Aromatic and antiaromatic interactions in rigid polycyclic systems : an orbital symmetry model description

Aromatic and antiaromatic interactions in rigid polycyclic

systems : an orbital symmetry model description

Citation for published version (APA):

Schipper, P. (1977). Aromatic and antiaromatic interactions in rigid polycyclic systems : an orbital symmetry model description. Technische Hogeschool Eindhoven. https://doi.org/10.6100/IR8747

DOI:

10.6100/IR8747

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AROMATIC AND ANTIAROMATIC

INTERACTIONS IN RIGID POLYCYCLIC SYSTEMS

AN ORBITAL SYMMETRY MODEL DESCRIPTION

PROEFSCHRIFT

TER VERKRIJGING VAN DE GRAAD VAN DOCTOR IN DE TECHNISCHE WETENSCHAPPEN AAN DE TECHNISCHE HOGESCHOOL EINDHOVEN, OP GEZAG VAN DE RECTOR MAGNIFICUS, PROF.DR. P. VAN DER LEEDEN, VOOR EEN COMMISSIE AANGEWEZEN DOOR HET COLLEGE VAN DEKANEN IN HET OPENBAAR TE VERDEDIGEN OP

DINSDAG 14JUNI 1977 TE 16.00 UUR

DOOR

PIETER SCHIPPER

DIT PROEFSCHRIFT IS GOEDGEKEURD DOOR DE PROMOTORS

PROF. DR. H.M. BUCK en

Aan mijn moeder

Ter nagedachtenis aan mijn vader

CONTENTS Chapter 1 Chapter 2 Chapter 3 General introduction References

Generation of 7-norbornenyl cations and the mechanism of their reaction with nucleophiles 2.1. Introduction

2.2. Preparation of norbornadienes substituted at the 7-position with elements of group VA

2.3. Generation of the 7-triphenylphosphonio-7-norbornenyl dication: a nonclassical dication

2.4. Experimental References

A Diels-Alder intermediate in the ionization reaction of 9-chloro-9-methoxy-endo- lo-[4.2.1.o2•5]nona-3,7-diene

3.1. Introduction 3.2. Synthesis

3.3. Generation and properties of cations derived from 9-chloro-9-methoxy-endo-tri cyclo[4.2.1.o 2 • 5 ]nonanes

3.4. Reaction products

3.5. Kinetics of the reaction of pyridine with various 9-chloro-9-methoxy[4.2.1.o 2 • 5]-nonanes 3. 6. Discussion 7 15 30

Chapter 4

Chapter 5

Summary

Samenvatting

Antiaromatic interaction in the 9-methoxy-9-bicyolo[4.2.1]nona-2,4,7-trienyl cation 4.1. Introduction

4,2, Reaction products

4,3, Kinetics of the reaction of pyridine with 9-chloro-9-methoxybicyclo [4,2.1] nonanes 4.4. Generation and properties of cations

derived from 9-chloro-9-methoxybicyclo-[4.2.1]nonanes and -bicyclo[4,4.1]un ...

de canes 4,5. Discussion 4.6. Experimental

References

Stereospecific reactions of the 9-phenyl-seleno-9-bicyclo [4. 2. 1] nona-2 ,4, 7-trienyl anion

5.1. Introduction

5.2. Preparation of the 9-phenylseleno-9-bi-cyclo[4.2.1]nona-2,4,7-trienyl anion 5.3. Stereospecific reactions 5,4, Discussion 5.5. Experimental References Curriculum vitae Dankwoord 58 83 97 100 103 104

CHAPTER 1

General introduction

One of the most significant advances in the study of sol-volytic mechanisms was the recognition by Winstein and Lucas1 that substituents which are not directly connected to the re-action center can strongly affect the rate and the stereo-chemical course of a reaction. If this phenomenon arises from an intramolecular nucleophilic attack of the functional group at the reaction center, it is known as "neighbouring group participation"2 • This participation may result in an increase in reaction rate. In this case the neighbouring group provides "anchimeric assistance". Three major classes of neighbouring groups can be chosen on the basis of the kind of electrons available for participation: the nonbonding electrons as present on oxygen, sulphur, nitrogen, phosphorus and the halo-gens; electrons provide? by a rr system and a electrons of a saturated bond.

An early example of a chemical consequence resulting from

R R TsO H 3

!

AcOH. R R TsO A cO

the participation of the rr electrons of a double bond is the enhanced rate of acetolysis of 3S-cholesteryl sulphonates (1), which proceeds 500 times faster than the acetolysis of satur ated 3B-cholestanyl compounds (2)3 • The former process proceeds

•

with retention, whereas the latter one occurs with inversion of configuration4 • The intermediate 3 has been described as a homoallylic cations, the homologue of an allylic cation, which has an additional methylene group between the double bond and the cationic center. It was further demonstrated that a proper orientation of the leaving group for backside attack by the double bond is critical. The 3a-cholesteryl derivatives (1a) are less reactive than the 3S derivatives (1) and give, as the principal product on acetolysis, cholesta-3,5-diene6.

R R

H

OTs

When the double bond is situated in a symmetric position with respect to the reaction center, even larger rate enhance-ments were observed7 • The neighbouring group participation of the double bond of anti-7-norbornenyl tosylate (5) results in a rate acceleration of 1011 with respect to the saturated analogue (4). The intermediate cation (6) has been described as a homoaromatic species, in which the overlap of p orbitals

4 5

gives rise to a set of molecular orbitals which are similar to the cyclopropenium cation.

Three types of homocyclopropenium ions can be chosen on the basis of the number of interruptions of the a framelc. The mono-, bis- and trishomocyclopropenyl cations, respectively

exemplified by the cyclobutenyl cationlc,a (7), the norbornen-yl cation (6)9 and the [3.1.0]hexennorbornen-yl cation (8)w.

w

.

.

7 6

A

~

8 The concept of homoaromaticity has been extended to bi-cycloaromaticity by Goldstein and Hoffmann in a series of papers in which they attempt to elucidate the nature of the interaction between ~ systems1 1 • In their study the fundamen-tal building block of an unsaturated compound is an intact conjugated polyene segment, which is designated in Figure 1 as an unbroken line, called a ribbon. Of the great variety of topologies which may be envisaged for the linkage of several ribbons, four have been selected. These topologies, the peri-cyclic, the spiroperi-cyclic, the longicyclic and the latiperi-cyclic, are depicted in Figure 1 together with some examples. For the pericyclic topology Hlickel's 4n+2 ~-electron prerequisite for cyclic stabilization does apply. The other topologies are pre-dicted to be stabilized if there are more stabiliz than destabilizing interactions between the ribbons. An interaction between two ribbons is stabilized, when 4n+2 ~ electrons are involved. Thus, the 7-norbornenyl cation (6) as well as the 7-norbornadienyl cation (9), respectively examples of the pericyclic and longicyclic topology, are stabilized ions.

The traditional tests for relative stabilities of inter-mediates are most indirect. The rate of solvolysis of a neu-tral precursor is usually compar~d with that of an appropria-tely hydrogenated derivative. However, the solvolysis of an

(..._____

0

Pericyclic topology

C

···~

.,,__,;

.n

~

..

~

6 8 Spirocyclic

topology Longicyclic topology

D

c____.: ..

_..

9 Laticyclic topology

n ...

g

....

n

,. . 'l... . . . ..

~

...

J Figure 1

this case it is difficult to decide which kind of activated complex is involved in the rate-determining step. Alternative-ly, the character of the activated complex is correlated to the structure of the corresponding ion which may be observed as a long-lived species in superacid media.

In this thesis the neighbouring group participation of rr and a electrons in polycyclic systems has been studied. Charge-stabilizing groups were introduced at the reaction center in order to prevent rearrangement reactions. In this way it was possible to identify the intermediates and to ascertain their relative order of stability. Thus, for the first time, the study of antiaromatic interactions appeared to be accessible along kinetic and spectroscopic lines.

charge-stabiliz-ing groups, derived from elements of group VA and VIA, at the 7~position of the norbornenyl system. Reaction of triphenyl-phosphine with the homoaromatic 7-norbornadienyl cation afford-ed 2,3-substitutafford-ed products as a consequence of charge deloca· lization, whereas the related reaction with the classical 7-methoxy-7-norbornenyl cation produced the ?-substituted tri-phenylphosphonium salt. The latter compound appeared to be a suitable precursor for the generation of the 7-triphenyl- , phosphonio-7-norbornenyl dication, a nonclassical dication.

