Synthetic Applications in Radical/Radical Cationic Cascade Reactions

FULL PAPER

Synthetic Applications in Radical/Radical Cationic Cascade Reactions^°

Heiko Rinderhagen and Jochen Mattay*^[a]

Abstract: Oxidative photoinduced elec-

tron transfer (PET) reactions have

been performed with various cyclic cy-

clopropyl(vinyl) silyl ethers bearing an

olefinic or acetylenic side chain. The

reactions result in bi- to tetracyclic ring

systems via a fragmentation radical/

radical cationic addition reaction path-

way with well defined ring juncture.

The mode of cyclisation (endo/exo) can

be partially controlled by addition of

nucleophiles due to the suppression of

radical cationic reaction pathways.

Quantum chemical calculation of the

cyclisation transition states underline

the experimentally found selectivities.

Additional mechanistic studies con-

cerning the saturation step reveal that

the final radical is saturated mostly by

the solvent and traces of water in the

solvent.

Keywords: domino

electron transfer

reactions

polycycles

¥

radical ions ¥ radical reactions

Introduction

sitizer is regenerated by back electron transfer. For generat-

ing radical cations 1,4-dicyanonaphthalene (DCN) or 9,10-

dicyanoanthracene (DCA) are often used as sensitizers. A

simplified mechanism of a sensitized PETreaction is shown

in Scheme 1 (top).

Radical cascade reactions had become very popular since

their introduction to synthetic chemistry in the early 70s es-

pecially for synthesizing polycyclic compounds.^[1Though

8]

the tin hydride method, which was introduced by Giese

et al., is still very important in radical chemistry, there are

considerable interests to circumvent the toxic trap of tin

chemistry.^[9]One possibility for starting radical or radical ion

reactions without tin chemistry is the electron transfer acti-

vation.^[10]In these reactions oxidizing or reducing agents

such as metal salts are usually used.

Sensitized PETreactions are often very slow and have

low quantum yields due to dominating back electron trans-

fer. In these cases the addition of cosubstrates (e.g. biphenyl

or phenanthrene to DCA or DCN sensitized reactions) is

useful. In these reactions the substrate is not oxidized (or re-

duced) by the excited sensitizer but by the radical ion of the

co-sensitizer via a thermal electron transfer step without the

Alternatively the methodology of the photoinduced elec-

tron transfer (PET) can be used for carrying out such reac-

tions.^[11]The advantage of the PET is that the addition of in-

organic salts can be circumvented, which among other ad-

vantages simplifies the work up procedures. The PET is

based on the fact that the redox properties of molecules are

drastically changed upon excitation, that is, both the elec-

tron donating as well as the electron accepting behavior of

the excited species are approximately enhanced by excita-

tion energy. For synthetic purposes PETreactions are often

carried out using a sensitizer which has three characteristics.

It is the substrate which is excited for the primary PET

process, its resulting radical ion or radical is so inert, that it

does not react with the substrate and in most cases the sen-

[a] Dr. H. Rinderhagen, Prof. Dr. J. Mattay

Organische Chemie I, Fakult‰t f¸r Chemie

Universit‰t Bielefeld, Postfach 100131, 33501 Bielefeld (Germany)

Fax : (+49)521-106-6417

E-mail: mattay@uni-bielefeld.de

[^°] Cyclopropyl silyl ether Radical Cations, Part 1.

Scheme 1. Simple sensitized (top) and co-sensitized (down) PETprocess.

Sens: sensitizer, D: donor (substrate), C: co-sensitizer, P: product.

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DOI: 10.1002/chem.200304827

¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

FULL PAPER

problems of back electron transfer

(ET_b). The key step is still the pri-

mary PETprocess (ET _a) in which

the co-sensitizer radical ion is

formed (e.g. F_fri=0.83 for DCA/bi-

phenyl).^[12]In co-sensitization sys-

tems the overall quantum yield is

high and the reaction is fast

(Scheme 1, bottom).

An additional effect of the co-

sensitization may lead to different

products or product ratios, which is

caused by the efficient sensitizer

radical ion substrate ion separation.

This separation inhibits the early

back electron transfer to the sub-

strate radical ion or early intermedi-

ates and favors products of complex

reaction

Scheme 1, bottom).

pathways

(late

ET_c,

Scheme 2. Radical and radical cationic reaction pathways.

For synthetically and mechanisti-

cally reasons, we are interested in

donor substituted strained systems, such as cyclopropyl silyl

ethers, which react under chemical oxidation processes as

well.^[13,14]In former investigations we could show that cyclo-

propyl silyl ethers attached to cyclic systems predominantly

undergo endo-cyclic fragmentation upon one-electron oxida-

tion; this resulted in distonic radical cations or the corre-

sponding radicals, which were formed by nucleophile assist-

ed cleavage of the formal trialkylsilyl radical cation

(Scheme 2).^[15,16]

These radicalic species can be trapped by radicalophilic

agents such as electron deficient alkenes. In the absence of

such reagents the endo radicalic species rearrange to the

corresponding exo radicals; the exo:endo product ratio is

mostly determined by the interaction between the radical

stability and the ring strain. In

Scheme 3. Simple cascade reaction for building up bicyclic systems.

addition, studies on the concen-

tration dependence have re-

vealed a slow termination step.

This complicates intermolecular

radical additions due to the pre-

dominant polymerization but

eases complex cascade reac-

Scheme 4. Complex cascade reactions for building up polycyclic systems.

tions by avoiding an early satu-

ration of intermediate radicals.

In this article we will focus

clopropanisation (Scheme 5, Table 1). The cyclopropanisa-

tion was monitored by GC/GC-MS to circumvent reactions

of the additional non-donor activated olefinic bonds in the

starting materials. The desired cyclopropylsilyl ethers were

obtained as colorless liquids after distillation or fast column

chromatography of the crude products. The cyclopropana-

on the synthetic scope and limitations of the PETinduced

fragmentation reactions of cyclopropyl silyl ethers suitable

for radical cascade reactions resulting in bicyclic and tricy-

clic systems. (Schemes 3 and 4).

Results and Discussion

Synthesis of the starting materials: All vinylcyclopropyl silyl

ethers 8 14 were synthesized starting from the correspond-

ing ketone in a two-step reaction, using LDA/trimethylsilyl

chloride for silylation and diethyl zinc/diiodomethane for cy-

Scheme 5. Synthesis of the vinylcyclopropyl silyl ethers.

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851 874

procedures (1b d, 3)^[17,18]or fol-

Table 1. Vinylcyclopropyl silyl ethers synthesized.

lowing strategies shown in

Ketone

Cyclopropyl silyl ether

Ketone

Cyclopropyl silyl ether

Scheme 6

enones.

for 3-substituted

After reaction with Grignard

or analogous lithium organic re-

agent of the semiprotected b-di-

ketone 15, the resulting b-hy-

droxy acetal 16 was hydrolyzed

to the corresponding b-hydroxy

ketone 17. Acid-catalyzed elim-

ination finally led to the desired

product 18.

For the elimination the use of

85% phosphoric acid and n-

pentane as solvent at room

temperature turned out to be

the method of choice. When an

acidic ion exchange resin under

azeotropic removal of the reac-

tion water was used instead, a

1:1 mixture of the enone and

the open chain retro-aldol

product was isolated as shown

for the cycloheptanone deriva-

tive 18 in Scheme 7.

The alternative synthesis of

3-substituted enones 18 starting

from the vinylogous esters 19 is

recommended if the synthesis

of the bromide is complicated

or the elimination partially

leads to retro-aldol products

even under phosphoric acid

conditions.

For the synthesis of the semi-

protected b-diketones 15 two

different strategies are suggest-

ed.^[19,20]Starting from the easily

accessible enone acetal 22 the

product can be synthesized by

oxymercuration and oxidation

of the resulting alcohol 23.^[19]

Alternatively the corresponding

enone epoxide can be reduced

to the alcohol which is again

oxidized to the desired prod-

uct.^[20]However, the latter syn-

thesis failed in our hands.

Though we could synthesize an

Scheme 6. Synthetic strategies for synthesizing 3-substituted cyclic enones.

alcohol and

a corresponding

tion reaction resulting in cyclopropyl silyl ether 13 and 14

showed only negligible diastereoselectivity and therefore the

products can be isolated in an approximately 1:1 mixture of

the two diastereoisomers. Only in the case of the 4-substitut-

ed derivative 14 the diastereoisomers have been separated

by preparative GC for mechanistic reasons (see below).

Most of the ketones were synthesized according to known

Scheme 7. Retro-aldol reaction during elimination.

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J. Mattay and H. Rinderhagen

FULL PAPER

ketone by applying the suggested synthetic procedures in

good yields (80 90%), the products turned out to be the a-

hydroxy or the a-diketo regioisomers, respectively, unequiv-

ocally proven by one- and two-dimensional NMR experi-

ments. To circumvent the use of mercury salts we developed

an alternative route for the synthesis. Starting from the

enone acetal after hydroboration using 9-BBN and Swern

oxidation the product was obtained in good yields. The use

of hydroboration reagents other than 9-BBN resulted in par-

tially reduction of the acetal function (Scheme 8).

ing the PETsensitizer, occasionally in presence of a co-sen-

sitizer, were irradiated in a Rayonet photochemical reactor

using the appropriate wavelength (DCN: 350 nm; DCA:

419 nm). The conversion of the starting material was moni-

tored by GC or GC/MS.

Simple cascade reactions: The results of the irradiations of

the simple substrates 8 10 in pure acetonitrile are summar-

ized in Scheme 10. The products were isolated by HPLC

and unambiguously identified by spectroscopic analysis

(mostly one and two dimensional NMR as reported in the

Experimental Section). The stereochemistry of the cyclisa-

tion products 28 and 29 was assigned by comparison with re-

ported NMR data.^[25]The structure of the tricyclic com-

1

pound 31 was established by comparison with the H NMR

data of the cyclisation products of the complex cascade reac-

tions, which were identified by qualitative and partially

quantitative NOESY spectroscopy (see Table 2).

Only the PETreactions of the seven- and eight-membered

ring derivatives 8b,c gave the desired cyclisation products.

For the six- or nine-membered ring starting materials the

ring strain of the four- (8a) or the seven- (8d) membered

rings in the potential products suppresses the transannular

cyclisation. The transannular addition towards the aromatic

system of 9 is obviously reversible resulting in the more

stable open chain product 33 as shown in Scheme 11 (for

simplification only the radical reaction pathways are

shown).

The unusual b,g-unsaturated product 30 can be explained

by a transannular hydrogen abstraction followed by a kinetic

saturation of the allyl radical (Scheme 12).

