Hückel and Möbius aromaticity in bicyclic systems

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Hückel and Möbius aromaticity in bicyclic systems

Citation for published version (APA):

Gillissen, H. M. J. (1982). Hückel and Möbius aromaticity in bicyclic systems. Technische Hogeschool Eindhoven. https://doi.org/10.6100/IR69545

DOI:

10.6100/IR69545

Document status and date: Published: 01/01/1982

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HUCKEL AND MÖBIUS AROMATICITY

IN BICYCLIC SYSTEMS

Proefschrift

ter verkrijging van de graad van doctor in de technische wetenschappen aan de Technische Hogeschool Eindhoven, op gezag van de Rector Magnificus, Prof. Ir. J. Erkelens, voor een commissie aangewezen door het college van dekanen in het openbaar te verdedigen· op

vrijdag 15 januari 1982 te 16.00 uur door

HUBERT MARIA JOZEF GILLISSEN

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DIT PROEFSCHRIFT IS GOEDGEKEURD DOOR DE PROMOTOREN

PROF. DR. H.M. BUCK EN

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Chapter I

Chapter 11

64

IV.1 Synthetia aonsidePations 64 IV.2 StePeoahemistPy of pPotonation 68 IV.3 NMR speatPosaopia investigations

of aaPboaations undeP ~ong ~ife

aonditions 10

IV.4 Disaussion 18

IV.

5

ExpePimental 81

RefePenaes and Notes 94

Sun:unary 97

Samenvatting 99

Curriculum vitae 101

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CHAPTER I

GENERAL INTRODUCTION

A concept, which has been of special interest for

or-ganic chemists, is the Hückel rule1_, _{which involves that}

for ground-state molecules with a cyclic array of atomie orbitals, 4n+2 electrens result in aromaticity and thermo-dynamica! stability. Fundamental in Hückel's reasoning is the large energy difference between ground-state and excited state(s) in a ring with 4n+2 electrons, whereas 4n electrens result in a smal! energy separation. This aspect has been nicely demonstrated in a quantitative way for the cycliza-tion of butsdiene using complete VB and MO calculacycliza-tions by van der Lugt and Oosterhoff2_, _{The same is also true fora}

cyclic array of orbitals with 4n and 4n+Z electrons, respec-tively, when this interchange is accompanied with an odd number of sign inversions for the orbitals in the ring. In the latter case, we are generally speaking of Möbius aroma-ticity: 4n electrens result in aromaticity. Using simple MO calculations, the Möbius aromaticity concept has been explored for a variety of reactions, which are commonly

known as Woodward-Hoffmann reactions3

'4•

It attracks attention that energy lowering of transi-tion states and stabilizatransi-tion of intermediates has been

hardly explained with the concept of Möbius aromaticity5_,

although the thermal conrotatory conversions and the thermal sigmatropie shifts with inversion of the migrating carbon are distinct examples for 4n electron aromaticity (Figure I).

(10)

b

Figure I: Transition state for a thermal aonrotatory con-version (~) and a thermal sigmatropie shift with

inversion of the migrating carbon (~).

Of course, ground-state Möbius aromaticity has never been observed in consequence of the steric strain, which imposes a sign inversion on a small cyclic polyene. One possible way to generate ground-state 4n electron aromaticity is the

preparation of bishomocyclic systems

l·

Sign inversion may

then be realized by a simple orientation of the carbon

p-orbital, which is homoconjugated with the two neighbouring carbons.

3

1

In fact, this resembles the transition state for the ther-mal [1

,3]

C and [1 ,4] C sigmatropie shifts.

In spite of the fact that the extended VB theory as was ~utlined by Oosterhoff et al. 6 _{is a direct tool in the}

search for the fundamentals determining aromaticity in the general sense, Möbius molecules seem to be exceptious or in other words their existence looks rare, whereas molecules possessing Hückel aromaticity are present in an overwhelming

(11)

quantity. A similar situation is encountered in

antiaroma-ticity7, i.e. 4n electrans in a Hückel arrangement or 4n+2

electrans in a Möbius cycle. From the work of Schipper and

Buak8 _{it appeared that if geometrical restrictions are}

di-minished, the system escapes the 4n electron Hückel

anti-aramaticity via 4n-2 electron Hückel aromaticity and the

simultaneous formation of a localized double bond (~).

Befare this fascinating observation Buak et aZ.9

investiga-ted the thermal D,j]shifts in cyclic systems with a pertu-bation approach and INDO calculations. It was clearly shown that the concept of Hückel aromaticity controls the supra-facial shift. Unfortunately, the antarasupra-facial shift was not discussed in a quantitative way. We may expect that the an-tarafacial shift results in Möbius aromaticity for the

transition state. Hückel

vs.

Möbius aromaticity is then

re-flected in the electron density on the migrating hydrogen. The value of this concept is clearly demonstrated when the

shift occurs between non-bonding carbons e.g. in the

supra-fadal [1,

s]

H shift in cycloheptatr.iene the hydragen carries

one electron, whereas in the suprafacial [1, 7] H shift, which is only of theoretica! interest, the electron density on hydragen increases.

In this thesis the concept of aromaticity is fully

explored with a number of experimental ex~mples. The systems

derived are cations and anions which demonstrate bishomo-conjugation resulting in Hückel and Möbius aromaticity. The

various structures were established by 1_{H and} 13_{C NMR}

mea-surements. Generally, the ions are derivatives of

bicyclo-~.2.1]nona-2,4,7-triene.

Chapter II deals with the chemistry of the

bicyclo-~.2.1] nona-2,4,7-trien-9-yl carbanion. According to

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besta-bilized by longicyclic interactions11

• The carbanions are

generated by the cleavage of arylselenoketals. This strate-gy leads to the introduetion of an arylseleno-group at the charge center. It is shown that the chemistry of the carb-anions is dominated by the stereospecific transposition of the negative charge from the anti-Cg carbanion to the aryl ring of the introduced substituent via proton transfer. Electrophiles tend to react with the èyn-Cg carbanion. This result is compatible with the notion of a bishomoaromatic

interaction12 _between

_Cg

_{and the diene moiety.}

In Chapter III the syn-c₁₀ carbocation derivatives of

bicyclo[4.2.1]nona-2,4,7-triene are introducedas possible model systems for the investigation of ground-state Möbius

aromaticity. 6-Hydroxy selenide derivatives of bicyclo~.2.1]

nona-2,4,7-triene were investigated in super acid media.

It is demonstrated that neighbouring group participation13

by selenium preelucles the formation of free c,o-carbocations. Instead, exocyclic olefins and selenenyl cations are produced in a solvent cage. This initiates a rearrangement reaction for which a mechanism is given.

Chapter IV describes the generation and investigation

of a-hetero-substituted

c

₁₀-cations. 13_{C and}1_{H NMR}

spec-troscopy suggest that the empty orbital at

c

_{1 0 is}

o.rienta-ted perpendicularly with respect to the mirror plane of the cations. The saturated analogues of these cations also adopt this configuration. The chemica! shift differences between the unsaturated cations and the saturated derivatives may

suggest a certain degree of charge delocalization via Möbius

(13)

References and Notes

1. E. Hückel,

z.

Phys., 1931 , ?0, 204.

2. a. W.Th.A.M. van der Lugt, L.J. Oosterhoff, Chem.

Com-mun., 1968, 1235.

b. W.Th.A.M. van der Lugt, Thesis, Leiden, 1968.

c. W.Th.A.M. van der Lugt, L.J. Oosterhoff, J. Am. Chem.

Soc., 1969, 91, 6042.

3. a. R.B. Woodward, R. Hoffmann, J. Am. Chem. Soc., 1965,

B?, 359, 2045, 2046, 2511 • 4511.

b. R.B. Woodward, R. Hoffmann, Angew. Chem., 1969, 81,

797.

4. a. H.E. Zimmermann, J. Am. Chem. Soc., 1966, BB, 1564.

b. H.E. Zimmermann, Accts. Chem. Res., 1971, 4, 272.

c. M.J.S. Dewar, Angew. Chem., 1971, 83, 859.

5. E. Parenhorst postulated a Möbius-type intermediate in the photochemistry of benzene: E. Farenhorst, Tetrahe-.

dron Lett., 1966, 6465.