In Chapter 3 the study of ionization reactions of

9-chloro-9-methoxy-endo-tricyclo [4.2.1.o2 •5]nona-3,7-diene

to-gether with some appropriate reference compounds is described, It was established that during the ionization of the diene anchimeric assistance is provided by an electron-delocalization process in which the two double bonds and one sigma bond are involved. Under solvolytic conditions no rearrangement react-ions took place, whereas in liquid so2 a rearranged structure was observed, which appeared to be in equilibrium with its neutral precursor. From this it was concluded that the struct-ure of the intermediate depends on the position of the gegen-ion.

In Chapter 4 the stability and bicycloaromaticity of the 9-bicyclo [4.2.1] nona-2,4,7-trienyl cation is discussed. Rate constants for the reaction of anti9chloro9methoxybicyclo

-[4.2.1]nona-2,4,7-triene and some appropriate reference com-pounds with pyridine were determined. The rate retardation of the triene with respect to the more hydrogenated derivatives indicates that the 9-bicyclo [4.2.1]nona-2,4,7-trienyl cation is destabilized by an antiaromatic interaction (4n electrons) between the cationic center and the butadiene moiety. This was confirmed by a study of the 9-methoxy-9-bicyclo[4.2.1] nona-2,4-dienyl cation under conditions of long life. PMR and CMR data indicate an asymmetric interaction between the 9-carbon and the butadiene bridge.

sta-trionyl anion generated from the corresponding phenylseleno ketal. Electrophilic addition reactions at this anion proceed stereoselective, consequent on a stabilizing aromatic inter-action (6w) of the anionic center (2w) with the butadiene bridge (4w). The highly preferential location of these 6w electrons controis the entrance of the electrophile.

References

1. S. Winstein and H.J. Lucas, J. Amer. Chern. Soc.,£.!_, 1576, 2845 (1939).

2. Reviews on neighbouring group participation:

a. B.C. Capon, "Neighbouring Group Participation", Quart. Revs. , , 4 5 ( 1 9 64) .

b. P.D. Bartlett, "Non-Classical Carbonium Ions", W.A. Benjamin, New York, 1965.

c. S. Winstein, "Non-Classical Ions and Homoaromaticity", Quart. Revs., 141 (1969).

d. P.R. Story and B.C. Clark, Jr., in "Carbonium Ions", Vol. 3, G.A. Olah and P. v. R. Schleyer, Ed., Wiley-Interscience, New York, N.Y., 1972, Chapter 23. 3. S. Winstein and R. Adams, J. Amer. Chern. Soc., 0, 838

(1948).

4. C.W. Shoppee and G.H.R. Summers, J. Chern. Soc., 3361 (1952). 5. M. Simonnetta and S. Winstein, J. Amer. Chern. Soc.,

22,

4183 (1955).

6. a. R.H. Davies, S. Meecham and C.W. Shoppee, J. Chern. Soc., 679 (1955).

b. C.W. Shoppee and D.F. Williams, J. Chern. Soc., 686 (1955).

c. J.H. Pierce, H.C. Richards, C.W. Shoppee, R.J. Stephen-son and G.H.R. Summers, J. Chern. Soc., 694 (1955). 7. S. Winstein, M. Shatawsky, C. Norton and R.B. Woodward,

J. Amer. Chern. Soc., 7, 4183 (1955).

8. a. T.J. Katz and E.H. Gold, J. Amer. Chern. Soc.,.§..§_, 1600 (1964).

9. M. Brookhart, A. Diaz and S. Winstein, J. Amer. Chem. Soc., ~. 3133, 3135 (1965).

10. S. Winstein, J. Sonnenberg and L. de Vries, J. Amer. Chem. Soc., .§J_, 6523 (1959).

11. M.J. Goldstein and R. Hoffmann, J. Amer. Chem. Soc., 93, 6193 (1971).

CHAPTER 2

Generation of 7 -norbomenyl cations

and the mechanism of their reaction with nucleophiles

2.1. Introduction

A vivid example of neighbouring group participation by nonallylic double bonds is found in the bicyclo

[2.2.1]

heptyl

(norbornyl) series 1,2. The relative rates of acetolysis of 7-norbornyl tosylate (4) and the unsaturated analogues syn-7-norbornenyl (10), anti-7-norbornenyl (5) and 7-norbornadienyl tosylates (11) are shown below:

T~

_£;'

T~

Th

f.

j

4 10 5 11

k _rel 104 1 0 11 1 014

The rate acceleration noted for 10 was attributed2 to cr parti-cipation of the

c

₁

-c

₆ bonding electrons, anti to the tosylate group, which afforded the incipient allylic cation 12. The i11creased acceleration and the retention of configuration of 5 and 11 were ascribed to rr participation of the double

12

bond anti to the tosylate group 1 . The intermediate cation 6 shows nucleophilic attack (AcOH) from the rearside, since

in-activated complex (Chapter 5).

T~

AcOH

6

The structure of the intermediate cation (6) has been the subject of major controversy. When anti-7-norbornenyl tosylate

(5) is solvolyzed under nonequilibrium conditions, tricyclic products (13) were obtained predominantly.

5

~

D

This was interpreted by H.C. Brown3 _{as an indication of two} tr lie cations in rapid equilibrium (14), whereas S.

Win-stein~ described the cation in terms of a bishomocycloprope-nium structure formed by the overlap of three carbon 2p orbi-tals at

c

₂,

c

₃ and

c

₇, as visualized in 6a. The latter

inter-14

pretation was supported by the direct observation of 7-norbor-nenyl cations in superacid solution. The PMR spectrum of 6 in FS0 3H-S0 2 indicates considerable positive charge at the

c

2 and

c

_{3 positions}5 • This could still be consistent with both inter-pretations. However, the PMR spectrum of the 2-methyl-7-nor-bornenyl cation 15 shows almost unchanged resonances of H₃ and H7 and therefore is inconsistent with the tricyclic structure 16 in spite of the generation of a tertiary cation at

c

2. Thus these observations are in support of the nonclassical

represen-tation as implied in 156.

Introduction at

c

_{7 of a charge-stabilizing substituent,}

e.g. p-anisyl, appeared to cancel neighbouring group partici-pation7. The 1011 rate difference between 4 and S is leveled to a factor 3 in 18 and 19.

Moreover, the solvolysis of 19 is not stereospecific, but provides an epimeric mixture. If less stabilizing groups are introduced at the 7-position, the influence of the double bond on the reaction rate increases. From this it was conclud-ed that r. part ion is strongly related to the electron demand of the incipient carbonium ion7

In order to get more insight into the nature of non-classical cations, the introduction of groups which are able to stabilize positive charge, such as derivatives of phos-phorus and the heavier elements of group VA and VIA, has been examined. A similar method has proved to be successful in the oxidation of diphenylmethyltriphenylphosphonium methylide when the related radical and dipositive ion were formeds.

2.2. Prepoyation of norbornadienes substituted at the ?-position with elements of group VA9,10

of group VA and sulphur to a solution of the 7-norbornadienyl cation (9). The nucleophiles are mentioned in Table I. Cation 9 was generated according to the method of Story and Saunders1 1 by treatment of a solution of 7-norbornadienyl chloride in liquid

so

_{2 with AgBF 4} at -70°. The reaction of the 7-norborna-dienyl cation with the nucleophiles was observed by PMR.

Re-Cl~

£I:?

£1$

-~·.

