Low-valent titanium reagent preparation

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... 

Recently, we developed a second route to 55a and 56a (Scheme 14) [41]. Bromocyclophane II was treated with a strong base to generate a benzyne intermediate, which was trapped with furan or isobenzofuran to afford [4 + 2] adducts 57 (two isomers 6 1 ratio) and 58 (two isomers 2 1 ratio), respectively. Deoxygenation of 57 and 58 with a low valent titanium reagent prepared from TiCU, LiAlH4, and triethylamine gave 55a and 56a, respectively. 

Reductive coupling of carbonyl compounds to olefins. Reductive coupling of carbonyls to olefins with a low-valent titanium reagent prepared from TiCla and LiAlHi (6, 589) tends to give erratic yields. McMurry and Fleming find that use of Ti(0) gives reproducible results. Yields are somewhat higher with metal prepared with potassium, but lithium is easier to handle. 1,2-Diols are also reduced to olefins. ... 

A one-pot procedure for the preparation of 1,2-diamines 161 (NR 2 = NMe2, NEt2 or piperidin-l-yl R = Ph, Ar or 2-furyl) has been described the lithinm amide LiNR 2 is added to an aldehyde R CHO and the mixture is treated successively with an equivalent of titanium(IV) chloride and a low-valent titanium reagent prepared by redncing titanium(IV) chloride with magnesium. The products are obtained in 23-81% yields as mixtures of DL- and meso-isomers . 

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>. 

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>. 

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. 

The MBH adduct shown in Scheme 3.162, prepared from aromatic aldehydes and methyl acrylate, can directly undergo smooth dehydroxylation with concomitant olefin isomerization with low-valent titanium (LVT, prepared from TiCls-LAH-THF) reagent to afford the trisubstituted alkenes 364 with high ( )-selectivity. However, it is unsatisfactory in view of the low yield and the purity of products.More recently, Zhang et al. developed the samarium diiodide-promoted hydroxyl elimination of MBH adducts to form trisubstituted alkenes 364 with total ( )-stereoselectivity in good to excellent yields. This method also provided a new route to synthesizing a class of 1,5-hexadiene derivatives 365 by temperature tuning (Scheme 3.162). ... 

An interesting strategy for the construction of 2,5-dihydrothiophenes employed nucleophilic displacement to introduce the sulfur atom into a diketone intermediate (9) or (12). This was followed by an intramolecular reductive coupling of the diketosulfide, using a low-valent titanium reagent generated in situ [88] (Scheme 6.4). Either symmetrical or unsymmetrical compounds could be prepared and converted to sulfolenes by treatment with mCPBA. 

The low valent titanium LVT reagent 4.94 is prepared by the reaction of Cp2TiCl2 with magnesium turnings and P(OEt)3 in THF under dry conditions. 

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