C&EN chemical science series
ELECTROPHILIC SUBSTITUTION AT SATURATED CARBON DONALD J. CRAM, Department of Chemistry, University of California, Los Angeles
Historically, classes of compounds served as the central organizing theme of organic chemistry. The first task of the chemists of the 19th century was development of a structural theory in terms of which constitutions and re actions of organic compounds could be described. Chemi cal reactions remained largely unclassified until the late 1930's, and only relatively recently have large numbers of organic chemists derived inspiration for research and teach ing based on correlations and analogies of reaction mech anisms. Organic transformations naturally fall into two large classes:
_4_α __ \
Carbonium ion
I . . . and when of SA~, or bimolecular variety: s Nû:
+
Ι·' C-Qfc
The terms nacleophilic (nucleus loving) and electrophilic (electron loving) have been applied to reagents in polar reactions. A nucleophile exhibits an affinity for a carbon nucleus, and an electrophile for the electrons of a carbon atom in a reactive organic compound. Perhaps the two broad classes of polar reactions sub jected to the most intensive study have been nucleophilic substitution at saturated carbon and electrophilic substitu tion at unsaturated carbon. The first of these includes most of carbonium ion chemistry, and the latter the ma jority of the aromatic substitution reactions. Both groups involve carbon which becomes positively charged in either transition states or intermediates of a reaction sequence. In the formulation of these reactions (and elsewhere), orientation of bonds in three dimensions is designated by the following conventions: bonds in the plane of the page are represented by solid lines, those that rise above the plane by solid wedges, and those directed below the plane by broken lines. The curved arrows indicate the fate of the electron pairs in the transformations. Nucleophilic substitution at saturated carbon with X as the leaving group and Nu as the nucleophile may thus be shown this way when of the SNj or monomolecular variety . . . 92
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A U G . 19, 1 9 6 3
— -
Νιι···-0-··Χ
/
à — * - Nu—C[
ι
+
Χ*
\
Transition state
Finally, electrophilic bon . . .
• Polar reactions, which involve charged or highly polar ized intermediates or transition states. • Nonpolar reactions, whose intermediates or transition states involve little generation of charge.
+χ
substitution
at unsaturated
1
\ H
car
H Allylic carbonium ion
H
This article is concerned with the character of electro philic substitution at saturated carbon. In this class of reaction, the carbon atom undergoing substitution is bound to four atoms or groups of atoms, and becomes at least partially negatively charged in either the transition or in termediate states of the transformation. The substituent which leaves the molecule is known as the "leaving group," and the group which becomes attached to carbon in its place is known as the "electrophile." Of the many kinds of organic substitution reactions, electrophilic substitution at saturated carbon has been the least studied from a mechanistic point of view. Of the three major intermediates in organic reactions α I b-C·
ι c Carbon radicals
α I , b-C+
ι c Carbonium ions
α Ib-C:
ι c Carbanions
carbanions have been the last to have their structures ex amined. Research conducted during the past five years in the U.S., Britain, Germany, and Russia is rapidly cor recting this situation. One of the tasks of the physical organic chemist is to conduct experiments which allow him to infer the detailed structures of short-lived intermediates. Stereochemical
Of the many kinds of organic substitution re actions, electrophilic substitution at saturated
In the SE2 or bimolecular variety, an electrophile attacks carbon and dislodges the leaving group in a single transi tion state:
carbon has been the least studied from a me
.E
+ L
;C—Ε
chanistic point of view. Transition state
Of the three major intermediates in organic reactions—carbon radicals, carbonium ions, and carbanions—carbanions have been the last to have their structures examined.
