CARBANIONS - SIUE

1 CARBANIONSC arbanions are units that contain a negative charge on a carbon atom. The negativecharge gives good nucleophilic properties to the unit that can be used in the formation ofnew carbon carbon bonds. CARBANIONS thus act as nucleophiles in substitution reactions, incarbonyl addition and substitution reactions, and in 1,4- addition (Michael) carbanionCarbanions bear many substituents that can affect the structure and reactivity of thecarbanion, and can affect the acidity of a parent C-H precursor. Halogens stabilizecarbanions in the order of Br > Cl > F. A prominent I- repulsion between the F andCarbanionic center causes some destabilization in alpha-fluorinated CARBANIONS .

2 Themagnitude of the destabilization depends on the carbanion structure. The destabiziationmaximizes as the carbanion structure approaces a planar configuration. Thus, fluorinatedcarbanions possess pyramidal structues with high barriers to StructureCarbanions are trivalent with sp3 hybridization. The lone pare of electrons occupiesone of the sp3 orbitals. The geometery is thus tetrahedral. The tetrahedron can undergoinversion or retain its stereochemistry depending on the attached substitutents. A methycarbanion has a barrier to inversion of about 2 kcal/ mole. The trifluoromethyl carbanionhas a barrier of 120 kcal/mole. A fluorine atom is however more stabilizing than ahydrogen atom because of the fluorine carbanionCRRR inversionR = H;barrier = 2 kcal/moleR = F;barrier = 120 kcal/moleThe rate of inversion in hydrocarbon system is slowed by incorporation of thecarbanion into a three membered kcalNSO2Ph10 kcalNH3 Experiments involving the use of chiral substrates aids the study of carbanionstereochemistry as inversion causes loss of optical activity.

3 Cleavage of the methyl ketonebelow with amide ion give a carbanion with a slow rate of inversion. The carbanionabstracts a proton to give an optically active product. CARBANIONS that contain fluorineatoms often show a slow rate of activeoptically activeWhen the rate of deuterium exchange at a chiral center is not equal to the rate ofracemization it shows that an intermediate is involved as an ion pair. Carbanion ion-pairsare show to be present through labeling at a chiral center. The rate of d exchange isdifferent from the rate of inversion, indicating that the ion pair is encumbered with the cationor the (CH3)2Ok D-exchangek racemization= 148 PhDNCEt= containing beta fluorine atoms are strongly stabilized.

4 Electronegativityof the fluorine atom is the main reason but some consideration must be given to "Negativehyperconjugation", as has been found from the crystal structure of the compound hyperconjugation is possible because fluorine atoms have a very low energy sigma* orbital to accept the electron. In the structures below the fluorine atom position is identicalin each formation of carbanion intermediates in the elimination of HF fromfluorcarbons often occurs (E1Cb) as shown +PhOF+BHPhOFPhO+Fk1k-1k2 AcidityThe conversion of carboxylic acids and phenols to carboxylate or phenolate ions iscommon because the proton is acidic, thus the proton is easily removed to form the anion inweakly basic medium.

5 Most organic compounds are much less acidic than carboxylic acids,and thus need stronger basic medium to ionize a carbon-hydrogen bond. Because of thehigh electronegativity of a fluorine atom, fluorinated compounds are always more acidicthan non-fluorinated compounds. Fluorination alpha to an anionic site can sometimes bedestabilizing depending on the geometry of the anion. Thus the p- backbonding fromfluorine is maximized in planar CARBANIONS . But fluorinated CARBANIONS tend not to beplanar. Beta fluorination increases acidity dramatically, and trifluoromethyl groups verymuch increase the planar fluroene systems shown below the decreasing acidity effect of thefluorine by p- interaction of the non-bonding fluorine atoms with the occupied p orbital isevident, as the rate of C-D exchange in the fluorinated compound is the slowest of all thecompounds.

