Nucleophilicity in Reactions at a Vinylic Carbon

28 Nucleophilicity in Reactions at a Vinylic Carbon Zvi Rappoport

Downloaded by MONASH UNIV on June 12, 2016 | http://pubs.acs.org Publication Date: July 1, 1987 | doi: 10.1021/ba-1987-0215.ch028

Department of Organic Chemistry, The Hebrew University, Jerusalem 91904, Israel

The probes and methods for determining the relative nucleophilicities of nucleophiles toward electrophilic olefins and toward vinyl cations were examined. Literature data were used in an attempt to construct a substrate-independent nucleophilicity scale toward vinylic carbon. The nucleophilicities are found to be dependent on electronic, steric, and symbiotic effects, and limited series obeyed a "constant selectivity", a "reactivity-selectivity", or a dual-parameter linear free-energy relationship. The conclusion made was that because of different blends of the effects, the construction of a substrate-independent nucleophilicity scale was impossible at present, but an approximate scale was presented. In nucleophilic reactions on relatively long lived vinyl cations, the steric effects predominate, but at constant steric effects, reactivity-selectivity relationships were found for very short series of substrates. Additional data are required for constructing more reliable nucleophilicity scales toward neutral and positively charged vinylic carbons.

^ Î U C L E O P H I L I C I T Y TOWARD VINYLIC CARBON is discussed in this review.

This review is not intended to be comprehensive and it avoids overlap with reviews of Bernasconi and Hoz in the present volume, which are related to this topic. We divide our discussion into two parts. In the first, we will discuss nucleophilicity in processes where bond formation between the nucleophile (Nu) and the vinylic carbon of a neutral electrophilic olefin is rate-determining. In the second, we will present the limited data related to nucleophilicity toward vinyl cations. Nucleophilicity in Reactions of Electrophilic Olefins Scheme I presents several nucleophilic reactions on electrophilic olefins 1 that lead to different processes and types of products (1-3). Y or Y ' are 0065-2393/87/0215-0399$06.50/0 © 1987 American Chemical Society

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

400

NUCLEOPHILICITY 1

carbanion-stabilizing groups. R is a substituent, X may be another substi tuent or a leaving group, and the nucleophile can be anionic as shown in Scheme I, can be neutral (e.g., R N H ) , or can carry a leaving group (e.g., C I O ) . The basic assumption is that the nucleophilic attack is rate-determin ing and it generates the carbanion 2 when the nucleophile is negatively charged or the corresponding zwitterion when the nucleophile is neutral. The fate of 2 depends on the system (1). Addition of proton can lead to an adduct in a Michael-type reaction. Intramolecular rotation around the cen tral C - C bond followed by expulsion of the nucleophile can lead to an Ε ^ Ζ isomerization. When X is a leaving group, its expulsion will give substitution (2-3), and if the nucleophile carries a leaving group X ' , it may be expelled with the formation of a (usually small) ring. 2


-

c=c\

Nu~ + X

1. internal rotation 2. - N u ~ Ri

X

Y'

Y'

Nu = N u ' X ' -Χ J'

x

=

Nu _ , Y

+H

-x-

+

Ιt

T C

Ri

c=

C

/ s X Y isomerization

Nu Y' substitution

R

J' N u —J2 —- C - H X addition

Scheme

1

y Nu'

x>cyclization

I

A priori, each of these processes, as well as others (i), can serve as a probe for evaluating the nucleophilicity order of a series of nucleophiles. However, several practical and mechanistic problems should be recognized in trying to chose a probe process or in assembling literature data in an attempt to construct a nucleophilicity scale. First, the process may not involve a nucleophilic attack on the vinylic carbon. This fact is well recognized in vinylic substitution (2, 3), and a typical example is the substitution of (£)- and (Z)^-halovinyl sulfones (3 and 4; X = CI or Br) by P h S " and M e O " in M e O H (4-6). Both reactions of both substrates are of a second order and give retention of configuration, and the "element effects" k Jk are 2.3 (E) and 2.2 (Z) with PhS" and 0.84 (E) with M e O , values that are consistent with rate-determining nucleophilic attack on the vinylic carbon (2). However, for the Ζ isomer, k Jk with M e O is 185, and because α-hydrogen exchange is rapid under the substitution conditions, the reaction of the Z-bromide probably proceeds via éliminah

c]

-

-

B

a


28. RAPPOPORT

401

Nucleophilicity in Reactions at a Vinylic Carbon

tion-addition. This finding would not be recognized if the only mechanistic information is the reaction order and the stereochemistry and could lead to a distortion in a nucleophilicity scale based on 4, X = Br. TolS0 v

H

H

Χ

2

TolS0

yX

2 V

H

H

A different problem exists if k is not the rate-determining step. This situation is sometimes easily recognized by the kinetics. A large number of nucleophilic additions (7, 8), isomerizations (9, 10) and substitutions (11, 12) by amines are of a kinetic order higher than that in the amine, and proton transfer in a step following the initial nucleophilic attack is probably the ratedetermining step. However, this result is not always revealed by the kinetics. An example is the use of Ε ±=r Ζ isomerization as a nucleophilicity probe. This process has practical advantages because it does not require the characterization of different products for each nucleophile, and the ther modynamics of the process is independent of the nucleophile. Table I gives the kinetic parameters for the amine-catalyzed (Z)-5 to (E)-5 isomerization (equation 1) (13, 14). The k values are easily interpreted in terms of elec tronic and steric effects on a rate-determining nucleophilic attack. However, the very low ΔΗ* values suggest that the observed rate constant is not ^ but a more complex expression, and the internal rotation step k may be ratedetermining. In view of this, this process should not be used as a probe. Very low activation enthalpies in several vinylic substitutions [e.g., ΔΗ* = 0.8-2.0 kcal m o l for the reaction of the para position of N,N-dialkylanilines with tricyanovinyl chloride in chloroform (15)] may also indicate a composite rate constant.


x

2

rot

- 1

R NH + o-MeOC H

R NH

2

6

2

4 N

.C0 Et 2

H

o-MeOC H J 6

fc

CN

C0 Et

4v

*-i

k^

2

H

CN

(Z>5 (D

o-MeOC H R NH 6

4

CN

2

X

C — C

o-MeOC H 6

v.