6. W.J. van der Hart, J.J.C. Mulder, L.J. Oosterhoff, J.

Am. Chem. Soc,, 1972, 94, 5724.

7. a. R. Breslow, J. Brown, J.J. Gajewski, J. Am. Chem. Soc., 1966, BB, 1564.

8.

9.

b. M.J.S. Dewar, G.J. Gleich, J. Am. Chem. Soc., 1965,

B7, 685.

a. P. Schipper, H.M. Buck, J. Am. Chem. Soc., 1978, 100,

5507.

b. P. Schipper, Thesis, Eindhoven, 1977.

a. J.R. de Dobbelaere, J.M.F. van Dijk, J.W. de Haan,

H.M. Buck, J. Am. Chem. Soc., 1977, 99, 392.

b. J.R. de Dobbelaere, Thesis, Eindhoven, 1976.

c. W.A.M. Castenmiller, Thesis, Eindhoven, 1978.

10. a. M.J. Goldstein, J. Am. Chem. Soc., 1967, B9, 6357.

b. M.J. Goldstein, R. Hoffmann, J. Am. Chem. Soc., 1971,

93, 6193.

11. A longicyclic interaction is an interaction between

three formally isolated n-systems in a longicyclic to-pology10. The building bleeks of an unsaturated com-pound are intact conjugated polyene segments, the

(14)

so-called ribbons. These are designated as unbroken lines. The mode of interaction is depicted by broken lines. A typical example of a bicyclic system with longicyclic topology is the 7-norbornadienyl cation 3:

+

LongicyaLia topoLogy

12. For reviews on the subject of homoaromaticity see

a. S, Winstein, Chem. Soc. Spec. Publ., 1967, 21, ~.

b. S. Winstein, Quart. Revs. Chem. Soc., 1969, 23, 141.

c. P.D. Bartlett, Non Classical !ons, New York, 1965.

d. P.M. Warner, Topics Nonbenzenoid Chem., 1976, 2.

e. L.A. Paquette, Angew. Chem., 1978, 90, 114.

13. For reviews on neighbouring group participation see

a. B.C. Capon, Quart. Revs. Chem. Soc., 1964, 18, 45.

b. B.C. Capon, S. Mc.Manus, Neighbouring Group Partici-pation, New York, 1976.

(15)

CHAPTER 11

INTRAMOLECULAR ELECTRON TRANSFER IN 9-(ARYLSELENO)BICYCLO [4. Z

.1)

NONA-Z ,4, 7-TRIEN-9-YL AND -BICYCLO

(4.

Z

.1)

NONA-Z

,4-DIEN-9-YL CAREANIONS PROMOTED VIA THE ARYL LIGANDS1

I I . l Introduetion

In recent years a number of studies have been reported

concerning the homo- and bicycloaromatic properties2 _{of the}

bicyclo [4. 2 .1] nona-2,4, 7-trien-9-yl cation

.!

3

• In

disagree-ment with the prediction4 _{this cation turned out to be}

de-stabilized • The corresponding carbanion

l

is expected to

be stabilized according to GoZdstein's prerequisite for

longicyclic stabilization2_• _{However, until now reports}

con-2

cerning the preparatien and properties of. the unsubstituted

carbanion 2 are almast completely lacking~

Photoelectron spectroscopit evidence5 _and 13_{C NMR}

data6 _{suggest bicycloaromatic interactions in the azabicycle}

l•

which is isoelectronic with carbanion

l·

In this

mole-cule, the lone pair is positioned syn to the diene segment.

According to CND0/2 calculations, this isomer is 5.4 kcal

more stable than its invertomer. The

(16)

ib

•

Ph ~

-4 Ph ",...

'P_,

4so•c~d::J

.§_

it is thermally generated from its epimer 47•

The base catalyzed decomposition of the pyrazoline

6 gave bicyclo~.Z.l]nona-2,4,7-triene

z,

presumably via

the intermediacy of carbanion 28

• When the reaction was run

8:

- - - - 2

-7

in a deuterated solvent, deuterium was incorporated prefe-rentially from the syn-direction (ratio>l.6). This result

is consistent with the proposition of favourable syn

bis-homoaromatic interactions in 2.

Carbanion

l

could not be prepared by the classica!

ether cleavage method9_, _{using the syn-9-methoxy ether and}

sodium-potassium alloy~. This reluctance for generating

l

is further exemplified by hydracarbon

z,

which does not

incorporate deuterium at

c

_{9 upon reaction with lithium}

cy-clohexylamide in cyclohexylamine-d?.10

,

Recently, the 9-carbonitrile substituted bicyclo ~.2.1]

nona-2,4,7-trien-9-yl carbanion

g

was generated in an

indi-rect manner by the rearrangement of

9-carbonitrile-ais-bicyclo[6.1.0]nona-2,4,6-trien-9-yl carbanion §_11_•

Carb-anion

g

reacted with HCl in a nonstereospecific way to

pro-duce the protic epimers syn- and anti~lQ. Quenching with

methyl iodide gave

(17)

CN CN

~

NC H

~

syn-10 onti-10 11

Direct generation of negative charge at

c

_{9 can be}

achieved by the introduetion of heteroatoms, which can be cleaved from carbon readily. From organoselenium chemistry it is known that seleneketals are excellent precursors for

the generation of a-seleno substituted carbanions12

' 13,

Therefore, seleneketals of the bicyclo[4.2.1]nonane series were investigated. In the studies documented below, the properties of the carbanions generated from these seleno-ketals are described. In the intermolecular reactions of these carbanions with various electrophiles, homoaromatic interactions play a smal! role. Much more important is the

intramolecular transfer of negative charge from

c

₉ to the

aryl ligands via proton transfer. This process proceeds

with 100% stereospecificity.

II.2 Quenah results of 9-arylseleno substituted aarbanions'

The seleneketals 12a-c reacted with n-BuLi in THF at

-78°C via C-Se bond cleavage to produce a-seleno substituted

carbanions ~· Direct quenching after carbanion formation

leads to

c

₉-substituted derivatives (Table II).

Deuterium-oxide (or methanol-d4) afforded

c

9-deuterated epimers 18b

and 19b in approximately equal amounts. Methyl iodide gave

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9-methyl-anti-(p-tolylseleno)bicyclo~.2.1]-R R

@-se se-@

d:J

n-Bu l1

...

R'@-hse

-f

~

-12 Q-E

_{- - -}

35 o-e a R=H c R=o-CH - 3

nona-2,4,7-triene 19c together with the substituted aromatic compound 20c. The reaction with prenyl bromide produced the expected

9-(3-methyl-but-2-enyl)-anti-'9-(p-tolylselerio)bi-cyclo [4.2.1] nona-2,4, 7-triene 1 Products like 20c,

attri-butable to electrophilic substitution in the aromatic ring, were formed in all reactions when electrophiles were added 0.5 hafter carbanion formation (Tables I and II). The

phe-nyl selenoketal 12a then led predominantly to products

ll•

with substitution in the phenyl ring (Table I). The

forma-tion of

c

_{9-substituted products could be suppressed}

comple-tely when the reaction was run in the presence of a crown ether. Complexation of the Li+-cation drastically increases

the basicity of the initially formed

c

_9-carbanions~.

which leads to the formation of aryllithium compounds 36

(vide infra). Thus, selenoketal 12b produced

ayn-9-(p-tolyl-seleno)bicyclo~.2.1]nona-2,4,7-triene 18a and ayn-9-(2,4-di-methylphenylseleno)bicyclo 4.2.1 nona-2,4,7-triene 20c upon the reaction with methyl iodide in the presence of 18-crown-6.

n-BuLi 12 b

-=---1-18-crown-6 2 _CH3I + 18 a CH3 H Se-@-CH3

tb

20c

The o-tolyl selenoketal 12c afforded a third kind of

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Tabte I: Products of the reaation of setenoketal 12a with n-BuLi and eteatrophiZea

x

26-©

©r:b

26-@

₈

1 n Buli 2 E

₀

....

-

_~ 12a

....

~

_f

_~ ~ -78°C T°C

f

--

...-:

x

11.

