Nonperfect Synchronization in Nucleophilic Additions to Carbon

8 Nonperfect Synchronization in Nucleophilic Additions to Carbon-Carbon Double Bonds

Downloaded by CORNELL UNIV on October 18, 2016 | http://pubs.acs.org Publication Date: July 1, 1987 | doi: 10.1021/ba-1987-0215.ch008

Claude F. Bernasconi Thimann Laboratories of the University of California, Santa Cruz, CA 95064

The principle of nonperfect synchronization states that any product -stabilizing factor that develops late along the reaction coordinate, or any reactant-stabilizing factor that is lost early along the reaction coordinate, has the effect of increasing the intrinsic barrier of a reaction. Much of the structure-reactivity behavior in nucleophilic additions to activated C=C double bonds can be understood as the manifestation of this principle. This behavior includes the effect of resonance by substituents adjacent to the site of negative charge development (or its disappearance) and the effect of remote substi tuents, the solvent, steric crowding, intramolecular hydrogen bond ing, and intramolecular electrostatic stabilization.

JL H E NATURE O F T H E INTERACTION MECHANISMS that stabilize the carb-

anion profoundly influences the rates of reactions that lead to the generation of carbanions. For the most thoroughly studied carbanion-forming reactions, the ionization of carbon acids, this fact has been recognized for a long time and discussed in a number of reviews (1-7). X RCHXY + B ^ R C ( -

+ ΒΗ

ϋ + 1

(1)

Y One characteristic feature of these reactions is that k , the intrinsic rate constant, tends to become smaller [or the intrinsic barrier increases] as X 0

1

1

1 T h e intrinsic rate constant, k0, is usually defined as k1 = k-1 when pKaBH = pKaCH, although sometimes statistical factors are included, k0 = k1/q = k-1/p when pKaBH = pKaCH + log (p/q). This intrinsic barrier, ΔG0‡, is ΔG1‡ = ΔG-1‡ for ΔG° = 0 or its statistically corrected counterpart.

0065-2393/87/0215-0115$06.50/0 © 1987 American Chemical Society

Harris and McManus; Nucleophilicity Advances in Chemistry; American Chemical Society: Washington, DC, 1987.

NUCLEOPHILICITY

116

Table I. log k for Deprotonation of CH XY by Amines and for Amine Addition to H C C H = C X Y in 50% (CH ) SO-50% Water at 20 °C 0

2

5

3

6

2

X
0; a < β, δ log Κ ^ ( Β Η ) > 0; and a " > β, δ log K * * ( B - ) < 0]. c

0

ο1

B H +

sol

+

s o l

B

d e s

Nucleophilic Addition to C=C Double Bonds Another important carbanion forming process is the addition of a nucleophile to an activated olefin. X

X u

C=C /

\ Y

+ N u T=^- — C — C V.*-i I \ r Nu Y

(9)

y + 1

In view of the similarity between the carbanions formed in reactions 9 and 1, reaction 9 might be expected to show similar reactivity patterns as reaction 1. However, an important difference between the two reactions is that in the nucleophilic addition the procarbanionic carbon is sp hybridized while in reaction 1 it is sp hybridized. This difference is likely to bring about some modifications in the reactivity pattern of the nucleophilic additions. Also, as will become apparent, several factors not observed in proton trans fers play an important role in nucleophilic addition reactions. These factors can also be understood in the context of the P N S . 2

3


120

NUCLEOPHILICITY

Intrinsic Rate Constants as a Function of X and Y. The largest set of data obtained under comparable conditions refers to the addition of piperidine and morpholine to benzylidene-type substrates in 50% ( C H ) S O - 5 0 % water at 20 °C. 3

2


IV

V

k for these reactions was obtained as k = k = k_ by interpolation or extrapolation of plots of log fcj (or log k_ ) versus log K to log K = 0 . Table I lists log k values along with data for the corresponding proton transfers. Figure 1 shows a plot of log k for reaction 10 versus log k for reaction 1 in which R' = H . Except for the strongly deviating point for benzylideneacetylacetone to be discussed, a remarkably good correlation between log fc (C=C) and log fc (C-H) exists: X and Y indeed affect the intrinsic rate constants for both reactions in a qualitatively similar way. Two different lines are present in Figure 1. One line is the best leastsquares line through all points except that for benzylideneacetylacetone. This line has a slope of 0.45 ± 0.06 and is based on the notion that the deviations from the correlation are random or caused by poorly understood factors. The second line is through the points for benzylidenemalononitrile and β-nitrostyrene only. This line has a slope of 0.38 and is based on the hypothesis that all other points deviate negatively because of a steric effect that lowers log fc (C=C). Regardless of which line is preferred, the small slopes show that the effect of X and Y on reaction 10 is strongly attenuated compared to that on proton transfers. Similar conclusions are reached when comparing the reactivity of ben zylidene-type substrates, IV, with respect to attack by hydroxide ion. If adjustments for the dependence of the equilibrium constants on X and Y are made (18, 19), the relative intrinsic rate constants can be estimated (Table III). As with the amine reactions, the k values follow the same order as for 0