\:0 Et

4

^ k > 1

2

CN .C=C

H

+ R NH 2

\ o E t 2

(E)-5 Equation 1 Finally, whereas most vinylic substitutions proceed via Scheme I, the nucleophilic attack and leaving-group expulsion may be concerted in rela-


402

NUCLEOPHILICITY N

Table I. Kinetic Parameters for the (Z)-5 ^ (E)-5 Isomerization in Benzene at 40 °C (14) Parameter

Ru NH i-Bu NH 2

10% (L mol-i s-i)

750

ΔΗ* (kcal mol-i)

4.4


-AS* (eu)

43

2

149 2.2 53

Bu N 3

i-Pr NH 2

CHN 5

5

2,6-Lutidine

10.6

5.8

1.1

0.09

2.1

4.0

2.5

2.6

54

58

63

66

tively unreactive systems (16). The nucleophilicity scales for processes that involve and that do not involve a C - X bond cleavage in the rate-determining step should not necessarily be identical, and data for processes of Scheme I and for a suspected concerted vinylic substitution should not be combined. Taking into account these reservations (as much as possible), we searched the literature to answer the following questions: (1) Is there a substrate-independent nucleophilic scale toward vinylic carbon? (2) If not, are different scales applicable for addition and substitution? (3) What is the role of electronic and steric effects and hard-soft interactions on the nu cleophilic order? Because of the lack of space, we will mention only briefly the solvent dependence of the nucleophilicity. In a search for a nucleophilicity scale, correlations of nucleophilic (17, 18) reactivities in terms of the Ritchies "constant selectivity" N scale, the Swain-Scott scale (19), or other scales should be attempted. A remarkable correlation with the N scale was reported recently by Hoz and Spiezman (20, 21). A plot of log k for the reaction of the fluorenylidene derivative 6 versus JV , which includes eight nucleophiles covering 11 orders of magni tude in reactivity (slower N u = M e O H ; faster N u = N in Me SO), was linear. Fewer nucleophiles gave a similar plot for 7, whereas 8 gave substitu tion of the nitro group by three nucleophiles and addition to C-9 by two nucleophiles. M e O " in M e O H gave reactions at both positions. The slopes for 6 and 7 were 1.23 and 1.29, and the conclusion is that a selectivity parameter should be incorporated in Ritchies equation. In spite of the position-dependent selectivity and the nonunity slope, the obedience to the N+ scale for 6 and 7 is remarkable. A n explanation in terms of an extensive electron transfer from the nucleophiles to the low lowest unoccupied mo lecular orbital ( L U M O ) substrates (e.g., 6) in the transition state was offered (20, 21). Few other attempts to correlate data with a constant selectivity scale were less successful. Ritchie studied the substitution of £rans-3-methoxy- (9) and £rans-3-(methylthio)acrylophenones (10) with nucleophiles (22). Ratios of nucleophilicities for two nucleophiles toward 9 and 10 were not constant, for example, k ~/k = 22 and 0.3, respectively, whereas a ratio of 7.4 is predicted from the Δ/ν* ". Correlations with N were not discussed, and we found them to be nonlinear. +

+

+

_

3

OH

2

MeONH

4

+


28. RAPPOPORT

403


Y

6, X = Y = N 0 7, X = Y = C N 8, X = H ; Y = N 0 Downloaded by MONASH UNIV on June 12, 2016 | http://pubs.acs.org Publication Date: July 1, 1987 | doi: 10.1021/ba-1987-0215.ch028

2

MeOCH=CHCOPh MeSCH=CHCOPh 9 10

2

MeOCH=CHCOC H OMe-p 11 6

4

The log k values were correlated with two other sets of data. When p l o t t e d against the log k for reaction of the [(p-dimethylamino)phenyl]tropylium ion with nucleophiles, two approximately parallel lines, one for reactions in M e O H and one for reactions with water, were obtained. A plot of log k for the reaction of 9 versus log k for the reaction of 2,4-dinitrophenyl acetate with several nucleophiles was linear; thus, similarities existed in the transition states for nucleophilic attack on activated vinylic and aro matic carbon. The substitution of the analogue 11 with imidazole, O H , n - B u N H ; and ethyl glycinate gave a linear log k versus N plot with a slope of 1.02 ± 0.23 (23). However, other nucleophiles, morpholine, for example, deviated from this plot. The possibility was raised that the N treatment is invalid for these systems. If the scale applies to another highly activated system, benzylideneMeldrum acid, 12, then the slope calculated for the pair of nucleophiles PhO~ and O H ~ is higher than unity, because log (fcpho-ÔH-) 1-39 whereas Δ Ν = 0.85, but the scale is lower than unity when calculated for the O H " - N 0 and P h O - H 0 pairs (24). -

2

+

+

=

+

2

2

CO-O £H

3

An extensive work by Friedman and co-workers (25-27) on the addition of amino acids and peptides to singly activated electrophilic olefins serves as