14 :!.§..

x

1§_ _11. y E

x

t~ _T°C _Products _(%).2.

H20 H 30 -78 92.5 13a (81.4) 14a (18.6) 15a 16a 17a

60 20 76.4 _{16a (100)}

D20 D 30 -78 90.6 13b (30. 8)!. 14b ( 24. 1) _{15b (45.1)!. 16b} _17b

CH₃I CH₃ 30 -78 96 13c 14c (15) 1 Sc (85) 16c 17c

60 zo 84.4 _16c (27)[. _{17c (73).1Z.}

PhC(O)H PhC(OH)H 30 -78 87 13d 14d (48.1) 15d (51.9) 16d 17d

PhzC(O) _{Ph 2C(OH) 30 -78 84.5} 13e (16) 1 Se (84) 16e 17e

DMF C(O)H 30 -78 81 13f (40)!. 15f (60)!. 16f 17f

C0 2 C(O)OH 30 -78 90

_11&

_~_(17.6)-d

_.!2..8.

_lZ8.

(20)

... Q) eZ.eatr>ophiZ.es

H

H Se

0

CH3 CH _..., X 3 l i

x

E

x

t~

_".è.

Products(%)~

H₂0 H 2 -78 80.4

_-

18a (56)

_-

19a (44)

_-

20a

_-

21a

_-

22a

30 -78 94.4

_-

18a (65)

_{l l i}

(35) 60 20 70 21a (100) D 0 ₂ D 2 -78 80.4

_-

18b (56) 19b (44) 20b 21b 22b d

-

d

-

-30 -78 94.4

_-

18b (19.3)-

_-

19b (35.8)

_-

20b (44.9)-CH 3I CH₃ 2 -78 88.3

_-

18c 19c (85) 20c (15)

_-

21c

_-

22c 30 -78 98.4 19c (72.1) 20c (27.9) R₁Br R

,-

e 2 -78 84.9

_-

18d

_-

19d ( 1 00)

_-

20d

_-

21d

_-

22d

PhC(O)H PhC(OH)Hl 30 -78 84.4 18e (23) 19e (59) 20e (18) 21e 22e

R2C(O)H R2C(OH)H.Il. 5 -78 100 18f (26) 19f (74) 20f 21f 22f

R3C(O)H R3C(OH)H 5 -78 100 _~(17)

_.:!28:

(83)

_12..&

_~ §

~In minutes after the addition of n-BuLi •

.è.

Calculated from isolatèd n-butyl p-tolyl selenide.

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Tab~e III: Produats of the reaation of se~enoketa~ 12a with n-BuLi and e~eatrophiZes CH₃

;!)~

;Elp

CH3 1 n Bu Li 2E

@-s·x'

;n

. r - - ,._,

0

12c · ,....

_,...

- -'78°C T°C ~

d:::;

~ .

---

...--:

x

23 21. ₂₅ ₂₆

'_:_J

x

t!! T°C

tk

products (%)~

H₂0 H 30 -78 86.4

_-

23a (68.5)

_-

24a (14)

_-

25a (17.5)

_-

2.7a

60 20 95 26a (100)

D₂0 D 30 -50 92.4

_-

23b (9. 2)-d

_-

24b

_-

25b (12.8)d

_-

26b (78)!. 27b

(13.7)t

-CH 3I -CH3 30 -78 92

_-

23c

_-

24c (39.4)

_-

25c (9. 9)

_-

26c

_-

27c

(37)i-!! In minutes after the addition of n-BuLi. É. Calculated from isolated n-butyl o-tolyl

selenide. ~ Calculated from isolated products. ~ Calculated from 1_{H NMR integrals.}

!. Predominantly (90-95%) endo deuterium.

i

Endo:ereo ratio 7:3. i. Methyl substituent

endo.

(22)

~ Table IV: Produate of the reaation of selenoketal 28 ~ith n-BuLi and eleatrophiles

x

'L_

-@-eH,

H

s,-@-cH

₃

a;:J

CH3-@-~se

x ; } ) ê6H

se-@-cH3

30 ~ "::

_...",

--30a

E

x

t~ %-b products (%)~

H 0 H 2 56.2 30a (20) 31a (80) 32a 33a

2

-

-30 84

_-

30a (70) 31a (30) d

-

_(7)~ 60 81 30a (30.1)- 33a

o

₂

o

D 2 56.2 30b (8) 31b (80) · 32b+30a ( 12) 33b

-

- -

-30 70

_-

30b (6.2) 1b (38.4)

_{- -}

32b+30a (55.4) CH₃I CH₃ 30 64.3

_-

30c 31c (42) 32c (20) 30a (38) 33c

-

-x

33

~ In minutes after the addition of n-BuLi. ~ Calculated from isolated n-butyl p-tolyl

(23)

together with

c

₉-substituted compounds ~ and 24 and

sub-stituted aromatic products ~ (Table III). Deuterium oxide

(and methanol-d₄) gave predominantly the

c

₅-substituted

tetracyclic compound 26b. Methyl iodide produced predomi-nantly the c3-endo substituted derivative 27c.

All triene selenoketals 12a-~ gave exclusively

tetra-cyclic products when the electrophile was added to the carb-anionic solution at room temperature.

The isolation of electrophilic aromatic substitution products indicated that the initially formed Cg-carbanions 35 isomerize stereospecifically to aryllithium cempounds 36 (vide infra).

Li

H se-@R

tb

₃₆

So, the intermediate aryllithium cómpound 36 plays a crucial role in the reactions of the triene selenoketals. This raised the question about the origin of the proton at Cg in intermediate 36. Therefore, the deuterium-labeled selenoketal 12d was synthesized. This selenoketal was reacted

D D D D

DS• SeD

_{o od:JÓ}

b

f

~ _.., 12 d

with n-BuLi and subsequently with water. A product 38 was isolated with deuterium at Cg and with protium in the aro-matic ring (singlet at 7.2 ppm).

(24)

with n-BuLi in the presence of furan. The benzyne-addition

n-Bu Li ,_78°

c

0

12e 39

compound ~was the only product isolated.

Thus, the proton at Cg resulted from a complete1y stereospecific electron transfer from Cg to the ortho-posi-tien of the aromatic ring via proton exchange.

In order to learn more about the possible homo- and bicycloaromatic properties in the arylseleno-substituted carbanions 35, the diene selenoketal 28 and the saturated selenoketal 2g were investigated.

CH3

-@-:b

-@-cH3 CH3

-@-dj

-@-cH3

28 29

The diene selenoketal 28 reacted somewhat slower with n-BuLi at -78°C than the triene selenoketal 12b. Reaction with an electrophile at this temperature gave three products:

c

₉-substituted products, compounds formed via electrophilic

aromatic substitution, and

syn-9-(p-tolylseleno)bicyclo-~.2.1]nona-2,4-diene 30a (Table IV).Deuterium oxide and

methanol-d₄ afforded directly after carbanion formation

mainly syn-C

9 deuterated product 31b. This contrasts with the

behaviour of the selenoketal 12b, which produced both Cg-deuterated epimers in approximately equal amounts (vide

(25)

later point in time predominantly syn-9-p-tolylseleno

deri-vatives 30a,~ and 32b (Table IV). At room temperature the

main product of the reaction of the anionic salution with

water was

22!•

Tetracyclic compound 33a was isolated in

very low yield (less than 7%), A remarkable difference be-tween diene selenoketal 28 and triene seleneketals 12 was

the formation of 30a in all the quench reactions with ~·

Apparently, anti-C

9 dienyl carbanions are more basic than

anti-Cg trienyl carbanions ~· In all likelihood, the dienyl

carbanions react partly with n-butyl p-tolyl selenide.

The saturated selenoketal ~ reacted very sluggishly

with n-BuLi. After 1.5 h at 0°C, quenching with water

afforded a product mixture which still contained 40% starting compound. Therefore, no further experiments were performed.

II.3 StruaturaZ assignment of the quenah produats

The stereochemistry of the bicyclic protic products is

assigned on the basis of the 1_{H NMR spectra which exhibit}

a triplet for H₉of the syn compounds (13a, 18a, 23a and

30a), whereas a singlet is observed for the anti compounds

(14a, 19a, 24a and 31a)3

, The stereochemistry of the

deute-rated products follows from a compàrison of their 1

H NMR

spectra with those of the

c

₉-protonated products (Table V).