6 The mechanism for exchange involves a carbanion intermediate which in thiscase is = HR = FR = ClR = equilibrium expression below how the pKa is related to the basic medium whereH- is the base constant. Thus for compounds of weak acid strength (high pKa) a large baseconstant is needed to form the + baseR- + base-H[R-][base-H][R-H][base]Ka = pKa -log[R-][base-H][R-H][base}=H-log RH/R-+pKa =The pKa values of some common organic compounds are shown which have pKa of about 48 are almost non-acidic, but with special structuralfeatures such as added benzene rings or adjacent carbony groups, the pKa values approacesthat of weak organic 41CH3 COO-H 10Ph2CH-H 33Ph3C-H 31H 49 HH 2318H OH (CH3)3C-OH 19(CF3)3C-OH CompoundsHydrocarbonsCH3CH2-H 48 Several basicity constants are show below.]

7 When a system has a basicity constanthigher that the pKa of an acid then a reaction will occur to form a carbanion. Thus anumber of bases are now known that can be used for the generation of CARBANIONS that arethen used in some synthetic 506M KOH 1610 M KOH M NaOCH3 in DMSO/MeOH 15NH Cs+NLi+4040 Solvents and BasesThe formation of CARBANIONS can occur in several solvent systems. Very strongbases cannot be formed in protic solvents because they abstract a hydrogen atom from thesolvent to form a Used SolventsEther, THF, Hexane--covalent aproticWater, Alcohols---polar proticDMSO, DMF, HMPA---polar, aproticThe strongest bases are obtained from the reaction of metal with organohalogencompounds to give reagents known as Grignard reagents or organolithium reagentsn-BuLi, PhLi.

8 MeLi commercially availablet-BuLi > sec-BuLi> n-BuLi in base strengthBu-Br + 2 Li Bu-Li + LiBrcoldether or hexaneThe organolithium reagents tent to exist as tetramers because of the covalent natureof lithium to carbon bonds. The tetramers are still very strong bases and stongnucleophiles, and can be converted to even stronger bases on coordination withtetramethylethylenediamine as (H3C)2NN(CH3)2(H3C)2NN(CH3)2N(CH3)2(H3C) 2 NLiLiRRPostassium tert-butoxide, commercially available, and lithium diisopropamide(LDA), easily prepared in the lab, are frequently used for reaction with the alpha hydrogenof carbonyl compounds to produce Lin-BuListrong basepoor nucleophilet-BuO KPotassium tert-butoxideStabilization of CarbanionsThe negative charge on a carbanion is stabilized by neighboring electronwithdrawing groups (WEG)

9 Such as carbonyl , nitro, and = C=O , NO2 , CN , SO2 The stabilizing dispersal of the electrons into the EWG is shown in the examplesbelow. carbonyl functions are very effective in stabilizing adjacent negative charge andwhen two carbonyl groups are present (as in diethyl malonate or acetylacetone) a veryuseful carbanionic intermediate is produced. The intermediate is called an enolate. Thedithane system is capable of stablizing the carbanion by dispersal of the charge into the dorbitals of the sulfur CARBANIONS are formed in unsymmetrical ketones, two CARBANIONS is , the more substituted carbanion and more stable, is called the thermodynamic anion;while the least substituted and first formed anions is called the kinteic anion.

10 LDA is a baseof choice for formation of kinetic products while hydroxide and alkoxides give thethermodynamic atoms alpha to a carbonyl group oppose the normal polarization of thecarbonyl which contains positive charge on the carbon and negative charge on the fluorinated aldehydes and ketones show higher enol content than the Applications of EnolatesProcesses in organic chemistry used for synthesis generaly include functional groupchanges and formation of new carbon-carbon bonds. CARBANIONS are very usefulintermediates for the formation of new carbon-carbon bonds. Thus carbanionsparticipate in 1) SN2 alkylation reactions, 2) in 1,2 additions to carbonylfunctions, and 3) in 1,4- additions such as Michael Reactions.