9 + Ph3P~

£lf

Table I PMR spectral dad' for 7-substituted norbornadienes in liquid so

2 ( lJ values)

~

3 6 2 Compound X H 2,3 H 7 Other + 20a S(CH 3)2 6,98 6.94 4,04 (m) 3.87 2. 87 (s, CH3) (t,J=2.1) ( dt,J=O. 5, 1. 9) (t,J=1.6) + b S(C6H5)2 6,95 6,93 3.88 (m) 4.62 7.45 ( m, phenyl) (t,J=2.2) (dt,J:0.4, 1.9) (t,J=1.4) c k(C

6

H

5

~ 7.10 6.60 4.20(m) 4.20 7. 65 (m, phenyl) (t.J~2.0) (dt,J:O.S, 1.9) (t,J=1.4) d _{Sb(C6HS)3 7.08} 7.00 4.40(m) 4.43 7. 72 (rn. phenyl) (t,J=2.0) (dt,J:O.S, 1.9) (t, J=l. 4) + e _{Bi(C6H5)3 6.80} 6.40 3. 70 (m) 3.68 7.54 (rn, phenyl) (t,J=2.1) ( dt,J:O. s, 1. 9) (t,J=1.4) + NC 5D5 6,82 6.60 4.40(m) 4.42 (t,J=2.2)

• J values refer to the observed line spacings in Hz and are not necessarily the true coupling constants.

markably, triphenylphosphine and pyridine afforded decomposi-tion products only, as indicated by the appearance of broad upfield-signals, whereas the other nucleophiles produced 7-substi tuted norbornadiene salts. The PMR data of 20 (a.- are summarized in Table I. The assignments were made on the basis of a long-range coupling between the top proton and one of the vinylic proton pairs, which coupling only exists in "W" type configuratiorP

Using the reaction conditions mentioned previously, all compounds were stable and two of them (20a,f) could be ob-tained in crystalline form. The compounds 20a and ZOe appeared to be suitable for substitution at the ?-position with pyri-dine (20f). However, a similar procedure with triphenylphos-phine failed. This remarkable behaviour of triphenylphostriphenylphos-phine towards the 7-norbornadienyl cation motivated the study of reactions with other tervalent phosphineslO. It appeared that reaction of phosphines with donating substituents like

P(n-C₄H₉)₃, P(OCH_{3) 3 , P(C 6H5) 3 and P(C6H5) 2Cl with the cation} leads to decomposition of the ion. Phosphines with

electron-Table II PM:R spectral data for 7-substituted norbornadiene phosphonium compounds in liquid so

2

''

"''"~'

x'b,_ '

6~

X 4 H7 JPH(Hz) + PBr 3 7.10 7.00 4.40 4.38 42 + PCJ 3 7.00 6.96 4.42 4.28 35 + P(C 6H5)Cl2 6.90 6.50 4.20 4.10 15 + P(Cls>3 7.30 6.52 4.34 4.62 14

withdrawing substituents, as mentioned in Table II, give 7-substituted norbornadiene phosphonium salts.

Only the bicyclic phosphine P(OCH

2)3CCH3 seems to show a dif-ferent behaviour. In this case the decrease in basicity is due to introduction of molecular constraint on quaternization of the phosphorus atom13,

It is known that reaction of the 7-norbornadienyl cation with nucleophiles under nonequilibrium conditions gives both

7- and 2,3-substituted products3 •14. It appeared that the

pro-duct ratio varies with the nature of the nucleophiles. Strong nucleophiles react at the 2,3-positions, weak nucleophiles at the 7-position1 4 . Therefore, the absence of 7-substituted products with the more nucleophilic phosphines may indicate substitution at the 2,3-positions. However, no evidence was found for the formation of tricyclic products in the previous reactions in liquid

so

2. Perhaps their instability under the prevailing conditions leads to decomposition. For this reason the reaction with P(C₆H₅)₃ was carried out in dry acetone in which the intermediate tricyclic product appeared to be more stable: Table III P·ositions PMR CMR PPh3,AgBF4 CH30CH3

NMR spectral data for compound 21 in acetone-d

0 ( 8 values) 7 7.26 6.46 4.47 4.61 147.55 143.53 53.33 77.20 7.85 121.5, 129.8, 135.2

Compound 21 is characterized by its NMR spectral parameters as summarized in Table III. The IR spectrum shows a C=C

stretch--1

ing bond near 1570 em characteristic of a norbornadienyl system. Compound 21 was isolated in a pure state. Spectral

parameters of compound 22 were obtained from mixtures of 21 and 22. In the IR spectrum of the mixture a C=C stretching was observed at 1615 cm- 1 . This band, which is very strong, points to an asymmetrically substituted double bond. The PMR spectrum of 22 show~ a perturbed doublet (two protons) at 6.33 ppm, a broad multiplet at 3.18 ppm (three protons) and a multiplet at 1.85 ppm (two protons). Extra aromatic signals were also ob-served. The CMR spectrum shows, apart from the aromatic sig-nals, two absorptions near 49.5 and 50.5 ppm, to be ascribed to vinylic carbon atoms. Moreover, five signals were observed in the aliphatic region between 85 and 150 ppm. The overall spectral evidence suggests a structure as depicted above. Specific assignments in the CMR spectrum were not made with the exception of a signal near 85 ppm which is tentatively ascribed to

c

₄(J_{13C_ 31 p=100 Hz). Compound 22 slowly}

decom-poses at room temperature. Dissolution of compounds 21 and 22 in liquid so2 also leads to decomposition of 22, whereas compound 21 is completely stable. Thus it would appear that 22 is the intermediate species in the reaction of triphenyl-phosphine with the 7-norbornadienyl cation in liquid so₂. It can be concluded that the reaction of the nucleophiles given in Table I and II, is thermodynamically controlled which re-sults in ?-substituted products. In contrast, the reaction with triphenylphosphine is more kinetically controlled, lead-ing to 2,3-substituted products in liquid so₂ and both 7- and 2,3-substituted products in dry acetone.

2.3. GenePation of the 7-tPiphenylphosphonio-7-norbornenyl dication: a nonclassical diaation15

Stabilization of charge by double bond participation in 7-norbornenyl cations decreases with increasing electron-donating ability of the 7-substituents (Section 2.1). Indeed, reaction of triphenylphosphine with 7-chloro-7-methoxynorbor-nene (23b,c) in liquid so₂ gives rise to ?-substituted

pro-pation in the intermediate 7-methoxy-7-norbornenyl cation (25) (vide infra).

Reaction of 7,7-dimethoxynorbornene (23a) with PC1₅ yields a mixture of e~imers of 7-chloro-7-methoxynorbornene, 23b (76%) and 23c (24%), which reacts rapidly with triphenylphosphine in liquid 60°) to yield a mixture of the epimeric phospho-nium salts 23£ (28%) and 23g (72%). At -60°, the ratio of the epimers does not change, but at ca -14°, compound 23g isomerizes to 23f. The latter one could be obtained in crystalline form at room temperature. Roth isomers 23f,g produce the dication 24 in FS0

3

H-so

2 at -60°. Quenching of this dication with me-thanol yields 23f only (Scheme I). The structure of compounds 23 was confirmed by their PMR and CMR spectra (Table V). The structure of cation 24 was assigned by comparing its PMR spec-trum with that of the 7-norbornenyl cation (6)14_{a and the} 7-methoxy-7-norbornenyl cation (25)14_{f (Table IV). In the} spec-trum of 24 all resonances occur downfield with respect to the corresponding resonances of 6. This effect can be ascribed to the o- and o-electron withdrawing ability of the positive

Table IV PMR spectral data for7-norbornenylcat!ons In FS0

3H-So2 ( 8 values) R + P(C 6H5)3(24) H (6) OCH 3 (25) H 2,3 7.45 7.07 6.58 H 1,4 4.63 4.24 3.70 3.47

+kA

z;C)a

6 2 2.8-3.1 2.44 2.2-2.4 H Sn,6n 2.2-2.5 1. 87 1.6-1.8 Other 7.65 (phenyl) 3.24 (H 7) 4.64 (OCH 3)

Scheme I

CH;t;H3

23a

l "''

:£H3

₊

CH;s

23c 23b

1

""'·'''so,

+ ₊

Ph?t;H3

+

CH;sh3

23g 23f 24

Formation of the 7-triphenylphosphonio-7-norborne-nyl dication

1\)

Table V PMR and CMR spectral datd' for compounds 23

( o

values) .j>.

d)

