carbonyl alpha-substitution

carbonyl alpha-substitution - SUMMARY Introduction to...

Info iconThis preview shows pages 1–19. Sign up to view the full content.

View Full Document Right Arrow Icon
Background image of page 1

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Background image of page 2
Background image of page 3

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Background image of page 4
Background image of page 5

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Background image of page 6
Background image of page 7

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Background image of page 8
Background image of page 9

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Background image of page 10
Background image of page 11

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Background image of page 12
Background image of page 13

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Background image of page 14
Background image of page 15

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Background image of page 16
Background image of page 17

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Background image of page 18
Background image of page 19
This is the end of the preview. Sign up to access the rest of the document.

Unformatted text preview: SUMMARY Introduction to Carbonyl nix-Substitution Reactions Reactions of Carbonyl OL-Substitution 0 Enolization Reactions 0 a-Halogcnation of Ketones via Acid Catalysis - Hell-Volhard-Zelinsky Reaction 0 u-Halogenation of Ketones via Base Catalysis ' Selenenylation 0 Preparation of Alkylated Malonic Esters I Preparation of Alkylated Acetoacetic Esters 0 Alkylation of Ketones, Esters, and Nitriles Carbonyl a-Substitution Carbonyl a—Substt'tution 1 Carbonyl (Jr—Substitution 2 Carbonyl tit-Substitution 3 Carbonyl til-Substitution 4 Carbonyl a—Substitution 5 Carbonyl a-Substitntion 6 Carbonyl Cit-Substitution 7 Carbonyl (rt-Substitution 8 Carbonyl (ll-Substitution 9 INTRODUCTION TO CARBONYL ot—SUBSTITUTION REACTIONS Carbonyl (it-Substitution 1 0 CH3 0 CH3 CH CH CH ii (I: ® Br: CH CH OH (I: (I: @ J 2 2— _ _\ ‘—+ "'— _ _ I 3 2 2 I CH3 CH3 2-Methyl-3-hexanone Z-Bromo-Z—memyl-B-hexanone m 1. The Ot-carbon is located immediately adjacent to the carbonyl carbon. The carbonyl—ot—substitution reaction replaces one or all of the protons attached to the a—carbon with substituents. 2. Only the protons on the ot-carbon are acidic as a result of stabilization by resonance. Because of their aci- dity, ot-protons can be abStracted by bases. Hence, carbonyl compounds with at least one hydrogen on the ot-carbon can undergo carbonyl otusubstitution. Protons not adjacent to an electron-withdrawing group (e.g., carbonyl, nitrile, phosphonium, sulfonyl) are not acidic and cannot be replaced. on Carboxyl at B 'y Carbon Carbon Carbon Carbon Carbon *Acidic protons (mprotons) 3. Carbonyl a-substitution reactions take place via the formation of an enol or an enolate ion intermediate. The following are classifications of carbonyl int-substitution reactions based on the type of intermediate formed. a. Via an enol intermediate ‘ ot-Halogenation of aldehydes/ketones via acid catalysis (Carbonyl a—Substitmion 3) otuBrornination of carboxylic acids (Carbonyl tit-Substitution 4) 13. Via an enolate anion intermediate ot—Halogenation of aldehydesfketones using base (Carbonyl (It—Substitution 5) Malonic ester synthesis (Carbonyl a—Substitution 7) Acetoacetic ester synthesis (Carbonyl (ac-Substitution 8) Alkylation of ketones, esters, and nitriles (Carbonyl a—Substimtion 9) 4. Enolate ions are more important than enols for two reasons: a. Enolate ions can be made in high concentrations, whereas most enols cannot. b. Enolate