Olefins Tebbe methylenation

Examples have also been reported in which glyconolactones are olelinated generating exoenitols (Fig. 10) for example by methylenation (Tebbe reaction),20 difluoromethylenation,21 and dichloromethylenation,22 the Wittig olefination.23... 

CPv. / Ti Al Tebbe reagent methylenation of aldehydes, ketones, esters, thioesters, amides, carbonates can also induce olefin metathesis in situ preparation [711-713]... 

Methylenation of complex aminoaldehyde derivative 315 (Scheme 102) has been achieved [141] using methyl PT sulfone and KHMDS in THE Noteworthy, neither Wittig, Tebbe nor Peterson olefination could be employed in this case. The diene 317 was further used in the synthesis of (-)-Agelastatin 318. 

Our next objective was to methylenate the hemiacetal 40a,so as to obtain diene 39 (Scheme 14). Standard Wittig olefination procedures on 40 with methyl triphenylphosphoranylidene, generated in situ from methyl triphenylphosphonium bromide and w-BuLi, or with KOBu-t in THF (Entries 1 and 2, Scheme 14) simply furnished unreacted starting material. Tebbe olefinations were also unsuccessful a complex mixture of products arising under the conditions investigated in Entry 3 (Scheme... 

There are other organometallic derivatives that give Wittig-type olefination reactions, with titanium derivatives being the most commonly used. The initial addition reaction to the carbonyl gives a transient metal-ated alcohol that leads to an alkene. An example is the Tebbe reagent, which exists as a bridged methylene species (see 683), where Cp is cyclopentadienyl. 9 The aluminum species can be varied to include chloride... 

Hydroxytetrahydrofurans. Triisobutylaluminum acts both as a Lewis acid to catalyze the isomerization of 4-methylene-1,3-dioxolanes to 2-oxotetrahydrofurans (via C-O bond cleavage and C-C bond formation) and as a reducing agent for the ketone group of the intermediate. The 4-methyIene-1,3-dioxolanes are available by a Tebbe 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 Lombardo reagent is usually prepared by addition of TiCU to a precooled suspension of zinc dust in a solution of dibromomethane in dry THF at very low temperature (e.g., -40°C), and aged for 2 days at 4°C before the methylenation." Different from the Wittig Reaction, the Lombardo methylenation is highly selective and occurs under nonbasic conditions. This reaction is especially valuable for the methylenation of keto ester, for which the Wittig Reaction fails, " and for the olefination of /3,y-unsaturated enones without enolization. Thus the Lombardo methylenation is an alternative olefination method when Wittig Reaction or Tebbe Olefination is not applicable. However, it also... 

It is plausible that the Lombardo methylenation proceeds via an analogous pathway of Tebbe Olefination, as illustrated below. 

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). 

I 4 Carbonyl Olefination Utilizing Metal Carbene Complexes Tab. 4.1. Methylenation of ketones with the Tebbe reagent 3. 

Methylenation of carboxylic acid derivatives The Tebbe reagent 3 is extremely valuable as a reagent for the methylenation of carboxylic acid derivatives, which is generally unsuccessful using phosphorus ylides. Esters and lactones are readily transformed into enol ethers (Table 4.3), especially when a Lewis base such as THE is present in the reaction mixture. In the methylenation of a,j8-unsaturated esters, the internal olefin is not involved in the reaction, and the configuration of the double bond is maintained (entry 4). When carbonyl compounds bearing a terminal double bond are subjected to the methylenation, significantly lower yields are observed (entries 6 and 11), which may be attributable to competitive formation of a titanacycle from titanocene-methylidene 4 and the terminal olefin. 

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