Titanium carbonyl olefination

The results presented in Section 6.4.3 revealed that the McMurry reactions of ster-ically hindered ketones can in fact be viewed as Wittig-like olefination reactions. While these two reactions were for a long time thought to be mechanistically different, formation of carbenoid species by reduction of ketones with low-valent titanium complexes is not really surprising in view of the highly oxophilic and reducing character of titanium. Carbonyl olefinations by means of titanium carbe-... 

Cydopentadienyl Titanium Derivatives for Carbonyl Olefination/Olefin Metathesis... 

Table 3.10. Carbonyl olefination with Tebbe-type titanium reagents.

A plausible intermediate of this olefination is the titanium-methylene sjtecies 4, which is formed from 1 by removal of AlMe2Cl with a Lewis base, from 2 by fragmentation with elimination of isobutene, and from 3 by a-elimination and release of methane. However, none of these three routes to titanium-carbene complexes of type 4 proved to be generally applicable. Consequently, the use of these reagents in synthesis is essentially limited to the transfer of a methylene unit 18]. From a synthetic viewpoint, a general and easy route to substituted titanium-alkylidene species and their use in carbonyl olefinations would be more desirable. 

Scheme 6. Carbonyl olefination with titanium-alkylidene species 12 prepared from dithioacetals according to Takeda et al.

Breit, B. Dithioacetals as an entry to titanium-alkylidene chemistry a new and efficient carbonyl olefination. Angew. Chem., Int. Ed. Engl. 1998, 37, 453-456. 

Petasis, N. A., Bzowej, E. I. Titanium-mediated carbonyl olefinations. 1. Methylenations of carbonyl compounds with dimethyltitanocene. J. Am. Chem. Soc. 1990,112, 6392-6394. 

The reduction of Cp2TiCl2 with Mg in the presence of P(OEt)3 affords the titanium(n) complex Cp2Ti[P(OEt)3]2 which was used as a catalyst for the carbonyl olefination of thioacetals through a titanium-alkylidene intermediate (see Section 4.05.4.2.4 alkylidene complexes).1148... 

The carbonyl olefination using a reagent formed from CH2(ZnI)2 and TiCl2 is thought to involve addition to a titanium carbene complex.1424... 

On the other hand, isolable transition-metal-bound cyclopropyl systems can also be used in coupling reactions. Thus bis(cyclopentadienyl)bis(cyclopropyl)titanium reacted, in a Tebbe-type transformation, with carbonyl compounds to give methylenecyclopropanes 3 and with alkynes to form vinylcyclopropanes 4 via carbonyl olefination. ... 

Tebbe found that titanocene complexes promoted olefin metathesis in addition to carbonyl olefination. Despite the fact that these complexes have low activity, they proved to be excellent model systems. For example, the Tebbe complex exchanges methylene units with a labeled terminal methylene at a slow rate that can be easily monitored (Eq. 4.6) [54]. This exchange is the essential transformation of olefin metathesis. When reactions with olefins are performed in the presence of a Lewis base, the intermediate titanium metallacycle can be isolated and even structurally characterized (Eq. 4.7) [61] These derivatives were not only the first metathesis-active metallacyclobutane complexes ever isolated, but they were also the first metallacyclobutanes isolated from the cycloaddition of a metal-carbene complex with an olefin. These metallacycles participate in all the reactions expected of olefin metathesis catalysts, especially exchange with olefins... 

The utility of the Tebbe type complex in carbonyl olefination is discussed in Chapter 4. The bridged complex may be regarded as a special type of a carbene complex where the Cp2Ti=CH2 unit is masked by interaction with the AlMe2Cl entity. Formation of the Tebbe s complex suggests the occurrence of a-hydrogen elimination in the preparation of the Ziegler-Natta and Kaminsky type olefin polymerization catalysts from titanium chlorides and methylaluminum compounds. 

A few years later, Tebbe and co-workers found that the methylene-bridged metallacycle 3, which has become known as the Tebbe reagent, is useful for the methylenation of ketones and aldehydes [5]. Titanocene-methylidene 4, the active species of this olefination, also transforms carboxylic acid derivatives into heteroatom-substituted olefins. Because the carbene complex 4 is much less basic than conventional olefination reagents such as phosphorus ylides, it can be employed for the olefination of carbonyl compounds possessing highly acidic a-protons or of highly hindered ketones, and has become an indispensable tool in organic synthesis. Various methods for the preparation of titaniumcarbonyl olefination. This chapter focuses on the use of metal-carbene complexes and some related species in carbonyl olefination (Scheme 4.2). 

Schrock-type carbene complexes of transition metals other than titanium are also utilized for carbonyl olefination, although their synthetic utility has not yet been fully investigated. In some cases, their reactions differ from those of titanium-carbene complexes in terms of stereo- and chemoselectivity and are complementary to olefination with titanium reagents. This section describes the use of carbene complexes of various transition metals in carbonyl olefination. 

Iyer and Rainier followed up on the gambieric acid studies (Scheme 3.57) to show that oxepines can generally be formed using titanium ethylidenes. One example is given in Scheme 3.59 [65]. In contrast to Nicolaou s Tebbe reagent protocol, evidence is suggestive of an olefin metathesis, carbonyl-olefination cychzation mechanism [63a,b,f], [64d], [66].Subsequently, this reaction has been used by the Rainier... 

Low valent titanium McMurry carbonyl coupling is believed to go through the vic-diol. vic-diols are smoothly converted to the corresponding olefins under these conditions. JOC 1976, 41, 896... 

Reductive coupling of carbonyl compounds to yield olefins is achieved with titanium (0), which is freshly prepared by reduction of titanium(III) salts with LiAIH4 or with potassium. The removal of two carbonyl oxygen atoms is driven by T1O2 formation- Yields are often excellent even with sensitive or highly hindered olefins. (J.E. McMurry, 1974, 1976A,B). 

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). 

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