Nitrile-stabilized anions

The same study shows that with the complex of A W-dimethyl-o-toluidine (38), the selectivity depends on time, temperature and the nature of the anion (Table 4 and equation 34).87 Again, equilibration occurs with the tertiary nitrile-stabilized anion, favoring the C-4 substitution product, while lithioacetonitrile favors addition at C-3. The 2-methyl-1,3-dithianyl anion gives precisely the same product mixture at -78 °C and at -30 C there is no evidence for equilibration with this anion. 

Nitrile-stabilized anions, generated for example by lithiation of benzyl cyanide and propionitrile, have been added diastereoselectively to aromatic aldimines.50 Acid workup gives /5-cyano amines. Alternatively, addition of RX gives /3-R-substituted-/3-cyanoamines. The factors determining des in both reaction versions have been investigated. 

Nitrile-stabilized anions are so nucleophilic that they will react with alkyl halides rather well even when a crowded quaternary centre (a carbon bearing no H atoms) is being formed. In this example the strong base, sodium hydride, was used to deprotonate the branched nitrile completely and benzyl chloride was the electrophile. The greater reactivity of benzylic electrophiles compensates for the poorer leaving group. In DMF, the anion is particularly reactive because it is not solvated (DMF solvates only the Na+ cation). 

OTHER STABILIZED ANIONS AS NUCLEOPHILES NITRILES AND NITROMETHANE... 

Other stabilized anions as nucleophiles nitriles and nitromethane... 

The above system failed entirely when nonstabilized carbanions such as ketone or ester enolates or Grignard reagents were used as carbon nucleophiles, leading to reductive coupling of the anions rather than alkylation of the alkene. However, the fortuitous observation that the addition of HMPA to the reaction mixture prior to addition of the carbanion prevented this side reaction1 extended the range of useful carbanions substantially to include ketone and ester enolates, oxazoline anions, protected cyanohydrin anions, nitrile-stabilized anions3 and even phenyllithium (Scheme 3).s... 

The reaction of aryl and hetaryl halides with the nitrile-stabilized carbanions (RC -CN) leads to derivatives of the type ArCH(R)CN. Sometimes, however, dimeric products of the type ArCH(R)CH(R)Ar are formed (Moon et al. 1983). As observed, 1-naphthyl, 2-pyridyl, and 2-quinolyl halides give the nitrile-substituted products, while phenyl halides, as a rule, form dimers. The reason consists of the manner of a surplus electron localization in the anion radical that arises upon replacing halogen with the nitrile-containing carban-ion. If the resultant anion radical contains an unpaired electron within LUMO covering mainly the aromatic ring, such an anion radical is stable, with no inclination to split up. It is oxidized by the initial substrate and gives the final product in the neutral form, Scheme 1-7 ... 

Several specialized cyclization strategies should not be dismissed. A novel rhodium acetate-mediated cyclization was employed for the first synthesis of 3-methyl-4,6-diphenylfuro[3,4-tf]is-oxazole (9) from the 5-(a-diazobenzyl)isoxazole (185) (Equation (56)). The reactive intermediate is believed to be a carbenoid species <9iCB248i>. Another strategy exploits the reactivity of 4-halo-pyrazol-5-ones (e.g., 186) with stabilized anions (e.g., cyanoacetate esters and nitriles) to afford the 4-cyanofuro[2,3-c]pyrazol-5-ones (187) and 5-aminofuro[2,3-c]pyrazoles (188) (Scheme 30) <84H(22)2523>. Also of interest is the trichloroacetonitrile cyclization of aminopyrazole ketones (189) to the pyrrolo[2,3-c]pyrazoles (190) (Equation (57)) <86S74>. The generality of this cyclization is not known. 

The tendency for a,j9-unsaturated carbonyl compounds to undergo nucleophilic addition is thus due not simply to the electron-withdrawing ability of the carbonyl group, but to the existence of the conjugated system that permits formation of the resonance-stabilized anion 1. The importance in synthesis of a,j3-un-saturated aldehydes, ketones, acids, esters, and nitriles is due to the fact that they provide such a conjugated system. 

Three examples of nitrile-stabilized enolates have been described by Boche et al. Two of these structures incorporate the anion of phenylacetonitrile. Hie TMEDA-solvated dimer (178) crystallizes out of benzene solution however, the mixed nitrile anion LDA-(TMEDA)2 complex (179) is obtained when excess LDA is present. This latter complex has often been mistaken as a geminal d anion since it frequently gives products that appear to arise from a dianion. The crystal structure of the anion l-cyano-2,2-dimethylcyclopropyllithium (180) consists of an infinite polymer (181) that is solvated by THF. Interestingly, there are C— Li contacts in this structure and the carbanionic carbon remains tetrahedral. 

The crystal structures of both Na Xr(CN)3 and K+C(CN)3 are known for comparison. In all examples of the nitrile-stabilized carbanions except the dianion (182), the metal coordination to the organic anion is through the nitrogen. No evidence of interaction between the metal and the nucleophilic carbon atom is seen. Lithiated imine (184) is somewhat analogous to dimer (150), although this species is not derived fiom an enolizable substrate. 

