Imines carbanions

The macrocyclization reaction proceeds by an analogous route when bifunctional methylene compounds, e.g., diethylmalonate, were used as cross-linking agents [133]. In this case as with nitromethane, the attacking imine carbanion is also formed under basic conditions. The diethoxycarbonylethylamine resulting from the addition of the carbanion to the coordinated imine undergoes two intramolecular condensations to a produce macrobicyclic structure (Scheme 107). 

Of some significance is the exteo als by reaction of a disilyl imine. carbanion. ... 

The imine-carbanion method was modified to accomplish the interesting ketone conjugated aldehyde transformation. The a-lithioimine (310) reacted with cyclohexanone to give 311. Hydrolysis at a carefully controlled pH of 4.5 led to a conjugated aldehyde 312 in 90% yield. 

F.ii. Hydrazone Carbanions. Corey and Endersl introduced an alternative to Wittig s imine-carbanion methodology discussed in Section 9.4.F.i. Changing the imine to a hydrazone unit led to a more controllable and useful reaction. A,A-Dimethylhydrazone 313 was formed by reaction of 2-methylcyclo-hexanone and dime thy Ihydrazine. Subsequent reaction with LDA was followed by addition of methyl... 

First stage of reaction essentially comprise of an attack on the substrate (i.e., an aromatic hydrocarbon) by another species containing the nitrile and HCl (and also the Lewis acid, if present) to produce a corresponding imine salt. The possible and probable attacking species could be either an imine carbanion or a zinc chloride alkyl nitrile complex. 

On the basis of these findings, the reaction of acyl imines with methanesulfony 1 chloride-triethylamine is not expected to proceed via a sulfene intermediate as previously proposed [99]. Again, a carbanion intermediate accounts nicely for the experimental facts. The electrophihcity of the hetero-l,3-diene is exdemely high, therefore the carbanion, formed on reaction of triethylamme with methanesulfonyl chloride, should undergo nucleophilic attack at C-4 of the hetero-1,3-diene faster than sulfene formabon by chloride elimination. 

The transaldolase functions primarily to make a useful glycolytic substrate from the sedoheptulose-7-phosphate produced by the first transketolase reaction. This reaction (Figure 23.35) is quite similar to the aldolase reaction of glycolysis, involving formation of a Schiff base intermediate between the sedohep-tulose-7-phosphate and an active-site lysine residue (Figure 23.36). Elimination of the erythrose-4-phosphate product leaves an enamine of dihydroxyacetone, which remains stable at the active site (without imine hydrolysis) until the other substrate comes into position. Attack of the enamine carbanion at the carbonyl carbon of glyceraldehyde-3-phosphate is followed by hydrolysis of the Schiff base (imine) to yield the product fructose-6-phosphate. 

A somewhat more complex side chain is incorporated by alkylation of the carbanion of the substituted cyanoacetate, 148, with 2-chloroethylmethyl sulfide. Condensation of the resulting cyanoester (149) with thiourea followed by hydrolysis of the resulting imine (150) affords methitural (151)... 

Unlike the parent system, 5-methyl-5//-dibenz[c,e]azepine (1, R1 = Me R2 = H) on treatment with lithium diisopropyl amide fails to yield the tautomeric phenanthridine-imine (see Section 3.2.1.5.4.2.), but forms the 5-carbanion, which on quenching with deuterium oxide furnishes 5-methyl-[5-2H,]-5//-dibenz[e,e]azepine (l).83 5,7-Diphenyl-5//-dibenz[r,e]azepine (1. R1 = R2 = Ph) behaves similarly. In contrast, however, 5,7-dimethyl-5//-dibcnz[c,e]azepine (1, R1 = R2 = Me) yields theazaallyl anion 3, which on addition of deuterium oxide deuterates regiospecifically at the 7-methyl group to give derivative 4. 

Reductive Dimerization2 5,6 can be competitive with the addition of Grignard reagents to the C —N double bond of nonenolizable imines, especially with increasing size and branching of the carbanion,... 

