Tebbe reagent / olefination reaction

Although the molybdenum and ruthenium complexes 1-3 have gained widespread popularity as initiators of RCM, the cydopentadienyl titanium derivative 93 (Tebbe reagent) [28,29] can also be used to promote olefin metathesis processes (Scheme 13) [28]. In a stoichiometric sense, 93 can be also used to promote the conversion of carbonyls into olefins [28b, 29]. Both transformations are thought to proceed via the reactive titanocene methylidene 94, which is released from the Tebbe reagent 93 on treatment with base. Subsequent reaction of 94 with olefins produces metallacyclobutanes 95 and 97. Isolation of these adducts, and extensive kinetic and labeling studies, have aided in the eluddation of the mechanism of metathesis processes [28]. 

Recently, Nicolaou and coworkers have devised a novel, one-pot strategy for the direct transformation of acyclic olefinic esters to cyclic enol ethers [34]. Unlike the molybdenum alkylidene 1 (see Sect. 3.2), initial reaction between the Tebbe reagent 93 and an olefinic ester results in rapid carbonyl olefination to afford a diene intermediate. Subsequent heating initiates RCM to afford the desired cyclic product (Scheme 17). 

Preliminary investigations in this area involved treatment of olefinic ester 125 with a large excess (4 equiv) of the Tebbe reagent 93 (Scheme 18) [34a]. After 20 min at 25°C, the mixture was heated at reflux for 5 h. This resulted in the formation of tricyclic enol ether 127 in 71% overall yield. If only 1.3 equiv of Tebbe reagent 93 was employed and the reaction stopped after 20 min at 25°C,the olefinic enol ether 126 could be isolated in 77% yield. The proposed intermediacy of diene 126 in the initial tandem sequence was validated by its subsequent conversion into the cyclic enol ether 127 under the original reaction conditions [34a],... 

A limitation to the use of the Tebbe reagent 93 was observed during the attempted conversion of substrates 139 and 142 to the tricyclic systems 141 and 144 respectively (Scheme 21). The major products from these reactions were olefinic alcohols 140 and 143. These products presumably resulted from sequential hydrolysis and olefination of the initially formed cyclic enol ethers. The problem associated with these sensitive substrates was overcome through use of the less Lewis-acidic Petasis reagent 110, which provided access to the desired products 141 and 144 [34a]. 

Aluminum-free titanocene-methylidene can be generated by thermolysis of titana-cyclobutanes 6, which are prepared by reaction of the Tebbe reagent with appropriate olefins in the presence of pyridine bases [9]. Alternatively, the titanacyclobutanes are accessible from titanocene dichloride and bis-Grignard reagents [10] or from 71-allyl titanocene precursors [11]. The a-elimination of methane from dimethyltitanocene 7 provides a convenient means of preparing titanocene-methylidene under almost neutral conditions [12] (Scheme 14.5). 

Tandem carbonyl olefmation—olefm metathesis utilizing the Tebbe reagent or dimethyl-titanocene is employed for the direct conversion of olefmic esters to six- and seven-mem-bered cyclic enol ethers. Titanocene-methylidene initially reacts with the ester carbonyl of 11 to form the vinyl ether 12. The ensuing productive olefm metathesis between titano-cene methylidene and the cis-1,2 -disubstituted double bond in the same molecule produces the alkylidene-titanocene 13. Ring-closing olefin metathesis (RCM) of the latter affords the cyclic vinyl ether 14 (Scheme 14.8) [18]. This sequence of reactions is useful for the construction of the complex cyclic polyether frameworks of maitotoxin [19]. 

The alkyl-substituted titanium carbene complex 18 reacts with norbornene 24 to form a new titanacycle 25, which can be employed for the ROMP of 24 (Scheme 14.13). The titanacycle generated by the reaction of the Tebbe reagent with 24 is also used as an initiator for the same polymerization [23]. These preformed titanacyclobutanes also initiate ROMP of various other strained olefin monomers [24],... 

The so-called Tebbe reagent 272 reacts with carbonyl compounds to form olefinic products 139a>, a reaction which is of particular synthetic value in case of esters (Equation 87) 139b). 

To a solution of the aldehyde (2.56 g, 4.40 mmol) in THF (50 mL) cooled to 0 °C was added the Tebbe reagent (0.5 M, 13.2 mL, 6.60 mmol). After being stirred at 0 °C for 30 min, the reaction mixture was treated with 0.1 M aqueous NaOH (30 mL) and diluted with ether. The resulting mixture was stirred at room temperature for 30 min, filtered through a pad of Celite, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, 10% EtOAc/hexanes) to give 2.30 g (90%) of the terminal olefin as a colorless oil. 

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... 

Other titanium-based olefination reagents have been developed. Eisch used a zinc analog of the Tebbe reagent (688) in a reaction with benzophenone to give 1,1-diphenylethene in 78% yield. Similarly, Clawson et al. used 689 in olefination reactions with ketones and aldehydes. Alkoxytitanium reagents such as 690 have been employed, as in the conversion of cyclohexane carboxaldehyde to 1-cyclohexyl-1,3-butadiene (691), in 86% yield.In this olefination reaction, the (Z)-isomer predominated over the ( ) (96 4 Z/E). 

Other Unsaturated Compounds. - The dienals 13 (with D-xylo-, D-lyxo- and D-arahino-configurations) have been condensed with the phosphonate 14 to give the enone adducts 15 the intramolecular Diels-Alder reactions of these adducts are mentioned in Chapter 22. Treatment of the unsaturated lactone 16 with the Tebbe reagent has afforded 17 its conversion into a cyclooctene derivative is covered in Chapter 18. Exposure of the cyclic sulfate 18 to base has afforded a mixture of the exo- and endo-olefins 19 and 20, ° and a syn-selective dihydroxyla-tion of the 3,4-unsaturated pyranoside 21 generated predominantly the D-allo product. Synthesis of the branched-chain 5,6-ene 22 using standard methods, and its conversion into a cyclitol during the first total synthesis of (—)-tetracyc-line is mentioned in Chapter 22. 

The utility of simple enamines in C-C bond-forming reactions has prompted continuing efforts directed towards improved methods of synthesis for more highly functionalised derivatives. The Tebbe reagent (6) has found use in the olefination of esters and recently... 

---