404

NUCLEOPHILICITY

an additional example for the operation of a constant selectivity relationship for closely related nucleophiles and substrates. The active nucleophile is the amino acid anion ( A ) (equation 2; R = H or M e ; Y = C N , C 0 M e , or C O N H ) and plots of log fc _ versus the pK of the acid are linear and parallel for addition to several R C H = C H Y systems ( β = 0.43) when the steric environments of the nucleophilic site are similar (26). For a few thio amino acids, β = 0.45 (27). Parallel lines were obtained in the addition of nucleophiles to the same substrate for amino groups attached to primary, secondary, and tertiary carbons (25). Three conclusions emerge from the data. (1) A nearly constant selectivity of pairs of amino nucleophiles or amino and thio nucleophiles of the same steric environment exist in their addition to different, but sterically similar, olefins. (2) Br0nsted plots with β < 0.5 reflect the response to basicity at a constant steric environment. (3) Steric effects decrease the reactivity of crowded nucleophiles. -

2

2

A

a

Νι1

Ν ι 1


Ν υ

- O O C C H C H N H + R C H = C H Y —• O O C C H C H N H C H C H Y -H+ OOCCH CH NHCH CH Y (2) 2

2

2

2

2

2

2

2

2

2

2

In the majority of reactions studied, a constant selectivity relationship does not apply. In the addition of morpholine, glycine, and M e O " to C H = C H X systems, X = P O ( O E t ) , C O N H , C N , C 0 M e , S 0 M e , C O M e , C O P h , and C H O plots of log k versus pK (MeX) are linear but not parallel (28); thus, the reactivity ratios for each pair of nucleophiles are not constant. The reactivity ratios of several pairs of nucleophiles in their reactions with different substrates are compared in Tables II-VIII. A constant ratio should indicate a Ritchie-type behavior. Each table reflects a different aspect of the nucleophilicity. Table II gives selected reactivity ratios for piperidine and morpholine, two amines of the same bulk that differ by 2.8 pK units in water. The ratios are not constant, and values between 1.5 and 22.3 were found. A characteristic feature is the decrease of the ratios from M e C N to tetrahydrofuran to E t O H (31). The lower values for substitution compared with addition in protic solvents may have mechanistic significance, but generalizations are unwarranted. In each case, β for these amines is low; this finding indicates an early transition state for the addition. 2

3

2

2

2

fl

fl

Ν ι 1

Table III gives fc _/fc ratios. The values for the three β-chlorovinyl ketones (35) demonstrate two important features. First, they increase in the dipolar aprotic solvent, by relative increase in the reactivity of the anionic nucleophile. Second, and less expected, the order of the ratios changes from N3 < p i p e r i d i n e for E - P h C O C ( P h ) = C H C l to N " > piperidine for the cyclic β-haloketone. Consequently, difficulties are ex pected in attempts to construct even a qualitative nucleophilicity scale toward vinylic carbon. N3

piperidine

3


28. RAPPOPORT

Nucle iphilicity in Reactions at a Vinylic Carbon Table II. Several

^ peridi„e/^ orphoiine p Î

Substrate 2

2

2

p-0 NC H C(OTs) = 6

C(C0 Et)

4

2

p-0 NC H C(OMs)=C(C0 Et) 2

6

4

2

(£)-PhC(Cl) = (E)-PhC(I) =

2

C(N0 )Ph 2

C(N0 )Ph 2

(E)-PhC(N0 ) =

C(N0 )Ph

2


2

2

.COO

C H

H 0

25

10.1

29

45

17.4

30

MeCN

30

15.2

31

THF

30

9.1

31

EtOH

30

5.5

31

EtOH

30

22.3

31

EtOH

30

3.2

32

EtOH

30

4.8

32

EtOH

30

3.4

32

20

1.5

33

20

3.4

34

50% M e S O 2

3

yi

PhCH = C X

C O O

PhCH=C(CN)

C H

50% H 0 2

3

50% M e S O -

2

2

50% H 0 2

Table III.

fc ,.(98% N

Reference

MeOH

2

CH =CHC0 Me

Ratios

τ (°c)

Solvent

CH =CHCN

2

m

405

EtOH)

fcpiperidiJEtOH)

{

A

)

a

n

d

t ,.(98% DMF) *piperidi„e(DMF) N

( B )

R a t i o s

Compound

Η

NC

0.04 ( E t O H )

J Ph

PhCO

= C

0.03

0.39

0.14

2.92

2.67

38.40

Cl

PhCO

Me

=c

/

COMe

c

of

"Reference 36. N o t determined Reference 35. b


406

NUCLEOPHILICITY Table IV. Several

k Jk vhs

Me0

Reactivity Ratios in M e O H at 0 ° C

Ε

2,4-(0 N) C H CH ==CHBr

13,445

2

2

6

3

a

p - M e O C H C O C H ==CHBr

540

— — — —

p-0 NC H S0 CMe =

43.3

128.8

p-0 NC H CH=CHBr

4,060

p-0 NC H CH=CHCl

1,069

2

6

2

4

6

4

28

p-0 NC H CH==CHF 2

6

4

6

2

6

4

4

2

CHBr

2

p-TolS0 CH=CHCl

6.3

2

13.7

p-0 NC H S0 CH =CHC1 2

a

6

4

0.14

16.2

p-TolS0 CH=CHBr


Reference

Ζ

Substrate

2

37 37 38 38 39 40 4

24.2

5, 6

17.1

5

N o t determined.