In reactions that involve the making of a carbon-carbon bond, frequently either of two classifications is possible. For example, the reaction between methyl iodide and the sodium salt of diethyl malonate can be classified as either electrophilic or nucleophilic, depending upon which car bon is designated as the seat of substitution:
Now research conducted during the last few years in the U.S., Great Britain, Germany, and Russia is rapidly correcting this situation.
techniques applied to starting materials and products have yielded the most information, particularly when carbanions intervene in organic reactions. Because of the negative charge on carbanions, their structures are affected by at tached substituents, by the accompanying cation, and par ticularly by the solvent. Carbanion structure in a sense extends into its immediate environment, since its structure is sensitive to solvation. Many varieties of solvated carbanions have been rec ognized:
M
ROH ·
ROH-
(C2H502C)2CH—Να +
r
CH3—I
+• (C2H502C)2CH—CH3
ΝαΙ
The desirability of referring to such reactions as being in either class depends entirely on the context and the type of analogy to be drawn. Just as many of the SN reactions involve carbonium ion chemistry, many SE reactions center about carbanion chem istry. Carbonium ions are usually powerful acids or electrophiles, whereas most carbanions are strong bases or nucleophiles. Many SN reactions that involve carbonium ions are acid-catalyzed, since one acid can generate another: CH. 1 C6H5C-0H
+
HC02H
-
C
1 , 6H5C
+
HC0 2
+
H20
CH 3
CH3
1 ?"*
• · c
/ \ Symmetrically solvated planar carbanion
+
L--*•
Asymmetrically solvated planar carbanion
Ο-Η,-C— OCH CH,
0
+
.K. C
* V ' >R
H — NR,
Asymmetry induced in carbanion by asymmetric solvation
Asymmetric solvation of an asymmetric carbanion-cation pair
A sizable fraction of all organic reactions involve at some stage the removal of a proton from a carbon acid by a base to generate a carbanion. One of the fundamental problems of organic chemistry is to establish in a single solvent a scale of carbon acidities that ranges from saturated hydro carbons to the polynitrocarbons. A complementary prob lem is determination of the relative rates of proton removal from the carbon acids. In principle, two general mechanisms are available for the electrophilic substitution reaction. In the SEt or monomolecular mechanism, a carbanion is formed in a first stage and consumed in a second by the electrophile. Here elec trophilic attack occurs on the carbanion intermediate, and not on the starting material. Clearly, the general designa tion, "electrophilic substitution at saturated carbon," applies to the over-all process, and not to a particular stage:
-C^-L
—c I
+ σ
Likewise, many SE reactions that have carbanion inter mediates are base-catalyzed, for one base often produces another:
C 6 H 5 C-H + NoNH2
%H5C
+
Να"" +
NH3
CN
CN
Ç2H5 C6H5C - C02Na CN
Thus the terms nucleophilic and electrophilic reciprocate in much the same way as do the terms acidic and basic. The types of leaving groups in electrophilic substitution at saturated carbon are listed below in generalized form, as are the ordinary electrophiles. Appropriate cross-breeding of leaving groups, electrophiles, and the substituents attached to the center of substitution (a, b, and c) leads to hundreds of known reactions. Although many of these are normally classified in other ways, in a formal sense they are members of the SE reaction class: Generalized SE reaction:
Carbanion
— c—Ε
Ε + b-C^-L
b-C-E + L
AUG.
19, 1 9 6 3 C & E N
93
Generalized leaving groups attached to carbon (C—L) :
V
-hu
ι
o-
?>
— (P-p^
I
Generalized (D-E): XrS
electrophiles
_-Ô-LH
(E)
and electrophile
— M^-H
c
I
1!