Interestingly all cyclisation products exhibit only cis-ring

connections. This is not surprising for products which con-

tain a bicyclooctanone substructure because of the high ring

strain of the corresponding trans products. Similar effects

may also govern the energy of the transition state as expect-

ed for kinetically controlled reactions of this type.^[26]

Scheme 8. Synthesis of the semiprotected b-diketone 15 and vinylogous

acetal 19.

The vinylogous esters 19 were synthesized by acid-cata-

lyzed esterification. When carrying out this reaction it is ad-

visable to thoroughly remove the reaction water, for exam-

ple, by molecular sieves, otherwise, retro-crossed Claisen

condensation products 24 are formed especially at longer re-

action times (Scheme 8).

The required alkyl bromides (Scheme 6) for the metal or-

ganic reagents were either commercially available or synthe-

24]

sized according to known procedures.^[21

For the synthesis

of enones 5a,b the corresponding trimethylsilyl protected

derivatives were used. After the reaction the protective

group was removed by tetrabutylammoniumfluoride

(TBAF) in an aqueous THF solution. In case of the cyclo-

hexenylmethyl side chain (product 6a,b) the use of lithium

organic compounds is necessary

Complex cascade reactions: The results of the irradiations

of the more complex substrates 11 14 in pure acetonitrile

are summarized in Table 2. The products were isolated by

because the analogous Grignard

reagent resulted in reduction of

the carbonyl group due to its

steric hindrance.

The 4-substituted derivative 7

was synthesized as shown in

Scheme 9. Besides the desired

enone the diastereoisomeric al-

cohols 26a and 26b were isolat-

ed, of which only the cis-isomer

26a could was successfully con-

verted to 7 by elimination.

Cyclization under PET condi-

tions: The deoxygenated solu-

tions of the respective cyclo-

propyl silyl ethers 8 14 contain- Scheme 9. Synthesis of the 4-substituted derivative 7.

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Scheme 10. Products of simple cascade reactions.

tion). The stereochemistry of

the cyclisation products was as-

signed

using

quantitative

NOESY spectroscopy support-

ed by molecular modeling as-

signments of the respective ge-

ometries using MMFF94 force

field calculations and thorough-

ly evalution of the ¹H NMR

coupling constants and the

chemical shifts. Especially for

the cyclisation products of the

cycloheptane starting materials

(11a/12a/13a), the relatively

simple latter method allows

Scheme 11. Reversible addition towards the aromatic system.

partially stereochemical assign-

ments due to the rigid molecu-

lar scaffold. For example, the

agreement of the respective

coupling constants and the

chemical shifts of the a-car-

bonyl protons and the bridge

head proton H^Cindicates that

all cyclisation products have

the same A/B and A/C ring

Scheme 12. Transannular hydrogen abstraction followed by kinetic saturation.

junction (Table 3). Additional-

ly the order of magnitude of

the respective coupling con-

HPLC and if necessary by preparative GC and unambigu-

ously determined by spectroscopic analysis (mostly one- and

two-dimensional NMR as reported in the Experimental Sec-

stants indicates a cis/cis junction. The relatively large cou-

pling constant of the bridge head proton H^Cand the cis con-

nected a-carbonyl proton H^Aindicates a small dihedral

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J. Mattay and H. Rinderhagen

FULL PAPER

Table 2. Isolated photoproducts.

using Boltzmann weighting are

also shown as well for compari-

son (see Table 4).

Not (completely)

cyclized Product [%]

endo-

Product [%]

exo-

Product [%]

exo-

Product [%]

The occurrence of the non-

cyclised products 34, 38 and 41

can be explained by a transan-

nular allylic hydrogen abstrac-

tion of the exo-methyl radical

(Scheme 13). The subsequent

kinetic saturation of the result-

ing allylradical led to b,g-unsa-

turated products. Probably the

3-substitution slows down the

desired transannular addition

(path A) and therefore the 1,2-

rearrangement (path B) occurs,

which results in the non-cy-

clised products. Interestingly

the non-cyclised products are

not stable upon prolonged reac-

tion times in contrast to their

cyclised counterparts. Obvious-

ly the non-cyclised products are

more oxidative labile due to

their highly substituted olefinic

bond. The cyclisation products

are resulting from two-step

radical addition cascade reac-

tions. All cyclisation products

show only cis-ring connec-

tion of either the first- or

the second step irrespective

of the mode of cyclisation

(endo or exo). Interestingly the

second addition step leads to

relatively large amounts of

endo products in comparison

to the classical exo preference

of radical cyclisation reac-

tions.^[27]One reason for these

11

a (n=1)

b (n=2)

20

15

19

12

22

15

9

6

17

12

a (n=1)

b (n=2)

6

32

30

12

13

a (n=1)

b (n=2)

11

10

12

14

a

b

40

angle between these protons. In contrast the trans proton

H^Bshows only a small coupling constant towards H^Cbut an

additional W coupling (⁴J^D) towards the cis-connected a-car-

bonyl proton H^D.

unusual behavior is a radical cationic reaction pathway

which will be discussed in more detail in the next paragraph

(see below).

The cyclisations of the cyclohexenyl methyl substituted

starting materials 13a,b gave an interesting selectivity be-

havior. During the cyclisation cascade four stereogenic cen-

ters are generated. Together with the stereocenter of the

side chain the possible exo and endo products have five ster-

eogenic centers. Though theoretically 16 exo- and endo-

therefore 32 different diastereoisomeric products might be

generated during the cyclisation cascade, only two diaster-

eoisomers are formed.

The relatively high diastereoselectivity can be explained

by the selectivities of the respective radical addition steps.

The first addition step is completely cis selective at the ring

junction but shows only negligible additional diastereoselec-

tivity. Consequently the primary addition product 45a,b is

formed as a 1:1 diasteroisomeric mixture. The second addi-

tion step is completely diasteroselective as shown in

3

Additionally, the order of the J^Ecoupling constants indi-

cates the cis/trans and the cisoid/transoid arrangement of the

products 36a/37a and 42a/43a, respectively, while the ³J^F

constant indicates a cis junction of both tetracyclic com-

pounds. However, especially the latter interpretations are

only possible with additional NOESY experiments. These

experiments were carried out and quantitatively evaluated

for all products using diastereoisomeric geminal methylene

groups as reference. In order to support these NOESY ex-

periments additional population analysis was carried out.

The respective H H distances in each of the resulting con-

formers were measured for comparison. The results of one

such evaluation are shown in Table 4.

Besides the NOESY evaluated distances the smallest, the

largest and the average distance of the population analysis

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851 874

Table 3. ¹H NMR chemical shifts [ppm] and J coupling constants [Hz].

H^A

H^B

H^C

H^D

²J^A

³J^B

³J^C

⁴J^D

³J^E

³J^F

2.447

2.144

2.080

2.027

19.3

8.8

2.8

1.6

2.374

2.004

2.162

2.107

18.4

10.2

3.3

2.0

10.5

2.560

2.024

2.158

1.803

18.5

9.2

4.8

1.9

5.5

2.626

2.023

2.272

2.760

18.8

9.7

4.5

1.9

2.506

2.111

2.183

2.530

18.9

9.0

3.8

1.6

2.644

2.104

2.333

2.482

19.2

9.9

4.6

2.1

8.2

5.0

2.557

2.076

2.222

2.011

18.4

9.3

6.1

1.8

3.0

5.3

insignificant

not existent

insignificant

Table 4. Exemplary NOESY evaluation.

Mechanistic investigations

Radical ion versus radical re-

action pathways: As mentioned

above the second cyclisation

step of the cascade reaction

shows unusually large amounts

of endo-cyclisation products.

Usually pure radical (non-radi-

cal ionic) reactions prefer 5-exo

cyclisations. This preference can

be partially or predominately

suppressed by steric effects. In

this case the rigid bicyclic struc-

ture of the first addition step in-

termediate may cause the oc-

currence of the 6-endo cyclisa-

tion products. On the other

hand radical cationic reaction

pathways may be the reason for

this unusual behavior. For ex-

No.

r_NOE

r_Bolz

r_MIN

r_MAX

1

2

3

4

5

6

7

1.79

2.28

2.13

2.62

ꢀ1.77

2.35

2.65

1.79

2.49

2.36

2.75

1.77

2.46

2.72

1.79

2.28

2.30

2.37

1.76

2.35

2.58

1.80

2.65

2.41

2.80

1.77

2.48

3.74

r_NOE: Distance evaluated by NOESY spectroscopy (reference: ™ꢀ∫). r_Bolz: Average distance of conformational

analysis using Bolzmann weighting. r_MIN: smallest distance of conformational analysis. r_MAX: largest distance of

conformational analysis.

Scheme 14. The subsequent saturation is not important for

the isomer distribution.

ample, silyl enol ether radical cations (e.g. 47) predominate-

ly cyclize in a 6-endo fashion, as we have shown in former

The 4-substituted starting material only partially cyclises

under PETconditions. This is caused by the selectivity of

the first addition step, which exhibits not only cis selectivity

but takes place under equatorial alignment of the side chain

(Scheme 15). This unfavorable alignment suppresses further

cyclisation. Interestingly the partially cyclised product 44 is

formed upon irradiation irrespective which diastereoisomer-

ic starting material (14a or 14b) is used, which underlines

the proposed stepwise mechanism (fragmentation, addition)

rather than a concerted one (e.g. cationic induced rearrange-

ment).

31]

studies.^[28By addition of strong nucleophiles such as alco-

hols the endo/exo product ratio can be lowered due to the

fast cleavage of the formal trimethyl silyl cation; this results

in the a-carbonyl radical 48 which cyclises predominately in

31]

a 5-exo mode (Scheme 16).^[28

Analogous to these results the occurrence of relatively

large amount of the endo products can be explained by radi-

cal cationic reaction pathways as shown in Scheme 17. On

the one hand the distonic radical cation 49, the result of the

first fragmentation process, may lose the silyl group; this

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radical cation should cyclise

predominantly in an endo fash-

ion if not suppressed by steric

31]

effects.^[28

An investigation of the influ-

ence of isopropanol on the

endo/exo ratio of the irradiation

products of the cyclopropyl silyl

ethers 11a,b and 12a,b in com-

parison with silyl enol ether 46

provides strong evidence that

the endo products are partially

caused by radical cationic reac-

tion pathways. The addition of

20% of isopropanol lowers the

amounts of the endo products

of all cyclopropyl silyl ethers,

caused by faster cleavage of

the silyl group resulting in pre-

Scheme 13. Reaction pathways in the cascade reactions.

dominant

radical

reaction

pathways (Scheme 18). As ex-

pected the effects are smaller

compared with silyl enol ether

46. The relevant cyclisation

step is the last one of a three

step (fragmentation; first cycli-

sation; second cyclisation) cas-

cade reaction. This allows

cleavage of the silyl group

even in the absence of addi-

tional nucleophiles.