ions are much more reactive than enols, as enolate ions are negatively Charged and therefore are more nucleophilic than the neutral enols. ENOLIZATION REACTIONS Carbonyl ot—Substitution 2 KETO-ENOL TAUTOMERIZATION VIA ACID OR BASE CATALYSIS 0 OH H keq = ID4 : | CchchCHZCHa Tm; CH3CH = CCHch5 3-Pemanone 2~Penlcne3eol (ketone) (enol) Keys: 1. The interconversion between carbonyl groups and enols is an example of tautomerization, a process in which two isomers equilibrate rapidly by shifting an atom or a group of atoms (in this case the hydrogen atom is being transferred). 2. Keto tautomers are carbonyl compounds (e.g., aldehydes and ketones) that have at least one ot—hydrogen. Enol tautomers have a hydroxyl group attached to a carbon-carbon double bOnCl (an alkenol}. 3. At equilibrium, the keto form predominates because the arrangement of bonds is more stable. 4. The keto-enol tautomerization reaction is catalyzed by either an acid or a base (see Mechanism). Note: For an illustration of ot-carbon and (Jr-hydrogen atoms, see figure set out second in Carbonyl a—Substimtion 1). Mechanism: Acid-catalyzed 1. The oxygen atom on the carbonyl a; carbon abstracts a proton from T o T (“Hi Remnants T H3O+ to form a cation interme- H—‘f—c—R‘ —\ R—‘I:“C—"' "—> 9—? diate: Two resonance structures H H H are important: (a) a protonated Kctonc FonnA FormB carbonyl a positive Charge cation inlermediate /9\ cation intermediate on the oxygen and (b) a hydroxyl- H H substituted carbocation. (2) Slow 2. A base (water) abstracts an ot- proton from the newly formed H OH cation. The pair of electrons | | I . . R—C=C—H + H30+ remalnlng on the ot-carbon are _ used to form a double bond With End Hydirgfum the carbonyl carbon, thus pro- ducing an enol and a hydronium ion. The proton abstraction is the rate-limiting step and also regenerates the acid catalyst. Base-catalyzed 1. A base abstracts an ot-proton from the keto to form an enolate anion ‘ H o H o H :Qnfijiu intermediate (e.g., resonance form I \I Slow RiéuchHI Resonance n_é=rls_n' A). This is the rate-limiting step. I W‘“ g (2) 2. The enolate ion has two important "Nags... Form A Form]? resonance structures: (a) a carbaniqn Km“ ” enolaleion “01mm” adjacent to a carbonyl group and (b) an oxide ion attached to a C=C double bond. 3. The negatively charged oxygen atom t“ CiiH '_ on the enolate ion (e.g., resonance R—c=c—n' + 60H form B) abstracts a prOton from Em. Hydroxide water to form an enol. The base cat- ion alyst is regenerated. ot-HALOGENATION OF ALDEHYDES/KETONES Carbonyl ot-Substitution 3 VIA ACID CATALYSIS O 0 II C13 || CchHzCCHa W CH3CH1CCH2CI + HCI liButanone 3 LChloroiZ-butanone (kelone) {halogenated kelone) Keys: 1. This reaction adds a halogen to the a-carbon on the ketone. The a—carbon is located next to the carbonyl carbon. 2. The reaction proceeds through an enol intermediate, which is formed via an acid-catalyzed step (see Mechanism). 3. The reaction follows second-order kinetics; the reaction rate depends only on the concentration of the acid and the ketone. The concentration of the halogen has no effect on the reaction rate. Rate 2 k [H+] [ketone], where k = equilibrium constant. 4. Bromine, chlorine, and iodine are halogens commonly used for this reaction. Note: ot-Halogenation of aldehydes is illustrated below. This reaction is similar to the halogenation of ketones. 0 Cl 0 ll C12 I II CflacHQCH W} cHa—f—CH + HCI Propanal l H (aldehyde) lChloropropanal (halogenated aldehyde) ' ‘ Mechanism: 1. The carbonyl oxygen of the ketone abstracts a proton from 1130+; the carbonyl oxygen becomes positively charged. The protonated ketone group has two important resonance structures. 