donors
—c
1
ΝΞ0-
1
In the following sections, aspects of the reaction mech anisms of the SE reaction are discussed in turn. The first sections are concerned with carbanion reactivity and struc ture, whereas the latter sections involve the SE2 reaction, in which the bonds to carbon are made and broken in the same transition states. A heavy emphasis is placed on stereochemistry, since determination of the three-dimen sional course of the reaction has provided a major amount of the information available on mechanism. The SEX Reaction Carbanions are most simply generated by treatment of certain types of organic compounds with appropriate bases. The base abstracts a proton from carbon in an acid-base reaction. Compounds subject to such reactions are called carbon acids. A discussion of the reactivities of carbon acids and their conjugate bases (the derived anions) pro vides a good entré into the general subject of the mechanism of the S £ i reaction. In the equations used to illustrate the general acid-base reaction of carbon acids, the symbol M+ denotes the metal cation, β - a basic anion (e.g., OH, OR, NRo), and HB a proton donor (e.g., KUO, HOR, HNR.>):
b — C — H + MB
b— C
M + H-
I Carbon Acids. The table on this page contains a rank ing of a large number of organic compounds in terms of relative pK a values. A number of different overlapping scales, standards, solvents, and techniques are reflected in this table. The exact pK a values listed should be viewed with considerable skepticism, particularly those of the weaker acids. A number of oxygen and nitrogen acids are interspersed among the carbon acids for purposes of comparison. The lower end of the scale was established in water, the middle part in diethyl ether, benzene, liquid ammonia, or cyclohexylamine, and the far end of the scale in saturated hydrocarbon solvents. Investigators who have been active in this field include J. B. Conant, G. W. Wheland, W. K. McEwen, H. Gilman, A. A. Morton, C. R. Hauser, G. Wittig, A. I. Shatenshtein, R. L. Burwell, Jr., R. G. Pearson, A. Streitwieser, Jr., R. Stewart, and their co-workers. A number of effects are visible in the series of carbon acidities. Those groups best at distributing negative charge are the most acidifying, and can be ordered as follows: 94
C&EN
AUG.
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1963
N 0 2 > CO > S 0 2 > COoR - C 0 2 > CN > SO > C 6 H 5 ~ C H 2 = C H > CH 3 . Both inductive and resonance effects are visible in this series. Multiple substitution of such groups has a cumulative effect at both ends of the scale. Thus C H ( N 0 2 ) 3 > C H 2 ( N 0 2 ) 2 > C H 3 N 0 2 , and (C G H 5 ) 3 CH > (C C H 5 ) 2 CH > C 6 H 5 CH 3 in acidity. The greater acidity of fluorene (pK a = 31) compared to diphenylmethane (pK a = 4 2 ) , and of indene (pK a = 23) compared to 1,1-diphenylpropene or diphenylmeth ane (pK a = 42-43) is associated with the aromatic char acter of the indene and fluorene anions. These anions are isoelectronic with naphthalene and anthracene, respec tively, and possess the stable electronic configuration char acteristic of aromatic systems. Even more striking is the difference between the acidity of cyclopentadiene (pK a = 15), and that of cycloheptatriene (pK a = 45). The anion of cyclopentadiene is isoelectronic with benzene and shares much of its aromatic character. The anion of cyclo heptatriene possesses the stability of a divinyl anion. Rough pKa Scale for Carbon Acids, Alcohols, and Amines Compound Trinitromethane Dinitromethane Nitromethane Cyclopentadiene Methanol Ethanol Isopropyl alcohol ierf-Butyl alcohol 9-Phenylfluorene Acetophenone Acetone Phenylacetylene Indene Diphenylamine Dimethyl sulfone Acetate anion
PKa Strong 4 10 15 16 17 18 19 19 19 20 21 21 23 23 24
Compound PKa Ethyl acetate 24 Acetonitrile 25 Acetamide 25 Fluorene 31 Aniline 33 Triphenylmethane 40 Dimethyl sulfoxide 41 Diphenylmethane 42 Ammonia 42 1,1-Diphenylpropene 43 Cycloheptatriene 45 Toluene 59 Propene Benzene Increase Ethylene Y Ethane