Deuterium labelling studies:

For the last reaction step, that

is the saturation of the radical,

two mechanisms can be dis-

cussed. On the one hand a

formal hydrogen radical trans-

fer of a suitable donor (e.g. the

solvent) by homolytic bond

cleavage is possible. On the

other hand a reduction of the

radical by the sensitizer radical

anion followed up by protona-

tion (e.g. by traces of water in

the highly hygroscopic acetoni-

trile) can be discussed as well

(Scheme 19).

Both mechanisms are consis-

tent with the observation that

the saturation step is relatively

slow, because neither good hy-

drogen-radical or proton-donor

Scheme 14. Diastereoselectivity of the cascade reaction of 13 (only one enantiomer is shown).

would yield the b-carbonyl radical 50 which reacts to the

endo or the exo products. On the other hand the radical

center of the distonic radical 49 may add vinylogously to the

cationic center resulting in the non-distonic radical cation 51

which is identical to the radical cation 47 of the silyl enol

ether 46. Analogous to our former published results this

sources are added under standard reaction conditions. In

order to elucidate this part of the reaction mechanism in

more detail, we carried out deuterium labelling experiments

using the easily synthesizable cyclopropyl ether 52 and vari-

ous mixtures of deuterated and non-deuterated solvents

(Scheme 20). The degree of deuteration was thoroughly ana-

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Chem. Eur. J. 2004, 10, 851 874

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851 874

lyzed by mass range optimized

GC-MS of the reaction mix-

tures.

At first sight two aspects can

be concluded from the experi-

mental results. Firstly, either

acetonitrile or water are sour-

ces for the saturation. Secondly,

at least one additional source is

responsible for the saturation of

the final radical. Additionally

the experiments show three in-

teresting effects.

Scheme 15. Partial cyclisation of the 4-substituted starting material 14a,b.

*

In deuterated acetonitrile

the deuteration degree of

the exo product is much

larger than that of the endo

product. In contrast in non-

deuterated acetonitrile con-

taining D₂O the endo prod-

uct exhibit the larger deut-

eration. This is consistent

with the assumption that

the primary exo radical is

predominately

saturated

radically by the acetonitrile

due to its higher reactivity,

while the back electron

transfer protonation reac-

tion pathway play a more

important role in case of the

endo radical.

Scheme 16. Regioselectivity controlled by radicalic and radical cationic reaction pathways.

*

The addition of water to

deuterated acetonitrile re-

sults in partially suppression

of the deuteration degree.

Obviously the added water

results in an acceleration of

the non-radical pathway

that is, in this case non-deu-

terated reaction.

*

The last effect is the most

interesting. If one compares

the results of CD₃CN/10%

D₂O with the two comple-

mentary experiments of

CD₃CN/10%

H₂O

and

CH₃CN/10% D₂O] one ob-

servation is amazing. The

grade of deuteration of the

fully deuterated experiment

is much larger than the sum

of the complementary ex-

periments. This indicates a

strong kinetic isotopic of

one or both of the discussed

saturation pathways.

Scheme 17. Radical and radical ionic reaction pathways.

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FULL PAPER

reversibility of radical addition reactions we calculated the

relative energies of the respective transition states. Due to

the large computational cost we confined our calculation to

the radical reaction pathways.

In case of the first (transannular) addition step one has to

take into consideration that the essential Z orientation of

the cyclic enone determines the stereoselectivity of the addi-

tion step. For this reason we calculated the relative energies

of the cis and trans transition states of either the (E)- or the

(Z)-2-heptenen-4-one radical resulting in the corresponding

cis-

or

trans-3,4-dimethyl-1-cyclopentanone

products

(Scheme 21). We used this open chain model compound for

simplification and for circumventing problems while search-

ing the transition states caused by ring strain effects. On the

other hand the geometries of the transition states of the

system are very useful for explaining the selectivities of the

transannular addition (see below).

Scheme 18. Amounts of endo and exo product with 0 and 20% isopropa-

nol.

Interestingly the corresponding cis- and trans-transition

states differ only slightly in energy while the structural dif-

Scheme 19. Possible saturation pathways.

Scheme 21. Transition states for the selectivity consideration of the first

addition step.

ferences mostly appear in the alignment of the methyl

groups. This alignment is finally the reason for cis-selectivity

in the corresponding cyclic systems. For example, the methyl

groups in the transition state TS1 leading to the trans-prod-

uct starting from the (Z)-olefin include a dihedral angle of

1528. In a cyclic system this dihedral angle would cause such

a large ring strain that the respective product cannot be

formed (Scheme 22).

Scheme 20. Deuteration experiments for elucidation of saturation path-

ways.

Finally it can be concluded that the solvent and additional

traces of water in the solvent are important sources for the

saturation of the final radical. One or more additional satu-

ration pathways (e.g. radical saturation pathways from the

sensitizer or the silyl group) are not negligible. On the other

hand, because of the strong kinetic isotopic effects of the

major saturation pathways (acetonitrile/water), these addi-

tional pathways are less important than the quantitative

values in Scheme 20 may suggest.^[32]

Theoretical investigation of the selectivities: All cyclisation

cascade reactions exhibit strong cis diastereoselectivities

concerning either the first or the second ring connection.

For a deeper understanding of this selectivity we carried out

quantumchemical calculations.^[33]Because of the general ir-

Scheme 22. Geometries (B3LYP6-31 G*), relative energies [kcalmol^À1

and dihedral angles [8] in the transition states of the first addition step.

]

860

¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemeurj.org

Chem. Eur. J. 2004, 10, 851 874

Cascade Reactions

851 874

The energy differences of the cis- and the trans transitions

states of the second addition step concerning the simple side

chain starting material 11a,b and 12a,b exhibit a strong

preference of the cis products underlining the experimental

results. Generally the differences of the bicylononenone sys-

tems (starting materials 11b and 12b) are smaller than

those of the bicyclooctanone systems due to the higher ri-

gidity of the latter systems. This indicates that the selectivity

of the second addition step is mostly caused by the rigid ge-

ometry of the bicyclic system formed in the first addition

step (see Table 5)

hexenyl methyl derivatives 13a,b two different diastereoiso-

meric intermediates 45a and 45b must taken into considera-

tion as depicted in Scheme 14. The energy differences in the

respective group of transition states reveal that one diaster-

eoisomer is energetically favored (Table 6). This underlines

the experimental result of finding only two products (start-

ing from two intermediate radicals) and the mechanistic ex-

planation as discussed above (Scheme 14). Interestingly

even simple AM1 calculations, which are known to be not

suitable for evaluating regioselectivities and electronic influ-

ences of radical addition processes,^[34]predict the selectivity

of the stereochemistry quite

well. This again indicates that

Table 5. Energy differences of the trans- and cis-transition states of the second addition step (B3LYP6-31 G*).

the stereochemistry of these re-

actions are mostly governed by

steric effects. In case of 13b we

only carried out AM1 calcula-

tion due to the large computa-

tional cost of this relatively

large system.

[a]

Substrate

Mode of Cyclisation

E=E_transÀE_cis

Substrate

Mode of Cyclisation

E=E_transÀE_cis

7.4

15.9

16

13.7

18.1

11a

6-endo

5-exo trans^[b]

5-exo cis^[b]

6-endo

11.4

20.2

21.4

13.8

21.0

11b

6-endo

5-exo trans^[b]

5-exo cis^[b]

6-endo

12a

12b

5-exo

[a] cis and trans concerning the ring junction of the second addition step. [b] cis and trans concerning the align-

ment of the methyl group (product 36 or 37).

Conclusion

Additionally stereoelectronic effects may support these

selectivities as shown in Scheme 23. Due to the quasiequato-

rial attack of the olefinic group towards the radical center,

the bond formed in the addition step and the carbonyl p-

bond are nearly perpendicular. This partially suppresses a

possible stabilizing conjugation, which results in a reduced

spin density on the carbonyl oxygen.

PET-oxidative initiated reactions of cyclopropyl silyl ethers

were carried out via b-carbonyl radical cationic and radical

species generated by nucleophile assisted cleavage of a

formal trimethyl silyl cation. These highly reactive inter-

mediates react in radical/radical cationic reaction cascade

reactions to polycyclic compounds, which have been struc-

turally assigned by multiple NMR experiments supported by

force field calculations. Due to the slow termination step

partially cyclized products were

For the selectivity calculations (relative energies of the

transition states) of the second addition step of the cyclo-

not observed except for 14. T he

termination step was proven to

be either a hydrogen radical

transfer from the solvent (ace-

tonitrile) or a stepwise electron

transfer/protonation by traces

of water in the solvent process.

The experimentally found ster-

eoselectivities were evaluated

and confirmed by quantum

chemical calculations.

Scheme 23. 6-endo cis- and trans-transition states geometries (spin density: balls).

Table 6. Relative energies of the transition states of the second addition step of the cyclisation of 13 (cf. Scheme 14).

Diastereoisomers

Precursor

radical

13a

AM1

13a

13b

AM1

B3LYP6-31 G*

5-exo

6-endo

5-exo

6-endo

5-exo

6-endo

cis/cis/cisoid/cis

45a

45b

ꢀ0.0^[a]

10.2

50.7

17.6

78.2

8.3

53.6

26.2

38.9

ꢀ 0.0^[a]

8.2

48.1

17.0

76.4

7.4

53.3

25.1

37.7

ꢀ0.0^[a]

13.3

51.3

25.4

73.2

9.8

50.5

30.0

66.6

cis/cis/transoid/trans

cis/trans/transoid/cis

cis/trans/cisoid/trans

cis/cis/transoid/cis^[a]

cis/cis/cisoid/trans

cis/trans/cisoid/cis

cis/trans/transoid/trans

8.7

7.5

10.1

17.6

15.0

20.2

41.3

39.2

37.7

ꢀ0.0^[a]

10.8

11.3

9.0

25.8

31.2

23.57

29.4

26.2

30.8

[a] Relative energies [kcalmol^À1] were calculated within a group of the same radical precursor (45a or 45b).