The syn disposition of the seleno moiety in the

aro-matic substitution products

(11,

~, ~ and ~) is

esta-blished on the basis of the triplets for H₉3

• Ovtho

substi-tution is evident from 1_{H and} 13_{C NMR speetral data (Tables}

VI and VIII).

The configuration of the methylated derivatives is ten-tatively assigned on the basis of product formation similar

to that in other quench reactions (vide infra). NOE

experi-ments did not provide further structural informations. The same arguments hold true for the product 19d.

The stereochemistry of the benzylic alcohols 14d, 18e and 19e can be established on the basis of their speetral properties (Tables V and VII). The diastereotopic ring car-bons all absorb at different field positions. The compounds

(26)

14d and ~display large 13_{C NMR shift differences between}

the diene carbons, whereas the chemica! shift differences between the monoene carbons are smal!. For the älcohol 18e the situatipn is reversed. The speetral data are consistent

with a syn disposition of the benzylic alcohol, with

res-pect to the diene bridge, in 14d and 19e, whereas 18e has

anti stereochemistry.

Additional stuctural information on compounds 14d-f, 18e and 19e is obtained by using lanthanide shift reagents.

Addition of Eu(fod)₃to the benzylic alcohols causes marked

nonequivalent downfield shifts of the bridgehead protons, the effect being the most pronounced for alcohol 18e (Figu-re I). The (Figu-results pointtoa time-averaged positioning of the hydroxyl function out of the plane bisecting the

bridge-head-bridge~ead axis. Dreiding models reveal that this mode of complexation can be realized. In 18e one bridgehead pro-ton is pointing towards the hydroxyl group, whereas in 14d and 19e the corresponding proton is pointing away. This explains why the bridgehead proton in 18e is shifting faster than those in 14d and 19e and confirms the assigned

stereo-chemistry. In spite of the syn disposition of the alcohol

function in 14d and 19e, the downfield shift of the monoene protons is larger than for the diene protons. This indicates that europium is located closer to the monoene bridge. In-spection of the Dreiding models indicates that this mode of complexation is realized. The downfield shift of the monoene protons of 18e is, as expected, significantly larger than that of the diene protons.

For the diphenyl carbinol 14e europium-induced shifts are very small, due to the crowded position of the hydroxyl function. Therefore, no extra structural information could

be obtained. The application of Eu(fod)₃is more

success-ful with 14f, which has a more approachable aldehyde

'

--functionality. The downfield shift of the diene protons is

larger than for the monoene protons, which confirms the syn

configuration of the aldehyde group with respect to the diene bridge (Figure I).

(27)

N :x: 120 80 40 N :x:

,.

14 f 80 120 Eu(fodJ 3tmg) N :x:

,.

<:] 160 120 80 N :x: 14d He 80 120 Eu lfod 1 3 ( mgl <:J 18e <:]

,.

_19e 300 200 100 300 200 100 100 150 100 150 Eu(fodJ₃1mg) Eu I fo d 1₃I mg l

Figure I: Plot of the induaed chemiaal shift. Av. versus the amount of added shift reagent for protons of 14d.

lil•

18e and 19e.

(28)

N J: :::. <:l 150 100 50 N J: :::. <:l 300 200 100 0 18g 18f 50 100 Eu(fod) 3 (mg) 50 100 N J: :::. <:l 19g ISO

...

,

""

100 He1

"1'

₅₀ H2.5T 50 100 Eu(fodl₃ (mgl Figur>e II: Eu I tod _{13 I}mg l Plot of the induaed

Eu(fod 1₃(mg)

ahemiaat shift~ 6v~ ver>sus the amount of added shift r>eagent for> pr>otons of

(29)

protons are respectively shifted 0,6 and 0.4 ppm upfield with respect to the corresponding seleneketals 12a and 12b, whereas in 18e the monoene protons are shifted slightly downfield (Table V). Due to the large steric interactions between the benzylic alcohol function and the seleno moiety, the latter is positioned time-averaged above the monoene protons of 14d and 19e, causing a shielding of these protons.

In 18e these large steric interactions do not occur. The

monoene protons of the diphenyl carbinol 1 display a 0.9

ppm upfield shift. Thus, the alcohol function of 14e is

assigned the syn configuration with respect to the diene

bridge.

The stereochemistry of the alcohols 18f,~ and 19f,~

follows straightforward from their NMR data (Tables V and

VII) and from LIS measurements (Figure II). Both

.:!!.&

and

~ are mixtures of the threo and erythro compounds. In

the 13_{C NMR spectra two sets of resonances appear.}

Further-more, the diastereoisomers interact differently with the

europium shift reagent (Figure II). The smal! vicinal

coupling constants (J approximately 3 Hz) indicate that the

threo compounds are produced predominantly

(.:!!.&:

62% threo;

~: 65% threo). The alcohols 18f and 19f consist of only

one diastereoisomer. Again, the coupling constants

(1

appro-ximately 6 Hz) point to the threo configuration. Thus, the

_,

arylseleno carbanions l§. fellow Cram s rule1

" upon reaction

with ebiral aldehydes.

The structure and stereochemistry of the tetracyclic

products are obtained from 90 MHz 1_{H NMR decoupling}

experi-ments. 1_{H NMR speetral data for these compounds are}

dis-played in Table IX.

II.4 Direct 1_{H NMR observation of anionic soLutions}

The reaction of the triene selenoketal 12a with n-BuLi

in THF-d8 was investigated with the aid of 1_{H NMR}

spectros-copy. The structure of one intermediate could be elucidated by 90 MHz decoupling experiments. This intermediate was formed at approximately -45°C. It was stable for several

(30)

37o 6 J 1,2 2,3 3,4 4,5 5,6 6,7 Hz 4.0 5.0 1 0.5 8.5 4.5 3.0 J 7,8 1,8 1,9 6,9 1,7 1,3 Hz 5.5 2.5 8D 7.3 1.0 1.5 . 5 4 3

Figure III: Part of the 1_H_{NMR spectrum of allylic anion}

37a. 1_H_{NMR speetral data for 37a.}

days at room temperature. Quenching with water afforded the tetracyclic derivative 16a as the sole product. The interme-diate had the tetracyclic stucture 37a (Figure III),

At temperatures below -45°C other intermediates were present. However, we were unable to identify these because

of fast intramolecular reactions (vide infra). No

interme-diate of the reaction of selenoketal 28 with n-BuLi in THF-d₈could be identified. An allylic carbanion

iQ,

com-parable with 37 was not observed.

II. 5 Discussion

The reaction of

(31)

metbod to generate seleno-substituted carbanions. High yields of products were isolated after quenching with

elec-trophiles. Three different products were isolated:

c

₉

-sub-stituted products, sub-sub-stituted aromatic compounds and

tetra-cyclic derivatives (vide supra), The composition of the

product mixture appeared to be dependent on time, tempera-ture and electrophile.

An acceptable mechanism for the product formation is affered in Figure IV. The seleneketals 12a-e react with

n-BuLi to produce the equilibrating anions syn- and anti-35.

"(Q>-se Se

-<g"

. tiJg

"\Q)-se ..

tiJ

-: Se-f{J/

dJ

syn-35 anti-35

n

s

R ' 36

Figure IV: Meahanism for the reaation of n-BuLi with seZe-noketaZs 12

The latter are unstable and rearrange to aryllithium

com-pound ~· This intermediate reacts intramolecularly with

the diene bridge to generate the stable allylic carbanion

37. The carbanion 37 was characterized with the aid of 1_H

(32)

the basis of the stucture of the isolated products.

Seleno- and thio-substituted enolates undergo

signifi-cant or even predominant alkylation at the heteroatom15

•

The carbanions 35, however, alkylate exclusively at

c

₉.When

prenyl bromide is used as the electrophile, only compound 19d is formed. Alkylation at selenium would lead to the ylid

!l;

a subsequent [2 ,3] sigmatropie shift would yield compound

,il (Scheme I).