Another series suggested by the data is R - C ^ C - H > C G H 6 > R C H = C H 2 > C H , C H 3 in acidity. The electrons in a 2s-orbital are more closely bound by the carbon nu cleus than are those of the 2p-orbitals. As a result, the electron pair in an sp orbital of a carbanion is closer to the positively charged carbon nucleus than that in an sp2 orbital of a carbanion. Likewise the electron pair in an sp2 orbital of a carbanion is more closely bound to the nucleus and less basic than that in an sp3 orbital of a carbanion: ~csc^
^
sp orbital, electrons most closely bound by nuclear charge sp2 orbital, electrons further from nucleus and less closely bound sp3 orbital, electrons furthest from nucleus and least closely bound
Superimposed on the above electronic effects are steric effects, particularly with respect to solvation of the anion. Probably triphenylmethane would be much more acidic if all three phenyl groups could become coplanar, and steric inhibition of solvation of the anion were not playing a role. The pK a 's listed in the table represent very approximate
thermodynamic acidities based on equilibria between acids and their conjugate bases. The question arises as to the relationship between the equilibrium constant (K) and ku the rate constant for proton abstraction by a given base. The rate constants measure the kinetic acidity of the car bon acids. For a limited series of closely related oxygen acids with a standard base and medium, a linear relation ship between log Κ and log k1 in a given solvent and tem perature has been established. For many of the stronger carbon acids, a similar but much more crude relationship also exists. Such a relationship has been useful in esti mating Κ from a direct measurement of k1, which is some times more readily determined: k
-
I — C—Η
+
+ MB
l
I
•.
+
—C~ +
k
l
k
-l
M
+
B-H
The two most useful means of measuring rate constants for carbanion formation (kt) involve measurements of rates of base-catalyzed bromination of many carbon acids, and rates of base-catalyzed hydrogen-deuterium exchange. In the former reaction, carbanion formation is rate limiting. Solvent Effects on Anion Activity. The relative kinetic acidity of carbon acids with a given base has been demon strated to be very sensitive to certain types of solvent changes. A striking example (author and co-workers) is provided by the change in rate of racemization of opti cally active 2-methyl-3-phenylpiOpionitrile: CH, J
CH_
3
C6H5CH2CCN
- -ROH +
H Optically active
RO
I3 C6H5CH2CCN . , Symmetrical carbanion
CH_ '3
ROD >
CgH5CH2CCN D Racemic nitrile
In this system in methanol, the rate of racemization by potassium methoxide was found to be equal to the rate of hydrogen-deuterium exchange. With the same base these rates increased by 10 8 as solvent was changed from pure methanol to almost pure dimethyl sulfoxide. An increase by a factor of 10(î was observed when the base was changed from potassium methoxide to potassium feri-butoxide, and the solvent from methanol to tert-butyl alcohol. With other optically active compounds, similar experiments demonstrated that potassium ieri-butoxide in dimethyl sulfoxide gave rates 10(; greater than the same base in teitbutyl alcohol. Thus with two alkoxide bases and three solvents, the rates were distributed over a range of 13 powers of 10. These large rate changes are associated with the differences in solvation energy of the alkoxide anions in the two types of solvent. In methanol, potassium methoxide is dissociated, and the methoxide anion is "hydrogen-bonded" to methanol. In the transition state for breaking the carbon-hydrogen bond, these "hydrogen bonds" to solvent also must be broken. In dimethyl sulfoxide, potassium methoxide is likewise dissociated, but the methoxide anion is relatively little solvated. In the transition state for breaking the carbon-hydrogen bond, no "hydrogen bonds'" have to be broken. As a result, the rate in dimethyl sulfoxide is dramatically enhanced over that in "hydrogen bonding" solvents. These principles have been applied with spectacular results to reactions in which the rate-controlling step involves desolvation of an anion. For example, bromobenzene reacts with potassium feri-butoxide in tert-butyl alcohol only
