Methyl anion formation

It looks as though all that is needed is to prepare the acetylenic anion then alkylate it with methyl iodide (Section 9 6) There is a complication however The carbonyl group m the starting alkyne will neither tolerate the strongly basic conditions required for anion formation nor survive m a solution containing carbanions Acetyhde ions add to carbonyl... 

Covalent hydration has been demonstrated in the following families of compounds 1,6-naphthyridines, quinazolines, quinazoline. 3-oxides, four families of l,3,x-triazanapththalenes, both l,4,x-triazanaphthalenes, pteridines and some other tetraazanaphthalenes, and 8-azapurines these compounds are discussed in that order. In general, for any particular compound (e.g. 6-hydroxypteridine) the highest ratio of the hydrated to the anhydrous species follows the order cation > neutral species > anion. In some cases, however, anion formation is possible only when the species are hydrated, e.g. pteridine cf. 21 and N-methyl-hydroxypteridines (Section III, E, 1, d). Table V in ref. 10 should be consulted for the extent of hydration in the substances discussed here. 

However, other reaction directions via the formation of the phosphorane structure with migration of the methyl anion from one phosphorus atom... 

The utilization of the dibromides 315 permitted the generation of 311 by MeLi. Since MeLi is less reactive as a nucleophile than wBuLi, the ring opening of 311 by addition of the methyl anion analogous to the formation of 314 (Scheme 6.67) was of no importance. However, in the case of 315 (R = CH2Ph), the intramolecular insertion of the transient carbenoid or carbene, leading to 312, was the main reaction and hence the cause of low yields of the respective cycloadducts 316, 317, 319 and 320. Whether such an insertion has to be blamed for the very modest yields of 316 and 317 with R= Me could not be proved [154]. 

The two catalyst components are rhodium and iodide, which can be added in many forms. A large excess of iodide may be present. Rhodium is present as the anionic species RhI2(CO)2. Typically the rhodium concentration is 10 mM and the iodide concentration is 1.5 M, of which 20% occurs in the form of salts. The temperature is about 180 °C and the pressure is 50 bar. The methyl iodide formation from methanol is almost complete, which makes the reaction rate also practically independent of the methanol concentration. In other words, at any conversion level (except for very low methanol levels) the production rate is the same. For a continuous reactor this has the advantage that it can be operated at a high conversion level. As a result the required separation of methanol, methyl acetate, methyl iodide, and rhodium iodide from the product acetic acid is much easier. 

An alio-threonine analogue was prepared in this way. The Nebraska group has also explored the use of diallyl phosphonates driven by the need to develop mild deprotection methods [77]. Treatment of ketophosphonates with alkoxide base led to the formation of difluoroenolates and thus difluoromethylketones [78]. The lithiophosphate then acts as a synthetic equivalent for the difluoro-methyl anion synthon (Eq. 21). 

An estimate of the standard enthalpy change for the formation of the methyl anion and a hydrogen cation from methane may be obtained by a calculation based on Hess s Law, as shown in Table 1. 

In these calculations, the electron affinity of the methyl radical has been taken1 as 27 kcal.mole-1. The other enthalpy terms are all well-known quantities the enthalpies of hydration of individual ions have been assigned as done by Valis ev (see ref. 2) and the enthalpy of hydration of the gaseous methyl anion has been taken as that of the bromide ion. It can be seen from Table 1 that not only is the formation of the methyl anion energetically very unfavoured in the gas phase, but it is also endothermic to the extent of 54 kcal.mole-1 in aqueous solution. A check on this final result can be made by consideration of the standard entropy change for the reaction... 

Similar calculations to those in Table 1 can be made for the formation of the methyl anion from a number of organometallic compounds, and the final results are shown in Table 2. 

STANDARD ENTHALPY CHANGES (kcal.mole- ) FOR THE FORMATION OF THE METHYL ANION FROM VARIOUS ORGANOMETALLIC COMPOUNDS... 

Shein (1983) pointed out that Solodovnikov s (1976) kinetic result may also be caused by a sequential reaction that led to the formation of the anion radicals of 4-nitro-1 -chlorobenzene and then of 4-nitroanosole. This is really possible when, say, the formation of the anion radical of the initial substrate as a result of its interaction with the methylate anion is the... 

In simple purines the imidazole ring is usually involved in anion formation. The strong resemblance shown between the spectrum of the anion (6) of 8-oxopurine and that of 7-methyl-8-oxopurine (7)... 

The spectra reported in Fig. 8, being unaffected by coadsorption of CO, are attributed to CH4 adsorbed on anions at low temperature. The methane molecule forms a weak CH 02 bond, which reduces its symmetry from Ta to C3V At elevated temperatures, methyl radical formation was reported (190-192). Ito et al. (192) reported a TPD study in the 220-600 K range of... 

Protection of 194 as a p-methoxybenzylether and subsequent epoxydation led to the trans-epoxide 195, which was transformed into the unsaturated aldehyde 196 by a three-reaction sequence, including regioselective oxirane opening with a 1,3-dithiane anion, hydrolysis of the dithioacetal formed, and dehydration. Chlorite promoted aldehyde oxidation, methyl ester formation, and removal of the hydroxyl protections delivered methyl (+)-shikimate 197 in a remarkable 12% yield from 193. 

Similarly, 144 has been obtained from the reaction of 1-trimethylsilylcyclopropyl methyl selenide with n-BuLi The a-bromosilane 147 underwent lithiation with n-BuLi in THF at —78 °C to provide 144 with superior efficiency to any other method, Eq. (46))81). 147 was prepared in large quantities by the Hunsdiecker degradation of the 1-trimethylsilylcyclopropanecarboxylic acid 146, obtained by successively reacting the commercially available cyclopropanecarboxylic acid with -BuLi (2 equivalents) and ClSiMe3 82). Uneventfully, 144 added to carbonyl compounds, except for cyclopentanone where enolate anion formation competed the 1-trimethylsilylcyclo-propylcarbinols 148 underwent acid-induced dehydration to the expected 1-trimethyl-silylvinylcyclopropanes 149 79-81) while base induced elimination (KH, diglyme, 90 °C) led to cyclopropylidenecycloalkanes 150 77), Eq. (47). 

The 3-bromomethyl derivative (482), after anion formation at C-3, has the choice of the ring opening reaction as above or elimination of the bromide. The latter pathway is preferred, giving the 3-methylene derivative (483) which very readily isomerizes to its aromatic thiazole isomer (484) (81H(15)1349>. Similarly, the 2-bromomethyl derivative (485) on treatment with morpholine undergoes elimination to give the 2-methylene derivative, which with acid catalysis undergoes a prototropic shift to the 2-methyl thiazole (486) (74M882). 

Though there are two sites for enolate anion formation, one would give a four-membered ring and can be ignored, Only enolization of the methyl group leads to a stable six-membered ring. 

One other example of alkane oxidative addition to a higher oxidation state late transition metal has been reported by Goldberg. Reaction of the trispyra-zolylborate complex K[r 2-Tp PtMe2] with B(C6F5)3 leads to the abstraction of a methyl anion and the formation of a transient species that adds to the C-H bonds of benzene, pentane, or cyclohexane (Eq. 15). This result provides the first example of the intermolecular addition of a C-H bond to a Ptn species to give a stable PtIV product [71]. Earlier work by Templeton had demonstrated that the trispyrazolylborateplatinumdialkylhydride product would be stable [72]. 

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