2. A water molecule abstracts an ot-proton from the protonated ketone (e.g., resonance form B), forming the double bond of an enol. 3. The double bond of the enol intermediate then attacks a halogen molecule to form a cation intermediate. Note that the positive charge on the cation is stabilized by resonance (e_g., B H A). 4. A base [e.g., halide ion (X_)] abstracts the hydroxyl proton of the cation intermediate to form the ot- halogenated product. The acid catalyst is regenerated. iii .. 9H2 HDOiH 3) J “Iii”; Q 0 ti”? imi' I Resonance F R——C—CH —“ R—C—C—H 4——+n—c—c—H ” ‘< | © | Return: H H Form A Form B n8 (:5: e ‘- HDOO x OH x X OH fl II I Resonance I I (3) I / FliCiCiH 4—--—> H—C—C—H FI—C=C | ‘5 | H H E l H FormB FormA “0 cation cation (4) ‘ a O X H | H—C—I—H + HX H Halogenated ketone (X = Br. C1. or I) ot—BROMINATION OF CARBOXYLIC ACIDS Carbonyl ot-Substitution 4 VIA HELL—VOLHARD-ZELIN SKY REACTION O H 0 ll Brg, P313 l CHacchHQCOH T» cHscfizfn OOH Bulanoic acid 2 Br (Garhm‘ylic 316M) 2-Bromobulanoic acid ( halogenated carboxylic acid) Keys: 1. This reaction converts carboxylic acids to ot—brorno acids (i.e., carboxylic acids with a bromine attached to the u-carbon). 2. This reaction takes place through an enol intermediate of an acyl halide. 3. The mechanism of this reaction resembles that of ketone bromination (see Carbonyl (tr-Substitution 3 for details). Alpha halogenation does not occur in carboxylic acids, esters, or amides because they do not eno- lize sufficiently to allow halogenation. 4. Phosphorus tribromide (PBr3) is the catalyst. Note: An important use of this reaction is in the industrial synthesis of ot—arnino acids from carboxylic acids through OL-bromination of carboxylic acids (see Amino Acids 2). Mechanism: 1. The carboxylic acid reacts with the catalyst PBr3 to form an acyl bromide. 2. Tautomerization takes place, converting the acyl bromide to its enol form. 3. This enol form then reacts with bromine to form an DL-bromo acyl bromide (the mechanism is analogous to ketone halogenation; see Carbonyl a—Substitution 3, Mechanism, steps 3 and 4). The hydroxyl proton of the enol is lost in the process {it becomes HBr). 4. The hydroxyl group of the unreacted carboxylic acid undergoes an exchange with the bromine (EH) on the carbonyl carbon of the u-bromo acyl bromide to produce the desired tx-bromo carboxylic acid and a new unsubstituted acyl bromide. The new acyl bromide can continue this reaction by repeating steps 2 through 4 until all carboxylic acids are converted to a-bromo carboxylic acids. H 54 o ’ H 0—H 1 II 1 =« II ® \ ,.. R—(f—C—Ofl Efficiflr. Q. /C=c\ n- R- w an Carboxylic acid Acyl bromide Bromo Brisk enol ,\ (3) HBr 3' 0 Br 0 B, o I ll ‘ | || @ I H H—C—C—Br' + H—C—CmoH fl HAG—c —B.- I-Il Fl.- R—CIH —CO0H A. Acyl bromide mammo Ufimacwd “Jammie CHTbOXyliC acid carboxylic acid acyl bromide ot-HALOGENATION OF KETONES Carbonyl (I-SflbStltthlOIl 5 VIA BASE CATALYSIS i? if if i l CHar—C—CHs —2> CHg—C—CHz—J —+ CHg—C—Cil NaOl-l | Acemnc HEQ lilodideipropanone [ [ketone) Ke s: fins reaction replaces the othydrogen of the ketone with a halogen and is comparable to the acid-catalyzed ot-halogenation reaction (see Carbonyl a-Substitution 2). 2. However, compared to its acid-catalyzed counterpart, this reaction has a few differences: a. This reaction is catalyzed by base (e.g., NaOH) and proceeds through an enolate ion intermediate instead of the enol intermediate involved in acid catalysis. b. This reaction generates a mixture of mono-, di-, and trisubstituted products instead of the sole mono- halogenated product observed with acid catalysis. Reason: The monohalo products are more acidic than the starting ketones and can react further with bases to form enolate ions which can be further halogenated to di- and trihalo products. For this reason, this is not a useful reaction for the t1- monohalogenarion of ketones. 