Little work could be found on the electrophilic amination of simple nitrile-stabilized carbanions. The lithium anion of propionitrile reacts normally with an N-substituted oxaziridine (Eq. 141).158 The amination of nitriles with a camphor-derived N-unsubstituted oxaziridine was discussed earlier (Eq. II).151 Aminoma-lononitrile is formed from malononitrile anion and 0-(mesitylenesulfonyl)hydro-xylamine (Eq. 142).463... 

The term Michael addition has been used to describe 1,4- (conjugate) additions of a variety of nucleophiles including organometallics, heteroatom nucleophiles such as sulfides and amines, enolates, and allylic organometals to so-called Michael acceptors such as a,p-unsaturated aldehydes, ketones, esters, nitriles, sulfoxides, and nitro compounds. Here, the term is restricted to the classical Michael reaction, which employs resonance-stabilized anions such as enolates and azaenolates, but a few examples of enamines are also included because of the close mechanistic similarities. 

Reversibility, even at low temperatures, has been shown to be fast for stabilized carbanions (e.g., nitrile stabilized carbanions, ester enolates) whereas (most) sulfur stabilized carbanions and simple organo lithium compounds add irreversibly. Nevertheless protonation is more rapid than anion dissociation even for the first category of anions mentioned and nucleophile addition/proto-nation reactions allows efficient conversion to a dearomatized product. 

Reaction of the anionic cyclohexadienyl CrfCOlj, obtained by addition of a nitrile stabilized carbanion to [CrfbenzeneffCOlj], with Mel, regenerates the starting complex. However, treatment of the same intermediate with a strong acid at low temperature affords a mixture of isomeric cyclohexadienes. With time, the reaction tends to converge to the most stable diene (Scheme 2) [ 15-18]. It has also been reported that protonation under a CO atmosphere allows recycling of Cr(CO)g [19]. 

The amine first attacks the alkene in a typical conjugate addition to make an anion stabilized by being next to the nitrile. The anion can have its charge drawn on C or N it is delocalized like an enolate. Do not be put off by the odd appearance of the enolate. The dot between the two double bonds is a reminder that there is a linear sp carbon atom at this point. 

Ester- and nitrile-stabilized ylid anions are more reactive than the corresponding neutral ylids and react with ketones (even enolizable ones) as well as aldehydes. E a,p- thylenecarboxylic acid esters. 2 eqs. BuLi (in hexane) added to a stirred suspension of startg. diphenylphosphonium bromide in THF, 1 eq. acetone added, and stirring continued at room temp, for 30 min product. Y 43% (Y 10% using 1 eq. BuLi and 0% with PhjP = CHC02Me). F.e. incl. a,p-ethylenenitriles, and trans stereo-selectivity with aldehydes, s. E.G. McKenna, B.J. Walker, J. Chem. Soc. Chem. Commun. 1989, 568-9 (E)-stilbene s. Tetrahedron Letters 29, 485-8 (1988). 

Based on van der Plas N-labeling study with pyrimidines, the following mechanism was deduced for the conversion of 9 to 10. Amide anion attack at the 2-position of pyrimidine 9 produces resonance stabilized anion 13. Fragmentation yields iminoyl bromide 14, which can directly form product (10), or alternatively can eliminate HBr to form nitrile 15, which then proceeds to 10. 

The a position of the nitrile is first deprotonated to give a resonance-stabilized anion (like an enolate), which then functions as a nucleophile to attack the alkyl halide. 

Reaction of the stabilized anions derived from )3-dicarbonyl compounds and related analogs (Table 23-1) with a,)3-unsaturated carbonyl compounds leads to 1,4-additions. This transformation, an example of Michael addition (Section 18-11), is base catalyzed and works with a,j8-unsaturated ketones, aldehydes, nitriles, and carboxylic acid derivatives, all of which are termed Michael acceptors. 

Three generations of latices as characterized by the type of surfactant used in manufacture have been defined (53). The first generation includes latices made with conventional (/) anionic surfactants like fatty acid soaps, alkyl carboxylates, alkyl sulfates, and alkyl sulfonates (54) (2) nonionic surfactants like poly(ethylene oxide) or poly(vinyl alcohol) used to improve freeze—thaw and shear stabiUty and (J) cationic surfactants like amines, nitriles, and other nitrogen bases, rarely used because of incompatibiUty problems. Portiand cement latex modifiers are one example where cationic surfactants are used. Anionic surfactants yield smaller particles than nonionic surfactants (55). Often a combination of anionic surfactants or anionic and nonionic surfactants are used to provide improved stabiUty. The stabilizing abiUty of anionic fatty acid soaps diminishes at lower pH as the soaps revert to their acids. First-generation latices also suffer from the presence of soap on the polymer particles at the end of the polymerization. Steam and vacuum stripping methods are often used to remove the soap and unreacted monomer from the final product (56). 

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