0

x

x

3

l

x

x

0

0

0

0

0

0

0

3

-

1

- 1

This definition of ko creates a problem of units because & is in units of M s and k_ in s . A possible solution to the problem was suggested by H i n e (17) but this solution suffers from the disadvantage of having to assume the same equilibrium constant for encounter complex formation between nucleophile and electrophile in all reactions. In terms of relative k^ values, little difference exists between our and H i n e s definitions. χ

-1


l

8. BERNASCONI

Nucleophilic Additions to Carbon-Carbon Double Bonds


6h

121

0 in proton transfers, 7 = a —β > 0 in nucleophilic additions except that the imbalances in the latter reactions are generally significantly smaller. The only exception is with X Y = (CN) ; here I for the n

n

n

n u c

n u c

n

n

n

n u c

η

η ι ι ε

n

n u c

η

η υ ο

2


8. BERNASCONI


123

proton transfer seems abnormally small, probably because this reaction behaves almost like a diffusion-controlled proton transfer (5).

Table IV. a

nuc

" and β ." Values in Nucleophilic Additions to Olefins ηιΜ

Nucleophile

«nue"

R NH

0.43»

0.30

0.13

ArCH=C(COO) C(CH ) * '

R NH

0.19»

0.07

0.12

ArCH=C(COO) (CH )//

ArO"

0.59*

0.39

0.20

ArCH=CHNO/*

R NH

0.51*

0.25

0.26

R NH

0.65*

0.34

0.31

Olefin ArCH=C(CN) *>* 2

2

2

3


2

2

2

3

2

C H C H = C(Ar)N0 «>« 6

5

2

2

I =

n

β r'nuc

n

α

-

β r'nuc

nuc

n

a

In 50% ( C H ) S O - 5 0 % water at 20 ° C . nuc 9n(C~), see the text. C . F. Bernasconi and R. A . Renfrow, unpublished results. C . F. Bernasconi and R. B . Killon, unpublished results. C . F Bernasconi and M . Panda, unpublished results. / In water at 25 ° C . s Reference 22. Reference 42. ' nuc Pn> the text. 3

b

a

n

2

=

c

d

e

h

a

n

=

s

e

e

The most obvious explanation for the smaller imbalances in the olefin reactions is that the lag in resonance development and solvation of the carbanion is less extreme than in proton transfers because the sp hybridiza tion makes it difficult to localize the negative charge on carbon, unless the carbon assumes substantial sp character in the transition state. Possibly, the negative charge does not accumulate at all on carbon and the imbalances may be entirely due to late solvation. In the context of this interpretation, the smaller sensitivity of log k (C=C) to X and Y compared with that of log fc (C-H) can be understood as a direct consequence of the smaller imbalances. This correlation is easily seen if equations 3 and 6 (after replacing β with β ) are applied to the present situation. A small imbalance implies that the o t — β and a — 3nuc in equations 3 and 6, respectively, are not strongly negative. Because, on the other hand, δ log K ^ C " ) and δ log K ^ C " ) for the nucleophilic additions are expected to be quite comparable to the same quantities in the proton transfers, the smaller sensitivity of log fc (C=C) to X and Y must be mainly the consequence of a —β and a —β being smaller than the corresponding terms for the proton transfers. This interpretation is not the whole story, though. In reactions of the type 2

