Carbonyl compounds Tebbe methylenation

Petasis, et al. have discovered that dimethyltitanocene is an excellent substitute for the Tebbe reagent" for the methylenation of heteroatom-substituted carbonyl compounds. ... 

Dormond ef rrZ. have exploited compounds 30 and particularly 32 as synthetically useful reagents. The uranium-mediated methylenation of carbonyl compounds (cf.. the Wittig, Peterson or Tebbe reactions) is illustrated in Equation (5.1). The instantaneous formation under ambient conditions of the insertion product 33 was essentially quantitative (e.g./ =... 

The Tebbe reagent (4.85) is used for methylenation of carbonyl compounds. ... 

For a comprehensive review detailing the scope and utility of methylenation of carbonyl compounds using Tebbe s reagent, see S. H. Pine, Org. React., 1993, 43, 1 for a more recent review, see R. H. Hartley and G. J. McKiernan, J. Chem. Soc., Perkin Trans. 1, 2002, 2763. 

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). 

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. 

The common element between Tebbe and Petasis methylenation is that both share the same reactive intermediate, titanocene methylidene 5, in the reaction pathway. Hughes has provided a strong evidence that the Petasis reaction proceeds by the rate-determining generation of titanocene methylidene 5 via an a-elimination to remove of methane, followed by a rapid reaction with the carbonyl compound. ... 

The carbonyl group of an ester function can be converted to the corresponding methylene compound using Tebbe s reagent. The reaction can thus be considered as a general method of enol ether synthesis. An example of this reaction is given in Scheme 5. The same conversion can be achieved by reagents prepared from the reduction of 1,1-dibromoalkanes with zinc and TiCU in the presence of TMEDA. °... 

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