al. [105]. The products are characterized... 

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). 

Scheme 14.28. Carbonyl alkylidenation utilizing gem-dihalides and low-valent titanium reagents.

Reduction of enedicarboxylates. A low-valent titanium reagent obtained from TiCL, and LiAlH, (about 2 1) can reduce enedicarboxylates in the presence of a trace of triethylamine. 

Lenoir, D. 1989. The application of low-valent titanium reagents in organic synthesis. Synthesis. 883-97. 

Et3N unquestionably played an important role. In the presence of 0.5 molar equivalent of this amine, endoxide 55 was reduced by low-valent titanium reagent (molar ratio of endoxide TiCl LiAlH4 EtjN = 1 6.9 2.7 0.5) to a mixture of products, namely endo,cis-9S and trans-95 in a ratio of 1 5 (Scheme 20). In many cases, this reducing system would reduce enedicarboxylates to succinates, while other unactivated olefinic functionalities in the molecules would remain intact. A fitting example was the convCTsion of 96 to 97 as shown in Scheme 20. ... 

The McMurry reaction (the reductive dimerization of carbonyl compounds giving olefins after treatment with the low-valent titanium reagents TiCla/Mg and TiCla/Zn in THF at 40°C) (CR891513) is a key step in the synthesis of photochromic cyclopentene derivatives. Later, it has been shown that TiCU, which is easier to handle than TiCls, can be used. The cyclization products are formed in 50-60% yields (98S1092,03EJO155). The advantages of this method are that the reactions can be scaled and inexpensive starting materials can be used. 

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. 

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 reaction between ClTi(Of-Pr)3 and 7-PrMgBr generates a low-valent titanium reagent, diisopropoxy(q2-prope-ne)titanium, which mediates the cyclization of the alkynic carbonates 1158 to isochroman-3-ones 1160 via the intermediate 1159 (Scheme 287) <1995TL6075, 1996JA2208>. 

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>. 

The minor isomer 57, which can be prepared in high yield using alternative pathway <1998BCJ1187> (see Scheme 40, Section 14.08.8.1.1), was converted back to unsubstituted dibenzo[4,g][l,3,6]trithiocine 56 by reduction with a low-valent titanium reagent in 95% yield <1996CC205, 1996BCJ2349>. 

A prototype example is the famous McMurry coupling of carbonyl compounds to alkenes (Scheme 1) [4]. The very high stability of the accumulating titanium oxides constitutes the thermodynamic sink which drives the conversion but demands the use of stoichiometric or excess amounts of the low-valent titanium reagent [Ti]. Only recently has it been possible to elaborate a procedure that for the first time enables us to perform intramolecular carbonyl coupling reactions catalyzed by titanium species [5]. 

Oxime — imine. The low valent titanium reagent prepared from TiClj and diisobutylaluminum hydride (1 3) in THF reduces the oxime 1 to the very labile imine 2. Reduction of 2 to the corresponding amine with diisobutylaluminum... 

Reductive cyclization of 2-(t>/X t>-nitro)phenyl imidazoles 817, 819 (Scheme 203) in the presence of an orthoester or a ketone is promoted by a low-valent titanium reagent TiCU-Zn to afford imidazo[l,2-f]quinazolines 818 and 5,6-dihydroimidazo[l,2-r ]quinazolines 820 <2005JHC173>. Notably, halogens are not reduced under these conditions. 

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