Carbanions formyl

A major advantage of the sequence presented here is that the aldehyde group is protected at the siloxycyclopropane stage, which allows convenient storage of this stable intermediate. Of equal importance is the valuable carbanion chemistry that can be carried out a to the ester function. Efficient substitution can be achieved by deprotonation with LDA and subsequent reaction with electrophiles.12-13-6 This process makes several a-substituted [1-formyl esters available. Other ring opening variants of siloxycyclopropanes - mostly as one-pot-procedures - are contained in Scheme I. They underscore the high versatility of these intermediates for the synthesis of valuable compounds.6 Chiral formyl esters (see Table, entries 2-5) are of special... 

It is assumed that the formyl derivatives form the 9-carbanions, e.g. 96, which then react with oxygen in the way outlined in VI.C. for linear hydrazides. 

Triethyl orthoformate is often used in reactions with enolates and carbanions to form diethyl acetals that on treatment with dilute acid give the corresponding formyl derivatives. However, when indole is heated at 160 C with triethyl orthoformate the locus of reaction is at N-1 rather than at C-3, and 1-(diethoxymethyl)indole is formed (Scheme 7.6). The A -substituent is easily removed by acidic hydrolysis to reform indole. 

With Dithiane. Dithiane is one of the most popular functionalized carbanion used for the ring opening of epoxides. This reaction has been studied by different groups [31,56], The anion of bis(phenylthio)methane has been successfully used for the opening of epoxides derived from furanose [56]. This method is an excellent way to prepare formyl derivatives that are suitable for chain extension by olefination. Alternatively formyl derivatives can be reduced to hydroxymethyl derivatives. A recent application of epoxide 33... 

The apparent fickleness of the acyl-pyrroles and -indoles in their reaction with carbanions to form new C—C bonds arises from the contribution made by the zwitterionic structure, e.g. (410b), to the resonance hybrid and the choice of the reaction conditions is critical for a successful nucleophilic reaction. Thus, formyl-pyrroles and -indoles do not normally undergo the Cannizzaro reaction nor do they form stable cyanohydrins or undergo benzoin-type reactions. However, surprisingly, 2-formylpyrrole reacts with arylaldehydes in the presence of potassium cyanide to yield (428), which is easily oxidized to (429) (B-77MI30505). It is noteworthy that the presence of an ester substituent adjacent to the formyl group modifies the mesomeric interaction to such an extent to allow the formation of (430) in low yield, as a result of an initial benzoin-type self-condensation (Scheme 76) (68BSF637). 

The 2-(6-formyl-2-pyridyl)-2-(4-tolyl)-l,3-dioxolan (2.5 g) was dissolved in 1,2-dimethoxyethane (10 ml) and added to a solution of the phosphonate carbanion produced from triethyl phosphonoacetate (2.0 g) and sodium hydride (0.22 g) in the same solvent. The mixture was stirred for 2 h, diluted with ether (25 ml) and treated with hydrochloric acid (5 ml, 2 mol). The organic phase was separated, washed with water, dried, and evaporated. The resulting oil was dissolved in ethanol (20 ml) containing concentrated hydrochloric acid (3 ml) and water (3 ml). After heating on the steam bath for 10 min, the solution was diluted with ice water, rendered alkaline with sodium bicarbonate solution, and extracted with ether. Evaporation gave 1.0 g ((E)-3-(6-(4-toluoyl)-2-pyridyl)acrylate as colourless platelets, melting point 108°-111°C (crystallized from cyclohexane). 

In addition to the stabilized carbanions, electron-rich aromatic compounds, for example indole derivatives have emerged as new Michael donors [25], In these reactions, aromatic sp2-C-H transformation is involved. These reactions are described in detail in Section 111.1.3.1.3. A highly enantioselective intramolecular Stetter reaction, in which umpolung reactivity of a formyl group was accomplished using a chiral triazolium salt, has also been reported by Rovis [26]. 

For instance, 4-aminopyridine 5.34 can be converted to amide 5.35 which, on treatment with two equivalents of butyl lithium, gives organometallic species 5.36. Formylation of the more reactive anion (the carbanion) then reprotonation of the amide anion gives 5.37. Acidic hydrolysis removes the activating group to release pyridine aldehyde 5.38. 