H;,c-@-se

41

Saheme I

The hard electrophiles water and methanol react in a

non-stereospecific way with bath

c

_{9-carbanions. Other}

elec-trophiles, even bulky ones like benzaldehyde, prefer to

attack syn-35, although this carbanion is sterically the

most hindered one.

The carbonitrile ~ubstituted anion

!

reacts with methyl

iodide at the sterically least hindered side (vide sup~a)11 _,

However,

c

₉of carbanion

!

is sp2 _{hybridized, due to the}

strong electron-withdrawing effect of the substituent. There is no need for homo- or bicycloaromatic stabilization. The

(33)

stereochemistry of the reaction of ~ with electrophiles is

controlled by steric interactions3

' 16•

In the g-seleno substituted carbanions

2i•

Cg is sp3

hybridized. Soft electrophiles attack predominantly syn-2i

because of the preferred localization of electron density at the diene side of the carbanion. This can be attributed to a small bishomoaromatic stahilizing 6 w-electron inter-action in this intermediate. This stahilizing interinter-action

is not possible in anti-35. Presumably, the latter carbanion

is a contact ion pair with the lithium cation associated very closely to the lone pair at Cg• The importance of this cation complexation is underlined in the experiments run in the presence of crown ether: no Cg-substituted derivatives

are formed because of the enhanced basicity of anti-2i in

this medium (vide supra),

To the anti-carbanions an alternative reaction path is

available, which leads tomare stable intermediates. Via a

stereospecific process, the anti-carbanions isomerize to aryllithium compounds 36. These react with electrophiles to produce substituted aromatic compounds.

Substituted aromatic compounds have already been

reported12

' 17• When phenyl vinyl selenide was reacted with

n-BuLi in ether at room temperature and subsequently quenched with methyl iodide, a mixture of hexyl tolyl selenides was

isolated17

• Transposition of negative charge on the phenyl

ring also occurs when carbanion generation is performed in

the presence of HMPT12

• Again, a mixture of substituted

aromatic compounds is formed. Evidently, selenium substi-tuted aryllithium compounds are more stable than a-seleno substituted carbanions.

In our experiments only ortho-substituted products are formed, implying that the negative charge is generated ex-clusively at the ortho-position. Dreiding models show that

in the carbanions anti-2i the ortho-proton approaches the

negative charge at Cg very closely. Intramolecular electron

transfer via proton exchange leads to the aryllithium

com-pounds ~· This was established by the use of the

(34)

Intermolecular proton transfer can be ruled out on the basis of steric hindrance and the absence of compounds 13a, 18a and 23a in the quench reactions with the aprotic

elec-trophile methyl iodide. The isomerization of the

c

₉

-carb-anions ~ to aryllithium compounds 36 is a 100~

stereospe-cific process. No product attributable to a rearrangement of syn-~ to aryllithium compound 43 was observed.

Apparent-Li H

se-@

d:J"

anti-35 36

x

syn- 35

ly, the bishomoaromatic stabilization in syn-~ decreasas

the basicity at

c

_{9 and disfavour intramolecular proton}

ex-change. However, this bishomoaromatic interaction does not overcome the tendency to generate the more stable aryl-.

lithium intermediatas 36 via prior equilibration of the

c

₉

-carbanions. Unfortunately, no data are available on the

difference in basicity between syn- and anti-35.

Hydragen-deuterium exchange experiments, using 13a and 14a and various bases and solvents, failed completely. Thus, the

degree of bishomoaromatic stabilization in syn-35 cannot be

(35)

The p-tolyl selenoketal 12b gives under identical experi-mental conditions less substitution in the aromatic ring than the phenyl selenoketal 12a. The p-methyl substituent

has no effect on the steric interactions at

c

₉• Therefore,

the lower tendency to isomerize has to be attributed to the electron-donating effect of the methyl substituent.

The o-methyl group in anti-~ exercises a similar

electronic effect as the p-methyl group in anti-35b. Once proton transfer has occurred, the negative charge in 36c comes very close te the diene bridge because of the steric requirements of the o-methyl group. The allylic carbanion 37c is then formed via direct intramolecular electron trans-fer. The other aryllithium compounds also produce allylic carbanions (vide supra).

CH3

dj~

V

36c

The allylic anions 37 are the most stable intermediatas

in the reaction pathway. The carbon atom

c

_{5 has the highest}

electron density as is revealed by the high upfield shift

of the H5-resonance in the 1_{H NMR spectrum (vide supra).}

Water and deuterium oxide react exclusively at

c

_{5 • Methyl}

iodide shows a preferenee to react at

·c

_{3 • A possible}

ex-planation for these results is that 37. exists in THF as a

contact ion pair with the lithium cation asociated to

endo-c5.

Water and deuterium oxide displace the metal cation to

form deuterium and hydrogen-bonded carbanions, which

rapid-ly collaps18

' 19• On these precedents endo protonation and

deuteration at

c

₅ is to be expected. Conversely, it is

pro-babie that quenching with methyl iodide occurs without the

involvement of hydragen bonding. The preferenee to attack

c

₃

(36)

cation associated to

c

5.

In the allylic carbanion 37 a bishomoaromatic interac-tion is possible between the allylic anion part and the proximate double bond. This kind of interaction has been reported to occur for the bicyclo[3.2.1]octa-2,6-dienyl anion

i i

20 _• _{However, recent theoretica! investigations}21

disclaim the bishomoaromatic character of anion 44.

There-fore, cyclic delocalization of negative charge in

lZ

is

extremely unlikely. Direct 1_{H NMR investigations of}

_lZ

_did

not provide evidence for stahilizing 6 TI-electron interac-tions·.

The mechanism for product formation out of the diene selenoketal 28 is almost the same as that encountered for the triene seleneketals 12. The selenoketal 28 reacts with n-BuLi via C-Se bond cleavage to produce syn-ii. The soft electrophile methyl iodide attacks exclusively this

bisho-moaromatic stabilized syn-carbanion. Equilibration affor~s

anti-ii, which appears to be more unstable than the

corres-ponding trienyl carbanion anti-~. It reacts with n-butyl

p-tolyl selenide to produce 9-(p-tolylseleno)bicyclo ~.2.1]

nona-2,4-diene 30a. It partially isomerizes to the aryllithium

(37)

carbanion 40 is formed in only minor amounts, as is evident

from the low yield of isolated tetracyclic product ~·

This low yield can be attributed to the side reaction of

anti-45 with n-butyl p-tolyl selenide.

From all these results it is evident that the chemistry

of 9-arylseleno- substituted bicyclo

~.2.1]nona-2,4,7-trien-9-yl and -bicyclo [4.2.1] nona-2,4-dien-~.2.1]nona-2,4,7-trien-9-yl carbanions ( 22,

and 45, respectively) is dominated by the availability of an unique stereospecific reaction path in which electrens

are transferred from

c

₉to the aryl ring via intramolecular

proton exchange. The driving force for this isomerization is the formation of the more stabie aryllithium compounds out of the "hot"

c

₉-carbanions. In the latter a small bis-homoaromatic stabilization occurs in the syn-carbanions; bicycloaromatic stabilization seems to be absent. The aryl-lithium compounds, finally, can transpose negative charge by intramolecular cyclization,which leads to stable allylic carbanions.

II,6 ExperimentaL

- Generat remarks

1_{H NMR spectra were recorded with Varian EM-360A,}

Va-rian T-60A, Bruker HX-90R and Bruker WM-250 instruments

using Me 4Si as internal standard. 13_{C NMR spectra were taken}

on Varian HA-100 and Bruker HX-90R instruments interfaced with a Digilab FTS-NMR-3 computer. Mass spectra were obtained with a Finnigan 4000 GS/MS instrument at an ionization po-tential of 70 eV. Infrared spectra were recorded with Perkin Elmer 237 and Beekman Acculab 9 spectrometers. UV spectra were measured withaPerkin Elmer 123 Double Beam instrument. Preparative high-performance LC separations were

accom-plished on Jobin Yvon Chromatospac 100 and on Jobin Yvon Miniprep. All seperations were performed on silica H (type 60, Merck). Microanalyses were carried out in our labora-ties by Messrs. P.v.d. Bosch and H. Eding.

