Double electrophile

Carbonyl compounds are in a rapid equilibrium with called keto-enol tautomerism. Although enol tautomers to only a small extent at equilibrium and can t usually be they nevertheless contain a highly nucleophilic double electrophiles. For example, aldehydes and ketones are at the a position by reaction with Cl2, Br2, or I2 in Alpha bromination of carboxylic acids can be similarly... 

The highly reactive DTT 15a undergoes double electrophilic substitution with 1,2-ethanedisulfenyl chloride in the presence of AICI3 or FeCl3 in dichloromethane to give compound 114, a very interesting donor that combines the DTT 15a aromatic core with extensive sulfur substituents for the first time (Scheme 6) <2001SM(120)1061>. 

In order to clarify the different behavior of anion 2 and 3 (Scheme 4.10) toward DMC, various anions with different soft/hard character (aliphatic and aromatic amines, alcohoxydes, phenoxides, thiolates) were compared with regard to nucleophilic substitutions on DMC, using different reaction conditions. Results were in good agreement with the hard-soft acid-base (HSAB) theory. Accordingly, the high selectivity of monomethylation of CH2 acidic compounds and primary aromatic amines with DMC can be explained by two different subsequent reactions, which are due to the double electrophilic character of DMC. The first... 

The double iron-mediated arylamine cyclization provides a highly convergent route to indolo[2,3-fc]carbazole (Scheme 16). Double electrophilic substitution of m-phenylenediamine 34 by reaction with the complex salt 6a affords the diiron complex 35, which on oxidative cyclization using iodine in pyridine leads to indolo[2,3-b]carbazole 36 [98].Thus,ithasbeen demonstrated that the bidirectional annulation of two indole rings can be applied to the synthesis of indolocarbazoles. 

With regard to functional groups of type A, their interest lies in the ambivalent character exhibited by such groups, which not only confer a double electrophilic and nucleophilic character to each of the carbon atoms of the carbon chain, but they may even violate, in some cases, the rule of alternating polarities postulated by Lapworth. 

Maruoka reported the use of the didentate catalyst 8 for double electrophilic activation of carbonyl compounds [70], but since no comparison with monofunctional phenolates was given it is not clear whether having two aluminium centres in the same catalyst offers any special advantages. They used this catalyst to effect transfer hydrogenation between remote aldehyde and alcohol groups in the same molecule [71], but again it is not clear whether the transfer is truly intramolecular or in any way different from that of reduction by an external alcohol using 8 or a monuclear aluminium catalyst. 

Iminium salts (182) were starting materials in reactions with enamines (93CB133 94CB1437), which proceed by two different pathways with the formation of bicyclic ketones (183) and with the formation of substituted pyridines. The authors assume that the reaction takes place by a double electrophilic attack of the salt (182) in the /3-positions of the enamine and the resulting immonium cations undergo a retro-Mannich type of reaction with the opening of one of the piperidine rings. 

Thioxanthone dioxide itself has been prepared directly from benzophenone by a double electrophilic substitution reaction with chlorosulfonic acid (Equation 190) <1995JCX321>. 

The same idea leads to the use of Carbonyl Dilmidazole (CDI) as a double electrophile when we want to link two nucleophiles together by a carbonyl group. Phosgene (COCl2) has been used for this but it is appallingly toxic (it was used in the First World War as a poison gas with dreadful effects). CDI is safer and more controlled. In these reactions imidazole acts (twice) as a leaving group, carbonyl diimidazole... 

The first strategy you should try out when faced with the synthesis of an aromatic heterocyclic ring is the disconnection of bonds between the heteroatom or atoms and carbon, with the idea of using the heteroatoms as nucleophiles and the carbon fragment as a double electrophile. 