The combination of formyl pyrrolidine acetal 7.21 and nitrotoluene 7.19 produces electrophilic cation 7.22 and nucleophilic carbanion 7.23a,b which react together affording enamine 7.20. 

A systematic study of some monosubstituted solvent-separated cyclopentadienide salts of Group 1 cations (Li, Na, K, Cs) in DMSO revealed the bonding preferences for the fulvenoid (4) over the cyclopentadienyl isomer (5). Three of the substiments contained an a-carbonyl group formyl, acetyl and benzoyl. From the viewpoint of the anions, there is a conflict between the inherent greater stability of oxyanions over carbanions and the aromaticity associated with the 6 jr-electron carbocyclic system. The authors demonstrated that the fulvenoid interaction is favored by strong electron-accepting substituents and... 

The potential of the reverse polarity approach has been spectacularly demonstrated in a plethora of synthetic studies. A representative example can be found in Seebach s preparation of the antibiotic vermiculin. The key step of this synthesis involved the preparation of a polyfunctional intermediate 253 via the sequence shown in Scheme 2.102. The first stage of this sequence couples the formyl anion equivalent 244 with bromoepoxide 254. The primary bromide is more active as an electrophile than epoxide and therefore, under carefully controlled conditions, the product 255 is formed selectively. Under somewhat more stringent conditions the epoxide ring present in the latter adduct reacts as an electrophile with the second acyl anion equivalent 256 to yield adduct 257. In this sequence, 254 was used as an equivalent to the 1,4-doubly charged synthon CH2CH2CH(OH)CH. In the final step of this scheme, carbanion 258 was generated and reacted with dimethylformamide to produce the required product 253. It is remarkable that all of these sequential operations are carried out in one reaction vessel without the isolation of any intermediate products. The overall yield of 253 is rather high (approximately 52%). 

Reduction of an aryl halide at a cadmium-modified nickel cathode in DMF containing TBABF4 leads to a formylation reaction between aryl carbanions and the solvent [186]. Two papers [187,188] have appeared in which reduction of aryl halides gives an aryl carbanion, which, by acting as a base to deprotonate a suitable nitrile, can cause coupling of the nitrile with esters, aldehydes, and ketones. Electrochemical trimethylsilylation of aryl halides can be effected at a stainless-steel or carbon-cloth cathode in THF-HMPA containing TEABF4 and trimethylchlorosilane [189]. 

Since the degree of stabilization of boron-stabilized carbanions is similar to that for anions stabilized by a formyl or a cyano group, the comparative lack of knowledge of boron-stabilized carbanions must be due either to kinetic factors associated with their production or to the availability and nature of their precursors. 

The most utilized Umpolung strategy is based on formyl and acyl anion equivalents derived from 2-lithio-l,3-dithiane species. These are readily generated from 1,3-dithianes (thioacetals) because the hydrogens at C(2) are relatively acidic (p f 31). In this connection it should be noted that thiols (EtSH, pi 11) are stronger acids compared to alcohols (EtOH, 16). Also, the lower ionization potential and the greater polarizability of the valence electrons of sulfur compared to oxygen make the divalent sulfur compounds more nucleophilic in Sj,2 reactions. The polarizability factor may also be responsible for the stabilization of carbanions a to sulfur. ... 

Organometallics bearing two heteroatomic moieties on their carbanionic center have found an important place in organic synthesis since the first report of Arens. In particular, they have played a crucial role as formyl or acyl anion equivalents. " " ... 

Further examples of the cyclisation of biphei ls to phenanthridines include carbanion based methods. In the case of the 2-amlnobiphenyl (38). metallation is directed to the 2 -position by the 3 -methoxy group, and cyclisation to the phenanthridine follows formylation (N. S. Narasimhan, F. S. Chandrachood and N.R. Shete. Tetrahedron, 1981, 37, 825). 

Thus, treatment of diethyl crotylphosphonate at low temperature with LDA (3 eq) followed by addition of McjSiCl provides exclusively the a-silylated crotylphosphonate carbanion. By virtue of the trimethylsilyl group, this carbanion reacts with ethyl formate in the y-position. On acidic hydrolysis, dietliyl (L>3-formyl-2-butenylphosphonate is isolated in 78% yield (Scheme 2.19). ... 

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