-

Table IV compares the reactivity ratios of a soft (PhS~) to a hard ( M e O ) nucleophile in vinylic substitution. P h S is always more reactive, and ratios lower than unity, as for 4, X = B r (4), are certainly due to elimina tion-addition with M e O . The ratios change by >2000-fold and are sensitive to the geometry of the substrate. A n important feature is that for β-halo-pnitrostyrenes the ratio decreases strongly with the increased "hardness" of the β-halogen (38). The lowest ratios are for the β-fluoro derivative, whereas the differences between the chloro and bromo compounds are not so large. This behavior is similar to that in S A r reactions. This behavior can be rationalized by symbiotic effects, which favor the soft-soft P h S - B r interac tion and the hard-hard M e O F interaction. A reactivity-selectivity rela tionship for vinyl bromides of different electrophilicities does not exist. Table V compares E t S and E t O " and shows similar features. The k ~/k ~ ratios are relatively low for the vinyl fluorides (41). Although values at the same temperature are not available for the heavier halogens, fc -(18 ° C ) / * - ( 0 °C) values for X C H = C H C 0 E t are 344 (Cl), 329 (Br), and 1991 (I) (42). The operation of steric effects is shown by the k _kl - ~ ratios of >20 in spite of the expected higher basicity of ί-BuS". A combina-

-

N

_

-

-

EiS

EtS

Et0

ElO

2

EtS

Table V. Reactivity Ratios for Substitutions in EtOH at 0 °C (41) ÊtS-

Compound

= CHCN (Z)-MeCF=CHCN (E)-MeCF=CHC0 Et (Z)-MeCF=CHCP Et

(E)-MeCF

2

2

&EtO-

fcf-BuS-

15.7 5.0 9.4 28.1

31.6 21.0 37.8 39.1

ÊtO-

2.0 4.2 4.0 1.4


f

BuS


30

substitution

TolS0 CH==CHOPh

p-0 NC H CH=C(Cl)Me

2

"Not determined.

2

4

substitution

PhS0 CH=CHBr

2

6

0 25

substitution

PhS0 CH = C H

2

2

20 25

addition addition

CH =CHCN

2

24

2

25

addition addition

CH =C(Me)COMe

2

C H = CHCOMe

Τ (°C)

Process

Substrate 4.0

15.4

5.4 (E); 9.0 (Z)

3.4 (E); 19.2 (Z)

6.1

—9.1

—

48

4 47

— —

45 46

—

44

43

Reference

49.6

3.3

8.1

(MeOH)

k

Me5

Me5

Kpràii-PrOH)

(MeOH)

Ei5

k (EtOH) k

Table VI. Reactivity Ratios of RO" in Vinylic Reactions



408

NUCLEOPHILICITY

tion of the symbiotic and steric effects makes E t O " a better nucleophile than f-BuS~. Again, the order of thio and oxygen nucleophiles seems to be substrate-dependent. Table V I shows that although the nucleophilicity of alkoxy nucleophiles follows their basicity, the ratios are substrate-dependent. Comparison of relative reactivities at constant steric effects in terms of a few selected Hammett s p values is shown in Table VII for ArS~ and in Table VIII for anilines. Although some of the data in Table VII are based only on two points, clearly the p values are structure-dependent. Moreover, these values show no clear trend. The reactivity of β,β-dihalovinyl sulfones are similar to those of the β-halovinyl sulfones, but their p values are much lower. The addition reactions with A r S " show higher p values than for most of the substitutions, but for the structurally similar vinyl sulfones, the p for the substitution is higher. In general, the p values for the anilines are signifi cantly higher, but this fact does not necessarily mean an earlier transition state for the anionic nucleophiles because the p values for the equilibrium acidities of the anilinium ions are higher than those for the thiols.

-

Table VII. Several p Values for Reactions of ArS with Electrophilic Olefins

Substrate

0

Process Τ (°C)1

p-ClC H S0 CH==CCl

2

s s

P-C1C H S0 CH=CC1

2

p-MeOC H S0 CH =

CBr

Solvent

b

N

p

Reference

0

MeOH

6

-0.8*

49

0

MeOH

l5

-0.72

e

50

S

30

MeOH

l5

-0.36

e

50

(£)-TolS0 CH=CHCl

S

0

MeOH

ί1

-1.55

5

PhS0 CH=CH

A

25

50% E t O H

(3

-1.22

51

6

6

4

4

6

2

2

4

2

2

2

2

2

(£)-ClCH=C(CN)Ph p-0 NC H C(OTs) = 2

6

4

C(C0 Et) 2

2

N-Ethylmaleimide

s s A

30

EtOH

ίl

-0.51

36

30

MeOH

ί1

-0.39

31

25

95% E t O H

;*

—2

52

fl

A represents addition; S represents substitution. ^Number of substituents studied. 'The best correlation is with σ . +

Table VIII. p Values for Substitution of Vinyl Halides by ArNH Substrate

Solvent

PhCOCH=CHBr ClCH=C(C0 Me) 2

2

(E)-PhC(Cl)=CHN0

2

p-0 NC H C(Br)=C(CN) 2

6

4

2

p-0 NC H C(Br) = C(CN) 2

6

4

2

T

(°C)

N«

P

2

Reference

i-PrOH

25

8

-2.35

53

MeCN

30

5

-2.40

54

MeCN

30

7

-2.99

55

MeCN

30

2

-3.5

31

THF

30

2

-3.5

31

"Number of substituents studied.