861

Chem. Eur. J. 2004, 10, 851 874 www.chemeurj.org ¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

J. Mattay and H. Rinderhagen

FULL PAPER

General procedure B (Swern oxidation): Oxalylchloride (20.0 mL,

220 mmol) and methylene chloride (250 mL) were placed in a dry appa-

ratus under argon atmosphere and cooled to À788C. Dry DMSO

(34.0 mL, 440 mmol) diluted with dry methylene chloride (30 mL) was

added at this temperature during 30 min. The respective alcohol

(100 mmol) dissolved in dry methylene chloride (100 mL) was added

during 30 min and the mixture was stirred for additional 30 min. Triethyl-

amine (70 mL, 500 mmol) was added during 30 min and the mixture was

warmed to À108C and kept at this temperature for 30 min. Water

(100 mL) was added and the mixture was warmed to room temperature.

The precipitating salts were mainly diluted by adding water. The organic

layer was separated and the aqueous was extracted five times with meth-

ylene chloride. The combined organic layers were dried over Na₂SO₄and

evaporated.

Experimental Section

General remarks: Melting points are uncorrected. IR: Perkin Elmer IR-

spectrometer

841

or

Bruker

Perkin Elmer

AC200P

FT-IR-spectrometer1600.

(200.132 MHz), AM250

¹H NMR:NMR:

(250.133 MHz), AM300 (300.133 MHz) or DRX500 (500.132 MHz); in-

ternal standard: TMS (0.00 ppm), CHCl₃(7.24 ppm), C₆H₆(7.15 ppm).

¹³C NMR: Bruker AC 200

P (50.323 MHz), AM250 (62.896 MHz),

AM300 (75.469 MHz) or DRX500 (125.772 MHz); internal Standard:

TMS (0.00 ppm), CDCl₃(77.00 ppm), C₆D₆(128.00 ppm). Mass spectrom-

etry: Micromass VG Autospec X or Finnigan MAT8230. GC/MS: Shi-

madzu GC-17A ver. 3/MS QP 5050 A using Hewlett Packard 5MS (25 m,

0.2 mm, 0.33 mm) column, carrier gas: helium, pressure: 0.95 bar. GC:

Shimadzu GC-17A/ver. 3, FID detector, using Class VP 4.2 software; Sie-

mens Sichromat 3, FID detector, Specta Physics Integrator SP 4290; Sie-

mens Sichromat 1-4, FID detector, Spectra Physics Integrator SP 4400;

columns: Hewlett-Packard Ultra 2 (25 m, 0.2 mm, 0.33 mm), Hewlett-

Packard 1MS (25 m, 0.2 mm, 0.33 mm), Hewlett-Packard 5MS (25 m,

0.2 mm, 0.33 mm); carrier gas: nitrogen. Preparative GC: Hewlett-Pack-

ard 5890 Series II; injektor and automatic fraction collector Fa. Gerstel;

autosampler Hewlett-Packard 7673; column: Hewlett-Packard HP5

(30 m, 0.53 mm, 5.0 mm); carrier gas hydrogen (0.35 0.5 bar). HPLC:

Kontron pump 420 or Merck pump L-6000; RI-detector Bischoff RI

The remaining residue was purified either by column chromatography or

by distillation.

1,4-Dioxaspiro[4.6]undecan-7-ol (23a): Hydroboration of 1,4-dioxaspiro-

[4.6]undec-6-ene (22a; 108 g, 700 mmol) was carried out according to

GPA. Chromatography on silica gel (cyclohexane/ethyl acetate 55:45)

yielded the title compound as a colorless oil (98.5 g, 82%). NMR (¹H,¹H-

COSY, ¹³C,¹³C-DEPT, HMQC); ¹H NMR (500 MHz, CDCl₃, ref. CHCl₃):

d=1.35 1.44 (m, 1H, 9-H), 1.41 1.58 (m, 2H, 10-H), 1.55 1.63 (m, 1H,

8-H), 1.60 1.68 (m, 1H, 11-H), 1.63 1.72 (m, 1H, 9-H), 1.803 (ddd, J=

3.4/8.0/14.6 Hz, 1H, 11-H), 1.896 (dddd, J=3.5/3.5/7.1/13.7 Hz, 1H, 8-H),

1.93 2.04 (m, 2H, 6-H), 3.80 3.91 (m, 4H, 3-H/4-H), 3.84 3.91 (m, 4H, 7-

H); ¹³C NMR (125 MHz, CDCl₃, ref. CDCl₃): d=22.71 (C-10), 24.08 (C-

9), 38.09 (C-8), 38.53 (C-11), 46.17 (C-6), 63.92 (C-2), 64.09 (C-3), 67.89

(C-7), 110.79 (C-5); IR (film): n˜ = 3432, 2951, 2678, 1451, 1370, 1299,

1211, 1184, 1131, 1094, 1027, 972, 947, 902, 870, 812, 785, 695 cm^À1; GC-

MS (70 eV): m/z (%): 172 (1) [M ⁺], 155 (10), 127 (3), 116 (6), 115 (100),

114 (3), 113 (7), 112 (3), 111 (4), 110 (5), 102 (9), 101 (4), 100 (9), 99

(81), 95 (3), 89 (3), 87 (18), 86 (22), 85 (9), 84 (10), 83 (5), 82 (5), 81 (7),

79 (5), 77 (3), 73 (7), 71 (16), 69 (6), 68 (3), 67 (15), 66 (3), 65 (3), 59 (3),

58 (11), 57 (22), 56 (10), 55 (58), 54 (5), 53 (10), 45 (14), 44 (11), 43 (61),

42 (20), 41 (34), 40 (4), 39 (11), 29 (16), 28 (8), 27 (10); GC-MS (CI): m/z

(%): 175 (1) [MH⁺+2], 174(9) [MH⁺+1], 173(100) [MH⁺].

8110; column 250 î 20 mm Merck LiChrosorb Si 60-7; flow 10 mLmin^À1

reversed phase HPLC: column Macherey und Nagel PREP 2025 (250î

;

20 mm) LiChrosorb RP 18 7.0 mm, precolumn: PREP 2005 (50 î 20 mm)

LiChrosorb RP 18 7.0 mm, flow 10 mLmin^À1

.

NMR spectroscopy: ¹H NMR chemical shifts have been assigned either

by thoroughly evaluation of the coupling patterns or by determination of

the center of gravity of the HSQC/HMQC^[35]correlation signals in case

of complex overlapping multiplet signals. In the latter case the stated ac-

curacy (digits) in experimental data reflects the resolution of the experi-

ments used. All experiments for accurate signal assignments are stated in

experimental data.

24,38]

Compounds 1b d,^[17,36]3,^[37]22,^[17]the bromides^[21

and the sensitiz-

ers^[39,40]were synthesized following known procedures.

1,4-Dioxaspiro[4.6]undecan-7-one (15a): 1,4-Dioxaspiro[4.6]undecan-7-ol

(23a; 164 g, 952 mmol) was oxidized according to GP B. The distillation

of the crude product in vacuo yielded in the title compound as a slightly

yellow oil (138 g, 85%). NMR (¹H,¹H-COSY, ¹³C,¹³C-DEPT, HMQC):

¹H NMR (500 MHz, CDCl₃, ref. CHCl₃): d=1.71 1.81 (m, 4H, 9-H/10-

H), 1.898 (m, 2H, 11-H), 2.473 (m, 2H, 8-H), 2.840 (d, J=0.7 Hz, 2H, 6-

H), 3.885 3.965 (m, 4H, 2-H/3-H); ¹³C NMR (125 MHz, CDCl₃, ref.:

CDCl₃): d=23.38 (C-9), 24.29 (C-10), 39.97 (C-11), 43.50 (C-8), 53.11 (C-

6), 64.31 (C-2/C-3), 107.35 (C-5), 209.14 (C-7); IR (film): n˜ = 2940, 1702,

1451, 1369, 1282, 1242, 1199, 1081, 1044, 1017, 1000, 978, 948, 909, 863,

835, 791, 737 cm^À1; GC-MS (70 eV): m/z (%): 170 (2) [M ⁺], 114 (3), 113

(40), 112 (82), 100 (11), 99 (100), 97 (7), 87 (5), 86 (51), 85 (3), 84 (3), 83

(4), 82 (3), 81 (5), 79 (4), 70 (4), 69 (12), 68 (7), 67 (10), 56 (12), 55 (63),

54 (7), 53 (11), 45 (5), 44 (3), 43 (29), 42 (48), 41 (43), 40 (8), 39 (26), 29

(17); GC-MS (CI): m/z (%): 172 (16) [MH⁺+1], 171 (100) [MH⁺].

General procedure A (hydroboration of olefins using 9-BBN): A 1.0m

borane solution (1.00 L, 1.00 mol) in THF was placed in a dry apparatus

under argon atmosphere and cooled to 0 58C. 1,5-Cyclooctadiene (110 g,

1.02 mol) was added while inner temperature did not raise above 258C.

The solution was diluted with dry THF (600 mL) and heated under

reflux for 1 h.

The above 9-BBN solution was cooled to 0 58C and the respective olefin

(700 mmol) was added while the temperature was kept below 258C. The

solution was stirred at room temperature for 48 h.

Ethanol (400 mL) and a 6n caustic soda solution (140 mL) were subse-

quently added. A 30% hydrogen peroxide solution (280 mL) was added

such that the solution was gently boiling. The reaction was heated under

reflux for 1 h and cooled to room temperature. The solution was saturat-

ed under vigorous stirring with potassium carbonate. The organic layer

was separated and the remaining viscous aqueous layer was washed sev-

eral times with Et₂O (4î50 mL). The volatile compounds were carefully

removed in vacuum from the combined organic layers using low water

bath temperature and protective shield. The residue was diluted in Et₂O

(500 mL), eventually separating water was pipetted out and the organic

layer was dried over potassium carbonate. The volatile components were

carefully removed using an rotational evaporator (see below). Finally the

remaining viscous residue had to be kept at for 2 h at 1 2 mbar in order

to remove last traces of THF and ethanol. The residue was diluted with

ethyl acetate (300 mL) and cyclohexane was added until slight persisting

turbidity. For crystallization of the by-product (1,5-dihydroxycyclooctane)

the mixture was first kept at room temperature and then at 48C for some

hours. The bulb was heated to room temperature and cyclohexane was

added again until slight persisting turbitity. The crystallisation procedure

was repeated until most of the 1,5 dihydroxycyclooctane was removed.

3-Ethoxy-2-cyclohepten-1-one (19a): 1,4-Dioxaspiro[4.6]dodecan-7-ol

(23a; 17.2 g, 100 mmol) was oxidized according to GP B without purifica-

tion. The crude product was diluted with Et₂O (300 mL) and 1m H₂SO₄

(50 mL) was added; the reaction mixture was vigorously stirred for 2 h.