3

6 2

Compound R _R2 Solvent Position 2,3 1,4 5,6 7 Other

1

23a OCH OCH

3 CDCJ3 PMR 5.96 2.74 (m) 1.90 (m,ex) 3.15 ( s) 3 ( t,J=2. 5) 1.05 (m,en) 3.11 (s) CDC! CMR 134.0 44.9 23,7 119.6 52.2 ( 1) 3 _{49.5 (2)} 23b OCH Cl CDC! PMR 5.95 2.93 (m) 1.85 (m,ex) 3.32 (s) 3 3 ( t,J=2. S) 1.05 (m,en) CDCJ 3 CMR 135.6 51.6 23.5 121.5 53.2 23c Cl CDC! PMR 5.92 2.93 (m) 1.85 (m,ex) 3.25 ( s) 3 ( t, }=2. S) LOS (m, en) CMR 134.0 51.2 24.4 122.3 55.5 + 23f OCH _P(C6HS)3 so 2 PMR 5.54 3.50 (m) 2.20 (m,ex) 3.01 7.65 3 (t,J=2.5) 1.15 (m,en) (d,J=2) (br s, 15H) so 2 CMR 104.1 48.5 22.8 103.2 54.4 c 134.6 (d,JPC=10) ( d,JPC=10) (d,JPC=47) cP134.8 C0130.0 (d,JPC=13) C:12o.6 (d,JPC=175) + 23g _flC6H5)3 OCH 3 so2 PMR 6.15 3.77 (m) 1. 2-1.6 2.68 7.65 ( dt, J=6, 2. 5) (br m) (d,J=2) (br s, 1SH)

triphenylphosphonium group, which results in an increased delocalization of TI electrons to the ?-position. In contrast,

the chemical shifts of cation 25 occur upfield with respect to comparable shifts of 6, which indicates absence of double bond participation. This is supported chemically by an ex-change reaction of the epimers 23b and 23c in liquid

so

₂ at higher temperatures and by the initial formation of a mixture of products in the reaction of 23b,c with triphenylphosphine. First-order kinetics were observed for the isomerization of compound 2 to 23f in liquid

so

₂ at -14° (k=2.7 x 10- -l). In liquid

so

₂ with 10 vol.% FS0₃H compound 23f is stable,

whereas 23g decomposes at a rate comparable to the rate of isomerization in liquid

so

₂. During the decomposition no 7-methoxycarbenium ion (25) was observed, although this cation was shown to be stable under these conditions by adding 23b,c. Thus, isomerization of 23g to 23f proceeds via the dication

24, which is not stable in liquid S0₂-FS0₃H (10:1). Double bond participation, which is increased by the PPh₃+ group, explains in this dication the irreversible formation of com-pound 23f.

2.4. Experimental

PMR spectra were obtained on Varian Model T-60A and HA-100 spectrometers, equipped with variable temperature probes. Chemical shifts are reported relative to TMS as internal standard.

CMR spectra were obtained using a Varian Model HA-100 NMR spectrometer, equipped with FT accessory and variable temperature probe.

• 7-Norbornadienyl fluoroborate (9)

A solution of 7-norbornadienyl chloride (1.0 g, 0.008 mol) in sulphur dioxide (10 ml) was added slowly during 15 min to a stirred suspension of silver fluoroborate (2.0 g, 0.01 mol)

complete, the solution was stirred for an additional 15 min. The volume was reduced by application of a vacuum. After fil-tration, the solution was transferred into an NMR sample tube.

• Reaction of 7-norbornadienyl fluoroborate with nucleophiles An equimolar amount of nucleophile was added to a solution of 7-norbornadienyl fluoroborate in sulphur dioxide in an NMR sample tube at 70°. After shaking vigorously, the PMR spectra were recorded at 20°. The PMR spectral data are· collected in Table I and II.

• 7-Norbornadienyltriphenylarsonium fluoroborate (20c) 7-Norbornadienyl fluoroborate was prepared in the usual way from 7-norbornadienyl chloride (2.0 g, 0.158 mol) and silver fluoroborate (3.11 g, 0.16 mol) in sulphur dioxide (40 ml). Triphenylarsine (4.9 g, 0.16 mol) was introduced into the solution and stirred for 30 min, whereupon removal of sulphur dioxide was started at reduced pressure. Concomitantly, me-thylene chloride (50 ml) was added in small portions. The resulting mixture was filtered and poured into dry ethyl ether. After filtration the precipitate was recrystallized from a mixture of chloroform and carbon tetrachloride to give 20c (5.8 g), mp 220-224°. PMR: see Table I.

• 7-Chloro-7-methoxynorbornene

To a stirred solution of 7,7-dimethoxynorbornene (13.53 g, 0.088 mol) in diethyl ether (15 ml) phosphorus pentachloride (18.72 g, 0.09 mol) was added in small portions at such a rate that the ether boiled gently. Sometimes heating and addition of some phosphorus oxychloride was required to initiate the reaction. Vacuum distillation provided pure 23b,c (6.89 g), bp 41-43° (2.0 mm). NMR: see Table V.

• 7-Methoxy-7-norbornenyltriphenylphosphonium chloride (23g) To a solution of 7-chloro-7-methoxynorbornene (1.0 g, 0.062

mol) in sulphur dioxide (10 ml) triphenylphosphine (1.65 g, 0.065 mol) was added. The solution was stirred for 30 min at -30°. Evaporation and recrystallization from chloroform and carbon tetrachloride yielded 23g (2.2 g), mp 182° (dec). NMR: see Table V.

References

1. a. S. Winstein, M. Shatavsky, C. Norton and R.B. Woodward, J. Amer. Chern. Soc.,]_]__, 4183 (1955).

b. S. Winstein and M. Shatavsky, J. Amer. Chern. Soc., 592 (1956).

c. S. Winstein and C. Ordronneau, J. Amer. Chern. Soc.,~. 2084 ( 1960).

2. S. Winstein and E.T. Stafford, J. Amer. Chern. Soc., 505 (1957).

3. H.C. Brown and H.M. Bell, J. Amer. Chern. Soc.,~. 2324 (1963).

4. a. S. Winstein, A.H. Lewin and K.L. Pande, J. Amer. Chern. Soc., ' 2324 (1963).

b. S. Winstein, "Non-Classical Ions and Homoaromaticity", Quart. Revs., 141 (1969).

5. M. Brookhart, A. Diaz and S. Winstein, J. Amer. Chern. Soc.,

~. 3135 (1966).

6. R.K. Lustgarten, M. Brookhart, S. Winstein, P.G. Gassman, D.S. Patton, H.G. Richey, Jr. and J.D. Nichols, Tetra-hedron Lett., 1699 ( 1970).

7. a. P.G. Gassman, J. Zeller and J.T. Lumb, Chern. Comm., 69 (1968).

b. P.G. Gassman and A.F. Fentiman, Jr., J. Amer. Chern. Soc., 2_!, 1545 (1969).

c. P.G. Gassman and A.F. Fentiman, Jr., J. Amer. Chern. Soc., 92,2549 (1970).

8. P. Schipper and H.M. Buck, Phosphorus,

1,

97 (1971). 9. P. Schipper and H.M. Buck, Phosphorus,

1,

93 (1971). 10. P. and H.M. Buck, Phosphorus, 3, 133 (1973). 11. P.R. Story and M. Saunders, J. Amer. Chern. Soc.,!±, 4876

12. E. I. Snyder and B. Franzus, J. Amer. Chem. Soc., (1964).

' 116 6 13. L.J. Vandegriend, J.G. Verkade, J.F.M. Penn~ngs and H.M.

Buck, J. Amer. Chem. Soc.,~ (1977), in press. 14. a. P.R. Story, J. Amer. Chem. Soc., 83, 3347 (1961).

b. H. Tanida andY. Hata, J. Org. Chem., 30, 977 (1964). c. H. Tanida, T. Tsuji and T. Irie, J. Amer. Chem. Soc.,

~. 864 (1965).

d. A. Diaz, M. Brookhart and S. Winstein, J. Amer. Chem. Soc., ~. 3133 (1966).

e. J.J. Tufariello, T.F. Milch and R.J. Lorence, Chem. Comm., 1202 ( 1967).

f. R.K. Lustgarten, M. Brookhart and S. Winstein, Tetra-hedron Lett., 141 (1971).