28. RAPPOPORT


409

The contribution of increased steric effects to a lower nucleophilicity was mentioned earlier. Russian workers (29, 56) who studied addition and substitution of a large number of amines with electrophilic olefins analyzed the reactions in terms of dual-parameter equations involving polar and steric effects. For example, substitution of the vinyl sulfone 13 by primary, secondary, and teriary amines (equation 3) obeys a single equation (equation 4) (56), where Σ σ * is the sum of the inductive effects of the amine substituents, and E is an isosteric parameter where the steric effect of an amine R R N H is taken as similar to E of C H R ^ . Twenty-two amines obeyed the equation with p* = —4.8 and δ = 1.70 where p* and δ are the sensitivity parameters to the inductive and steric effects, respectively. As a demonstration of the electronic effects, fc i i nine aniiine ~ P > whereas steric effects are reflected in the ^Εί ΝΗ^ι-ΡΓ ΝΗ °f approximately 3000 in spite of the similar basicities. Similar L F E R s were observed in other reactions (Table IX) (29). 1

2

N

2

s

1 0 4


/fc

i n

s

i t e

o f

t h e i r

s i m i l a r

s i z e

cyc ohexy ar

2

J

2

2

R R NH >p-0 NC H S0 CH=CHNR R (3) R R R N ^p-Ο Ν0 Η 8Ο 0Η=0ΗΝ^Ή 1

2

(Z)-p-0 NC H S0 CH=CHCl2

6

4

2

1

13

2

6

4

2

2

3

3

2

6

4

2

log k = log k + p*Σσ* + bE 0

(4)

N

Nevertheless, the less bulky primary amines are often less reactive than secondary amines. In addition to tolyl vinyl sulfone, ^ E t N ^ B u N H 2.9 in E t O H (57). A preferred solvation of the primary amine was held responsible for this result, and indeed, in the bulky, less solvating f-BuOH, the ratio decreases to 0.09. An interesting contribution of steric effects to solvation is the addition of benzenethiolate ions to N-ethylmaleimide in 95% E t O H (52). The reactivity ratio of the 4-H:4-Me:2-Me:2,6-Me derivatives is 1:2.16:1.6:1.6; thus, a small steric retardation is superimposed on a small electronic acceleration. However, the 2-f-Bu derivative is 8.7 times faster than its 4-f-Bu isomer. This finding was ascribed to a rate-enhancing steric inhibition to solvation of the anion, which raises its reactivity by more than the reactivity decrease due to crowding in the transition state. Both electronic and steric effects also operate in addition reactions of carbon nucleophiles. For addition of R C ( N 0 ) to methyl acrylate, the reac tivity order for R of 1 (Me) < 1.2 (Et) < 1.6 (Cl) < 3688 (F) was observed (58) and ascribed to the destablization of the ground state of the fluorocarbanion, for example, by a p(F)-p(C~) electron repulsion. The electronic effects are less pronounced in the addition of X C H C ( N 0 ) to methyl vinyl ketone, =

2

2

2

2

6

4

2

2

2



6

4

2

S

A EtOH

3

6

u

4

4

2

b

d

e

1.36

0.63

0.84

1.70

δ

2.07

3.58

1.67

4.00

logVo

0.98f 0.16 — — — 0.041

191 1.0 IlOf 0.19&

—a

(Z)-ClCH = C(CN)Ph, EtOH, 30 °C (36)

N O T E : T h e nucleophilicities are relative to piperidine for each substrate. "Not determined. X = Me. X = H. R = Me.

2

6

6

17.4 1.1 1.0 0.67* — 0.1P — 0.048 0.038 — 0.024

PhCH Sp-TolSPiperidine p-XC H S" p-XC H 0" ROMorpholine Bu NH c-C H NH SCNN -

2

(Z)-TolS0 CH = CHCl, MeOH, 0 °C (5)

2

4.0

3.4

3.9

4.8

—p*

Table X. Nucleophilicities in Substitutions of Chloroolefins

A represents addition; S represents substitution. Number of amines used in the correlation.

2

10% E t O H

2

H 0

PhCl

Solvent

Nucleophile

b

fl

2

TolS0 CH=CH

4

A

6

2

=CHC1

p-MeOC H COCH = C H

2

A

2

Process*

CH =CHCN

(E)-p-0 NC H S0 CH

Substrate

13,625 1.0 5,875< 6.3; f-BuS" > E t O ~ order can be taken from Table V. In the substitution of fran5-3-methoxy-4 -(dimethylamino)acrylophenone, *OH^morphoiine °- > > morpholine > O H " (64). In addition to substituted 12, the order H 0 « O H " < p - B r C H 0 " < P h O " was established (24). The order M e O " > C N in M e O H for 6 and 7 can also be added (20, 21). In the basic epoxidation of o-chlorobenzylidenemalononitrile, where the nucleophilic species is X O ~ (X = CI, OH), the reactivity order is H O O " > C l O ~ (65). In addition to acrylonitrile, the relative order is piperidine (51) > S 0 - (18) > B u N H (0.76) (29, 66), whereas in the Michael addition to acrylonitrile, the reactivity order is M e O ~ > C H ( C O M e ) > C H ( C O M e ) C 0 E t (67). We tried to construct a qualitative nucleophilicity scale by combining the data for the three main systems of Table X and addition of the other data from the short reaction series. In most cases, the relationship between a nucleophile from the main series and only one of the nucleophiles in the short series is known. Hence, our combined nucleophilic scale is given in Figure 1 in the form of two lines. The main one (in boldface type) is a single reactivity scale, whereas short series are introduced above in the appropriate places (other orders are H O O " > C l O ~ and F C " ( N 0 ) > R C " ( N 0 ) where


Ν υ

To]

pipendine

,

=

27

t n a t

is

2

6

4

-

2

3

2

2

2

2

2

2


2


2

PhCH S

i-PrO" > 2* 2

NH OH; > C N ~ >CH(COMe) 2

>

2

2

3

2

S0 -

>MeCOCHC0 Et

pyrrolidine >

2

Figure 1. A qualitative nucleophilic scale for reactions at vinylic carbon.