The aqueous layer was separated and additional 1m H₂SO₄(50 mL) was

added to the organic layer and the reaction mixture was stirred for 2 h.

The procedure was repeated until complete removal of the acetal group

(GC control).

The combined aqueous layers were extracted with Et₂O (6î50 mL). The

combined organic layers were dried over Na₂SO₄and the solvent was re-

moved in vacuo. The residue was diluted in dry chloroform (400 mL) and

ethanol (14.5 mL, 250 mmol) and p-toluenesulfonic acid (1.0 g, 5.8 mmol)

were added. The mixture was heated under reflux for 36 h while the

water formed was removed by a dropping funnel filled with freshly acti-

vated molecular sieve (4) ä). The solution was cooled to room tempera-

ture, water-free sodium carbonate (10 g) were added and the mixture was

stirred for 10 min. The solid residue was filtered out and the filter cake

was washed with chloroform. The solvent was removed and the residue

was preliminarily cleaned by kugelrohr distillation (0.05 mbar). Chroma-

The supernatant was decanted and the remaining 1,5-dihydroxycyclooc-

tane was washed with cyclohexane/ethyl acetate (95:5). The combined or-

ganic layers were evaporated and the remaining residue was purified by

fast chromatography.

862

¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemeurj.org

Chem. Eur. J. 2004, 10, 851 874

Cascade Reactions

851 874

tography on silica gel (cyclohexane/ethyl acetate 30:70) yielded the title

compound as a colorless oil (9.56 g, 62%).

heated under reflux for 1 h and the respective semiprotected b-diketone

(35.0 mmol) in dry THF (20 mL) was added followed by heating under

reflux for 1 h. Water (5 mL) and a saturated ammonium chloride solution

(15 mL) were added carefully for hydrolysis and the mixture was stirred

for 10 min.

Note: Both the acetal cleavage and the vinylogous esterification should

be carried out under GC control while the probe should be deacidified

before analysis by filtration over sodium carbonate. NMR (¹H,¹H-COSY,

¹³C,¹³C-DEPT, HMQC): ¹H NMR (500 MHz, CDCl₃, ref. CHCl₃): d=

1.299 (t, J=7.0, 3H, 2’-H), 1.72 1.85 (m, 4H, 4-H/7-H), 2.50 2.56 (m,

4H, 5-H/6-H), 3.753 (q, J=7.0 Hz, 2H, 1’-H), 5.330 (s, 1H, 2-H);

¹³C NMR (125 MHz, CDCl₃, ref. CDCl₃): d=13.96 (C-2’), 21.01 (C-6)*,

23.28 (C-5)*, 32.71 (C-4), 41.37 (C-7), 63.90 (C-1’), 105.50 (C-2), 176.04

(C-3), 202.12 (C-1); *: signal assignments are mutual interchangeable; IR

(film): n˜ = 2986, 2945, 2873, 1699, 1647, 1607, 1476, 1453, 1423, 1378,

1361, 1340, 1324, 1266, 1238, 1184, 1145, 1112, 1092, 1055, 1032, 957, 898,

865, 810 cm^À1; GC-MS (70 eV): m/z (%): 155 (5) [M ⁺+1], 154 (49) [M ⁺

], 126 (15), 125 (62), 112 (2), 109 (7), 108 (3), 98 (18), 97 (76), 85 (5), 84

(12), 83 (7), 82 (10), 81 (12), 80 (3), 79 (7), 77 (3), 71 (4), 70 (9), 69 (100),

68 (5), 67 (13), 66 (3), 57 (6), 56 (2), 55 (43), 54 (12), 53 (16), 43 (10), 42

(8), 41 (42), 39 (22), 29 (41), 28 (12), 27 (41); GC-MS (CI): m/z (%): 156

(10) [MH⁺+1], 155(100) [MH⁺].

Acetone (20 mL), a saturated ammonium chloride solution (10 mL),

water (10 mL) and 85% phophoric acid (8 mL) were added and stirred

over night for complete hydrolysis of the acetal. The organic layer was

separated and the aqueous layer was extracted with Et₂O (4î50 mL).

The combined organic layers were evaporated, the residue was diluted in

Et₂O (100 mL), washed with saturated sodium bicarbonate (10 mL) and

dried over Na₂SO₄. The solution was evaporated, the residue was diluted

in n-pentane (200 mL), 85% phosphoric acid (5 mL) were added and the

mixture was vigorously stirred for 24 72 h until complete conversion.

Water (10 mL) and a saturated sodium bicarbonate solution (60 mL)

were added and the aqueous layer was saturated with sodium bicarbon-

ate. The aqueous layer was separated and extracted Et₂O (3î). The com-

bined organic layers were dried over Na₂SO₄and evaporated. The re-

maining residue was purified either by column chromatography or by dis-

tillation.

1,4-Dioxaspiro[4.7]dodecan-7-ol (23b): Hydroboration of 1,4-dioxaspiro-

[4.7]dode-6-ene (22b; 108 g, 700 mmol) was carried out according to

GPA. Chromatography on silica gel (cyclohexane/ethyl acetate 50:50)

yielded the title compound as a white solid (70.8 g, 76%); m.p. 488C;

NMR (¹H,¹H-COSY, ¹³C,¹³C-DEPT): ¹H NMR (500 MHz, CDCl₃, ref.

CHCl₃): d=1.34 (ddddd, J=2.0/3.2/9.2/9.2/14.8 Hz, 1H, 10-H), 1.44 1.53

(m, 2H, 11-H), 1.59 (m, 1H, 8-H), 1.57 1.79 (m, 4H, 9-H/10-H/12-H),

1.85 (ddd, J=0.9/10.0/14.9 Hz, 1H, 12-H), 2.01 (m, 1H, 8-H), 2.03 (dd,

J=6.8/14.8 Hz, 1H, 6-H), 2.07 (dd, J=3.2/14.8 Hz, 1H, 6-H), 2.46 (s, 1H,

7-H(OH)), 3.87 3.97 (m, 5H, 2-H/3-H/7-H); ¹³C NMR (125 MHz, CDCl₃,

ref. CDCl₃): d=22.36 (C-9)*¹, 22.36 (C-11)*¹, 28.90 (C-10), 35.70 (C-

12)*², 36.32 (C-8)*², 40.03 (C-6), 63.98 (C-2)*³, 64.47 (C-3)*³, 68.55 (C-7),

111.54 (C-5); *: signal assignments are mutual interchangeable; IR (film):

n˜ = 3432, 2931, 1693, 1468, 1359, 1282, 1224, 1146, 1114, 1050, 1006, 976,

948, 860, 836, 813, 777, 739 cm^À1; GC-MS (70 eV): m/z (%): 186 (<1)

[M ⁺], 169 (14), 143 (4), 141 (6), 125 (6), 124 (5), 116 (5), 115 (74), 113

(8), 102 (4), 100 (5), 99 (68), 97 (3), 96 (3), 95 (3), 94 (3), 87 (24), 86 (81),

83 (3), 81 (10), 80 (3), 79 (7), 73 (7), 72 (4), 71 (22), 70 (3), 69 (8), 68 (3),

67 (10), 65 (3), 59 (7), 58 (11), 56 (9), 55 (86), 54 (8), 53 (14), 51 (3), 45

(15), 44 (19), 43 (100), 42 (37), 41 (46), 40 (7), 39 (22), 32 (9), 31 (8), 29

(32), 28 (36), 27 (25), 26 (3).

Note: Both the acetal cleavage and the elimination should be carried out

under GC control.

General procedure D (synthesis of 3-substituted enones by reaction of vi-

nylogous esters with Grignard reagents): The Grignard reagent was pre-

pared analogously to the GP C. The respective vinylogous ester

(35.0 mmol) in dry THF (20 mL) was added and the solution was heated

under reflux for 1 h. Water (10 mL) was added carefully. The mixture

was acidified (pH 1 2) by adding 2m HCl and stirred for 2 h. The organic

layer was separated and the aqueous was extracted four times with Et₂O

(50 mL). The combined organic layers were washed with aq sat NaHCO₃

and dried over Na₂SO₄. The solvent was evaporated and the residue was

purified by column chromatography.

General procedure E (synthesis of 3-substituted enones by reaction of

semiprotected b-diketones with lithium organic reagents): Lithium

(1.04 g, 150.0 mmol) as a suspension in n-hexane were placed in an dry

apparatus under argon atmosphere. A large excess of lithium generally

did not reduce the yield, but in these reactions the hydrolysis must be

carried out very cautiously. The solvent was carefully evaporated, dry

Et₂O (70 mL) was added and the mixture was treated with ultrasound at

08C for 3 h. A solution (0.5 mL) of the respective bromine (50.0 mmol)

in dry Et₂O (10 mL) was added at room temperature. The mixture was

cooled to À188C and the remaining bromine solution was added within

30 min and stirred for additional 60 min. While cooling the reaction

vessel with dry ice/acetone, the respective carbonyl compound

(40.0 mmol) in dry Et₂O (10 mL) was added to the lithium organyl solu-

tion within 10 min. The mixture was stirred for 2 h at À188C and for

30 min at 08C. The hydrolyzation was carefully (!!) carried out by succes-

sive addition of ethanol and water saturated ammonium chloride solu-

tion. The organic layer was separated and the aqueous was extracted

with Et₂O (5î50 mL). The combined organic layers were evaporated,

the diphasic residue was diluted with Et₂O (50 mL), acetone (20 mL) and

2m phosphoric acid (20 mL) and stirred until complete hydrolysis of the

acetal group (GC control). The aqueous layer was separated and extract-

ed with Et₂O (4î50 mL). The combined organic layers were evaporated

and the residue was disoolved in Et₂O (100 mL), washed with aq sat

NaHCO₃(10 mL) and dried over Na₂SO₄. The solution was evaporated

and diluted with n-pentane (200 mL). 85% Phosphoric acid (5 mL) was

added and the mixture was vigorously stirred for 24 72 h until complete

conversion.

3-(Ethoxy)-2-cycloocten-1-one (19b): 1,4-Dioxaspiro[4.7]undecan-7-ol

(23b; 18.6 g, 100 mmol) was treated analogously to the synthesis of 3-

(ethoxy)-2-cyclohepten-1-one (see above). Purification by kugelrohr dis-

tillation (0.05 mbar) and chromatography on silica gel (cyclohexane/ethyl

acetate 20:80) yielded the title compound as a colorless oil (10.8 g, 64%).