Bicyclo [4. 2 .1] nona-.2 ,4, 7-trien-9-one

C.i.Z)

3

(38)

bicyclo-[4.2.1]nonan-9-one (48)3_, _{benzeneselenol (49a)}22

,

p-toluene-selenol (49b)22_, _{o-tolueneselenol (49c)}22_, _benzene-d

5 -sele-nol (49d)22

, m-chlorobenzeneselenol (49e)22 were prepared

according to literature.

- 9 ~ 9-bis (pheny Lee Leno) biayalo

[4.

2. 1] nona-2., 4.,?- triene (12a)

A stream of dry HCl gas was passed through a salution of ketone 47 (7.8g; 59 mmol) and benzeneselenol 49a (15.6g; 99 mmol) in dry Et₂

o

(20 mL) at 0°C during 15 min. The re-sulting mixture was poured onto a saturated sodium

bicar-bonate salution and extracted into Et 2

o.

The organic layers

were washed with water, 7% aqueous KOH and water, dried (MgS04) and concentrated. High-performance LC with

benzene-hexane (10/90) gave 11.3 g (53%) of 12a; 1

H NMR (CC1 4)

o

7.9-6.8 (m,tO); 6.1 (m,4); 5.3 (d,2); 3.1 (m,2); 13_{C NMR} (CC1 4)

o

56.02 (C_{1 6); 134.22 (C 2 5); 128.01 (C 3 4); 122.23} ' ' J (C 7, 8); 56.02 (C9); 134.22 and 131.28 (Ci); 129.60 (C 0); 134.10 and 138.42 (Cm); 129.60 (CP).

- 9 .. 9-bis (p-to lylse 1-eno) biayal.o [4. 2, 1] nona-21 4 .. ?-triene

( 12b)

Selenoketal 12b was prepared in the same way as 12a, Trituration with n-hexane gave pure ketal in 55,7% yield:

mp 79-80°C; 1

H NMR (CC1 4) 6 7.6-6.67 (m,8); 5.93 (m,4); 4.92

(d,2); 3.00 (m,2); 2.53 (s,3); 2.30 (s,3); 13

C NMR (CC1 4)

o _{55.80 (C 1, 6); 134,01} (c_{2 , 5); 121.97} (c_{7 , 8); 127.97 (C 3 , 4);}

57.26 (C 9); 127.84 and 128.94 (Ci)i 130.17 (C0 ) ; 138.77 and

139.09 (Cm); 138.47 and 137,98 (CP); _{22,54 (CH 3);}

Anal. Calcd. for

c

₂₃H₂₂se₂: C, 60.53; H, 4.86. Found: C, 60.72; H, 4.91.

- 9,9-bis(o-tol.yLsel.eno)biayalo 4.2.1 nona-2,4,?-triene ( 12c)

(39)

82-83°C; 1 H NMR (CCI 4) 6 7.77 (m,8); 5.93 (m,4); 4.83 (d,Z); 3.37 (m,2); 2.40 (s,3); 2.27 (s,3); 13_{C NMR (CC1} 4) 6 57.08 (c_{1 , 6); 134.19} (Cz,sli _{127.66 (C 3, 4); 121.62 (C 7, 8);} 56.95 (C₉); 134.01 and 133.0 (Ci); 139.97, 136.48, 143.01 and 143.76 (C 0); 130,97, 126.51 and 126.60 (Cm); 129.12 and 129.78 (CP); _{24.57 and 24.66 (CH 3).}

Anal Calcd. for

c

₂₃H₂₂se₂:

c,

60.53; H, 4.86. Found:

c,

60.76; H, 4.91.

- 9~9-bis(phenyl-d

0

-seleno)biayalo[4.2.1]nona-2~4~?-tPiene (12d)

is prepared and isolated as for 12a: yield 45%; 1_H

NMR (CC1 4) 6 5,9 (m,4); 4.87 (d,2); 3.03 (m,Z).

-

9i9-bis(m-ahloPophenylseleno)biayalo[4.2.1]nona-2~4i?-tPiene (12e)

is prepared and isolatedas for 12a: yield 42%; 1_H

NMR (CDC1 3) 6 7.83-7.17 (m,8); 6.20 (m,4); 5.20 (d,Z); 3,23 (m,Z).

- Biayalo [4,2.1]nona-2i4-dien-9-one (50)

The nickel boride catalyst29 _{used was prepared under}

nitrogen in the hydragenation flask by adding dropwise a solution of sodium borohydride (0.033 g; 0.87 mmol) in 20 mL of EtOH to a stirred solution of nickel(II)acetate

te-trahydrate (0.23 g; 0.92 mmol) in 20 mL of EtOH. Ketone ±1,1 g, dissolved in 20 mL of EtOH, was introduced into the reaction flask and 169 mL of H2 was taken up under stirring. The resulting mixture was poured onto 50 mL of saturated aqueous

sodium bicarbonate, filtered and extracted into Et 2

o.

The

water phase was. stripped from EtOH and subsequently

ex-tracted with Et 2

o.

The combined organic layers were dried

(MgS0

4) and concentrated, yielding 0.87 g (861) of ketone

50: 1

H NMR (CDCI 3) 6 5.44 (m,4); 2.42 (m,2); 2.00 (m,4);

(40)

- 9 ~ 9-bis (p-_to ly lse leno) biayalo

[4.

2 .1] nona-2., 4-diene ( 28) Toa solution of ketone SO (0.5 g; 3.7 mmol) and p-to-lueneselenol 49b (1.09 g; 6.4 mmol) in 5 mL of dry Et 2o was added 0.2 mL of concentrated H₂so₄24

• After being stirred

for 1 h at room temperature under a nitrogen blanket, the reaction mixture was poured onto a saturated aqueous sodium

bicarbonate solution.and extracted into Et 2

o.

The organic

layers were washed with water, saturated aqueous sodium

bi-carbonate solution and water, dried (MgS0₄) and

concentra-ted, High-performance LC with benzene-hexane (10/90), fol-Iowed by recrystallization from n-hexane gave 0.47 g· (32%) of pure~. mp 95.2-95.7°C; 1_{H NMR} _ö _{7.72-6.63 (m,8); 5.73}

(m,4); 2,38 (s,6); 2.4 (m,4); 13

C NMR (CC1 4) ö 51,26 (C_{1 6);}

'

135.60 (C 2, 5); 127.13 (C 3 , 4); 41.55 (C7, 8); 63.87 (C9);

128.50 and 127.84 (Ci); 130.26 and 130.57 {C₀) ; 137.81 (Cm);

139.26 and 139,88 (CP); 22.45 (CH 3),

Anal. Calcd. for

c

₂₃H₂₄se₂:

c,

60.26; H, 5.28, Found: C, 60.07; H, 5,35.

- 9.,9-bis(p-tolylseZeno)biayaZo~.2.1]nonane (29)

is prepared in the same way as selenoketal ~. yield

25$; mp 93-94°C; 1_{H NMR} _ö _{7.67-6,9 (m,8); 2.6-1.23 (m,12);}

2.3 (s,6).

Anal. Calcd. for

c

₂₃H₂₈se₂: C, 59,74; H, 6.10. Found: C, 59.95; H, 6.18.

- General procedure for the quench reactions

A salution of 1 g of triene selenoketal 12a-d in 10 mL of dry THF was treated with 2 mL of n-BuLi (15% in hexane, Merck) at -78°C under a nitrogen atmosphere. In the direct quenching experiments the electrophile was added 2 min af-ter carbanion generation. In the other low temperature ex-periments the anionic solution was stirred for 0,5 h prior to the addition of the electrophile. For the room tempera-ture experiments the triene seleneketals were reacted 0.5

(41)

h with n-BuLi at -78°C and 0.5 h at room temperature. After being quenched, the reaction mixtures were allowed to warm to room temperature, poured onto water and extracted into Et₂

o

_{or CHC1 3 • The organic layers were washed with water,}

dried {MgS0₄) and concentrated. The products were isolated

with the aid of high-performance LC. Por 1_{H and} 13_{C NMR}

speetral data see Tables V-IX. Some products were solids:

12&

(mp 213-214°C); 18e (mp 156-158°C); 19e (mp 122-123°C); 19f (mp 88-90°C); 21a (mp 113-114°C); 26a (mp 89-91°C); 27c (mp 115-119°C). All these compounds gave satisfactory

microanalyses. The products of the reactions of ~-E with

n-BuLi and water, deuterium oxide or methyl iodide were examined with the aid of GLC/MS. All derivatives gave the expected molecular ion.