Cl-, Γ

6

n

>i-Pr NH 2

3

EtO" > SCN" > morpholine 2* MeO" > ~ P h O " > B u N H > c - C H N H > N " »

> OH-

τ ArS- > ArO" « piperidine >

EtS- > f - B u S -


2

H 0 > Br",

a ο r m Ο X

28. RAPPOPORT


413

Table XI. α and a' Values for Capture of a-Anisylvinyl Cations Formed in the Solvolysis of AnC(Br)=CRR' (69) α

—

Br

S0H

in

80% EtOH

TFE

in AcOH

Ion

0.0

b

0

4.3

394

0

2

21.7

78

3

An-é=Q=0

75.0

1200

158

An-(5=CH

Û 2

An-(Î=CMe An-(Î=CAn


a' — k _ / k

^Br-ÂcO-

a

b

2

A n = p-Anisyl Not determined.

R = M e , Et, or CI). We are well aware of the limitation of this series, such as the possibility of reversal of the order (hence the question mark before N ~ and the ~ sign for A r O ~ and piperidine) as a function of the substrate and the reaction conditions. These drawbacks were mentioned previously. Solvent effects that should be important were also neglected. We believe that a further study of a few selected series with a large series of nucleophiles would be very helpful in solving some of the discrepancies and in filling the gaps. 3

A n interesting conclusion is that in spite of the fact that the chlorosubstituted vinylic carbon is relatively soft, several of the reactive nu cleophiles of the Swain-Scott scale such as N ~ , Br~, S C N ~ , and S 0 ~ show relatively low nucleophilicity in Table X I . When a more quantitative scale will be available, comparing it with the nucleophilicity order toward acti vated aromatic carbon would be constructive. 2

3

3

Nucleophilicity toward Vinyl Cations A complementary part to the reaction with neutral, although polarized, vinylic carbon is the reaction of nucleophiles with vinyl cations 14 (equation 5). The data in this case are much more limited, for two reasons: (1) very few vinyl cations had been prepared with sufficiently long lifetime that allows their direct reaction with nucleophiles to be followed and (2) a very few capture experiments of a solvolytically generated vinyl cation by several nucleophiles were conducted. R

2

R

C=C

/ R

3

i

R

2

R 2

^

L

\ X

C=C-R

/ R

3

/ R

3

^

R

i

C=C

\ Nu

R

+

N

U

2 ^

y

/ R

3

C=C

(5)

\ R

14


1

414

NUCLEOPHILICITY

Four different probes gave short reactivity orders toward vinyl cations: (1) common ion rate depression in solvolysis; (2) competitive capture of solvolytically generated ions; (3) direct reaction of a vinyl cation with nu cleophiles; and (4) competition between intra- and intermolecular nu cleophilic capture. A short reactivity order is obtained in each case, but because of the different solvents and conditions the orders cannot be com bined to a single series. However, a selectivity rule that governs the relative reactivities toward different vinyl cations in terms of a constant selectivity or a reactivity-selectivity relationship can be determined. According to the Winstein-Ingold solvolysis scheme (68), the observa tion of a rate decrease in the solvolysis of R X by either the formed or an added X ~ ("common ion rate depression", CIRD) serves as evidence for product formation from an intermediate free vinyl cation R . The simplified solvolysis scheme, when ion pairs are neglected and both the solvent S O H and its conjugate base S O " may be present, is shown in Scheme II.


+

SOH 1

•ROS

*SOH fcion

RX

R +

s +

_ so—— *so

χ-

>ROS

Scheme II The rate equations for Scheme II are *

= kj(l

t

+ a'[X"]/[SOH]); a ' =

k = kj(l

fc^son

(6)

+ a[X-]/[SO-]); a = J ^ s o "

t

(7)

The appearance of C I R D is a relatively rare phenomenon because it is observed only when R is sufficiently selective to react competitively with the more nucleophilic X ~ that is present in low concentrations and with the less nucleophilic S O H that is present in much higher concentrations. The selectivity constants α and a ' are the ratios of the rate constant for the reverse reaction with X ~ (k_ ) to the product-forming rate constant (k or k -). Consequently, α or a ' could be used to evaluate the selectivity behavior. The experimental difficulties associated with the measure of α in vinylic systems, the question whether the capturing nucleophile in a buff ered solvent is S O H or S O " , and the reasons for the high selectivity are discussed extensively in reviews (69, 70) and will not be repeated here. The largest number of α and a ' values are available for the solvolysis of a-anisyl-p^-disubstituted vinyl bromides. Evidence exists from C I R D that product formation is mainly or exclusively from the free ion (69), and α and a ' +