Maruoka and co-workers reported a conceptually new MPV reduction system based on bidentate Lewis-acid chemistry [29]. The initial formation of bidentate aluminum catalyst 9 derived from (2,7-dimethyl-l,8-biphenylenedioxy)bis(dimethylalu-minum) (8 prepared from 2,7-dimethyl-l,8-biphenylenediol and 2 equiv. MesAl) and i-PrOH (4 equiv.), followed by treatment of benzaldehyde with the in situ generated (2,7-dimethyl-l,8-biphenylenedioxy)bis(diisopropoxyaluminum) (9) at room temperature instantaneously produced the reduced benzyl alcohol almost quantitatively (Table 2, entry 2). Even with 5 mol% catalyst 9 the reduction proceeds quite smoothly at room temperature to furnish benzyl alcohol in 81 % yield after 1 h (Table 2, entry 3). This remarkable efficiency can be ascribed to the double electrophilic activation of carbonyls by the bidentate aluminum catalyst (Sch. 7). 

Scheme 1-16. Double electrophilic activation by bidentate aluminum Lewis acid 49 in the reduction of ketones.

Maruoka et al. have developed the aluminum-based bidentate Lewis acid 14 for double electrophilic activation of carbonyl compounds (Scheme 10.9) [37]. The aldol addition of cyclohexanone TMS enolate to benzaldehyde is effected by the bidentate 14, whereas its monodentate counterpart 15 shows no evidence of reaction under similar conditions. In competitive reactions of aldehydes and acetals, 14 effects aldehyde-selective addition [38]. 

Dichloromethylphosphonate carbanions are generally prepared in situ from dialkyl trichlorometh-ylphosphonates by a halogen-metal exchange reaction under Barbier conditions, by electrophilic chlorination of a chloromethylphosphonate carbanion, or by a double electrophilic chlorination of methylphosphonate with phenylsulfonyl chloride (2 eq) in the presence of n-BuLi (3 eq). ... 

But before we go, a special example40 of double regioselectivity with a doubly nucleophilic enol equivalent attacking a double electrophile. When the pyrrolidine enamine 112 of cyclohexanone attacks the unsaturated ester 113, the bicyclic ketone 114 is formed in good yield. 

One successful approach imagines two C-C disconnections around that carbon atom 75 using a nitro group to stabilise the anion 76 and a double electrophile 77 with a Michael acceptor on one side and some suitable a2 reagent, perhaps an epoxide, on the other.29... 

An excellent illustration of both these types of vinyl anion equivalent appears in Corey and Wollenberg s synthesis40 of the antibiotic brefeldin A 163. This interesting molecule has two E-alkenes, one attached to a hydroxyl group as an allylic alcohol, and so accessible by direct addition of a vinyl lithium 165 to an aldehyde, and one in a 1,3-relationship with an alcohol and so accessible in theory by conjugate addition of a vinyl copper (or cuprate) 166 to the simple double electrophile 164. Each OH group must be protected. 

Carbon suboxide, 0 OC=C=0, an unusually reactive bisketene, functions as an efficient double electrophile, in the synthesis of heterocyclic compounds (1). One would expect that the molecule, having four cumulative ir bonds, should be of considerable interest in the field of polymer chemistry and should have been investigated vigorously. On the contrary, not only has the structure of its polymer not been unequivocally established, but also the physical properties of the polymer and the kinetics and mechanism of the polymerization process have not been studied to any significant extent, even though its polymerization product... 

A double electrophilic alkylation was effected by the sequential addition of... 

The cyclic sulfites or sulfates thus obtained can be employed as synthetic equivalents of epoxides, which can react with a number of nucleophiles often, they are more reactive than the oxirane analogs and thus can lead to disubstitution products <1997AHC89, 1994CRV2483>. The cyclic sulfate 42, for example, has been used as a double electrophile in a [3+3] annulation procedure, which combines C-C-C and N-C-C moieties (Scheme 14)... 

The tailored dinuclear aluminium Lewis acid displayed a high Lewis-acid catalytic activity due to a double electrophilic activation of a substrate s carbonyl group. This skilful ligand design turned a standard alkoxide into a real multitool for carbonyl chemistry. This type of catalyst was employed for instance in Mukaiyama aldol reactions, in MPV reductions and Oppenauer oxidations and related Tischchenko coupling reactions. 

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