at about 180° C. In dimethyl sulfoxide, reaction occurs at room temperature to give a mixture of f erf-butyl phenyl ether and phenol, a transformation which occurs by a mixture of mechanisms: -f-
Direct
C6H5Br + KOC(CH3)3
Substitution
'
C 6 H 5 0C(CH 3 ) 3 + KBr
I -KBr j ^ j ] | + (CH3)3C0H
J
Benzyne
The Wolff-Kishner reaction also proceeds at room temperature in dimethyl sulfoxide with potassium ferf-butoxide as catalyst, whereas ordinarily, temperatures of 180° to 200° C. are employed. The Cope elimination reaction (amine oxide —> olefin), which is ordinarily conducted without solvent at 120° to 150° C , can be run in dimethyl sulfoxide at 50° C. Other applications of the same principles have been made to the base-catalyzed elimination of alkyl halides and sulfonate esters to give olefin, base-catalyzed fragmentation reactions, base-catalyzed isomerization of olefins (C. C. Price, A. Schriesheim, and their coworkers ), and to solvent control of oxygen vs. carbon alkylation of ambident anions (N. Kornblum and co-workers). Many more applications will undoubtedly be made in the future. The kinetic effects of solvent on alkoxide ion activity are reflected in the thermodynamic base strength of the same species. A linear free energy relationship has been observed between the kinetic activity and thermodynamic basicity of potassium methoxide in methanol-dimethyl sulfoxide mixtures (Stewart, the author, and co-workers). A visual demonstration of the thermodynamic-basicity effect depends on the red color of the fluorenyl anion. No color is observed when fluorene is dissolved in potassium methoxide-methyl alcohol. A pronounced color is visible when dimethyl sulfoxide is substituted for the hydroxylic solvent:
Fluorene (colorless)
Fluorenyl anion (red)
Mechanism of Dissociation of Carbon Acids. The detailed mechanism of proton abstraction from weak carbon acids is complicated by the fact that the carbanion forms "hydrogen bonds" with the leaving group. In many solvents, the carbanion recaptures the proton faster than the "hydrogen bond" is broken, and the starting material is regenerated: I
_
— C-H+B
k
i
ι—-
!
*2
—C"-H—Β
*-
L —C
+ H - Β
Mk2 Two interesting consequences of this phenomenon have been observed (author and co-workers). Treatment of 3phenyl-1-butene with base in a deuterated hydroxylic sol vent gives the isomerized olefin, c/s-2-phenyl-2-butene. The fact that the product contained less than one atom of deuterium (from 0.3 to 0.7 depending on solvent and base) indicates the reaction to be partially intramolecular. The leaving group became "hydrogen bonded" at the allylic position before leaving the molecule. Collapse of the "hydrogen bonded" carbanion to rearranged material AUG.
19, 1 9 6 3 C & E N
95
occurred at a rate comparable to the rate at which deuterated solvent became "hydrogen bonded" to the anion. The electronic counterpart of this phenomenon in carbon ium ion chemistry is now well known and has been called "internal return': CCH, '6 n 5
υ
C,H,
6π5.
C=C
- C - C H = C H 2 + RÔ
Γ··Η·· ι
I H
CH3
+ RO CH,
Η
0
3-Phenyl-l-butene
CH,
Ambident Anions. Perhaps the most common carbanionstabilizing groups are those in which negative charge is delocalized onto atoms more electronegative than carbon. The many substituents which contain the carbonyl group are in this category, as are the cyano, imino and nitro groups. Carbanions stabilized by such groups are usually planar since partial double bond formation at the carbanionic site requires such a geometry: ο
cis-2-Phenyl-2butene
R
\_
ROD
•6 5
X
C
^
/
H
CH, 3
CH.
/
N -
^CH-D
.
In a second experiment, an optically active 9-deutero-9methylfluorene system was treated with dry ammonia in tetrahydrof uran :
ko
Dissociated *- ions, optically inactive
.
·*-*-
c—c
f /
+ '.NH,
I
C—C=N-«-*-
C = C =
N
c=c
4
cis-4-Deutero2-phenyl-2-butene
R
—*-
/
A = H, C, 0 — C , X , N , e t c .