• PPenyl bPomide quench e~periment

The procedure was as described under general procedures. The electrophile was added 2 min after carbanion generation. Yield after work-up 77% of 19d; mp 82-84°C.

Anal. Calcd. for

c

₂₁H₂₄se: C, 70.97; H, 6,81. Found: C, 70,91; H, 6.81.

• Furan-trapping e~periment

A salution of~ (0.15 g; 0.55 mmo!) in 8 mL of a

mix-ture of furan-THF (1:1)25 _{was treated with 0.4 mL of n-BuLi}

at -78°C under a nitrogen atmosphere. After stirring for 5 h, the salution was allowed to warm to room temperature. The

usual work-up afforded 0.08 g (66%) of~; 1

H NMR (CDC1 3) ö 7.37-6.73 (m,3); 6.15 (m,4); 5.82 (d,2,J= 7.5 Hz); 3.63 (t,l); 3.20 (m,4).

• Quenohing in the presence of 18-crown-6

A salution of 12b (0.5 g; 0,55 mmo!) and 50 mg 18-crown-6 in 5 mL of dry THF was treated with 1.3 mL of n-BuLi at

(42)

methyl iodide. LC yielded 0.2

(3g,4%) of

After the usual work-up, high-performance g (80.4%) n-butyl p-tolyl selenide, 0.13 g

and 0.10 g (31.8%) of 18a.

- Reaations with diene selenoketaZ 28

The procedure was the same as described for the triene seleneketals 12a-c. Reaction with water afforded 30a and 31a.

_{- -}

-30a: 1 H NMR (CDC1 3) ó 7.50-6,73 (AB,4); 5.70 (m,4); 3,85 (t,1); 2.77 (m,2); 2.27 (s,3); 1.92 (m,4). 13_{C NMR} (CDC1 3) 45,13 (C 1, 6); 136.31 (c_{2 , 5); 126.60 (C 3 , 4);} 40.1g (C 7 8); 46.00 (Cg); 129.42 (Ci); 130.44 (C0 );

'

135.16 _{(Cm); 137.10 (CP); 22.19 (CH3). Mass spectrum} m/e 290. 31a: 1_{H NMR (CDC1} 3)ó 7.47-6.78 (m,4); 6.03-5.27 (m,4); 3,93 (s,1); 2.57 (d,2); 2.27 (s,3); 2.07 (m,4). 13_{C NMR} (CDC1 3) ó _{46.76 (C 1, 6); 137,85} (c_{2, 5);} 39.52 (C 7, 8); 50.86 (Cg); 128.19 (Ci); 134.89 _{(Cm); 137.37 (CP); 22,19 (CH3).} m/e~290. 124.93 (C 3 4);

,

130.66 (C 0 ); Mass spectrum Reaction with deuterium oxide afforded 30a, 30b, 31b and 32b.

30b and 32b: mass spectra m/e 291; 1_{H NMR and} 13_{C NMR as}

for 30a. 31c: 1

H NMR (CDC1 3) ó 7.47-6.73 (AB,4); 6,03-5.10 (m,4);

2.60 (m,2); 2.27 (s,3); 2.06 (m,4), 13_{C NMR as for 30a.}

Mass spectrum m/e 291.

Reaction with methyl iodide afforded 30a, 31c and 31c: 1 H NMR (CDC1 3) ó 7.60-6,93 (AB,4); 5,87 (m,4); 2.50 (m,2); 2.43 (s,3); 2.13 (m,4); 1.43 (s,3), 13_{C NMR} (CDC1 3) ó 22.78 and 29.73 (CH_{3); 39,66 (C 7 , 8); 50.20} (C 9); 51.21

cc

1 6); 126.47

_'

cc

3 4); 136.3g

_,

cc

2 5

,

), Mass spectrum.m/e 304. 32ci 1_{H NMR (CDC1} 3) 6 7.60-6.70 (m,3); 5.74 (m,4); 3.54 (t,1); 2.70 (m,Z); 2.23 (s,6); 2.00 (m,4). Mass spec-trum m/e 304.

(43)

.. Reaation of selenoketal 29 with n-BuLi and water This reaction was performed at room temperature.

Quenching and work-up afforded a mixture of n-butyl p-tolyl

selenide (m/e 228), syn-9-(p-tolylseleno)bicyclo~.2.1]no

nane _{(m/e 294; 3.5 ppm, t, H9) and}

anti-9-(p-tolylseleno)-bicyclo[4.2.1]nonane (m/e 294; 3,6 ppm, s, H₉), which could

(44)

~ TabZe V: 1_H_{NMR SpeatraZ data for} _c 9-substituted produats R1 Rz Hl, 6 Hz-s H7 8

_,

Hg Har Hothers 13a H Ph Se 3.27(t) 6.03(m) 5.27(d) 3.77(t) 7.53-6.87(m) 14a Ph Se H 3.20(d) 5.90(m) 5.23(d) 3.47(s) 7.53-6.87(m) 13b D Ph Se 3.3(d) 6. 1 (m) 5,33(d) 7.53-6.87(m) 14b Ph Se D 3.20(d) 5.90(m) 5.23(d) 7.53-6.87(m) 14c Ph Se _CH3 2.87(m) 6.07(m) 5.07(d) 7.67-6-87(m) 1.33(s) 14d Ph Se

-

PhC(OH)H 2.97(m) 6.07(m) 4.53(d) 7.70-6.70(m) 3,53(s) 3.43(m) 4.33{s) 14e Ph Se _{Ph 2C(OH) 3.93(m) 5.90(m) 4.23(d)} 7.70-6.70(m) 3.40(s) 14f Ph Se C(O)H 3.30(m) 6.13(m) S.ZO(d) 7,60-6,70(m) 9.07(s)

-1'8a H p-tolSe 3.17(t) 5.9(m) 5.13(d) 3.57(t) 7.36-6,73(AB) 2.33(s)

19a p-tolSe H 3,10(d) 5.78(m) 5,08(d) 3.27(s) 7.36-6.73(AB) 2.27(s)

18b D

-

p-tolSe 3.2(d) 5.9(m) S.13(d) 7.37-6.7(AB) 2.33(s)

19b p-tolSe D 3.10(d) S.SO(m) S.lO(d) 7.4-6.77(AB) 2.27(s)

(45)

-Tab~e V ( Continued) R' _R2 _{H1 6} _H2-s _{H7 8} _Hg _Har _Hothers 1

_•

'

19c p-tolSe _CH3 2.82(m) 6.03(m) 5.07(d) 7.47-6.77(AB) 2.28(s); 1.3(s) 19d

-

p-tolSe prenyl 2.92(m) 6. 17 (m) 5.23(d) 7.63-6.93(AB) 5.73-5.23(m); 2.3

(s); 2.1(d); 1. 73 ( s) ; 1.4S(s), 18e

-

PhC(OH)H p-tolSe 3.2(m) 6.09(m) 5.09(m) 7.67-6.67(m) 2.52(s); 2.3(s);

2.SS(m) 4.38(s).

19e p-tolSe PhC(OH)H 2.97(m)

-

6.08(m) 4,52(d) 7.60-6.73(m) 3.53(s); 2.3(s); 3.53(m) 4.33(s). 18f RC(OH)

-

p-tolSe 2.88(m) 6.10- 4.8(m) 7.67-6.83(m) 3.6-3.1(m); 2.3 2.47(m) 5.43(m) ( s) ; 1.36(d) 19f p-tolSe RC(OH) 3. 1 (m)

-

6,03(m) 4.92(m) 7.33-6.8(m) 3.67(d); 2.9-2.7 3.0(m) (m) i 2,27(s); 1 • 2 (d)

.!!&

RC(OH) p-tolSe 2.8- 6.0(m) 5.33- 7 .67-6.93(A:6) 3.3-2.8(m); 2.28(

2.S(m) 4.83(m) s}; 2.28-0.57(m).