Note: Both the acetal cleavage and the vinylogous esterification should

be carried out under GC control, while the probe should be deacidified

before analysis by filtration over sodium carbonate. NMR (¹H,¹H-COSY,

¹³C-APT, HMQC); ¹H NMR (500 MHz, CDCl₃, ref. CHCl₃): d=1.30 (t,

J=7.0 Hz, 3H, 2’-H), 1.52 1.57 (m, 2H, 6-H), 1.61 1.72 (m, 4H, 5-H/7-

H), 2.73 (t, J=7.4 Hz, 2H, 8-H), 2.75 (t, J=7.0 Hz, 2H, 4-H), 3.77 (q,

J=7.0 Hz, 2H, 1’-H), 5.54 (s, 1H, 2-H); ¹³C NMR (125 MHz, CDCl₃, ref.

CDCl₃): d=13.92 (C-2’), 22.76 (C-5)*, 22.97 (C-7)*, 23.39 (C-6), 32.76

(C-4), 41.13 (C-8), 63.61 (C-1’), 108.19 (C-2), 171.91 (C-3), 200.85 (C-1);

*: signal assignments are mutual interchangeable; IR (film): n˜ = 2986,

2938, 2863, 1639, 1602, 1475, 1451, 1379, 1363, 1343, 1308, 1259, 1229,

1178, 1161, 1129, 1112, 1092, 1075, 1036, 946, 850, 825, 786, 748 cm^À1

;

GC-MS (70 eV): m/z (%): 169 (4) [M ⁺+1], 168 (27) [M ⁺], 141 (4), 140

(40), 139 (11), 126 (10), 125 (83), 113 (8), 112 (13), 111 (12), 110 (8), 98

(20), 97 (100), 96 (3), 95 (4), 94 (3), 86 (9), 84 (37), 83 (27), 82 (7), 81

(10), 80 (10), 79 (10), 77 (7), 71 (7), 70 (9), 69 (76), 68 (17), 67 (15), 66

(9), 65 (5), 58 (9), 56 (7), 55 (78), 54 (8), 53 (18), 52 (3), 51 (3), 43 (32),

42 (23), 41 (44), 40 (11), 39 (35), 29 (46), 28 (15), 27 (33); GC-MS (CI):

m/z (%): 170 (11) [MH⁺+1], 169 (100) [MH⁺].

Water (10 mL) and aq sat NaHCO₃(60 mL) were added and the aqueous

layer was saturated with sodium bicarbonate. The aqueous layer was sep-

arated and extracted with Et₂O (3î). The combined organic layers were

dried over Na₂SO₄and evaporated.

The remaining residue was purified either by column chromatography or

by distillation.

General procedure C (synthesis of 3-substituted enones by reaction of

semiprotected b-diketones with Grignard reagents): Magnesium (1.23 g,

50.0 mmol) and dry THF (30 mL) were placed in a dry apparatus under

argon atmosphere and treated with ultrasound at 08C for 1 h. The cool-

ing source was removed and the bromine compound (45.0 mmol) was

added such that the solution was slightly boiling. Then the mixture was

Caution: Both the acetal cleavage and the elimination should be carried

out under GC control. The excess of the ultrasound activated lithium

powder is highly pyrophoric.

General procedure F (synthesis of 3-substituted enones by reaction of vi-

nylogous esters with lithium organic reagents): The lithium organyl solu-

863

Chem. Eur. J. 2004, 10, 851 874

www.chemeurj.org

¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

J. Mattay and H. Rinderhagen

FULL PAPER

tion was prepared analogous to GP D. The respective vinylogous ester

(40.0 mmol) in dry Et₂O (10 mL) was added at À788C (dry ice/acetone

cooling) within 10 min. The mixture was warmed to À188C, stirred for

2 h, warmed to 08C and stirred for 30 min. Then it was carefully (!!) hy-

drolyzed by successive addition of ethanol and aq sat NH₄Cl.

121 (4), 120 (9), 119 (17), 118 (6), 117 (5), 115 (3), 109 (13), 107 (5), 106

(15), 105 (34), 104 (6), 103 (6), 95 (14), 94 (7), 93 (11), 92 (31), 91 (100),

89 (3), 84 (3), 81 (14), 80 (6), 79 (40), 78 (19), 77 (33), 68 (4), 67 (18), 66

(8), 65 (19), 63 (4), 55 (16), 54 (4), 53 (25), 52 (11), 51 (15), 50 (4), 43 (3),

42 (5), 41 (32), 40 (7), 39 (39), 38 (3), 29 (7), 28 (7), 27 (19); GC-MS

(CI): m/z (%): 165 (2) [MH⁺+2], 164 (11) [MH⁺+1], 163 (100) [MH⁺];

HRMS: m/z: calcd for C₁₁H₁₃O: 161.0959, found: 161.0966 [(MÀ1)⁺].

The mixture was acidified (pH 1 2) by adding 2m HCl and stirred for

2 h. The organic layer was separated and the aqueous was extracted with

Et₂O (4î50 mL). The combined organic layers were evaporated and the

residue was diluted with Et₂O (100 mL), washed with aq sat NaHCO₃

and dried over Na₂SO₄. The solvent was evaporated and the residue was

purified by column chromatography.

3-(2-Cyclohexenylmethyl)-2-cyclohepten-1-one (6a): According to the

GP E 1,4-dioxaspiro[4.6]undecan-7-one (15a; 2.21 g, 13.0 mmol) was

treated with 3-bromomethyl-1-cyclohexene. Chromatography on silica gel

(cyclohexane/ethyl acetate 9:1) yielded a colorless oil (1.25 g, 47%).

NMR (¹H,¹H-COSY, ¹³C,¹³C-DEPT, HMQC, HMBC); ¹H NMR

(500 MHz, CDCl₃, ref.: CHCl₃): d=1.16 1.24 (m, 1H, 6’’-H), 1.45 1.55

(m, 1H, 5’’-H), 1.65 1.75 (m, 2H, 5’’-H/6’’-H), 1.75 1.79 (m, 4H, 5-H/6-

H), 1.94 1.98 (m, 2H, 4’’-H), 2.10 (dd, J=8.2/13.1 Hz, 1H, 1’-H), 2.18

(ddd, J=0.9/6.9/13.1 Hz, 1H, 1’-H), 2.26 2.35 (m, 1H, 1’’-H), 2.38 2.41

(m, 2H, 4-H), 2.54 2.57 (m, 2H, 7-H), 5.48 (dddd, J=2.4/2.4/2.4/10.0 Hz,

1H, 2’’-H), 5.68 (dddd, J=2.4/3.8/3.8/10.0 Hz, 1H, 3’’-H), 5.88 (s, 1H, 2-

H); ¹³C NMR (125 MHz, CDCl₃, ref.: CDCl₃): d=20.99 (C-5’’)*, 21.08

(C-6)*, 24.93 (C-5), 25.03 (C-4’’), 28.83 (C-6’’), 32.17 (C-4), 33.21 (C-1’’),

41.98 (C-7), 47.74 (C-1’), 127.86 (C-3’’), 130.32 (C-2’’), 130.72 (C-2),

160.25 (C-3), 203.81 (C-1); IR (film): n˜ = 3022, 2934, 2865, 1660, 1447,

1371, 1344, 1320, 1267, 1201, 1045, 953, 882, 863, 722, 699, 676 cm^À1; GC-

MS (70 eV): m/z (%): 204 (3) [M ⁺], 125 (5), 124 (54), 109 (6), 96 (5), 95

(3), 91 (8), 83 (3), 82 (10), 81 (100), 80 (7), 79 (39), 78 (3), 77 (15), 69 (3),

67 (10), 66 (6), 65 (7), 55 (14), 53 (27), 51 (3), 43 (7), 41 (40), 39 (18), 29

(7), 27 (9); GC-MS (CI): m/z (%): 207 (2) [MH⁺+2], 206 (17) [MH⁺

+1], 205 (100) [MH⁺]; HRMS: m/z: calcd for C₁₄H₂₀O: 204.1514, found:

204.1518; elemental analysis calcd (%) for C₁₄H₂₀O (204.31): C 82.30, H

9.87; found: C 82.20, H 10.20.

3-(3-Butenyl)-2-cyclohepten-1-one (4a): Following GP C 1,4-dioxaspiro-

[4.6]undecan-7-on (15a; 7.54 g, 44.3 mmol) was treated with 4-bromobut-

1-ene. Chromatography on silica gel (cyclohexane/ethyl acetate 9:1)

yielded 3-(3-butenyl)-2-cyclohepten-1-one (4a; 4.36 g, 60%). NMR

(¹H,¹H-COSY, ¹³C,¹³C-DEPT, HMQC, HMBC); ¹H NMR (500 MHz,

CDCl₃, ref.: CHCl₃): d=1.70 1.76 (m, 2H, 6-H), 1.74 1.80 (m, 2H, 5-H),

2.18 2.25 (m, 2H, 2’-H), 2.25 2.29 (m, 2H, 1’-H), 2.32 2.36 (m, 2H, 6-H),

2.47 2.51 (m, 2H, 7-H), 4.913 (tdd, J=1.3/2.9/10.2 Hz, 1H, 4’-H), 4.96

(tdd, J=1.5/2.9/16.9 Hz, 1H, 4’-H), 5.70 (tdd, J=6.3/10.2/16.9 Hz, 1H, 3’-

H), 5.82 (s, 1H, 2-H); ¹³C NMR (125 MHz, CDCl₃, ref.: CDCl₃): d=21.07

(C-6), 24.88 (C-5), 31.57 (C-2’), 32.42 (C-4), 40.11 (C-1’), 42.00 (C-7),

115.32 (C-4’), 129.35 (C-2), 137.01 (C-3’), 161.01 (C-3), 203.88 (C-1); IR

(film): n˜ = 3082, 2942, 2870, 1660, 1452, 1417, 1372, 1344, 1266, 1199,

1122, 1050, 995, 912, 877 cm^À1; GC-MS (70 eV): m/z (%): 164 (8) [M ⁺],

149 (3), 136 (8), 135 (22), 122 (5), 121 (9), 120 (10), 109 (25), 108 (7), 107

(19), 106 (3), 105 (5), 104 (5), 98 (5), 97 (3), 96 (3), 95 (31), 94 (19), 93

(48), 92 (8), 91 (38), 82 (10), 81 (36), 80 (37), 79 (93), 78 (13), 77 (42), 68

(7), 67 (40), 66 (12), 65 (17), 55 (18), 54 (7), 53 (26), 52 (4), 51 (6), 43 (5),

42 (7), 41 (100), 40 (13), 39 (78), 38 (3), 29 (35), 28 (13), 27 (43), 26 (4);

GC-MS (CI): m/z (%): 167 (1) [MH⁺+2], 166 (12) [MH⁺+1], 165 (100)

[MH⁺]; elemental analysis calcd (%) for C₁₁H₁₆O₁(164.24): C 80.44, H

9.82; found: C 80.37, H 9.85.