3. Bromine, chlorine, and iodine can be used as halogens for this reaction. Mechanism: 1. The base abstracts an ot-proton frbrn the ketone to produce the enolate ion. This is the rate-limiting step. 2. The enolate ion (e.g., resonance form A) is very nucleophilic and reacts with halogen to form a C—X bond. This completes the monohalogenation reaction. H20 9 .. 0 H 0 H :0: H II | {D Slow 2 ll | i l n—c—c—H fl R—C—C—H 4——fi+> RiC=C-H El! é . Resonance Resonance 6.. r‘ Ketone k4?” form A xix it?) form B 0 X 0 H H l IE I e R—C—(f—X 4—— 4— 4— Fl—C—?—H + X X X Trihalo ketone Monohalo ketone (X : Br, C], or I) Note: Unfortunately, the monohalo products are easily deprotonated to form enolate ions that react further to form di- and trihalo products. This subsequent halogenation reaction that produces a mixture of products can be avoided if the starting ketone has only one Int-hydrogen (e.g., see sample reaction above). SELENENYLATION Carbonyl tit—Substitution 6 0 CH3 0 CH, Ii | NaH \I | CH3— C — C — CHZCHa ——> CH3 7 C i C — CHZCHa | CeHSSeBr I H SecsHs 3-Methyl—2—pcnlanone 3vMethyl-3-phenylscleno-Z-pemanone (Hume) {seleno ketone) Keys: 1. The important value of this reaction is not formation of the ot—phenylseleno ketone product but rather the subsequent conversion of this product to an cub-unsaturated carbonyl compound, that is, an enone {see Note). 2. The reaction places a selenium atom on the (It-carbon of carbonyl compounds. 3. The reaction proceeds through two stages: a. The ketone is converted to an enolate ion intermediate. A strong base (i.e., NaH in THF) is used for this part of the reaction. b. The enolate ion then reacts with phenylselenenyl bromide (C6H5 SeBr) to form the a—phenylseleno ketone product. This part of the reaction proceeds via an 5N2 mechanism (see Alley! Halides 6). Note: The synthesis of an enone (an 0t,B—unsaturated carbonyl compound) is illustrated. The seleno ketone can be oxidized to a selenoxide with H202. The selenoxide undergoes a syn-elimination reaction to produce the carbonvcarbon double bond product, enone. n. nn 0 n. H" o l l ll NaH 1 | || R—C—C—C—H'” —-——> R—C—C—C—Fl'" l l C5H55eBr | | H H H Se—C5H5 H303 Ketone Seleno ketone l" 7‘" if T' T" 1? S H—C=C—C—H“‘ if". . n—cjc—cvn'" ; elimination | 1—} Enone PhsBOH H @382 — c5145 Selenoxide “9 Most carbonyl compounds (e.g., esters, ketones, and nitriles) undergo this reaction and produce good yields. Aldehydes should not be used as the carbonyl source because their enolate ions are very reactive and generate a mixture of products. Mechanism: ‘ 1. NaH, a strong base, abstracts an ot—proton from the ketone to form an enolate ion. One equivalent of base is required. 2. The enolate ion then reacts with phenylselenenyl bromide through an 8N2 mechanism (see Alley! Halides 6 for details on the 5N2 reaction). The nucleophilic enolate ion attacks the selenium atom, displaces the bro- mide ion, and forms the ot—phenylseleno ketone product. . H R" 0 H n" o H R" o nééln-uafitnéélmi—W utiliziin'" l l 33 E e | I Fr H R' (N Br ['1' SE‘cSHS CgHs—Se—Bl‘ Kelone Enolate (LPhenylseleno kelone 10D PREPARATION OF ALKYLATED MALONIC ESTERS MALONIC ESTER SYNTHESIS ll T ll ll T 3 1 N +‘OCH CH ‘ h 1 OchHZOC — c — COCHcha w enacngoc — c — seamena t 2) CH3CH2C] I H CHZCHS Dielhyl malonalc (malonic ester) Diethylilethy] malonaie (Alkylated malonic ester) Keys: Carbonyl ot-Substitution 7 + CHZCH30H Ethanol 1. This reaction adds alkyl groups to the malonic ester. This reaction is very similar to the preparation of alkylated acetoacetic esters {see Carbonyl tit-Substitution 8). 