An efficient procedure for the synthesis of 2,4,6-trisubstituted and 2,3.4,6-tetrasubstituted pyridines 5 and 6 involves the one-pot reaction of in situ generated a,p-unsaturated imines with carbanions <95TL(36)9297>. 

The reductive couphng of imines can follow different pathways, depending on the nature of the one-electron reducing agent (cathode, metal, low-valent metal salt), the presence of a protic or electrophihc reagent, and the experimental conditions (Scheme 2). Starting from the imine 7, the one-electron reduction is facihtated by the preliminary formation of the iminiiim ion 8 by protonation or reaction with an electrophile, e.g., trimethylsilyl (TMS) chloride. Alternatively, the radical anion 9 is first formed by direct reduction of the imine 7, followed by protonation or reaction with the electrophile, so giving the same intermediate a-amino radical 10. The 1,2-diamine 11 can be formed from the radical 10 by dimerization (and subsequent removal of the electrophile) or addition to the iminium ion 8, followed by one-electron reduction of the so formed aminyl radical. In certain cases/conditions the radical 9 can be further reduced to the carbanion 12, which then attacks the... 

The condensation of nitro compounds and imines, the so-called aza-Henry or nitro-Mannich reaction, has recently emerged as a powerful tool for the enantioselective synthesis of 1,2-diamines through the intermediate /3-amino nitro compounds. The method is based on the addition of a nitronate ion (a-nitro carbanion), generated from nitroalkanes, to an imine. The addition of a nitronate ion to an imine is thermodynamically disfavored, so that the presence of a protic species or a Lewis acid is required, to activate the imine and/or to quench the adduct. The acidic medium is compatible with the existence of the nitronate anion, as acetic acid and nitromethane have comparable acidities. Moreover, the products are often unstable, either for the reversibility of the addition or for the possible /3-elimination of the nitro group, and the crude products are generally reduced, avoiding purification to give the desired 1,2-diamines. Hence, the nitronate ion is an equivalent of an a-amino carbanion. 

Like the nitronate ion, the cyanide ion is synthetically equivalent to the aminomethyl carbanion (CH2NH2) , because of the possible reduction of - CN to the - CH2NH2 group. Consequently, the addition of cyanide ion to imines to give a-aminonitriles (Strecker-type reaction) is a viable route to 1,2-diamines. As a matter of fact, a number of diastereoselective and catalytic... 

Additions of stabilized carbanions to imines and hydrazones, respectively, have been used to initiate domino 1,2-addition/cyclization reactions. Thus, as described by Benetti and coworkers, 2-subshtuted 3-nitropyrrolidines are accessible via a nitro-Mannich (aza-Henry)/SN-type process [165]. Enders research group established a 1,2-addition/lactamization sequence using their well-known SAMP/ RAMP-hydrazones 2-308 and lithiated o-toluamides 2-307 as substrates to afford the lactams 2-309 in excellent diastereoselectivity (Scheme 2.72) [166]. These compounds can be further transformed into valuable, almost enantiopure, dihydro-2H-isoquinolin-l-ones, as well as dihydro- and tetrahydroisoquinolines. 

Although the sequence of the reaction steps remains uncertain, the mechanism may involve the nucleophilic attack of an acetonyl carbanion on the carbon of a coordinated imine as in [2.6]. 

It is assumed that the mechanism proceeds via activation of the imine by the ruthenium catalyst (structure 169), followed by reaction with ethyl diazoacetate to generate a metal-bound ylide intermediate. Intramolecular ruthenium- assisted attack of the carbanion 170 onto the iminium ion provides the corresponding aziridine with moderate to high // selectivity. Imines bearing electron-donating groups (R2) showed significant rate enhancement. 

The assumed mechanism includes the activation of acetonitrile by iV-coordination to the metal center, followed by deprotonation with DBU. The generated carbanion, iV-coordinated to the ruthenium atom, adds to the corresponding electrophile, while the presence of the sodium salt allows the regeneration of the ruthenium catalyst. Both various types of aldehydes as well as activated aromatic imines have been successfully employed as electrophiles, providing the corresponding adducts 171 in good to high yields. 

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