3

0

0

η

ηιιε

c

Μ

res

n t

e

r

m

c

η υ ε

s o l

s

0

c

r e s

η

η υ ο

c

s o l


η

η ι ι ε

124

NUCLEOPHILICITY

Χ (11) Η

Υ

Ο

the sensitivity of log k to X and Y is comparable to that of log fc (C=C) (18, 19). A large uncertainty in the relative k values of these reactions exists, which renders this conclusion rather tentative, but even when these uncer tainties are taken into consideration, the sensitivity of log k to X and Y in these reactions does not approach that of log k (C-H). This fact is surprising because in reaction 11 the procarbanionic carbon is sp -hybridized just as in a proton transfer, and therefore, reaction 11 would be expected to behave more like a proton transfer than a nucleophilic addition. These results suggest that in proton transfers an additional factor, not present in the other carbanion-forming processes, determines relative intrin sic rate constants. We tentatively suggest that this factor is the difference in the hydrogen-bonding capabilities of the carbon acids and the carbanionic carbon mentioned in the introduction. In other words, the hydrogen-bond ing factor may be important not only in distinguishing most carbon acids as a class from the normal acids but also in discriminating among various types of carbon acids according to the ττ-acceptor ability of X and Y. In fact, our results, if they can be corroborated, may eventually constitute the most compelling evidence for the importance of the hydrogen-bonding factor. 0

0

0

0

0


3

Electrostatic Effects on Jt . As mentioned earlier, for the reactions with amine nucleophiles, the sensitivity of log k (C=C) to X and Y is smaller (slope of 0.38 or 0.45) than that in the reactions with hydroxide ion (slope of 0.57). This smaller sensitivity can be understood in terms of an electrostatic effect. The internal electrostatic stabilization of the zwitterionic adduct should enhance the equilibrium constant of the reaction. If this effect were poorly developed in the transition state ( a < β ) , it would depress k according to 0

0

η

el

el

δ log fc

0

= (a

el

ηυο

- β - ) δ log ηικ

0

(12)

Equation 12 raises two questions: (1) Is it reasonable to assume that a < β ? (2) Does δ log k depend on X and Y in such a way as to decrease d log k (C=C)/d log k (C-H) for amine addition compared with the addition of an anionic nucleophile? As to the first question, because the stabilization energy is proportional to the product of the charges, this stabilization cannot be very extensive before the charges are fully developed, and thus the energy of the transition state should not be affected very much. This problem of small charges is somewhat counteracted by having the negative charge closer to the positive e l

η

e]

ηι10

0

0

0


8. BERNASCONi


125

charge in the transition state than in the adduct, although this advantage in turn is reduced by the longer C - N bond in the transition state. O n balance, apparently a < β Λ Regarding the second question, the electrostatic stabilization energy of the zwitterionic adduct should be reduced when X and Y become better IT acceptors because the center of gravity of the negative charge is farther away from the center of the positive charge. Hence, δ log K is reduced in equation 12, which renders δ log fc less negative for better IT acceptors. As a consequence, a plot of log fc (C=C) for amine addition versus log fc (C-H) should have a smaller slope than a similar plot for the addition of an anion. This fact is illustrated schematically in Figure 2. e l

η ι κ

e l

x

el

0


0

0

good 7Γ acceptors

poor 7Γ acceptors

^ l o g ko

ο II Ο ο JE ο

log k

0

(C-H)

Figure 2. Schematic representation of the electrostatic effect on a plot of log k (C=C) versus log k^C-H). The upper line refers to addition of an anionic nucleophile where electrostatic stabilization does not occur; the lower line refers to amine addition. δ log k becomes less negative for better it acceptors. 0

el

0

Polar Effects of Remote Substituents. Even though the identity of X and Y is the major factor in determining k , intrinsic rate constants show a small dependence on the remote substituent Ζ in IV or VI. In analogy to the situation in proton transfers (8), the effect of Ζ on log k can be expressed by 0

0

δ log fc P°'(Z) = (ct » - β « ) δ log KfW 0

nuc

ηικ


(13)

126

NUCLEOPHILICITY n

In cases where a = p , δ log K ^ Z ) is simply the experimentally measurable change in log Κ induced by a change in Z. When ot ^ p , experimental δ log K^°\Z) in equation 13 can still be used, but a must be replaced by p . Alternatively, if a is used, δ log K^°\Z) refers to the contribution that comes only from the interaction of Ζ with the negative charge of the adduct (22). Equation 13 indicates that electron-withdrawing substituents increase k because δ log K^°\Z) > 0 while electron-donating substituents decrease it. However, just as for proton transfers, the effects of Ζ on k are quite small compared to the effects of X and Y. n u c

