Nitrile-stabilized carbanions

Addition and substitution reactions of nitrile-stabilized carbanions S. Arseniyadis, K. S. Kyler and D. S. Watt, Organic Reactions 31,1 (1984). Note. Includes ArC (OTMS)CN, and HetAr (OTMS)CN. 

A nitrile-stabilized carbanion is also involved in a synthesis of a fused pyranone system (81S225). A range of 2-ureidomethylenecyclohexane-l,3-diones, e.g. (308), react with activated acetonitriles in the presence of a strongly basic catalyst to produce 5-oxo-5,6,7,8-tetrahydrocoumarins (309). Since the substrates are readily available from cyclohexane-1,3-diones by reaction with triethyl orthoformate and a urea, the synthesis is attractive (Scheme 88). Furthermore, it has been applied to a pyran-2,4-dione, whereupon the 2,5-dioxopyrano[4,3-6]pyran (310) is formed. 

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 ... 

Quantum yields of photoinitiated reactions have been used as a qualitative measure of the chain length. The quantum yields for substitution of haloarenes with nitrile-stabilized carbanions range from 7 to 31 in liquid ammonia [24]. Quantum yields from 20 to 50 have been determined for the substitution of iodobenzene by (EtO)2PO ions [25]. 

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. 

Intramolecular alkylations of nitrile-stabilized carbanions have been used to synthesize large rings such as those with 10 and 14 members. Tsuji and coworkers carried out a synthesis of the macrocy-clic antibiotic zearalenone by this route. As shown in Scheme 70, conversion of either of the protected cyanohydrins (144) or (145) to the corresponding dianions, resulting from deprotonation at the benzylic positions and a to the nitrile groups, gave the same cyclization product (146) in excellent yields. Dianion formation (i) provided control of the conformation of the side chain (ii) protected the ester from nucleophilic attack and (iii) appeared to increase the rate of the intramolecular cyclization. 

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... 

Addition and Substitution Reactions of Nitrile-Stabilized Carbanions ... 

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]. 

Semmelhack s results in this area are centered on menthol derived chiral auxiliaries [23]. Product yields are good but diastereoselectivity in these reactions are modest (<48% ee). The example in Scheme 6 shows that higher enantiomeric excesses are obtained at elevated temperatures (0 °C as opposed to -78 °C) and this could be indicative of a change in the reaction from kinetic control at low temperature to thermodynamic control at the higher temperature. This is in keeping with the ready reversibiUty of nucleophilic addition of nitrile stabilized carbanions at temperatures above -70 °C [24,25]. 

During the course of studying the photostimulated addition of nitrile-stabilized carbanions to halopyridines and haloquinolines, Wolfe found that alternative products were produced if the reaction was performed in the dark. In the absence of light, reaction of 28 with the potassium salt of acetonitrile produced 29 via the proposed ANRORC pathway. 

Moon, M.P., Komin, A.P., Wolfe, J.E, and Morris G.F., Photostimulated reactions of 2-bromopy-ridine and 2-chloroquinoline with nitrile-stabilized carbanions and certain other nucleophiles, /. Org. Chem, 48, 2392, 1983. 

For a given aryl moiety, a rough correlation exists between the reduction potential and its reactivity in ET reactions.The order of reduction potential in Hquid ammonia. Phi > PhBr > PhNMe, > PhSPh > PhCl > PhF > PhOPh, coincides with the reactivity order determined under photoinitiation. By using competition experiments of pairs of halobenzenes toward CH2COBu-t ions under photoinitiation, the span in reactivity from fluorobenzene to iodobenzene was found to be about 100,000. Quantum yields of photoinitiated reactions have been used as a quahtative measure of the chain length. The quantum yields for substitution of haloarenes with nitrile-stabilized carbanions range from 7 to 31 in Hquid ammonia. " Quantum yields from 50 to 20 have been determined for the substitution of halonaphthoxides and iodobenzene by (EtOljPO ions. ... 

Reactions with Active Methylene Compounds. Enolates of ketones," esters," enediolates," 1,3-dicarbonyl compounds," amides and lactams," as well as nitrile-stabilized carbanions," can be alkylated with benzyl bromide. Cyclohexanone may be benzylated in 92% ee using a chiral amide base." Amide bases as well as alkoxides have been employed in the case of nitrile alkylations." Benzylation of metalloenamines may be achieved and enantioselective reactions are possible using a chiral imine (eq 3). However, reactions between benzyl bromide and enamines proceed in low yield. The benzylation of a ketone via its enol silyl ether, promoted by fluoride, has been observed. ... 

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