Carbanions a-nitro

The mechanism of these reactions is usually Sn2 with inversion taking place at a chiral RX, though there is strong evidence that an SET mechanism is involved in certain cases, ° especially where the nucleophile is an a-nitro carbanion and/or the substrate contains a nitro or cyano group. Tertiary alkyl groups can be introduced by an SnI mechanism if the ZCH2Z compound (not the enolate ion) is treated with a tertiary carbocation generated in situ from an alcohol or alkyl halide and BF3 or AlCla, or with a tertiary alkyl perchlorate. ... 

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. 

It is most likely that silylation of AN with silyl derivatives of amides, like the processes considered in Section 3.2.3.2, involve the formation of a-nitro-carbanions as the key step. It is also possible that only aci forms of AN can react with DPSU. This is evidenced by a comparison of the results of entries 8 and 9 in Table 3.3. 

Classical C,C-coupling reactions of AN anions (Henry, Michael, and Mannich) involve complex systems of equilibria and, consequently, generally not performed in protic solvents. The introduction of the silyl protecting group allows one to perform these reactions in an aprotic medium to prepare or retain products unstable in the presence of active protons. In addition, the use of nucleophiles which are specifically active toward silicon (e.g., the fluoride anion) enables one to design a process in which the effective concentration of a-nitro carbanions is maintained low. 

In the first case, SENAs in the presence of various catalysts (primarily salts containing the fluoride anion) generate the corresponding a-nitro carbanions, which are poorly solvated in aprotic solvents and, consequently, rapidly react with substrates R3— Y = X to give functionalized nitro compounds through the transition state A. 

The reaction starts with desilylation of nitronate. The a-nitro carbanion which is eliminated gives (through the transition state A) the coupling product, the anion B. The latter desilylates the next nitronate molecule to form the target product and continues the chain. 

Under the action of a base, the first step (Ki) reversibly produces the a-nitro carbanion A, which then rapidly reacts with Si X (K2) to form SENA. The latter is reversibly silylated by the second equivalent of SiX (K3) to give the cationic intermediate B, whose deprotonation with the base (K4) affords the target nitroso acetal (or BENA). 

In any case, if the protocol aims for discovery of all sequences within the defined criteria, any published synthesis from this bondset should turn up, and indeed one combination here has been successfully executed by Corey and his group this synthesis is outlined at the bottom of Fig. 10 and is written directly as derived from the /-lists in the second matched sample above it. In the actual work, the C—9—Z was a nitro-carbanion (Bi), the C—13—Z was C —P03 for the B2 reaction of synthon III and implicit refunctionalization occurs in protection and release of the C—11 aldehyde as acetal before construction 3. The first matched sample shown is an afiy) pattern of otherwise very similar chemistry for comparison. 

Aliphatic nitro compounds serve as good acyl anion equivalents. After electrophilic alkylation at the a-carbon atom, they can be converted into carbonyl compounds by the Nef reaction or by reductive hydrolysis with titanium(III) chloride. The a-nitro carbanions serve as excellent donors in Michael addition reactions with a, -unsaturated systems and therefore the sequence of Michael addition followed by reductive hydrolysis of the nitro group provides a good route to 1,4-dicarbonyl compounds. ds-Jasmone, for example, was readily obtained by using this strategy (1.111). 

Cyclopropanecarboxylic esters have been prepared, in 75—86 % yield, by intramolecular alkylation of 4-chloroalkyl esters, using phase-transfer catalysis. Monoalkylation of nitro-alkenes by acrylic esters occurs in a controlled manner if a two-phase system is used, to give products of Michael addition in 45—65 % yield for five examples. An interesting variant on this reaction involves the generation of the a-nitro-carbanion by conjugate reduction of a nitroalkene with sodium borohydride followed by its conjugate addition to methyl acrylate yields of 62—95% are reported for five cases (Scheme 39). ... 

Unlike such unstable intermediates, the first, rare example of reversible dissociation of a carbon-carbon a bond into a stable carbocation and carbanion was reported for a nitro-dicyano compound (20) prepared from trimethyl- and triphenyl-cyclopropenylium tetrafluoroborate ([4" ]BF4 and [5 JBFJ) with the potassium salt of p-substituted-phenylmalononitrile anions (Arnett et al., 1983 Troughton et al., 1984 Arnett and Molter, 1985). Other ionically dissociative malononitrile derivatives have been prepared from such carbocations as the tropylium [S ] (Arnett and Troughton, 1983) and the tris(p-methoxyphenyl)methylium [93 j (Arnett and Troughton, 1983) ions. 

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. 

The acylation of the carbanions derived from nitroalkanes with acyl imidazoles or alkoxy-carbonylimidazoles takes place at the carbon atom to yield a-nitro ketones or a-nitro esters, respectively (Eq. 5.10).21 The lithium salts of nitroalkanes were isolated and used in THF or DMSO in the original procedure. Later, potassium salts generated in situ on treatment with r-BuOK in DMSO are reactive enough to give a-nitro ketones in good yield (Eq. 5.11).22... 

The ability of a nitro group in the substrate to bring about electron-transfer free radical chain nucleophilic substitution (SrnI) at a saturated carbon atom is well documented.39 Such electron transfer reactions are one of the characteristic features of nitro compounds. Komblum and Russell have established the SrnI reaction independently the details of the early history have been well reviewed by them.39 The reaction of p-nitrobenzyl chloride with a salt of nitroalkane is in sharp contrast to the general behavior of the alkylation of the carbanions derived from nitroalkanes here, carbon alkylation is predominant. The carbon alkylation process proceeds via a chain reaction involving anion radicals and free radicals, as shown in Eq. 5.24 and Scheme... 

Chiral crown ether phosphine-palladium complexes have been used to catalyse the alkylation of carbanions derived from a-nitro ketones and a-nitro esters,63 and proline rubidium salts have been used to catalyse asymmetric Michael addition of nitroalkanes to prochiral acceptors 64 80% enantioselectivity can be achieved in each case. 

The SiMe3 group does not stabilize an a-carbanion to the same extent as a nitro group, as shown by the regioselectivity of the reaction shown in equation 121194. 

Thus, a domino-Heck-Michael reaction has been reported by Yamada and co-workers [87]. This transformation allowed the formation of three contiguous cycles in one single operation. The mechanism involves first a Heck alkenylation of the iodide 95 which after a /1-hydride elimination step leads to intermediate 96 which undergoes attack of the a-nitro group carbanion to produce the tricyclic compound 97 (Scheme 37). 

The mechanism involves addition of an a-nitro group carbanion issued from 111 to a jr-allylPd complex generated from allylic acetate 112. This latter intermediate can further undergo ring closure through intramolecular Michael addition delivering substituted cyclohexane 113 which has been transformed into dihydroerythramine in several steps. 

The nature of nitrooleflns has little influence on the efficiency of this one-pot process, and other functionalities snch as cyano, ether, and chlorine can be preserved. The role of the nitro gronp is crncial in the reported process since its electron-withdrawing effect firstly helps the nncleophilic attack of the amino or hydroxyl fnnctionality to the alkene, then it allows a stabilized carbanion with the consequent formation of an intramolecnlar C-C bond (nitroaldol reaction) and, finally, favors the elimination of water (ElcB). Moreover, the nse of solvent-free conditions (SFC) in combination with heterogeneons catalyst represents one of the more powerful green chemical technology procednres. 

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