15. P. Schipper, W.A.M. Castenmiller, J.W. de Haan and H.M. Buck, J.C.S., Chem. Comm., 574 (1973).

CHAPTER 3

A Diels-Aider intermediate in the ionization reaction of 9-chloro-9-methoxy-endo-tricyclo [ 4.2.1.02,5] nona-3, 7 -diene

3.1. Introduction

The study of strained polycyclic small ring compounds has revealed unusual solvolytic reactivities, numerous skeletal rearrangements and novel degenerate isomerizations1 • In parti-cular, when three- and four-membered carbocyclic rings are incorporated in norbornyl systems, enhanced reactivities were observed1_{c. The geometry of the system is crucial, as may be} seen from the following examples:

B:b

_{B~ ~s}

1.7 37

26 27

Only the isomer with the cyclopropyl group in endo-anti posi-tion shows an assisted ionizaposi-tion. The intermediate involved has been interpreted in terms of a nonclassical trishomoaro-matic cation (26). However, the products of acetolysis were rearranged completely {27). Therefore, the alternative pair of classical ions (28) could not be excluded unequivocally2 • Similar observations were made for the four-membered ring. However, the rate enhancements observed are smaller than for the cyclopropyl compounds, whereas the product mixtures are

T?b

even more complex3,4.

When solely rearranged products are observed, it is dif-ficult to decide whether enhanced solvolytic rates arise from electronic factors or from factors, associated with possible low-energy routes prone to skeletal rearrangements. A charge stabilizing group, in particular methoxy, attached to the cationic center, has proved to be capable (Chapter 2) to

suppress cationic rearrangements. In view of these observations ionization reactions of 7-chloro-7-methoxy derivatives of nor-bornene with appropriately positioned four-membered carbocyclic rings (compounds 29-32) have been studied. The parent cations of the a-chloro ethers were generated as long-lived stable species by using polar solvents (e.g. liquid S0₂), Bronsted acids (e.g. H

2

so

4 or HS03F), Lewis acids (e.g. SbF5, SbC15 or AlC1

3) or mixtures of these. Furthermore, the ionization reactions under short-life conditions were studied quantitati-vely by monitoring the reaction of the a chloro ethers with pyridine in methylene chloride.

3. 2. Synthesis

The ketals 29a and 30a could be from ketone 33, which was readily available according to the method of Ant-kowiak and Shechters.

0

II

C H ' ) ) H3

CH

3

~H

3

£b

CH30H, BF3 hV 33 34 29a j

l

"'!''''

0

II

C H ' ) ) H3

CH~H

3

;})

CH30H,BF3 ~~ hv 35 36 30a j Scheme I I

Treatment of 33 with methanol in the presence of produced the triene ketal 34. Irradiation of 34 in

ether through Quartz, using a high-pressure mercury lamp, yielded ketal 29a. Selective hydrogenation of 33 on NiB

26 produced compound 35, which was similarly converted to the monoene ketal 30a (Scheme II). Hydrogenation of compound 37, prepared according to the method of Anderson et aZ. 7 on Pd-C, yielded 38. Dechlorination, using metallic sodium in THF-t-butyl alcohol8 , gave tfie monoene ketal 31a. Similarly, the benzocyclobutene compound 32a was prepared from the Diels-Alder adduct 399, obtained by the generation in situ of benzo-cyclobutene in the presence of 5,5 dimethoxy-1,2,3,4-tetra-chlorocyclopentadiene (Scheme III).

CH~O

OCH3 Cl Cl H2fPti-C

f.