3-(3-Butenyl)-2-cycloocten-1-one (4b): Following GP D 3-(ethoxy)-2-cy-

cloocten-1-one (19b; 2.50 g, 14.9 mmol) was treated with 4-bromobut-1-

ene. Chromatography on silica gel (cyclohexane/ethyl acetate 9:1) yield-

ed the title compound (1.87 g, 71%). NMR (¹H,¹H-COSY, ¹³C-APT,

HMQC, HMBC): ¹H NMR (500 MHz, CDCl₃, ref.: CHCl₃): d=1.50 (m,

2H, 6-H), 1.61 (tt, J=6.0/6.8 Hz, 2H, 5-H), 1.714 (m, 2H, 7-H), 2.17 2.26

(m, 4H, 1’-H/2’-H), 2.56 (t, J=6.8 Hz, 2H, 4-H), 2.68 (t, J=7.2 Hz, 2H,

8-H), 6.00 (s, 1H, 2-H), 4.96 (tdd, J=1.2/2.0/10.2 Hz, 1H, 4’-H), 5.00

(tdd, J=1.3/2.0/18.6 Hz, 1H, 4’-H), 5.75 (m, 1H, 3’-H), 5.99 (m, 1H, 2-

H); ¹³C NMR (125 MHz, CDCl₃, ref.: CDCl₃): d=22.77 (C-7), 23.55 (C-

6), 23.84 (C-5), 31.51 (C-2’), 31.89 (C-4), 40.52 (C-1’), 41.87 (C-8), 115.18

(C-4’), 130.41 (C-2), 137.05 (C-3’), 155.58 (C-3), 203.69 (C-1); IR (film):

n˜ = 3082, 2936, 2860, 1648, 1482, 1449, 1343, 1305, 1282, 1259, 1217,

1161, 1135, 1084, 994, 912 cm^À1; GC-MS (70 eV): m/z (%): 178 (7) [M ⁺],

163 (3), 150 (11), 149 (24), 137 (8), 136 (7), 135 (21), 134 (4), 124 (3), 123

(15), 122 (5), 121 (15), 120 (3), 117 (3), 111 (3), 109 (7), 108 (9), 107 (32),

105 (7), 104 (5), 96 (5), 95 (23), 94 (24), 93 (41), 92 (8), 91 (37), 83 (6),

82 (9), 81 (31), 80 (37), 79 (100), 78 (11), 77 (37), 69 (4), 68 (8), 67 (48),

66 (13), 65 (18), 55 (42), 54 (12), 53 (35), 52 (4), 51 (6), 43 (8), 42 (8),

41 (62), 40 (7), 39 (36), 29 (19), 28 (8), 27 (20); elemental analysis

calcd (%) for C₁₂H₁₈O (178.27): C 80.85, H 10.18; found: C 80.56,

H 10.34.

3-[4-(Trimethylsilyl)-3-butynyl]-2-cyclohepten-1-one: Following GP C

1,4-dioxaspiro[4.6]undecan-7-on (15a; 16.5 g, 96.9 mmol) was treated

with 4-bromo-1-trimethylsilylbut-1-yne. Chromatography on silica gel

(cyclohexane/ethyl acetate 8:2) yielded 3-(2-butynyl)-2-cyclohepten-1-one

(5a; 1.10 g, 7%) and 3-[4-(trimethylsilyl)-3-butynyl]-2-cyclohepten-1-one

(7.27 g, 32%) as colorless oils. NMR (¹H,¹H-COSY, ¹³C-APT, HMQC):

¹H NMR (500 MHz, CDCl₃, ref.: CHCl₃): d=0.10 (s, 9H, 1’’-H), 1.73

1.89 (m, 4H, 5-H/6-H), 2.35 2.43 (m, 6H, 4-H/1’-H/2’-H), 2.55 (m, 2H, 7-

H), 5.89 (s, 1H, 2-H); ¹³C NMR (125 MHz, CDCl₃, ref.: CDCl₃): d=

À0.12 (C-1’’), 18.49 (C-2’), 21.03 (C-6), 24.91 (C-5), 32.29 (C-4), 39.35 (C-

1’), 42.03 (C-7), 85.85 (C-4’), 105.14 (C-3’), 129.93 (C-2), 159.13 (C-3),

203.70 (C-1); IR (film): n˜ = 2960, 2871, 2177, 1664, 1451, 1424, 1372,

1331, 1249, 1199, 1040, 842, 759 cm^À1; GC-MS (70 eV): m/z (%): 234 (5)

[M ⁺], 233 (5), 220 (8), 219 (30), 206 (6), 205 (7), 193 (4), 192 (3), 191 (8),

177 (6), 165 (4), 163 (4), 161 (7), 160 (5), 159 (3), 151 (3), 149 (5), 147

(6), 146 (3), 145 (13), 143 (7), 135 (6), 133 (8), 132 (40), 131 (11), 130 (6),

129 (9), 128 (4), 121 (4), 119 (4), 117 (14), 116 (3), 115 (8), 110 (3), 109

(9), 106 (3), 105 (6), 104 (8), 99 (3), 97 (7), 96 (9), 95 (9), 93 (5), 92 (4),

91 (18), 89 (3), 85 (3), 83 (15), 82 (3), 81 (17), 80 (3), 79 (11), 77 (11), 76

(5), 75 (60), 74 (9), 73 (100), 69 (6), 68 (3), 67 (8), 66 (3), 65 (4), 61 (4),

59 (16), 55 (8), 53 (7), 51 (4), 45 (9), 43 (9), 41 (11), 39 (7).

3-(3-Butynyl)-2-cycloocten-1-one (5b): Following GP D 3-(ethoxy)-2-cy-

cloocten-1-one (19b; 4.71 g, 28.0 mmol) was treated with 4-bromo-1-tri-

methylsilylbut-1-yne (8.00 g, 39.0 mmol). The raw product was diluted in

THF (50 mL)/water (1 mL) and cooled to À188C. Tetrabutylammonium

fluoride hexahydrate (11.5 g, 36.7 mmol) in THF (50 mL) was added and

the mixture was allowed to warm slowly to room temperature and stirred

for 30 min. Brine (20 mL) was added, the organic layer was separated

and washed with brine (20 mL). The combined aqueous layers were

washed three times with Et₂O (100 mL). The combined organic layers

were dried over Na₂SO₄and the solvent was evaporated. Chromatogra-

phy on silica gel (cyclohexane/ethyl acetate 9:1) gave a colorless oil

(3.51 g, 71%). NMR (¹H,¹H-COSY, ¹³C,¹³C-DEPT, ¹³C-gated, HMQC,

3-(2-Butynyl)-2-cyclohepten-1-on (5a): 3-[4-(Trimethylsilyl)-3-butynyl]-2-

cyclohepten-1-one (6.50 g, 27.7 mmol) was diluted in THF (50 mL) and

water (1 mL) and cooled to À788C. Tetrabutylammonium fluoride hexa-

hydrate (14.5 g, 39.5 mmol) in THF (50 mL) was slowly added, the solu-

tion was slowly warmed to room temperature and stirred for 30 min.

Brine (20 mL) and Et₂O (200 mL) were added and the organic layer was

separated, dried over Na₂SO₄and evaporated. Chromatography on silica

gel (cyclohexane/ethyl acetate 85:15) yielded

a colorless oil (4.36 g,

97%). NMR (¹H,¹H-COSY, ¹³C,¹³C-DEPT, HMQC): ¹H NMR (500 MHz,

CDCl₃, ref.: CHCl₃): d=1.72 1.82 (m, 4H, 5-H/6-H), 1.958 (t, J=2.3 Hz,

2H, 4’-H), 2.33 2.42 (m, 6H, 4-H/1’-H/2’-H), 2.55 (m, 2H, 7-H), 5.90 (s,

1H, 2-H); ¹³C NMR (125 MHz, CDCl₃, ref.: CDCl₃): d=16.88 (C-4’),

21.00 (C-6), 24.88 (C-5), 32.28 (C-4), 39.07 (1’), 42.02 (C-7), 69.40 (C-4’),

1

HMBC): H NMR (500 MHz, CDCl₃, ref.: CHCl₃): d=1.50 1.56 (m, 2H,

6-H), 1.59 1.66 (m, 2H, 5-H), 1.71 1.77 (m, 2H, 7-H), 1.95 1.97 (m, 1H,

4’-H), 2.36 2.37 (m, 4H, 1’-H/2’-H), 2.55 (t, J=6.9 Hz, 2H, 4-H), 2.69 (t,

J=7.1 Hz, 2H, 8-H), 6.00 (s, 1H, 2-H); ¹³C NMR (125 MHz, CDCl₃, ref.:

CDCl₃): d=16.90 (C-2’), 22.70 (C-7)*, 23.78 (C-5)*, 23.80 (C-6), 31.82

(C-4), 39.52 (C-1’), 42.04 (C-8), 69.39 (C-4’), 82.59 (C-3’), 130.63 (C-2),

153.37 (C-3), 203.95 (C-1); *: signal assignments are mutual interchangea-

82.47 (C-3’), 129.77 (C-2), 158.88 (C-3), 203.76 (C-3); IR (film): n˜

=

3297, 2938, 2871, 2175, 1660, 1450, 1373, 1345, 1258, 1201, 1118, 1053,

877, 844, 760, 632 cm^À1; GC-MS (70 eV): m/z (%): 163 (1) [M ⁺+1], 162

(7) [M ⁺], 161 [(MÀ1)⁺] (8), 147 (9), 134 (10), 133 (23), 131 (3), 129 (6),

864

¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemeurj.org

Chem. Eur. J. 2004, 10, 851 874

Cascade Reactions

851 874

ble; IR (film): n˜ =3295, 2935, 2862, 2120, 1648, 1483, 1447, 1345, 1305,

1283, 1259, 1218, 1158, 1134, 1066, 1024, 957, 889, 820, 634 cm^À1; GC-MS

(70 eV): m/z (%): 176 (4) [M ⁺], 161 (4), 148 (6), 147 (12), 137 (5), 135

(3), 134 (10), 133 (52), 123 (8), 121 (4), 120 (23), 119 (26), 118 (3), 117

(5), 115 (4), 109 (3), 108 (4), 107 (10), 106 (14), 105 (61), 104 (3), 103

(11), 95 (9), 94 (8), 93 (12), 92 (30), 91 (100), 83 (3), 82 (3), 81 (11), 80

(8), 79 (53), 78 (17), 77 (48), 68 (4), 67 (25), 66 (8), 65 (27), 63 (4), 55

(35), 54 (4), 53 (35), 52 (9), 51 (11), 50 (4), 43 (5), 42 (7), 41 (43), 40 (5),

39 (41), 29 (14), 28 (6), 27 (22); GC-MS (CI): m/z (%): 179 (1) [MH⁺

+2], 178 (14) [MH⁺+1], 177 (100) [MH⁺]; elemental analysis calcd (%)

for C₁₂H₁₆O (176.25): C 81.77, H 9.15; found: C 81.09, H 9.86.

