METHYLENATION OF CARBONYL COMPOUNDS

Another titanium-based reagent for the methylenation of carbonyl compounds is that prepared from dibromomethane/zinc/titanium tetrachloride and related systems (Scheme 14.25) [48]. These systems transform a wide variety of carboxylic acid derivatives to terminal olefins in the same way as titanocene-methylidene does. 

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 Peterson silyl-Wittig methylenation of carbonyl compounds has been significantly improved by performing the elimination of the trimethylsilanol form of the intermediate /3-hydroxysilanes with Nafion-H under mild conditions1001 [Eq. (5.362)]. 

METHYLENATION OF CARBONYL COMPOUNDS (+)-3-METHYLENE-cis-p-NEKTHANE (Cyclohexane, 4-Bethyl-2-methylene-l-(l-methylethyl)-, R,R-)... 

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

The Petasis reagent, dimethyl titanocene (4.93) can also be used for the methylenation of carbonyl compounds. The Petasis reagent (4.93) is prepared by the reaction of methyl magnesium chloride or methyllithium with titanocene dichloride (Cp2TiCl2). Carbonyl compounds on heating with 4.93 at 60-65° C in a toluene solution give the corresponding alkenes or enol ethers. 

Metal aUcylidene complexes (see Schrock-type Carbene Complexes) have been proposed as intermediates in many catalytic reactions, including alkene metathesis (see Organic Synthesis Using Metal-mediated Metathesis Reactions), alkene and aUcyne polymerization, methylenation of carbonyl compounds, and cyclopropanation of alkenes. ... 

Olah, G. A., Reddy, V. P., Prakash, G. K. S. Catalysis by solid superacids. 26. Peterson (silyl-Wittig) methylenation of carbonyl compounds using Nafion-H catalyzed hydroxy-trimethylsilane elimination of P-hydroxysilanes. Synthesis 1991,29-30. 

Petasis, N. A., Bzowej, E. I. Titanium-mediated carbonyl olefinations. 1. Methylenations of carbonyl compounds with dimethyltitanocene. J. Am. Chem. Soc. 1990,112, 6392-6394. 

Methylenation of carbonyl compounds. The Nysted reagent (BrZnCH2)2Zn(thf) is... 

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. 

Treatment of ketones wifh a mixture of CH2I2, TiCl4, and zinc in THF at 0°C for 90 min produced fhe mefhylenation product in 5-8% yield whereas when lead dichloride was added the reaction proceeded smoothly at 0 °C to give the product in 81% yield wifhin 30 min (Scheme 13.68) [85]. A catalytic amount of lead dichloride probably promotes furfher reduction of zinc carbenoid (ICH2ZnI) by zinc in THF to give a geminal dizinc compound (CH2(ZnI)2) which is a key intermediate for the methylenation of carbonyl compounds. 

Nafion resins have been used not only for the opening of epoxides but also for their isomerization to aldehydes or ketones [137]. Various other rearrangements and isomerizations are catalyzed by this solid acid, in some cases with selectivities higher than those obtained with other solid catalysts [138-140]. Other reactions that have been studied include the Peterson methylenation of carbonyl compounds [141], hetero-Michael additions to unsaturated ketones [142], the Koch-type carbon-ylation of alcohols to form carboxylic acids [143], dimerization of a-methylstyrene [144], addition of carboxylic acids to olefins [145] and Diels-Alder reactions [146]. Notably, in most cases, reutilization of the catalyst is considered but only after an appropriate washing protocol to regenerate its acidity/activity. 

An isolable imminium salt 3 for a-methylenation of carbonyl compounds, analogous to the Mannich reaction (see 1st edition). 

Methylenation. Methylenation of carbonyl compounds using Me3SiCHN2 in some situations is followed by cycUzation of tbe products, for example, to give indoles from o-aminobenzaldehyde and in a synthesis of the indoUzines. ... 

Methylenation of carbonyl compounds. The reagent reacts with aldehydes and ketones in THF at 0° to give 0-hydroxy sulfoximines (2). On reduction of (2) with aluminum amalgam in aqueous THF containing acetic acid, reductive elimination occurs to give an olefin (3). 

Zirconocene dichloride (bis[cyclopentadienyl]zirconium dichloride, Cp2ZrCl2) [1291-32-3] M 292.3, m 242-245 , 248 . Reciystalhse the dichloride from CHCI3 or xylene and dry it in a vacuum. H NMR (CDCI3) has 5 at 6.52 from Me4Si. Store it dry in the dark under N2. [Reid et al. Aust J Chem 18 173 1965, Beilstein 16 IV 1770.]. Together with Zn and CH2CI2 it is used for methylenation of carbonyl compounds [Tour etal. 

The B-alkyl-9-BBN undergoes an interesting reverse reaction to afford the parent alkene when treated with benzaldehyde. Consequently, the reaction is uniquely employed for the synthesis of exocyclic olefins (Chart 24.3). The hy-droboration of cyclic olefins with an internal double bond, followed by homologation with carbon monoxide in the presence of lithium trimethoxyaluminum hydride afford B-(cycloalkylmethyl)-9-BBN. This intermediate on treatment with benzaldehyde leads to an exocyclic methylene compound (Chart 24.3) [16]. Since the synthesis proceeds from the cycloalkene, thus it provides a valuable alternative to the customary methylenation of carbonyl compounds by Wittig and related procedures. The method also provides a clean synthesis of deuterium-labeled compounds (Eq. 24.10) [16], without positional scrambling or loss of label. Consequently, methylmethylene-d -cyclopentane in 52% isolated yield is obtained. 

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