n

n

γ

nuc

n

n

n u c

n

n

n u c

0

0

Solvent Effects on k . Only a few studies so far allow an assessment of solvent effects of k . The change from water to 50% ( C H ) S O - 5 0 % water enhances log k from 2.10 to 2.55 in the reaction of piperidine and mor pholine with β-nitrostyrene (22) and from 4.55 to 4.94 with benzylidenemalononitrile (C. F. Bernasconi and R. B. Killion, unpublished results). O n the other hand, the change from water to acetonitrile either leaves k unaffected or even decreases it slightly in the reaction of benzylidenesubstituted Meldrum s acid with the same amines (23, 24); the uncertainty is due to a lengthy extrapolation in water that renders k uncertain in this solvent. The observed increases in k upon addition of ( C H ) S O are consistent with similar increases in proton-transfers (13, 15, 16, 25-27) and are easily understood in terms of a reduced δ log K ^ C " ) in the (CH ) SO-containing medium (equation 6, β instead of β). The magnitude of the effects is smaller than in the proton-transfer reactions, though. For example, δ log k = 0.45 for nucleophilic addition to β-nitrostyrene contrasts with δ log k = 1.35 for the same solvent change in the deprotonation of nitromethane anion by the same amines (C. F. Bernasconi, A . Mullin, and D . Kliner, un published results). This attenuation of the solvent effect is another manifesta tion of the smaller imbalances in the olefin reactions. An additional factor that may reduce the solvent effect on k with amine nucleophiles is the internal electrostatic stabilization of the zwitterion. This electrostatic effect decreases k according to equation 12. This reduction should be larger in a less polar solvent because electrostatic stabilization in the zwitterion is stronger (larger δ log Kj ), and hence, the solvent effect on k should be correspondingly reduced. This factor may be a contributing reason why k for the reaction of amines with β-nitrostyrene increases so little upon addition of ( C H ) S O . The very small or nonexistent solvent effect on /ÎQ for the benzylidenesubstituted Meldrum s acid reaction upon transfer from water to acetonitrile is surprising because acetonitrile is a poorer solvator than (CH ) SO-water mixtures. In principle, the smallness of this effect could be attributed to an unusually large electrostatic effect that completely compensates for the


0

0

3

2

0

0

0

0

3

2

3

2

η

η υ ε

0

0

0

0

el

0

0

3

2

3

2


8. BERNASCONi


127

normal solvent effect on k . More likely, though, intramolecular hydrogen bonding enters as an additional factor in this reaction, as discussed in the next section. 0

Effect of Intramolecular Hydrogen Bonding on Jr . In the reaction of amines with olefins, the possibility exists of intramolecular hydrogen bond ing between the Ν H proton and one of the electronegative atoms in X or Y of the zwitterionic adducts. With the adducts of benzylidene Meldrum s acid (VII) and benzylideneacetylacetone (VIII), this intramolecular hydrogen bonding appears quite strong. Downloaded by CORNELL UNIV on October 18, 2016 | http://pubs.acs.org Publication Date: July 1, 1987 | doi: 10.1021/ba-1987-0215.ch008

0

yCO

CH

/ ^ r °

3

C » ^I R N

C H C H — C \C ~_ 6

CO +

2

5

I

CH,

Ο

R N

N

+

3

Ο

0

VII

C - C H

VIII

The main evidence for its existence is the high p K value of the Ν Η proton ( p K ) in V I I and VIII. For most adducts of type V (equation 10), p K is lower than the pK of the parent amine. For example, p K pK = - 0 . 7 2 for X Y = (CN) (28), - 2 . 3 3 for X Y = ( C N ) C H - 4 - N 0 (29), and - 2 . 7 0 for X Y = H ( N 0 ) (30). These values contrast with p K / - ρΚ/*ΝΗ = + 0.24 for V I I (24) and +2.50 for VIII (C. F. Bernasconi and A . Kanavarioti, unpublished results). The intramolecular hydrogen bond adds stability to the adduct and hence a late development would decrease, and an early development in crease, k according to a

±

±

û

fl

R2NH2+

±

a

RzNH2+

fl

2

6

4

a

2

+

2

2

0

Ô lug AT,™ = ( a

H b

-

P n u c

n

) 8

l o g

Ki

Hb

( 1 4 )

Because the stability of the hydrogen bond depends on the nearly full development of both the acidic properties of the Ν Η proton and the basic properties of the acceptor oxygen, little stabilization in the transition state is expected, that is, a < β . The two sets of experimental data that allow us to test this prediction are consistent with it. The first data set is the observation that in the reaction of amines with benzylidene-substituted Meldrum s acid, k is essentially un changed or even slightly reduced upon transfer from water to acetonitrile η