Cl Cl

#

37

~~~'·©a

Cl Cl

CH~O

OCH_Cl 3 Cl Najt-BuOH Cl Cl 38 Scheme III

The ketals 2932a were converted to their corresponding a-chloro ethers 29b,c-32b,c by PC1

510, The PMR spectra (Table XI) revealed the existence of two isomers by the occurrence

R~~

~

R~~

~

R~~

~

R 1=Cl, R2=0CH3: b R 1;0CH3, R2;Cl: c

of two singlet methyl resonances. The ratio of epimers of the a-chloro. ethers is specific to each compound (Table IX). The epimers are in equilibrium as revealed by their interconversion in more polar solvents (liquid

so

2,

cn

2

c1

2), similar to the behaviour found for 7-chloro-7-methoxynorbornene (Chapter 2), and consequently are inseparable.

3.3. Generation and properties of cations derived from 9-chZoro-9-methoxy-endo-tricycZo[4.2.1.02'5]nonanes

Compounds 29, the most unsaturated in the series, exhibit unusual reactivities with respect to 30 32. Dissolution of 29b,c in liquid

so2

at -60°

c

resulted in the ionization of the C-Cl bond, as revealed by the NMR spectra (vide infra),

whereas the cations derived from 30b,c-32b,c could be obtained in strong proton acids like FS0

3H only. Although addition of

Liq,S02 40 29QC 40 29b,c 9 8 7 6 5 4 3 ppm F 2 PMR spectra of 9-chloro-9-methoxytricyclo[4.2.1.o2 •~-nona-3,7-diene in liquid

so

_{2 at various temperatures}

methanol to 29b,c in liquid so 2 gives exclusively the starting ketal 29a, the structure of the intervening cation appeared to be rearranged completely to 40. Moreover, cation 40 is in equilibrium with its covalent precursors 29b,c, as indicated by the temperature dependent PMR spectrum (Figure 2), which shows an increasing amount of 29b,c at higher temperatures. The decrease in dipole moment of liquid so 2 at increasing temperatures may account for this phenomenonll. When FS0₃H was added to the solution, 40 was observed only even at tem-peratures up to 10° C. However, in this medium two isomers of 40 were present (40a,b, vide infra), which apparently inter-change in pure liquid so

2, in which only one structure could be observed. Structure 40 was also formed in aprotic media. Addition of AlC1

3 to 29b,c in CD2

cr

2 gave rise to 40, which was stable up to 20° C. The assignment of rearranged structure 40 is based on the NMR data, compared to those of the closely related structure 41. The latter compound was prepared by dis-solution of its corresponding a-chloro ether in FS0

3H-so2. The NMR spectral data are collected in Table VI.

The PMR data of 40 in FS0₃H-S0₂ show two singlet methyl re-sonances in a 1:4 ratio whose mean position (o 4.76) is 1.4 ppm downfield relative to the mean methoxyl position(o 3.38) in the covalent precursors 29b,c. Such shifts are typical for methoxy groups attached to cationic centers. The small separation (0.04 ppm) between the two methoxy peaks indicates existence of syn

(40a) and anti (40b) forms, due to restricted rotation around the C-0 bond. This interpretation is confirmed by the CMR spectrum which shows two signals for each carbon in a ratio of 1:4. Furthermore, the PMR spectrum of both isomers of 40 shows comparable resonances at o 9.10, 7.57 and 8.87, 7.30 which are ~onsistent with methoxy stabilized allylic systems. The mutual coupling of 5 Hz indicates that the allylic

system forms part of a five-membered ringl2 , Ion 41, which occurs similarly in two isomeric forms 41a and 41b in a ratio of 1:2, shows analogous spectral data (Table VI).

(,)

Table VI PMR and CMR spectral datl for ions 40a, b and 41a, bin FS0

3H-so2 ( 8 values) (J) H3C "-0 a b c d e g h

~

PMR 8. 87 7.30 6.00 3.9-4.2 4.2-4.5 4. 78 (s) b _{(dd,J=S, 2) (d,J=S) (br m) (br m) (br m)} d _CMR 191.93 138.26 226.22 134.31 138.26 39.80 46.9 67.34 h f 39.61 45.4 40a O...----CH3

~

PMR 9.10 7.57 6.00 3.9-4.2 4.2-4.5 4. 74 (s) (dd,J=5,2) (d,J=S) (br m) (br m) (br m) CMR 196.33 134.28 225.44 135.29 136.86 40.61 46.4 67.34 40b 42.4 47.2 PMR 9.13 7.25 6.19 (m) 3.51(brm) 4.25 (br m) 2. 25 (br s) 4. 78 (s) (dd,J=5,2) (d1J=5) CMR 201.83 130.73 227.37 131.22 133.28 45,0 53.14 54.11 54.96 47.62 67.88 41a

~~

PMR 8.89 6.93 0 :

~

( dd, J=S, 2) ( d, J=5) 6.12 (m) 3.61 (br m) 4.05 (br m) 2.35(br s) 4.97 (s) •+

....

CMR 196.37 133.95 228.83 129.83 134.86 45.62 52.72 55.26 55.81 47.32 67.88 41b

and 32 are consistent with the unrearranged structures 42, 43 and 44. The data are collected in Table VII, together with those of the 7-methoxy-7-norbornenyl cation (25}.

Table VII PMR spectral dat~ for 9-methoxy-9-tricyclo[4. 2. 1. o2• 5]nonyl carbenium ions in F,SO H-SO 3 2 ( 8 values)

;~

~

pcH3

+:

J;,

6 2 25 H 1,6 H 2,5 H 3,4 3. 30 (m) 3. 30 (m) 6.50 (s) 3.67 (m) 3.50 (m) 3.10 (m) 2.17 (m,ex) 3.73 (m) 1.50 (m,e!!) 4.27 (m) 4.20 4,03 (m) (d,j=4.5) H H 1,4 2,3 3.83(m) 2.23 (m,ex) 3. 53 (m) 1. 78 (m,e!!)

• J values are expressed in Hz.

Other 2.11-1.56(m) 4.95 (s) 6.83 (t,J=2.5) 6.45 (t,J=2.5) H 5,6 6.82 (t,J=2,S) 4,80 (s) 4. 90 (s) 7. 33 (m, aromat) OCH 3 4.67 (s)

All spectra reveal the nonequivalence of the bridgehead positions, due to the restricted rotation around the C-0 bond13 •

positions. Apparently, the charge-stabiliz ability of the methoxy gr~up overwhelms the potential available " participa-tion of the double bond or the cr partie ion of the four-membered carbocyclic rings.

3.4. Re~otion products from 9-ohloro-9-methoxy-endo-trioyolo[4.2.1.o2•5 ]-nonanes

Compounds 29b,c yield products in nucl lie substitu-tion reacsubstitu-tions with an unrearranged structure. The reacsubstitu-tion of 29b,c with methanol afforded the starting ketal 29a, whereas the reaction with pyridine in CH

2

c1

2 at 0° C gave rise to a mixture of epimeric pyridinium salts 29d and 29e. At room temperature the isomer, with the pyridinium group syn to the

C

5

_H~H

3

~H,

29d j C5H5N + Ll j

CH~

5

_H

5 29e j

cyclobutene moiety (29e), isomerizes to the anti epimer (29d). A similar reaction pattern was tound for the reference com-pounds 30b,c-32b,c.

In contrast with the previous behaviour of 29b,c, the pyridinium salt of rearranged structure 40 (40c) was observed when the reaction was performed in CH 2

c1

2 with AlC13. Similar structures were obtained with other nucleophiles like (CH₃) under nonequilibrium conditions. These compounds were

• [ 2, 5] ( "' I

Table VIII PMR and CMR spectral data for tricyclo 4.3.0.0. nona-3,7-dienes ova ues)

X 3,4 7 8 9 1,6 2,5 OCH 3 Other + c 6H5N PMR 6.16 (m) 5.10 5.53 3.6-3.9 3.3-3.6 3.77 7.98-9.03 6.50(m) ( d,J=2. 5) (t,J=2. 5) (br m) (br m) (aromat) + (CH 3)2S PMR 6.10(m) 4.95 4.60 3.3-3.7 3.82 2. 66(s, CH3) 6.35(m) (d,J=2.5) (t,J=2.5) (brm) CMR 140.31 153.14 90.92 63.30 34.47 46.00 58.30 28.35 (CH 3) 137.70 44.09 44.09

•J values are expressed in Hz.

However, reaction with methanol afforded the starting ketal 29a again. This compound was also recovered after dissolution of 40c in methanol. The use of liquid

so

_{2 instead of CH 2}cl₂ -A1Cl3 gave similar results. The structure of the reaction

~H,

29b,c 40c

the unrearranged structures were observed.

3.5. Kinetics of the reaction of pyridine with various

9-chloro-9-methoxy-2 ,:)

[4.2.1.0 ~ ]nonanes

In order to study the reactivity of 29b,c under conditions of short life which proceed without skeletal rearrangements, the reaGtion of the a-chloro ethers of structures 29, 31, 32 and norbornene (23) with pyridine in CH₂c1₂ has been studied

);H'

23b,c

quantitatively. The reactions were monitored by PMR spectro-scopy. Under the solvolytic conditions used, all reactions afforded an epimeric mixture of pyridinium salts. The ratio's of epimers of the starting a-chloro ethers and those of the products were independent of time. They are collected in Table IX.

Table IX Composition of epimeric mixtures of starting a-chloro ethers (b, c) and their reaction products ( d, e) with pyridine ( %) Compound b c d e 29 92 8 63 37 31 72 28 35 65 32 69 31 69 31 23 76 24 33 67

In all cases, the epimeric ratio's of the products differ from those of the starting a-chloro ethers. Thus, the reactions proceed with racemization. Furthermore, the reaction rates appeared to be proportional to the pyridine concentration,