C«H C=C
Optically active
\
c—c
Η I C R Hn ,
ο
v
//
A
N-
c=c /
N
C—
Ν
·*-*•
\
A
C=
N
/
\
0
0
Stereochemical evidence for the above conclusion was obtained in 1936-38 by C. L. Wilson, Sir Christopher Ingold, E. D. Hughes, and co-workers, who studied the rates of base-catalyzed racemization, hydrogen-deuterium exchange, and bromination of an optically active ketone. The three rates were found equal to one another, a fact which points to formation of an optically inactive carbanion in the rate-limiting step of each reaction:
Optically active Ammonium ion rotates
CH C
CH,
3
H
H
6 5— C— ^ — °2 5 + Ο
\
RÔ
0
Η
C
/
/ c = c\ C
6H5,
2H5
0
Planar and symmetric carbanion /
\ 4
+
NH2D
—=L
k-i and k^ »
/
k? Fast
Optically active
Br?
Fast
ROD
Optically active
?"3
The deuterium in the 9-position underwent isotopic ex change with the hydrogen of the ammonia with negligible loss of optical activity of the fluorenyl system. The free carbanion of the fluorenyl system is planar and incapable of optical activity, and therefore the isotopic exchange must have occurred without formation of the free car banion. Thus an optically active "hydrogen bonded" car banion must have formed, the ammonium ion must have rotated to give an isotopically "hydrogen bonded" car banion, and this must have collapsed faster than free carbanion was generated.
5
II
I
Ο
D
Racemic deuterated ketone
\C—
C = N + HB
-B
-Β
\
+B
/
Carbanions bound only to hydrogen or saturated carbon have been little studied because of their extreme instability. In most cases, substituents are attached which stabilize negative charge by one means or another. Ammonia serves as a model for carbanions in which charge is com pletely localized on carbon. Ammonia is known to be pyramidal and to undergo successive inversions with high frequency at ordinary temperatures. Since carbanions of the above type are isoelectronic with ammonia, they prob ably also have rapidly inverting, pyramidal configurations: H
Vs.
Nitrile tautomer
^ Carbanion with localized charge
C&EN
AUG.
19,
1963
+ Br
-c— c
I
'
V
V ι
+ HB
-Bt '+B
1
- ο -
Ι
Ester
4Bt
\
ι
+ HB
-B
V Amide tautomer
Carbanion
Η
96
C= C= N— Η
Η Nitrile
HN
Racemic bromo ketone
This pattern of results led to the widely accepted view that carbanion formation was inevitably accompanied by racemization. Indeed, the rates of base-catalyzed race mization and isotopic exchange reactions of nitriles, amides, and esters proved to be equal (author and co-workers):
-C==N
Structure of Carbanions
CLH_—C-C-C.H 6 5 || | 2 0 Br
2 5
\ /° H +B
/ C
=
C
OR
OR
OR Carbanion
Ester tautomer
Symmetrical intermediates appear to intervene in these reactions as well. The carbanions are "ambident," since they can react with proton donors either at carbon or at the more electronegative atom (oxygen or nitrogen). Re actions at the latter centers give tautomers of the original compounds. Such tautomers usually rapidly revert to the original and more stable structure through repeated carbanion formation. Other experiments have demonstrated that at least cyanocarbanions made from optically active starting mate rials need not produce completely racemic products. De carboxylation of salts of 2-cyano-2-phenylbutyric acid in volves a carbanion intermediate; and, under the proper conditions, partially optically active 2-phenylbutyronitrile is formed. For example, in solvents of low dielectric con stant such as tert-butyl alcohol or phenol, the ammonium salt gave 16% net retention of configuration. In solvents of high dielectric constant such as ethylene glycol, either metal or ammonium salts gave 12% net inversion of con figuration : C
2H5?N
NCS -C
H
+
H
NH4 I
this species is generated with different leaving groups in a variety of solvents. Hydrogen or deuterium served as leaving group in a study of the stereochemical course of the base-catalyzed isotopic exchange reactions of 2-phenylbutane: CH.