x

so


SOH


28. RAPPOPORT

415

values for the derived ions (An = p-methoxyphenyl = anisyl) are given in Table X I . Clearly, Ritchie s constant selectivity (which requires that α and a ' will be constant for different substrates) does not hold. The ratios change strongly with the nature of the ion. Comparison of the solvolytic reactivities of the precursor bromides shows that a reactivity-selectivity relationship, which calls for a higher fc for the more selective ion (i.e., higher α or a ' accompanies higher fc ) does not hold. Instead, the selectivities are gov erned mainly by steric effects: the bulkier is the β-substituent, the higher is the a's in A c O H - N a O A c or the a ' in 80% E t O H and trifluoroethanol (TFE) (with one exception). This finding was ascribed to the severe steric hindrance to the in-plane approach of the nucleophiles to the vacant orbital. Because of this hindrance, a polarizable nucleophile such as Br~, which can form a bond from a longer distance than a less-polarizable harder nucleophile such as AcO~, becomes more reactive. The difference between the selectivities, that is, α (or α'), should therefore increase with the increased bulk of the βsubstituents as was indeed observed. What happens when the bulk of the β-substituents remains constant? Difficulties in obtaining the order of α values if their difference is small results, but for the anthronylidene derivatives 15 (Ar = A n , Toi, o-An, or Ph), R a p p o p o r t et a l . (71) showed that the log α values i n 1:1 A c O H - A c 0 : A c O " and the log a ' values in TFE-2,6-lutidine increase linearly with log k (equation 8). The solvolysis rate constant k should be close to log k (72), and for these structurally related systems, strong evidence exists that the products are formed from the free ion (71, 72). This apparent reactivity-selectivity behavior finds strong support in the study of the solvolysis and B r " exchange of 15, A r = A n or Toi, and of three triarylvinyl bromides in A c O H - A c O ~ - E t N B r (73). This technique meas ures independently k and α and is therefore superior to the C I R D method where k and α are obtained from a single experiment. The fc (exchange rate constants corrected for the natural decay of Br), k , and α values are given in Table X I I . Clearly, the α values for both series increase with the increase in k . Evidently, at constant steric effects, reactivity-selectivity behavior is obtained. ion


ion

2

t

t

ion

8 2

8 1

4

t

cor

t

ex

82

t

t

Ar Ο

C \

X

15


416

NUCLEOPHILICITY

log k ° = - 2 5 . 5 + 8.12 log a '

(8)

t

An interesting observation is that in the presence of a large excess of B r " , the reaction of AcO~ with 15, A r = A n , is of a second order (71). This result is a rare example of an S 2 ( C ) route where the cation-anion recom bination is rate-determining in a solvolysis reaction, and in principle, such a process could be used for obtaining directly rate constants for capture of vinyl cations. Common ion rate depression for solvolysis of R X with the same R but with different leaving groups X was followed only for a single system. From the α values obtained in the solvolysis of (£)- and (Z)-l,2-dianisyl-2-phenylvinyl-X, 16, in A c O H - A c O (equation 9), relative reactivities toward the derived ion 17 were measured (74) (nucleophile, relative reactivity): OMs~, 0.16; OAc, 1.0; C I " , 15.2; B r " ; 45.5; and A c O H , 0.0024. From other data, Γ will probably be at the top of a similar order (75) and 2,4,6-trinitrobenzenesulfonate at the bottom (76). +

N


-

An —X

AnC(Ph) = C(X)An 16

^

c

, \

k~ X

+

*AcO

^ = Ο Α η Ph 17

+ X"

* AnC(Ph)=C(OAc)An (9)

The order of these data is similar to the Swain-Scott order in spite of the different solvents and the degree of hardness of the electrophilic center.

Table XII. Reactivity-Selectivity Relationships from Exchange-Solvolysis Experiments in AcOH-NaOAc-Et N Br at 120 °C (73) 82

4

a

10%

Compound*

ΙΟ !*,/*»"

A n C = C(Br)An

22

114

21.7

±

( £ ) - P h C ( A n ) = C(Br)An

13

75

19.5

±

1.6

53

18.6

±

0.8

96

75.0

±

1.4

12.2

±

0.8

5

2

8.8

P h C = C(Br)An 2

0.7

Ο Ar 0

\

V— Cy

64 Ar =

Ar = û

An

= p-anisyl; Toi =

Toi

An

0.084

0.77

p-tolyl.


28. RAPPOPORT

417


Table XIII. Capture Ratios in the Solvolysis of 18a in Binary Solvent Mixtures at 35 ° C (77, 78) % TFE in TFE-H 0 2

1.50 1.43 1.25 1.45

97 94 90 80 a

% TFE in TFE-EtOH

ÊPH^TFE

90 80 70 60

11.0 9.4 11.5 12.2

(0.93) (0.85) (0.96)* (0.76)

T h e value for 18c is in parentheses. for 18b.


H.37

Interestingly, the order of the fractions of ion pairs returned from the 17·Χ~ ion pairs (0.47, 0.38, and 0.24 for X " = B r " , C l ~ , and O M s , respectively), which reflects the intramolecular nucleophilicity in the ion pair, is parallel to the α values (74). The order of return from ion-paired X " or from external X " seems therefore to be governed by similar factors. Solvolysis reactions of vinylic substrates in binary protic solvents are numerous (69), but in the majority of cases, the distribution of the two products is not useful for evaluating the relative reactivities of the two solvents. The main reason is that the vinyl ethers formed in H 0 - R O H mixtures, the vinyl formates, and sometimes the vinyl acetates formed in H C O O H - A c O H or A c O H - H 0 mixtures are frequently unstable under the solvolytic conditions. Their hydrolysis to the ketones will give erroneous capture ratios. In addition, in most cases the nature of the product-forming intermediate is not clear and it is frequently the ion pair. The only values that seem reliable to us are given in Table XIII. Solvolysis of 18a in buffered T F E - H 0 (77) and buffered T F E - E t O H (78) mixtures and of 18c in buffered T F E - H 0 mixtures (77) was conducted over an extensive solvent composition range. The ethers are stable under the reaction conditions and 18b forms the products from the free ion (77). The similarity of products from 18b and 18a suggested that products are formed in all cases from the free ion. The k ^ /k and k /k los calculated from the product ratios (cf equation 10) and found to be reasona bly constant in 97-80% T F E - H 0 and in 90-60% T F E - E t O H . A large change was observed in more aqueous solvents. -

