Lactones Tebbe reagent

The Tebbe reagent [//-chloro-bis(cyclopentadienylXdimethylalumin-ium)-/r-methylenetitanium] in its pure, crystalline (70,71) or crude (72) forms has been employed for the methylenation of aldonolactones. Thus, D-ribono- 1,4-lactone derivatives 71a and 71b reacted with Tebbe s reagent to give (70,71) the exo-methylene compounds 72a and 72b. 

Dimethyltitanocene (213), called the Petasis reagent, can be used for alkenation of carbonyls (aldehydes, ketones, esters, thioesters and lactones). This reagent is prepared more easily than the Tebbe reagent by the reaction of titanocene dichloride with MeLi. However, this reagent may not be a carbene complex and its reaction may be explained as a nucleophilic attack of the methyl group at the carbonyl [67], Alkenylsilanes are prepared from carbonyl compounds. Tri(trimethylsilyl)titanacyclobutene (216), as a... 

A reaction that appears to be mechanistically similar to the Tebbe reaction was developed by Oshima in 1978. Diiodomethane or dibromomethane in the presence of zinc is treated with a Lewis acid to form, presumably, a divalent complex (72), which reacts with aldehydes and ketones to produce the corresponding methylene derivative (73 Scheme 18). This reagent complements the reactivity of the Tebbe reagent, in that the zinc methylenation is not reactive towards esters or lactones. Because it is an electrophilic reagent, it is suitable for the methylenation of enolizable ketones and aldehydes. 

The enantioselective total synthesis of the cyclooctanoid natural product (+)-epoxydictymene was accomplished in the laboratory of L.A. Paquette. The entire tricyclic framework was constructed by the application of a Claisen rerrangement via a chairlike transition state. The precursor for this / 3,37-sigmatropic rearrangement was obtained by treating a lactone precursor with the solution of the Tebbe reagent in the presence of pyridine. The corresponding enol ether was formed in almost quantitative yield, and immediately after isolation it was treated with triisobutylaluminum to effect the Claisen rearrangement. 

The Julia-Julia coupling reaction has been extended to sugar derived lactones to furnish methylene exoglycals in good yields as exemplified by the conversion of lactone 188 to exomethylene derivative 190 upon treatment with lithiomethyl benzothiazolyl sulfone from 189 <05SL520>. This approach serves as an alternative to the Tebbe reagent commonly used... 

The Tebbe reagent is quite useful in that it reacts with the carbonyl of esters to give vinyl ethers. Pine showed that 683 reacted with methyl benzoate to give an 81% yield of 1-methoxy-l-phenylethene. O Similar reaction of lactone 686 with 683 gave the exo-methylene vinyl ether 687 in Holmes synthesis of (+)-laurencin.571 The Tebbe reagent also reacts with conjugated esters via 1,2-addition to give the vinyl ether. ... 

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. 

This first class of exo-glycals was not as reactive as methylene-exo-glycals obtained by reaction of lactones with Tebbe reagent. In... 

A number of hexopyranose epoxides have been treated with UBr to furnish ring-contracted dihydrofuran aldehydes. Epoxides (58) and (59) afforded unsaturated aldehydes (60) and (61), respectively. Conjugate addition of LiMeCuCN to aldehyde (61) with m situ trapping of the enolate produced the enol silyl ethers (62). The branched nitro compound (63) has been converted separately into the aldehyde (64) and the thioglycoside (65). Whereas previous applications of the Tebbe reagent have used specially purified material, apparently the crude reagent system can be employed on sugar esters and lactones CHoOR... 

I 4 Carbonyl Olefination Utilizing Metal Carbene Complexes Tab. 4.3. Methylenation of esters and lactones 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. 

Carboxylic esters undergo the conversion C=0— C=CHR (R = primary or secondary alkyl) when treated with RCHBr2, Zn, and TiCl4 in the presence of A,A,A, iV -tetramethylethylenediamine. Metal carbene complexes R2C=ML (L = ligand), where M is a transition metal such as Zr, W, or Ta, have also been used to convert the C=0 of carboxylic esters and lactones to CR2. It is likely that the complex Cp2Ti=CH2 is an intermediate in the reaction with Tebbe s reagent. 

Similarly, compound 73 was prepared from a persilylated D-galactono-1,4-lactone precursor in 60-80% yield (71). However, when unpurified Tebbe s reagent was employed, 1,4-lactones (for example 71a) gave a mixture of 72a and the product (74) of hydration of the double bond. The... 

Methylenation.1 When heated in THF at 60-65°, this reagent effects methy-lenation of ketones, even readily enolizable ones, in 60-90% yield and of aldehydes (45-60% yield). It also converts esters and lactones into enol ethers, but this reaction is generally slower. It is thus an attractive alternative to the Tebbe and Grubbs reagent. 

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