2. The reaction proceeds through two stages: a. Malonic ester is converted to its enolate anion. Because of the presence of two flanking carbonyl groups, the ot-hydrogens of malonic esters are very acidic and are easily abstracted by a strong base (e.g., sodium ethoxide in ethanol). One equivalent of base is required. b. The enolate anion reacts with an alkyl halide via an 5N2 mechanism {see Alkyl Halides 6} to form the final monoalkylated malonic ester product. Note: Since malonic esters have two or—hydrogcns, they can react a second time to yield dialkylated products. if 7' fl if T ‘u’ 151 reaction ' CH36H200 — c — COOH20H3 —H—> cmcmoc e c _ cocflzcns 2'“ ream“ l l) NaOEl/ethanol ; l] NaOEt/ethanol H 2) RX H 2) Rx Malunic ester , Mono-Alkylated malonic ester (X = Cl. Br, or I) if 7‘ l? CH3CH20C — ?— C0CH2CH3 Fl Di-Alkylated malonic ester an 3. This is a very useful reaction because the alkylated malonic ester product can be further hydrolyzed and decarboxylated with strong, hot acid to generate a carboxylic acid that has two more carbon atoms than the alkyl halide (see Note for details). Note: Decarboxylation of a mono- or dialkylated malonic ester to form carboxylic acids is shown. Briefly, the reac- tion initially produces a dicarboxylic acid, which then loses one carboxyl group in a decarboxylation reaction. Note that the R group is from the alkyl halide. C|)H H COOEt H (3:0 - OH OH \ / [130* \ Decarboxyiallon \ / /c\ ch >7“ fl /c=c\ n CODE! Hem R c—o co OH OH ll 2 Diesler 0 I i Diacid H 0 I ll R—f— 0—0" H Note: R group is from Alkyl Halide Cflfbflxylic acid Important: Malonic ester synthesis followed by the decarboxylation step is one of the easiest methods for con- verting an alkyl halide to a carboxylic acid product with two extra carbons. Mechanism: 1. The ethoxide ion abstracts one of the Ot-pI'OtOl'lS on a malonic ester to form an enolate anion. 2. An 5N2 reaction takes place between the enolate anion and the alkyi halide, forming the monoalkylated malonic ester product. Note: The alkylated malonic ester can react again with a second equivalent of base to yield another enolate ion, leading to a dialkylated malonic ester product. i R" .11 o H o ‘QCHzcfls o o o n- 0 1| l II (i) ll .9.‘ M Q) Ii | || HOC—C—COR f HOG—(II—COFI —r> HOC—f—COR | H CH30H20H H H Malonic ester Enolale ion Alkylated intermediate malonic ester PREPARATION OF ALKYLATED ACETOACETIC ESTERS Carbonyl a-Substitution 8 0H0 0H0 II I II 1) Na‘aBOCHZCHJ in ethanol II I II cHacHzoc — c — CCHa —-—-————> CH36H20C — c — CCH; + CHJCHZOH I 2) CH3CH2C1 I H CH CH 2 3 Alcohol Aceloacelic ester Alkylated acetoacetie ester Keys: 1. This reaction adds alkyl groups to the acetoacetic ester. This reaction is very similar to the preparation of alkylatecl malonic esters (see Carbonyl a—Substitution 7). 2. The reaction proceeds through two stages: a. The acetoacetic ester is converted to its enolate anion. Because of the presence of two flanking carbonyl groups, the OL-hydrogens of the acetoacetic ester are very acidic and are easily abstracted by a strong base (e.g., sodium ethoxide in ethanol). One equivalent of base is required. b. The enolate anion reacts with an alkyl halide via an 8N2 mechanism (see Alkyl Halides 6) to form the monoalkylated acetoacetic ester product. Note: Since acetoacetic esters have two a—hydrogens, they can react a second time to yield dialkylated products. 