which indicates second-order kinetics. The second-order rate constants, together with some activation parameters, are summarized in Table X.

Table X Rate data for the reaction of pyridine with various 9-chloro-9-methoxytricyclo[ 4. 2.1] nonanes

Compound Temp. C 0 k x104 rel.k LlHf Llst 2

-1 -1 -1

I. mol sec ked mol eu

29b,c -11.0 9.23 20.0 108 45 11.4 -26.6 31b,c 20.0 19.3 8 32b,c 20.0 14.2 5.9 23b,c 20.0 2.4 35.6 7.3 12.0 -24.0

The large negative entropy of activation, observed for corn-pounds 29 and 23 is in accord with a second-order process and similar to other "Menschutkin" reactions 14 • As can be seen from the data in Table X the reaction rate of 29b,c is enhanced with respect to the norbornyl system 23. The rates of

endo-fused cyclobutane and benzocyclobutene systems are enhanced to a lesser extent. Thus, the order of reactivities in nucleo-philic displacement reactions is analogous to that observed under low-nucleophilic conditions.

3. 6. Dt~saussion

A. The stability of the 7-rnethoxy-7-tricyclo ~.3.o.o2•5]­ nona-3,9-dienyl cation

The relative ease with which the C-CI bond of compounds 29b,c are ionized with respect to the reference compounds 30b,c-32b,c, may be attributed to the stability of the ulti-mate ion 40, as revealed by its existence under relatively mild conditions (Section 3.3). The stability of 40, with respect

40

Probably, in 29+ no resonance stabilization is present in view of the results of the closely related ions 42, 43 and 44. The PMR data of the latter compounds did not reveal any charge delocalization (Section 3.3). However, the gain in resonance energy of 40 with respect to 29+ is reduced by the increased ring strain of the ring contracted structure . The difference in strain energy is probably in the order of 14 kcal/mol. This figure is the difference in standard free energy of

bicyclo-~.2.~ heptane and bicyclo[3.2.~ heptane systemsl5. The estim-ated resonance energy of an allylic system is 60 kcal/moll6, Thus, compound 40 will be stabilized substantially with

h d . +

respect to t e unrearrange cat1on 29 .

The existence of 40, under relatively mild conditions (liquid

so

₂), suggests an enhanced stabilization with respect to other comparable allylic systems. The related structure 41 does show quite different properties. Its preparation could only be achieved under strongly acidic conditions, such as

41

FS0_{3H-S0 2. Comparison of the NMR data of 40 with those of 41} (Table VI) may indicate some additional charge stabilization of the allylic system in 40. The differences in the allylic resonances (65) in the PMR spectra of both isomers of 40 (1.53 ppm for both) are s ficantly smaller than the comparable values for both isomers of 41 (1.88 and 1.96 ppm). The CMR

values for these positions show a similar trend (Table VI). The charge may be delocalized by interaction with the cycle-butene double bond. This of interaction has been proposed by Olah in ion 46 to account for the fluorosulfonation of the

c

₈

-c

₉ double bond of the protonated ketone 45,

HQ~·:

FS03H •+ •••• 45

H3C~···

.. .

.

: + ••••• ... '..j~

whereas the isolated double bond in 46, with the less stabil izing methyl group at the allylic center, remained unaffect-edl7. This kind of charge delocalization would be favoured in 40 relative to 41, in consequence of the shorter distance be-tween the double bond and the allylic cation. However, the NMR parameters for these positions in both ions do not give any indication fa.£ this phenomenon. Moreover, it is highly unlikely that this kind of interaction would result in a net stabilization of the system, because the interaction of an allylic system with the monoene unit is antiaromatic (4TI electrons). Another possibility of charge delocalization in 40 may proceed via the Walsh orbitals3 _{of the adjacent} cyclo-butane ring. This may be indicated by the downfield shift of the cyclobutane protons in 40 (o 3.9-4.5), with respect to the comparable positions in 41 (o 3.5-4.25).

40

to be a second-order process with racemization. This kinetic behaviour can be rationalized by assuming the reaction of pyridine with an intermediate ion to be the rate determining step: RX k1 R+x- k2 RN+ + _X

k_,

N k = k_{1 k 2 [NJ} obsd k_, + kz [N]

when k_₁ »kz (N), kobsd=k_{1k 2 (N)/k_1}, so that the reaction is first order in pyridine and second order overalll8.

However, the occurrence of an intermediate ion seems to be contradicted by the ionization of 29b,c under nonequilibrium conditions, which gave rise to the rearranged structure 40. Appa.rently, structure 29+ does not exist as a free carbonium

ion. Thus, it seems reasonable to assume that the intermediate ion, under solvolytic conditions, is not free but "encumber ed"19 • This behaviour can be best understood on the basis of Winstein's ion pair scheme20, According to this mechanism the

ionization of an alkyl halide A proceeds through a series of progressively more dissociated intermediates:

R X :;;;;=.===:=:: R+ X";;::====~ R+ II X-+====~ R+ +

X-A B C D

an "intimate" or "internal" ion pair B, a "solvent separated" or "external" ion C and a dissociated cation and gegen-ion D. Since the reactgegen-ion of pyridine with compounds 29b,c in CH 2c1₂ proceeds with racemization, it can not proceed through stage B. The close association of the anion X in the intimate ion pair should effectively block nucleophilic attack from that side. Consequently, attack of nucleophiles at this stage would be expected to afford products of inverted configura-tion. Because at stage D the rearranged structure 40 would arise, the reaction should proceed at stage C. The structural

dependence on the position of the gegenion X implicates that at those stages, in which R+ has its original structure, the

+

charge at R has not completely developed, probqbly because there is some interaction between the cationic center of R+ and the gegenion x-21. Apparently, this observation applicates also to the external ion pair stage C, where racemization is possible. This conclusion is consistent with the equilibration of 29b,c and 40 in liquid

so

2 and the formation of the starting R'+

RX+==~R+

II

X-+====~

R'+llx_/

II

Ill'

+ IV G II a

~

R'X v 40 lila .1GT

T

___ _t!lla

t

111 .1Gv v LlGv-1 - - - _j_ Reaction co-ordinate X

structure 29 after quenching ion 40 with methanol. When nu-cleophiles, such as C and CH₃0H, approach ion 40 in a thermo-dynamically controlled reaction, the rearrangement to its initial structure 29 precedes its collapse with the nucleo-phile. When stronger nucleophiles were used, such as pyri-dine, ion 40 was trapped prior to rearrangement. Apparently, this reaction is kinetically controlled. The reaction pattern is visualized in Figure 3.

Quenching of ion 40 at stage IV gives rise to the initial formation of ion pair III which can collapse to R'X (V). Alternatively, 40 in III may rearrange to structure 29+ re-sulting in the formation of ion pair II, which subsequently collapses to RX. The free energy of activation ~Gtiiia of the former process, an association of ions, will probably be small-er than that (6GTIII) of the lattsmall-er one, a rearrangement re-action (Figure 3). Therefore, in the first instance R'X (V) will be formed predominantly. However, when X is a weak nu-cleophile, such as Cl and CH₃0H in liquid

so

₂, R'X will dis-sociate again. This process will lead to the ultimate formation of RX (I), which is thermodynamically most stable (6Gv-I=14.5 kcal/mol, see Section 3.5 A). When X is a stronger nucleo-phile, such as pyridine, the dissociation of the initially formed compound R'X (V) does not take place and the kinetical-ly controlled product (40c) is observed.

Apparently, the interconversion of ion pairs II and III is induced by a balancing of the allylic resonance energy of 40 versus'its strain energy. At stage III the allylic reso-nance is encumbered by the presence of the anion (vide supra). The release of ring strain after ring expansion to 29+ will now overbear the delocalization energy of the encumbered allylic resonance, which results in a conversion of III to II. The interconversion of II and III even at temperatures down to -80° C, suggests a lowered transition state. If one of the double bonds of 29 is saturated like in 30 and 31 or forms part of an aromatic system ~32), rearrangement reactions are not observed. Apparently, the two isolated double bonds are