~ p-tolSe RC(OH) 2.83- 6.0(m) 4.93(m) 7.4-6.7(AB) 3.47-2.97(m); 2.27

2.47(m) (s); 1,6-0.43(m).

23a H o-tolSe 3.33(t)

-

6.33(m) 5.4(d) 3.8(t) 7.7-6.9(m) 2.33(s)

24a o-tolSe H 3.17(d) 5.83(m) 5.17(d) 3.37(s) 7.4-6.73(m) 2.33(s)

(46)

-t

~able VI: 1H NMR Speatral data aompounds formed via eleatrophilia aromatia eubstitution R

x

_{H1 6} _Hz-s _{H7 8} _Hg _Har _Others

•

15b H D 3.30(t) 6.10(m) 5.33(d) 3.77(t) 7.53-6.87(m)

-15c H CH₃ 3.23(t) 6.00(m) 5.23(d) 3.66(t) 7.53-6.73(m) 2.37(s) 15d H PhC(OH)H 3.13(t) 5.90(m) 5.13(d) 3.SO(t) 7.70-6.70(m) 6.1(s); 2.8(s)

-15e H Phz(OH) 3.07(t) 5.90(m) S.ZO(d) 3.52(t) 7.60-6.70(m) 5.67(s)

15f H C(O)H 3.30(t) 6.03(m) 5.30(d) 3.77(t) 7.60-6.70(m) 10.20(s) .!.§.& H C(O)OH 3.40(m) 6.00(m) 5.37(d) 3.83(t) 8.67-7.00(m) ZOb _p-CH3D 3.20(m) 5.90(m) 5.13(d) 3.57(t) 7.37-6.70(m) 2.27(s)

-20c p-CH 3 CH3 3.17(t) 5.97(m) 5.20(d) 3.53(t) 7.40-6.73(m) 2.33(s); 2.22(s) 20d p-CH_{3 PhC(OH)H} 3.50(t) 5.98(m) 5.18(d) 3.70(t) 7.67-6.73(m) 2.28(s); 2.9(s); 6.18(s)

-25b _{o-CH 3}D 3.33(t) 6.33(m) 5.40(d) 3.80(t) 7.70-6.90(m) 2.43(s) 25c o-CH_{3 CH 3} 3.20(t) 6.00(m) 5.18(d) 3.60(t) 7.50-6.70(m) 2.33(s)

(47)

-Table VII: 13_{C NMR Speatral data for}

_c

9-substituted produats~ c 1 '6 c2,5 c3 4 c7,8 Cg

ei

c c c cothers

'

0 m p 13a 49. 10 135.32 127.22 125.10 42. 13 132.41 130.0 134.41 129.87 14a 51.33 136.31 125.37 122.54 41.95 1 31 • 90 130. 1 7 134.10 1 28. 1 0 14b 51.33 136.31 125.37 122.54 41.95 1 31 • 90 130. 17 1 34. 1 0 128.10

-14c 55.63 135.69 127.35 121.93 46.76 129.03 129.56 137.85 129.56 29.30 14d 47.11 134. 19 128.63 119.63 76.09 128.37 130.04 136.92 129.64 63.70

-51.08 135.51 127.44 1 20. 16 14e 51 • 12 135.34 127.22 117.56 68.99 128.94 126.75 129.25 129.95 84.73 18a 48.79 134.89 127.22 124.62 42.26 128.76 130.39 134.89 137. 1 22.14 19a 51.39 136.00 125.23 122.19 46.80 128.19 130.66 134.63 137,32 22.19 19b 51.39 136.00 123.23 122. 19 46.80 128.19 130.66 134.63 137.32 22.19 19c 55.49 135.03 127.48 121.57 46.10 126.38 130.09 137.98 137.98 22.28; 29.73

-18e 53.95 135.69 127.31 123.34 73.76 126.25 130.22 139.09 139.61 22.28; 66.17

-52.05 126.56 122,06 19e 50.99 134.23 127.57 120.07 76.01 124.62 130.92 137.06 139. 19 22.36; 63.52

-46.89 135.64 128.10 119. 59 8f 54.26 136.58 127.48 123.94 68.02 7 8. 1 2; 21 • 68; 58.84 134.73 125.32 121.65 46.88; 22.81 19f 51.34 135.68 128.67 120.83 65.56 77.51; 43.55;

(48)

-Table VII (aontinued) c1,6 Cz s

,

c3 4

,

c7,8 Cg

c.

'1-

co

c

m CP cothers b .1.§..&T- 48.84 133.80 1 26. 51 117.83 61 • 1 0 73.00; 35.25; 45.65 132.89 125.34 117.23 29.43; 20.24; b 12.99; 11 • 1 3 1..2..g_T- _51.69 _133.50 _124.87 _121.07 _65.84 _72.96; _38.27; 132.81 1 24.39 120.47 26.92; 20.24; 14.11; 1 0. 61 23a 48.92 135.12 127. 26 124.70 40.94 133.57 140,63 127.44 127.70 23.86 134.37 130.62 24a 51 • 26 136.04 125.41 122.32 45.39 133.30 140.14 127.31 127.44 23.42

-132.42 130.79 24c 58.58 135.04 127.27 121.76 58.32 131.20 138.65 126.79 129.13 23 134.82 130.54 27.09

~See Table V for structures and numbering scheme. ~T designates the threo diastereoisomer;

the speetral data for the erythro diastereoisomer could not be ànalyzed.

(49)

Table VIII: 13C NMR Speetral data for compounds foPmed via eleat~ophilic aromatic substitution~ R

x

_{c1 ,6} _{c2 5} _c3,4 _{c7 8} _Cg _car Others

'

15b H D 49.10 135,32 127.22 125.10 42.13 132,41 130.00 134.41

-129.87 15c H CH₃ 48.92 135.12 127.26 124.70 40.94 133.57 140.63 127.44 23.86

-127.70 134.37 130.62 1Sd H PhC(OH)H 48.79 135.47 127.22 124.88 43.10 146.85 144.47 136.62 67.23 131 • 63 129.25 128.45 15e H _{Ph 2C(OH) 48.53 135.42 127.46 124.92 44.05 150,38 1 48. 1 3 1 38. 64 84.00}

-131 • 23 129.73 128.90 127.62

.!i&

H C(O)OH 48.41 136.0 8 127.28 125.04 37.55 139,66 133.30 132.50 169.20 130,80 130.56 125.71 20b p-CH₃ D 48.79 134.89 127.22 124.62 42.26 137.10 134.89 130.39 22. 14 128.76 20c p-CH₃ CH 3 48.96 134.98 127.18 124.62 41.24 140.94 137.98 131.45 23.87 127.88 135.16 125.71 21 • 96 25b _{o-CH 3} D 48.92 135.12 127.26 124.70 40.94 140,63 134.33 133.57 23.86

-130.62 127.70 127.44

(50)

Tabt.e IX: 1 _{H NMR Speatroal data foro tetroaayalia aompounds}

H

H Se R .

' x

R

x

_{Hl ,6} _Hz _H3 _{H3 4} _{H4 5} _H5 _H7,8 Others

'

' 16a H

-

5-H 2,85(m) 3.50(m) 5,07(d) 2.85(m) 5.88(t) 7.4-6.7(m) 2.30(m) 17c H _{3-CH 3 2.80(m)}

-

2.15(m) 2.47(q) 5.45(m) 6.10(t) 7.4-6.67(m) 2.15(m) 1.15(d) 21 a p-CH3 5-H 2. 7 5 (m) 3.SO(m) 5.13(d) 2.75(m) 5.93(t) 7,3-6.67(m) 2.06 2.06(s) 26a o-CH3 5-H 2,53(m)

-

3,50(m) S.OO(d) 2.53(m) 5.90(t) 7,2-6.9(m) 2.30(m) 2.30(s) 26b o-CH₃

-

5-D 2.88(m) 3.60(m) 5.20(d) 2.30(m) 6.10(t) 7.2-6.8(m) 2.30(s) 27c o-CH 3-CH₃ 3.25(m)

-

3 3.25(m) 2.40(q) 5. 1 0 (m) 6.17(t) 7.06-6.7(m) 3.03(m) 1.20(d)

Hückel and Möbius aromaticity in bicyclic systems