Aldehydes Tebbe methylenation

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

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. 

The methylenation of ketones and aldehydes by the Wittig reaction is a well-established and selective methodology. Unlike addition-elimination methods of alkene formation, the Wittig proceeds in a defined sense, producing an alkene at the original site of the carbonyl. The Wittig reaction is not considered here, but is used as the standard by which the methods discussed are measured. The topics covered in the methylenation sections include the Peterson alkenation, the Johnson sulfoximine approach, the Tebbe reaction and the Oshima-Takai titanium-dihalomethane method. 

In 1973, Johnson reported the use of (N-methylphenylsulfonimidoyl)methyllithium (26) for addition to carbonyls, followed reductive elimination to produce the methylene derivative (28 Scheme 7). As with the Tebbe and Oshima procedures discussed in Sections 3. l.S and 3.1.6, this method can be applied to enones, ketones and, with comparatively diminished efficiency, aldehydes. The anion appears to be more nucleophillic than methylenetriphenylphosphorane, and there are several examples, detailed below, in which the Wittig reaction failed but the Johnson procedure succeeded. The addition and reductive cleavage can be combined into a single operation without isolation of the p-hydroxysulfoximine. ... 

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. 

Notwithstanding us having side-stepped the internal hemiacetalisation problem, difficulties were once again encountered when we attempted to methylenate 66 under Wittig or Tebbe conditions. In both cases, starting aldehyde was always recovered untouched from either reaction. Fortunately, when 66 was subjected to Kocienski/Julia olefmation with 5-methanesulfonyl-1-phenyl-1//-tetrazole and potassium hexamethyl-disilazide at low temperature, diene 67 was formed in 77% yield. 

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). 

Since esters and amides are much less reactive than aldehydes and ketones towards the Tebbe reagent 3, chemoselective methylenation of dicarbonyl compounds has been achieved, as illustrated in Scheme 4.6 and in the examples in Table 4.2. 

Methylenation of ketones and aldehydes Similarly to the Tebbe reagent, dimethyltitanocene 30 is compatible with hydroxyl groups, and its low basicity also ex-... 

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