Methylen-transfer reaction

Several variations and extensions of this HHT method have recently been reported. The mildness of this reaction was exemplified through the synthesis of glyphosate thiol ester derivatives 35. The requisite thioglycinate HHT 34 was prepared in high yield by a novel, methylene-transfer reaction between r-butyl azomethine and the ethyl thioglycinate... 

Phosphaalkenes -P=C<, and phosphaimines -P=N- react with 1 to give secondary zirconated aminoalkyl or diamino phosphines, respectively, with P-coordination to the metal fragment (Scheme 8-24) [207]. An unexpected methylene-transfer reaction was observed upon reaction of 1 with Ph3P=CH2 (Scheme 8-24) [208],... 

However, their potentialities as synthetic intermediates were shown much later by the work of Corey and Chaykovsky [201,202] on the preparations and methylene transfer reactions of dimethylsulfonium methylide (1) and dimethylsulfoxonium methylides (2). 

The coverage of this chapter emphasizes category (i) reactions in which a simple methylene group is transferred, or added, to an alkene substrate. Also covered is transfer of nonfunctionalized alkylidene groups when these reactions may be regarded as simple extensions of the methylene transfer reactions. Whenever appropriate, aspects of the stereoselectivity, enantioselectivity, regioselectivity and chemose-lectivity of these reactions will be emphasized by means of specific examples. 

M. H. Ali, P. M. Collins, and W. G. Overend, Titanium-mediated methylene transfer reactions on sugar esters, lactones and uloses, Carbohydr. Res., 205 (1990) 428 434. 

At room temperature, methylene trimethylarsorane (73) is a colorless crystalline compound, mp 33°C, which sublimes in a vacuum at 20°C/0.1 mm Hg. It is rapidly decomposed above 33°C trimethylarsine and polymethylene are the main products formed. Blue and brown colors develop and some gas is evolved, predominantly ethylene. With trimethylphos-phine, a methylene transfer reaction takes place yielding trimethylarsine and methylene trimethylphosphorane ... 

An unusual methylene-transfer reaction along with [4-I-4] cyclodimerization was observed, when 5,A-d5-tert-butylthiophene 1-oxide was refluxed in toluene with 2-methylene-l,3-dimethylimidazolidine <2001GL758>. Initially a Michael adduct is formed by the addition of 104 to 103. This adduct upon intramolecular cyclization gives the cyclopropyl compound with elimination of a carbene. This on further oxygen-transfer reaction gives products 105 and 106. The 1,4-Michael adduct on further Michael reaction with 103 produces another adduct, which on cyclization followed by elimination of 104 gives 107 (Scheme 25). 

Starting olefins. No insertion of methylene group into the C—H bond linked to the olefinic double bond is observed. Thus the mechanism of reaction (8) is closely related to that of the Simmons-Smith reaction. However, reaction (8) is much more rapid than the corresponding Simmons-Smith reaction, and methylene iodide must be added slowly to moderate the reaction. The first step of reaction (8) was shown to be the formation of ethyl iodide and iodomethylethylzinc (XIII), which undergoes methylene transfer reaction with olefins. Since two ethyl-zinc... 

Wittig and Jauterat 547) prepared a complex (XV) from diazomethane and zinc benzoate, which undergoes the methylene transfer reaction with olefins. Reactions (2), (5), (8), and (13) can be understood as transfer... 

Pine, S. H., Zahler, R., Evans, D. A., Grubbs, R. H. Titanium-mediated methylene-transfer reactions. Direct conversion of esters into vinyl ethers. J. Am. Chem. Soc. 1980, 102, 3270-3272. 

The methylene transfer reaction from ylides to ketones has been developed as a convenient synthetic method for obtaining oxiranes [24]. However, the experimental procedure is complex. For example, a THF solution of dimethylsulfonium-methylide (61) is obtained by treatment of trimethylsulfonium iodide (60) with BuLi in THF at 0°C, and after addition of the ketone the mixture is heated at 50-55 °C under nitrogen to yield the oxirane. Throughout the reaction and separation of the product, the organic solvent is essential [25]. 

This methylene transfer reaction can also be accomplished without using solvent, and the reaction product isolated from the reaction mixture by distillation. For example, a mixture of propiophenone (62a) (0.5 g), 60 (0.9 g) and powdered Bu/OK (0.5 g) was heated at 60 °C for 1 h in a flask, and then the reaction mixture was distilled using a Kugelrohr apparatus at 150°C under 18 mmHg, to give 63a (0.4 g, 75% yield). By a similar procedure, 63b-j were prepared from the corresponding ketones (62b-f), and the products were isolated by distillation to give the yields shown in Table 15-16 [25]. 

Table 15-16. Preparation of 63 by the combination of methylene transfer reaction to 62 in the absence of solvent and by Kugelrohr distillation.

The nucleophilic methylene transfer reaction can be realized with substances other than aldehydes and ketones. Thus the reaction of benzalaniline (7) with either (3) or (ft) gives the nziridine (8) in 86% yield,... 

A new synthesis of ( )-colchicine (138 R = Me) has been reported using an elegant methylene-transfer reaction as the key step (Scheme Reduction... 

The common overall reaction in carbene chemistry is methylene transfer. A (substituted) methylene fragment is eliminated from the "carbene precursor and inserted into the carbene acceptor . Kinetic methods have been widely employed to determine whether divalent carbon intermediates are involved in these reactions. Two major lines of investigation may be distinguished, (/) kinetic studies of the decomposition of carbene precursors, and ( ) determination of the relative rates of product formation. The mechanistic possibilities range from the intervention of free carbenes to fully concerted methylene transfer reactions. 

The following reactions have been excluded as being beyond the scope of this chapter the variety of synthetically useful reactions of dimethyl sulphoxide (DMSO) and dimethyl sulphide, which include reactions involving dimsyl anion, oxidation reactions involving DMSO, methylene transfer reactions of corresponding sulphonium methylides, and reaction of stabilized sulphonium ylids normally prepared from dimethyl sulphide. ... 

Trimethylsulfonium iodide undergoes ylid formation by reaction with 50% aqueous sodium hydroxide in the presence of catalytic tetrabutylammonium iodide [16]. The ylid thus formed reacts with aldehydes and ketones to form the corresponding epoxides (Eq. 14.7). The yields with aldehydes are considerably better than those with ketones. The fact that the reaction is slow (48 hours) may be due to the iodide of the catalyst. On the other hand, lauryldimethylsulfonium chloride undergoes reaction with ketones and aldehydes to yield epoxides under alkaline phase transfer conditions considerably more rapidly (6—10 hours). The enhanced rate of this methylene transfer reaction is probably due to the greater organic solubility of the lauryldimethylsulfonium cation [17]. Catalyst poisoning is observed with lauryldimethylsulfonium iodide. Similar reactions have been conducted under ion pair extraction conditions [18]. 

The interesting methylene-transfer reaction allowing direct conversion of esters into vinyl ethers using the Tebbe reagent (10) has been examined in more... 

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