Titanium compounds intermolecular reactions

In Section 9.2, intermolecular reactions of titanium—acetylene complexes with acetylenes, allenes, alkenes, and allylic compounds were discussed. This section describes the intramolecular coupling of bis-unsaturated compounds, including dienes, enynes, and diynes, as formulated in Eq. 9.49. As the titanium alkoxide is very inexpensive, the reactions in Eq. 9.49 represent one of the most economical methods for accomplishing the formation of metallacycles of this type [1,2]. Moreover, the titanium alkoxide based method enables several new synthetic transformations that are not viable by conventional metallocene-mediated methods. 

Simple diastereoselectivity comes into play when allenylmetal compounds are added to aldehydes, since adducts such as 1 a/b contain both an axis and a center of asymmetry. Hence, diastereomeric mixtures are produced. When chiral aldehydes are used in such reactions, the diastereoselectivity also depends on the relative rate by which the enantiomers of the racemic allenylmetallic species interconvert, i.e., relative to the rate of addition to the chiral aldehyde. Apart from reactions of allenyllithium and -titanium reagents with aldehydes90-94, few such intermolecular, simple diastereoselective reactions yielding allenes have been reported. 

It is difficult to obtain cross-coupling products of two different carbonyl compounds by an intermolecular version of the McMurry reaction. Examples that use excess amounts of one carbonyl component are few. "" When one carbonyl component is replaced by a 1,1-dihalo compound or dithioacetal and the alternative is reduced with a low-valent metal such as low-valent titanium or chromium(ii), cross-coupling products, that is, Wittig-type olefins, are produced in high yields. Because the alternative approach is described elsewhere, we concentrate on only its important features here. 

Cycloalkenes. McMurry and Kees have described an intramolecular coupling of dicarbonyl compounds to cycloalkenes. In the intermolecular version of this reaction titanium(O) powder obtained by reduction with potassium or lithium is used (7, 368). In the intramolecular reaction a superior coupling reagent is prepared by reduction of TiClg with a zinc/copper couple in DME. 

Mechanistically related to the Mukaiyama aldol reaction, the carbonyl ene reaction is the reaction between an alkene bearing an allylic hydrogen and a carbonyl compound, to afford homoallylic alcohols. This reaction is potentially 100% atom efficient, and should be a valuable alternative to the addition of organometallic species to carbonyl substrates. However, the carbonyl ene reaction is of limited substrate scope and works generally well in an intermolecular manner only with activated substrates, typically 1,1-disubstituted alkenes and electron-deficient aldehydes (glyoxylate esters, fluoral, a,p-unsaturated aldehydes, etc.), in the presence of Lewis acids. The first use of chiral catalyst for asymmetric carbonyl ene was presented by Mikami et al. in 1989. ° By using a catalytic amount of titanium complexes prepared in situ from a 1 1 ratio of (rPrO)2titaniumX2 (X = Cl or Br) and optically pure BINOL, the homoallylic alcohols 70a,b were obtained in... 

McMurry reactions will be presented in the following order intermolecular, intramolecular, mixed (tandem) couplings of aldehydes and ketones, and finally keto ester, oxoamide, and acetal couplings. All the compounds which serve as illustrations are listed in Tables 6.1-6.10, along with the titanium reagents and solvents used for their preparation and the yields of isolated products where not specified, the reactions were performed at solvent reflux temperature. 

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