+

involved in the conversion of 29 to 40. These observations are in accord with several mechanisms which account for the observed path of rearrangement. One of these mechanisms is the concerted [3,3] sigmatropic shift ("Cope rearrangement")2 2 with one transition state, observed in neutral molecules such as semibullvalene (47)23.

47

Alternatively, the reaction may proceed through Woodward and Katz's intermediate24 _{which has been postponed to account for} the rearrangement of dicyclopentadiene-1-keton 48. This re-arrangement which proceeds through two transition states

in-0

~~

~

48 49

A4~

l(:~

0

volves fragmentation of the

c,-c2

bond to yield intermediate 49 which may reclose to give either 48 or SO. The Cope re-arrangement can be excluded, based on the observation of the kinetically controlled product 40c. This structure reveals that cation 40 is captured at the 9 position. At ion pair stage III (Figure 3), in which the nucleophile resides close to the

that this type of rearrangement does not occur. The involve-ment of intermediate 52, in which the interaction of the allylic system with the butadiene unit results in a 6n elec-tron homoaromatic system, accounts for all the observations. A rupture of the

c

₁

-c

_{2 bond in} 4~ yields intermediate 52.

CI-J:

~

_II 52

pcH

₃

tio

cr

1 2 40 Ill

Subsequently, the approach of a chloride ion, according to path a, produces ion pair II, whereas path b affords ion pair III. These processes depend clearly on the stability of the intermediate 52. When the double bond in the cyclobutene ring forms part of an aromatic system (32), no rearrangement re-actions were observed. This may be due to a less stabiliz

interaction of the resulting benzylic system with the butadiene moiety in the intermediate 53. Otherwise the rearrangement mechanism which has been encountered in 29, will lead to an untenable strained olefin (54), which furthermore has sacri-ficed the initial aromatic ring.

53 54

The fragmentation of the

c

₁

-c

_{2 bond in compounds 29b,c} to produce a stabilized intermediate 52, may provide anchi meric assistance to the ionization of the C-Cl bond, even under solvolytic conditions by which no rearranged structures were observed. The enhanced rate of the reaction between pyridine and compounds 29b,c with respect to the analogous 48

~H,

CIJ)'

c_5H5N

C

5

H~H

3

f..

-<}

_j

' ',

29b,c 55 29d,e

reaction of the reference compounds 31-, 32- and 23b,c, indeed suggests that the ionization of the C-Cl bond in 29b,c is as-sisted by an electron delocalization process as depicted in 55. This kind of participation does not imply a stereoselective reaction. Therefore, the observed epimeric ~ixtures 29b,c and 29d,e are consistent with this mechanism.

Table XI o PMR spectral dat.l' for bi-and tricyclic compounds in co 2c12 ( 8 values) a b c d e a b c 8 R1 R2 Ht 6 ' H 2,5 H3,4 OC:H3 OC:H3 2.66 (m) 2.98 5.60 (s) (d,J=4) Cl 3.10 (m) 3.16 5.86 (s) (d,J=4) OC:H3 Cl 3.10(m) 3.16 5.82 (s) (d,J=4) c 6H5N+ OC:H3 4.13 (m) 3.46 5.93 (s) (d,J=4) OC:H3 C₆H₅N+ 4. 37 (m) 2.83 5.80 (s) (d,J=4) OC:H3 OC:H ₃ Cl OC:H3 Cl

~

0 2.08 (m) 3.00 (m) 6.16 (s) 2.41 (m) 3;00 (m) 6.08 (s)

~~

~

a OC:H 3 OC:H3 2,73 (m) 2.73 (m)1.83 (m,ex) 1.23 (m,en) H OC:H 7,8 3 5.67 2.98 (s) (t,J=2.3) 3.10 (s) 5.93 3.43 (s) (t,J=2. 3) 5.95 3.33 (s) (t,J=2.3) 6.00 3,23 (s) (t,J=2. 3) 6.17 3.27 (s) (t,J=2.3) 1.60 (m,ex)3.20 (s) 1.22 (m, en) 1.60 (m,ex)3.33 ~s) 1.38 (m, en) 6. 30 3.03 (s) (t, J=2. 3) b Cl oc:H 3 3.00 (m) 2.83 (m) 2.00 (m,ex) 6.42 3.23 (s) 1. 33 (m, en) ( t, J=2. 3) Other 8.30 (m,3H) 9.83 (d,J=7,2H) 8.30 (m, 3H) 10.23 (d,J=7, 2H)

Table XI (continued) Rl R2 H1,6 H 2,5 H3 4 _• H7,8 OCH3 Other c OCH 3 Cl 3.00(m) 2.83 (m) 2.00 (m,ex) 6.42 3. 30 (s) 1.33 (m,en) (]=2. 3) d c 6 H 5N+ OCH3 4.06 (m) 3.17 (m) 2.17 (m,ex) 6.43 3.08 (s) 8.26 (m, 3H) 1.43 (m, en) (t,J=2.3) 9.73 (d,J=7,2H) + 8.26 (m,3H) e OCH 3 c6H5N 4. 30 (m) 2.83 (m) 2.46 (m,ex) 6.63 3.27 (s) 2.43 (m,en) ( t, J=2. 3) 10.00 (d,J=7,2H) a OCH 3 OCH 3 3.15 (m) 3.73 5.56 3.03 (s) 7.02 (m,4H) (d,J=4) (t,J=2.3) 3.15 (s) b Cl OCH 3 3. 33 (m) 3.81 5.64 3.43 (s) 7.12 (m,4H) (d,J=4) (t,J=2.3) c OCH 3 Cl 3.33 (m) 4,02 5.64 3.30 (s) 7.12 (m,4H) (d,J=4) (t,J=2. 3) d c 6H5N+ OCH3 4,20 (m) 4.10 5.68 3.25 (s) 7.05 (m,4H) ( d,J=4) (t,J=2.3) 8.45 (m,3H) 9.55 (d,J=7,2H) e OCH 3 c6H5N+ 4.45 (m) 3.51 5.85 3,45 (s) 6.96 (m,4H) ( d, J=4) (t,J=2.3) 8.45 (m,3H) 10.00 (d,J=7,2H)

:;s

5 1 2 6 23 R1 R2 H2 3 H H OCH3 Other ' 1,4 5,6 a OCH OCH 3 5,96 2.74(m) 1.90 (m, ex) 3.15 (s) 3 (t, J=2. S) 1.05 (m,en) 3.11 (s) b Cl OCH 5.95 2.93 (m) 1. 85 (m, ex) 3.32 (s)

Table XI (continued) Rl R2 H2 3 _• H 1,4 H 5,6 OCH3 Other c OCH Cl 5.92 2.93 (m) 1.85 (m,e.x) 3.25 (s) 3 ( t, J=2. 5) 1.05 (m,en) d C 6H5N+OCH3 6.14 4.07 (m) 2.20 (m,e.x) 3.20 (s) 9.14-8,30 (m,3H) (t,J=2. 5) 1.15 (m, eo) 10.00 (d,J=7,2H) e OCH 3 C H N+ 6 s 6.34 4.34 (m) 1. 2-1. s 3.26 (s) 9.14-8, 30 (m, 3H) (t1J=2.S) (br m,ex-en) 10.37 (d, J=7, 2H)

*J values are expressed in Hz.

3.7. Experimental

• 9,9-Dimethoxybicyclo [4.2.1] nona-2,4,7-triene (34)

Boron trifluoride etherate (0.5 ml, 48%) was added to a solu-tion of trienone 33 (1.0 g, 7.5 mmol)S in methanol (25 ml) at 0°. The mixture was allowed to stand overnight in a refrige-rator. After neutralization with saturated sodium bicarbonate at 0°, the solution was extracted with ether. The ether layer was washed.with saturated sodium chloride, dried (MgS0₄) and concentrated. The product was purified by chromatography on a silica gel column, eluting with ether-hexane mixtutes to give the dimethyl ketal 34 (0.95 g, 76%): &TMSCDC1 3 5.92 (m,4H), 5.21 (d,J=1.S Hz,2H), 3.12 (s). 3.07 (s) and 3.12 (br).

• 9,9 Dimethoxy-enda-tricyclo [4.2.1.o2•5]nona-3,7-diene (29a) A solution of ketal 34 (1.0 g, 5.6 mmol) in ether was purged with nitrogen and irradiated at room temperature for 4 hr with an SP 500-W Philips high-pressure mercury lamp through Quartz. A positive nitrogen pressure was maintained above the solution during the photolysis. The solution was filtered and concen-trated. The crude product was chromatographed on a column of

aluminum oxide, which was eluted with ether-hexane mixtures to give 29a (0.80 g, 80%): oTMS CDC1 3 5.87 (t,J=2.5,2H), 5.80

(s,2H), 3.10 (s), 2.98 (s), 2.98 (d,J=4), 2.66 (m,2H). • Bicyclo [4.2. ·11 nona-2,4-dien-9-one (35)

Dienone 35 was prepared by hydrogenation of trienone 33 using a nickel boride catalyst, which was obtained according to the procedure of Brown6. To a solution of nickel acetate (320 mg) in ethanol (20 ml) under a hydrogen atmosphere was introduced a solution of sodium borohydride (45 mg) in ethanol (20 ml). Hydrogenation was initiated by injecting trienone 33 (1.38 g). After the absorption of hydrogen (235 ml, 15 min) the reaction was stopped. The reaction mixture was poured into an aqueous solution of sodium bicarbonate (100 ml) and extracted with ether. The etheral solution was wa~hed with water, dried

(MgS0₄) and concentrated. Analysis of the crude product with GLPC and PMR indicated 92% conversion to dienone 35. The

mixture was chromatographed on a column of aluminum oxide with ether-hexane mixtures. A liquid product was isolated: oTMS CDC1₃ 5.74 (m,4H), 2.67 (m,2H) and 2.20 (m,4H).

• 9, 9-Dimethoxybicyclo [4. 2. 1] nona-2, 4-diene (36)

The ketalization of 35 was accomplished similar to the proce-dure described for 33. The product was about 95% pure according to GLPC and PMR. The material was not purified furtheron,

because of its easy conversion to ketone 35. NMR of 36: oTMS CDC1 3 5.93 (m,4H), 3.34 (s,6H), 2.75 (br s,2H) and 2.12 (m,4H).

• 9,9-Dimethoxy-endo-tricyclo[4.2.1.o2•5] non-3-ene (30a) Compound 30a was prepared as described for 29a from 36 (1.0 g). Work-up afforded 30a (0.82 g):oTMS CDC1₃ 6.16 (s,2H), 3.20

(s,6H), 3.00 (m,2H), 2.08 (m,2!-I) and 1.41 (br m,4H).

• 1,6,7,8-Tetrachloro-9,9-dimethoxy-endo-tricyclo[4.2.1.02•5 ]-non-7-ene (38)