0 H 0 _ O H 0 ll I II Isl rxn 2nd rxn ll I II CH3CHzoc c CCHa > + CH3CHZOC — c — CCHI | 1) NaOEtJEtOH l) NaOEthtOI-i | H 2) RX 2) Rx R Acetoacelic ester Dialkylated acctoacetic ester 3. This is a very usequ reaction because the alkylated acetoacetic ester product can be further hydrolyzed and decarboxylated with strong, hot acid to generate a ketone product that has three m‘ore carbon atoms than the alkyl halide (see Notes for details). Notes: 1. Decarboxylation of an alkylated acetoacetic ester to a ketone involves conversion of the alkylated ace- toacetic ester to a ketone by formation of a B—keto carboxylic acid, which is decarboxylated. H o H I H H I ll H30+ | Decarboxylauon l I H—C—C—CHa fl H—CJ—C—CHg —> H—C=C—CH3 —> R—C—C—CH: I Heat I H | l N c — 0E: _ 9 O H o u c .3) H a 0 ll H Ketone O Enol Alkylaled aeetoacelie ester (Note: R group is from Alkyl halide) 2. Important: Synthesis of alkylated acetoacetie esters followed by the decarboxylation step is one of the easi- est methods for converting an alkyl halide to a ketone product with three extra carbons. Mechanism: 1. The ethoxide ion abstracts one of the ot—protons of an acetoaeetic ester to form an enolate anion intermediate. ‘ 2. An 5N2 reaction takes place between an alkyl halide (RX) and the enolate anion to form the alkylated ace- toacetic ester. -}.. Emma RI} 0 H 0 O f 0 Fl 0 ll i II (‘D I! g ll ® “I i || Cch i (I: i cocnzcm f» cnac i (I: i cocmcm —-——~—> cmc i e i cocuzcm H CHJCHZOH H H Acetoacetic ester Enolate ion Monoalkylated intermediate aceloaeetic acid Depending on the number of alkylation steps, a mono- or dialkylated acetoacetic ester is formed. PREPARATION OF ALKYLATED KETONES, ESTERS, AND NITRILES Carbonyl ot—Substitution 9 O H O H \I I LDA in THF \l | CH3; C i C * CHZCH3 —> CH3CH2 — C — C — CH20H3 + HCI | CH3CI | CH3 CH3 3-Melhyl-2-pentanonc 47Methyli3ihexanone (ketone) (alkyluled ketone) /CH3 @e/CH— CH; Li‘ N\ Lithium d CH; CH3 \ CH3 EYE 1. This reaction is very useful for adding primary alkyl groups to the (la-carbon of ketones, esters, or nitriles. It is conceptually similar to the alkylation of malonic esters and acetoacetic ester reactions (see Carbonyl a- Substitution 7 and 8). 2. The advantage of this reaction is that it directly adds the alkyl group to the substrate {e.g., ketone). No subsequent decarboxylation step is required. (For comparison see Carbonyl (ll-Substitution 7 and 8, Notes.) . This reaction proceeds through two stages: formation of enolate ion followed by an 5N2 reaction. . The a—hycirogens of ketones, esters, and nitriles are much less acidic than those of malonic esters or ace- toacetic esters; consequently a much stronger base [e.g., lithium diisopropylamide (LDAH is required to form the enolate ion. hue Notes: . 1. Reaction with asymmetric ketones inevitably yields product mixtures. However, the major product is a ketone alkylated on the less sterically hindered carbon. 2. Aldehydes cannot be used for this reaction. Reason: Aldehyde enolate tends to undergo a carbonyl conden- sation reaction, not an alkylation reaction. Mechanism: 1. The strong, bulky base, LDA in tetrahydrofuran (THF), abstracts an oc-proton from a ketone, ester, or nitrile to generate an enolate ion intermediate. 2. An 8N2 reaction takes place between the alkyl halide (RX) and the enolate anion to form the alkylated product. 0 H 9 o o H... II I [—\®=LDA II 9“ n (2) II I R—C—C—R' ————> R—C—C—R‘ R'“—X —> FI—C—C—H' | THF I I R F... Ru Ketone Enolate ion Alkyl halide Alkylated kelone O H 8 O O H" II I (1:, =LDA || .62’5‘\ n (2) II I RO—C—C—R' —> RO’C’C’H' H"-"~X —> RO—C—C—R' i THF I I H H H Ester Enolate ion Alkyl halide Alkylaled ester H e R' | Wu» fifi {1 ® I NEG—C—R fi'fi—w—F NEC*C_FI H'—X —> NEG—C—FI | THF I I H H H Nilrile ' Enolate ion Alkyl halide Alkylated nitrile ...
View Full Document

Page1 / 19

carbonyl alpha-substitution - SUMMARY Introduction to...

This preview shows document pages 1 - 19. Sign up to view the full document.

View Full Document Right Arrow Icon
Ask a homework question - tutors are online