™3
KOR
• D -f C
HOR
^C2H5—*C—H
+
DOR
C«H, M
H
6 5
-6 5
Information concerning the course of the reaction can be gained by comparing the rate constant for isotopic exchange (ke) with that for racemization (/c a ). As exchange approaches 100% retention, kv/ka approaches infinity; as exchange approaches 100% racemization, kc/ka approaches unity; as exchange approaches 100% inversion, kG/ka approaches 0.5. The last condition can be understood as follows: Of a hundred molecules, after 50 have undergone exchange with complete inversion, the mixture of exchanged and nonexchanged molecules is racemic, since the rotations of deuterated and nondeuterated 2phenylbutane are identical in magnitude but opposite in sign.
CO-
°6Η5
Ion pair
Solvent
Asymmetric ion pair |-C02
Product of partially retained configuration
ç ^Η '°2 ' 5 < γ ÇRH,
/
Base
(CH3)3COH (CH3)2SO· (CH3)3COH 0(CH 2 CH 2 OH) 2
(CH3)3COK (CH3)3COK HOCH2CH2OCH2CH2OK
ke/ka
Steric Course
10 1
Retention Racemization
0.7
Inversion
,H CI
NCN
.0 HOCH,CHoOH H0CHoCHo0H----C· C«H K
Free anion
Asymmetrically solvated carbanion -C0o
Product of partially inverted configuration
^ C 2 H ,r , '2 5
\
Vs
These results are interpreted in terms of ''asymmetric solvation" of symmetric carbanions. In solvents of low dielectric constant, the ions of salts are largely associated, and loss of carbon dioxide produces an ammonium carbanion ion-pair, which collapses to product at a rate competitive with the rate at which it dissociates. In solvents of high dielectric constant such as ethylene glycol, the starting salts are largely dissociated, and the free carboxylate anion is the reactive species. The carbon-carbon bond is broken at the same time that a hydroxyl group of ethylene glycol becomes "hydrogen bonded" to the carbanion from the face remote from that occupied by the carbon dioxide formed. The carbon dioxide partially shields the carbanion on its side from attack by ethylene glycol molecules, and collapse to product occurs with partial inversion of configuration ( author and co-workers ). Aryl as Stabilizing Group. Aryl groups stabilize carbanions through charge derealization to give what are planar or near-planar species. Benzyl anions are essentially nonambident, since electrophiles usually react almost exclusively at the benzyl position. Detailed studies have been conducted by the author and his students on the stereochemical fate of the 2-phenyl-2-butyl anion when
These data reflect the importance of solvation in determining the fate of the 2-phenyl-2-butyl anion. The planar or near planar carbanion has two faces, one on the side of, and one on the side remote from, the leaving group. These are termed the front and back sides. The pK a of 2-phenylbutane is probably around 59, whereas that of hydroxylic solvents is about 14 to 19. This large difference means that the carbanion captures a proton from solvent in an extremely fast reaction, probably one that is diffusion controlled. Consequently, the stereochemical fate of the anion is controlled by the proximity of proton donors (solvent) at the front and back sides of the carbanion as it is formed. In tert-butyl alcohol, kc/ka ~ 10. This solvent is poor at dissociating the potassium terf-butoxide base, and a solvated ion-pair is the basic species that abstracts a deuteron from carbon. A new solvated ion-pair is formed, which collapses to exchanged product before the ion-pair dissociates. The molecule of feri-butyl alcohol oriented at the front of the carbanion is coordinated with the potassium ion of the base and provides the proton captured by the carbanion. Retention of configuration is the result:
3 C2H C
C
H0C(CH3)3
CH
5
^_
D
+
H
""
6 5 Optically pure
2H5^H3.-HOC(CH3)3
C 6 Hs
'••Î--"0C