H b

η ι κ

0


128

NUCLEOPHILICITY

(23, 24). As discussed in the previous section, the normal solvent effect would be to increase k . The anomalous solvent effect may be a consequence of the intramolecular hydrogen bond being stronger in acetonitrile than in water for which independent evidence exists (23). The stronger hydrogen bond is tantamount to a larger δ log K^, which leads to a correspondingly more negative δ log fc in acetonitrile. The second example is the reaction of benzylideneacetylacetone with piperidine and morpholine in 50% ( C H ) S O - 5 0 % water (C. F. Bernasconi and A. Kanavarioti, unpublished results). As noted earlier, k for this reaction shows a strong negative deviation from the correlation in Figure 1. Probably, part of this deviation is caused by intramolecular hydrogen bonding, al though a steric contribution also occurs, as discussed next. 0

Hb

0

3

2


0

Steric Effects on k . At least two types of steric effects occur: direct repulsion between the attacking nucleophile and the olefin and steric inter ference with the optimal π overlap among X , Y, and the carbanionic carbon in the adduct. Both effects have their counterpart in proton transfers, but as long as R' = Η in R ' C H X Y , these effects are small unless very bulky bases are used (32, 33). In proton transfers and transfer reactions in general (e.g., S 2), direct repulsion between reactants can occur only in the transition state, and hence the result is always to lower k . In an addition reaction, repulsion occurs in the transition state as well, but in the adduct, repulsion is even more severe. Hence, according to equation 15 (δ log K j < 0), the effect on k depends on whether 0

N

0

st

0

δ log ko* = (α„ - β

ηιιε

»)δ log Κ,*

(15)

the steric interaction develops ahead of C - N u bond formation (a > β Λ δ log k < 0) or lags behind it (a < β Λ δ log k > 0). No conclusive data exist yet that bear on the timing of this direct steric effect. With respect to hindrance of the π overlap, we have encountered two systems where this effect is clearly affecting the stability of the adduct. These systems are the reactions of a-cyano-2,4-dinitrostilbene (29) and ben zylideneacetylacetone (C. F Bernasconi and A . Kanavarioti, unpublished results) with piperidine and morpholine. In theses reactions, the equilibrium constant for the formation of the anionic adduct (IX), which is the product of Kj for zwitterion formation (equation 10) and K , the acid dissociation constant of the zwitterion, is abnormally low, particularly so for the benzylideneacetylacetone reaction (C. st

st

ηικ

st

0

st

ηικ

0

±

5

a

5

ΚγΚα* is a better gauge of the steric effect than Kx because Κγ may include a contribution from intramolecular hydrogen bonding, as is the case for the benzylideneacetylacetone reaction.


8. BERNASCONi

Nucleophilic Additions to Carbon-Carbon Double Bonds 129

F. Bernasconi and A. Kanavarioti, unpublished results). This reaction is also the oneforwhich log k (C=C) shows a dramatic negative deviation in Figure 1. This deviation appears too large to be accounted for by intramolecular hydrogen bonding only, and hence we conclude that part of it is caused by steric hindrance of the π overlap. 0

X C H C H = C X Y + R NH — ^ C e H s Ç H C ^ - ' " 6

5

+H

2

RN

+

Y""

2

(16)


IX The decrease in k can be expressed by the same equation used for the direct steric effect (equation 15 with a > β ). However, the negative δ log fc will be counteracted by a less negative δ log fc because of the dimin ished resonance in the adduct. The results indicate that the former effect dominates, at least in the case of benzylideneacetylacetone. Further evidence for steric hindrance to π overlap comes from the crystallographic structure of (4-methoxybenzylidene)acetylacetone, which indicates that one of the acetyl groups is strongly turned out of the plane defined by the C = C double bond and the second acetyl group. If no good ττ overlap occurs in either the reactant or the product, probably ττ overlap does not occur in the transition state, and thus a may be « 1 . 0 . We suspect that in all olefinic systems listed in Table I except for βnitrostyrene and benzylidenemalononitrile a slight to moderate steric hin drance to optimal ττ overlap in the adduct occurs that is not present in the corresponding proton transfer. This could be the reason all the points in Figure 1 deviate negatively from the line defined by β-nitrostyrene and benzylidenemalononitrile. On the other hand, possibly this steric effect is of minor importance in all except for the a-cyano-2,4-dinitrostilbene and of course the benzylideneacetylacetone systems, as reflected in the negative deviations for these two compounds from the least-squares (dashed) line in Figure 1. 0

η

st

ηι10

st

res

0

0

st

Generalizations.