2

2

2

2

r a t

H

0

TFE

Et0H

w

e

r

e

T¥E

2

ArC(X)=CMe 18a, A r = A n ; X = OTs 18b, A r = A n ; X = B r 18c, A r = o - A n ; X = OTs 2

fc

[H 0][ROCH CF ]

TFE

2

fc o H2

2

3

[TFE][ROH]


(10)

418

NUCLEOPHILICITY

The ratios of Table XIII give the approximate reactivity order E t O H (11) > H 0 (1.4) > T F E (1.0) toward A n - C = C M e and H 0 (0.9) T F E (1.0) for its o-methoxy analogue. The former order is reasonable in terms of nu cleophilicities of both species. The nearly similar reactivities of T F E and H 0 are somewhat surprising, but they do not differ much from the k /k values calculated for the solvolysis of 1-adamantyl bromide and f-BuCl (78). In a single unpublished study ( M . O k a , H . Taniguchi, and S. Kobayashi), Taniguchi s group studied the competitive capture of the vinyl cation formed in the solvolysis 19 in 0.1 Ν aqueous N a O H by several nucleophiles. C I R D studies showed that >90% of the products are formed from the free ion. The data that are given in Table X I V in terms of log (k ~/k ^) compared with Richie's ΔΝ+ values of the two nucleophiles. The agreement between only half of the values argues against correlation with N . 2

2

2

2

TFE

a


N

r

H2Q

e

0

+

Me C=C(Br)C H OCH COO-p 19 2

6

4

2

A "direct" determination of the relative nucleophilicities of neutral nucleophiles toward vinyl cations was recently reported (79). The vinyl cations 20a-c were generated by flash photolysis and their decay was fol lowed simultaneously by U V spectroscopy and photocurrent measurements. The similar rates, the absence of effect of oxygen, and the identical spectra of 20b formed from the precursor chloride and bromide argue strongly that the species studied are indeed the ions 20. R C=C-An 20a, R = A n 20b, R = Ph 20c, R = M e 2

The decay rates in M e C N increased in the presence of nucleophiles such as alcohols, water, and T H E The order of decay rates M e O H > E t O H > i - P r O H > H 0 > f-BuOH was established for both 20a and 20c and log k for 20c was linear with that for 20a with a slope of 0.83. The reactivity order of the alcohols probably reflects the increased steric hindrance to capture with the increased bulk of the alcohol (the deviation of H 0 was ascribed to cluster formation). Because 20a is more reactive than 20c, the reac tivity-selectivity principle applies for this limited series. A similar reactivity order was found recently for competition between intramolecular cyclization and intermolecular capture. The AgBF -assisted solvolysis of trimesitylvinyl chloride 21 in alcohols gives both the ether 23 and 2,3-dimesityl-4,6-dimethylindene, 24 (equation 11; Mes = 2,4,6M e C H ) (80). These compounds are derived from the trimesitylvinyl cation 2

2

4

3

6

2


28. RAPPOPORT

419


Table XIV. Reactivity Ratios [log (A -/k ~)] for Capture of Nu

OH

M e C = C - C H O C H C O O - p by Nucleophiles in 0.1 Ν NaOH at Room Temperature 2

6

Nu~

log

SCNN CNFN0 -

4

2

(k Jk _) Nu

0H

0.14 -0.57 -1.19 -1.97 -1.97

3

2

N+(Nu-) - N (OH~)» b 2.85 -1.08 -1.30 -1.71 +

N O T E : Data are from O k a , M . ; Taniguchi, H . ; Kobayashi, S . , unpublished results. F r o m reference 17. Not determined. a


fc

22 by capture and by cyclization on a β-ο-methyl group, respectively. The 23:24 ratios given in equation 11 strongly decrease with the increased bulk of the alcohol. Because the cyclization rate was assumed to be relatively sol vent-insensitive, the main effect is on the capture rate. A log (fc 0H^cyc) P ' for R = M e , Et, and i-Pr is linear with log k for the reaction of 20a with the three alcohols. Consequently, steric effects on the nucleophilicity play a similar role in both cases. o t

R

Mes \

Mes

Mes

Mes

Mes

/ AgBF \ \ / C=C • C=C-Mes— C=C / \ ROH / / \ Mes Cl Mes Mes OR 21 22 23 4

Mes

+

+ _ Nfe

^ 24

R O H 23:24 M e O H 89:11 E t O H 82:18 i - P r O H 24:76 f - B u O H 95

Mes

(H)

Other aspects of nucleophilicity toward vinyl cations are the site of capture of ambident ions and the easy intramolecular cyclization by omethoxy and o-thiomethyl substituents on a β ring. The extensively studied β-aryl rearrangement across the double bond could be regarded as intra molecular substitution by the aryl ring, and data are available on the relative rate of rearrangement and capture by the solvent (69, 70). These topics are not discussed here for lack of space but should be addressed in a more complete discussion of the nucleophilicity.


NUCLEOPHILICITY

420 Acknowledgment ts

I am indebted to my students who contributed to our studies on this topic. Thanks are due to H . Taniguchi for his permission to use the unpublished data of Table XIV.


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Nucleophilicity in Reactions at a Vinylic Carbon

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