Are There Exceptions?

In the quest for generalizations or a search for exceptions, generalizations that simply spring from the definitions that underlie the PNS must first be distinguished from those that bear on the question of what happens during a chemical reaction. In the first category, we have the fact that as long as the PNS is defined on the basis of equation 6 (or its equivalent for nucleophilic additions) the PNS is universal, that is, it can have no exceptions. This universality,


130

NUCLEOPHILICITY

however, does not mean that every change in k can be attributed to a P N S effect. Factors that are present in the transition state but not in the reactants or products do influence k , but these factors cannot be treated in the framework of the P N S . The factors mainly occur in proton transfers and include direct steric repulsion, hydrogen bonding to the carbanion carbon, and electrostatic effects (8). However, the validity of equations such as equation 6 does not bring us any closer to an understanding of what transition-state property is being measured by β or β . The usual working hypothesis is that those param eters are an approximate measure of the charge change on the base or nucleophile or of the degree of bond formation between the base and the proton (or the nucleophile and carbon). Even if this working hypothesis were proven wrong in the future (34), the validity of equation 5 would remain intact. The second category of generalizations is the one of real interest because it, along with possible exceptions from typical behavior, provides insights into how chemical reactions occur. One of the safest such generalizations is that the development of resonance and the concomitant solvation of the carbanion invariably appear to lag behind other bond changes. These PNS effects thus typically lead to a lowering of k . The possible reasons why reactions proceed in this fashion are discussed elsewhere (8, 37-40). These reasons include quantum mechanical (resonance) and entropy effects (solva tion). Are there exceptions? We have uncovered one exception thus far. This exception refers to water (rather than O H " ) addition to benzylidene-type substrates. X 0

0

η


η υ ο

6

0

/,--

, C H CH=CXY 6

5

N

+ H 0 s 2

C H CH i 6

5

N

OH

+ H

+

(17)

Y

In this reaction, k for benzylidene-substituted Meldrums acid is higher than for benzylidenemalononitrile {log [fc /fc ] « —0.7}, while for benzylidene-l,3-indandione, k is about the same as for the malononitrile derivative (19). This finding contrasts with the "normal" behavior where k for benzylidene-substituted M e l d r u m s acid and benzylidene-l,3-indandione should be much lower than that for benzylidenemalononitrile (Table III). The likely reason for the unusually high reactivity of the Meldrum s acid and 1,3-indandione derivatives is that the transition state is subject to extra stabilization by intramolecular hydrogen bonding solvation as shown in X for 0

(CN)2

0

XY

0

0

0

6

η

Increasing evidence indicates that β and β may contain contributions that are unre lated to charge change. These contributions include solvation effects (11, 12, 14-16, 34, 35) as well as others (36). η ϋ 0


8. BERNASCONi

Nucleophilic Additions to Carbon-Carbon Double Bonds 131

the benzylidene-l,3-indandione case. This intramolecular hydrogen bonding essentially provides a way to avoid the late solvation of one of the oxygens of the 1,3-indandione moiety and with it its fc -lowering effect.


0

X Another generalization that appears safe, even though it is based on only two examples so far, is that intramolecular hydrogen bonding in the forma tion of zwitterionic amine adducts such as V should always be late and hence lower k . We believe this generalization is safe because hydrogen-bonding stabilization cannot be extensive before the acidic properties of the Ν H proton and the basic properties of the acceptor atom are nearly fully devel oped. For similar reasons, electrostatic stabilization of zwitterionic adducts probably always develops late. The intramolecular hydrogen bonding in water additions (X) represents quite a different situation from that encountered in amine additions. In the water addition, the hydrogen-bonding proton is eventually lost to the sol vent. This result means we are not dealing with a P N S effect because hydrogen bonding is present only in the transition state and thus can only lead to an increase in k . Whether steric hindrance always develops early and thus always lowers k cannot be determined on the basis of the limited data obtained so far. For steric hindrance of π overlap, the problem is complicated by the fact that the reduced resonance in the adduct leads to a less negative δ log fc , which tends to counteract the decrease in k according to equation 15. Thus, whether k increases or decreases depends on a delicate balance between these two effects. For the direct steric interaction between the approaching nucleophile and electrophile, no data are available. 0

0

0

res

0

0

0

Acknowledgment This research was funded by Grant CHE-8315374 from the National Science Foundation.


132

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8. BERNASCONi 38. 39. 40. 41. 42.


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