(31), 80 (15), 79 (40), 78 (4), 77 (17), 71 (14), 70 (10), 69 (100), 68 (20),

67 (28), 66 (6), 65 (10), 58 (4), 57 (9), 56 (4), 55 (51), 54 (19), 53 (28), 52

(5), 51 (4), 43 (40), 42 (15), 41 (81), 40 (15), 39 (48), 29 (53), 28 (13), 27

(36), 18 (18); GC-MS (CI): m/z (%): 196 (13) [MH⁺+1], 195 (100)

[MH⁺], 194 (4) [M ⁺]; HRMS: m/z: calcd for C₁₂H₁₈O₂: 194.1307, found:

194.1306 [M ⁺].

4-(2-Propenyl)-2-cyclohepten-1-one (7): LiAlH₄(420 mg, 11.1 mmol) and

dry Et₂O (50 mL) were placed in a dry apparatus under argon atmos-

phere. 3-(Ethoxy)-7-(2-propenyl)-2-cyclohepten-1-one (2.52 g, 13.0 mmol)

in dry Et₂O (20 mL) was added within 10 min and the suspension was

heated under reflux 3 h. After hydrolysis by successive addition of wet

Et₂O, water and saturated ammonium chloride solution the mixture was

acidified (pH 1 2) by slow addition of 2m HCl and stirred for 2 h. The

aqueous layer was separated and extracted four times with Et₂O

(40 mL). The combined organic layers were washed with saturated

sodium bicarbonate solution and dried over Na₂SO₄. The solvent was

evaporated and the residue was purified by column chromatography on

silica gel (cyclohexane/ethyl acetate 75:25) to yield 4-(2-propenyl)-2-cy-

clohepten-1-one (7; 680 mg, 4.53 mmol, 34%), (3R*,4S*)-4-allyl-3-hy-

droxy-1-cycloheptanone (26a; 690 mg, 4.10 mmol, 32%) and (3R*,4S*)-4-

allyl-3-hydroxy-1-cycloheptanone (26b; 350 mg, 2.08 mmol, 16%).

3-(2-Cyclohexenylmethyl)-2-cycloocten-1-one (6b): Following GP F 3-

(ethoxy)-2-cycloocten-1-one (19b, 2.50 g, 14.9 mmol) was treated with 3-

bromomethyl-1-cyclohexene (2.09 g, 18.6 mmol). Chromatography on

silica gel (cyclohexane/ethyl acetate 9:1) gave a colorless oil (1.82 g,

56%). NMR (¹H,¹H-COSY, ¹³C-APT, HMQC, HMBC): ¹H NMR

(500 MHz, CDCl₃, ref.: CHCl₃): d=1.21 (m, 1H, 6’’-H), 1.44 1.56 (m,

3H, 6-H/5’’-H), 1.57 1.63 (m, 2H, 5-H), 1.63 1.76 (m, 4H, 7-H/5’’-H/6’’-

H), 1.92 1.97 (m, 2H, 4’’-H), 2.07 (dd, J=8.1/13.2 Hz, 1H, 1’-H), 2.14

(dd, J=7.0/13.2 Hz, 1H, 1’-H), 2.29 (m, 1H, 1’’-H), 2.53 2.63 (m, 2H, 4-

H), 2.66 2.75 (m, 2H, 8-H), 5.48 (dddd, J=2.3/2.3/2.3/10.1 Hz, 1H, 2’’-

H), 5.67 (dddd, J=3.1/3.2/3.3/10.1 Hz, 1H, 3’’-H), 6.01 (s, 1H, 2-H);

¹³C NMR (125 MHz, CDCl₃, ref.: CDCl₃): d=20.94 (C-5’’), 22.90 (C-7),

23.41 (C-6), 23.98 (C-5), 24.98 (C-4’’), 28.83 (C-6’’), 31.65 (C-4), 33.05 (C-

1’’), 41.76 (C-8), 48.27 (C-1’), 127.71 (C-3’’), 130.32 (C-2’’), 132.01 (C-2),

154.79 (C-3), 203.41 (C-1); IR (film): n˜ = 3022, 2933, 2861, 1648, 1619,

1481, 1447, 1364, 1258, 1128, 890, 722 cm^À1; GC-MS (70 eV): m/z (%):

219 (1) [M ⁺+1], 218 (7) [M ⁺], 203 (2), 200 (3), 190 (5), 175 (9), 147 (8),

139 (4), 138 (36), 133 (3), 123 (5), 121 (4), 120 (3), 119 (6), 110 (21), 109

(11), 105 (5), 96 (5), 95 (14), 94 (8), 93 (5), 92 (4), 91 (17), 83 (13), 81

(100) [(cyclohexenÀH)⁺], 80 (17), 79 (49), 78 (5), 77 (17), 68 (3), 67 (13),

66 (6), 65 (8), 55 (16), 54 (3), 53 (20), 52 (3), 43 (5), 41 (24), 39 (10); GC-

MS (CI): m/z (%): 220 (16) [MH⁺+1], 219 (100) [MH⁺]; elemental anal-

ysis calcd (%) for C₁₅H₂₂O (218.33): C 82.52, H 10.16; found: C 81.12, H

10.28.

Synthesis of 7 starting with (3R*,4S*)-4-allyl-3-hydroxy-1-cycloheptanone

(26a): The alcohol (500 mg) was diluted in n-pentane (50 mL). 85%

Phosphoric acid (3 mL) was added and the mixture was vigorously stirred

for 24 72 h until complete conversion. Water (10 mL) and saturated

sodium bicarbonate solution (40 mL) was added. The aqueous layer was

separated and extracted three times with Et₂O (50 mL). The combined

organic layers were dried over Na₂SO₄, the solvent was evaporated and

the residue was purified by column chromatography (see above).

4-(2-Propenyl)-2-cyclohepten-1-one (7): NMR (¹H,¹H-COSY, ¹³C,¹³C-

DEPT, HMQC); ¹H NMR (500 MHz, CDCl₃, ref.: CHCl₃): d=1.48

(dddd, J=5.8/7.2/10.4/13.8 Hz, 1H, 5-H), 1.747 1.81 (m, 2H, 6-H), 1.94

(m, 1H, 5-H), 2.16 2.26 (m, 2H, 1’-H), 2.49 2.62 (m, 3H, 4-H/7-H), 5.03

5.09 (m, 2H, 3’-H), 5.75 (dddd, J=6.8/7.0/9.6/17.6 Hz, 1H, 2’-H), 5.90

(dd, J=2.6/12.3 Hz, 1H, 2-H), 6.37 (ddd, J=0.9/3.8/12.3 Hz, 1H, 3-H);

¹³C NMR (125 MHz, CDCl₃, ref.: CDCl₃): d=20.54 (C-6), 31.79 (C-5),

39.87 (C-4), 40.25 (C-1’), 43.23 (C-7), 117.27 (C-3’), 131.33 (C-2), 135.71

(C-2’), 149.74 (C-3), 204.19 (C-1); IR (film): n˜ =3326, 3081, 2937, 2868,

1668, 1450, 1417, 1399, 1350, 1282, 1262, 1201, 1178, 995, 916, 794,

725 cm^À1; GC-MS (70 eV): m/z (%): 151 (3) [M ⁺+1], 150 (12) [M ⁺], 149

(3), 135 (6), 132 (3), 122 (8), 121 (8), 117 (4), 109 (6), 108 (7), 107 (11),

106 (6), 105 (3), 104 (10), 95 (6), 94 (19), 93 (25), 92 (6), 91 (28), 84 (3),

82 (6), 81 (53), 80 (32), 79 (100), 78 (14), 77 (35), 68 (11), 67 (26), 66

(13), 65 (14), 55 (24), 54 (10), 53 (39), 52 (11), 51 (11), 50 (3), 43 (4), 42

(7), 41 (57), 40 (10), 39 (51), 29 (8), 28 (7), 27 (31); GC-MS (CI): m/z

(%): 152 (11) [MH⁺+1], 151 (100) [MH⁺]; HRMS: m/z: calcd for

C₁₀H₁₄O: 150.1045, found: 150.1042 [M ⁺].

3-Ethoxy-7-(2-propenyl)-2-cyclohepten-1-one (25): Diisopropylamine

(3.55 g, 35.1 mmol) in dry THF (40 mL) was placed in a dry apparatus

under argon atmosphere and cooled to À788C. n-Butyllithium (20 mL,

32.0 mmol, in n-hexane) was added within 5 min. The mixture was

warmed to 08C and stirred for 30 min. After cooling to À788C 3-

(ethoxy)-2-cyclohepten-1-on (19a; 4.20 g, 27.2 mmol) in dry THF

(25 mL) was added. The solution was stirred for 1 h and allyl bromide

(3.30 g, 27.2 mmol) was added followed by stirring for 12 h at À788C

(dry ice/acetone cooling), warming to room temperature within 1 h and

again stirring for additional 30 min.

After hydrolysis with water (15 mL) the volatile compound except water

were removed in a rotary evaporator and the diphasic residue was dilut-

ed in Et₂O (80 mL) and water (20 mL). The aqueous layer was separated

and washed four times with Et₂O (50 mL). The combined organic layers

were dried over Na₂SO₄and the solvent was evaporated. Chromatogra-

phy on silica gel (cyclohexane/ethyl acetate 7:3) yielded 3-(ethoxy)-7-(2-

propenyl)-2-cyclohepten-1-one (2.71 g, 13.9 mmol, 51%) and the starting

material 19a (1.26 g) as colorless oils. NMR (¹H,¹H-COSY, ¹³C,¹³C-

DEPT, HMQC, HMBC); ¹H NMR (500 MHz, CDCl₃, ref.: CHCl₃): d=

1.30 (dd, J=7.0/7.0 Hz, 3H, 2’-H), 1.41 (m, 1H, 6-H), 1.68 (m, 1H, 5-H),

1.85 1.95 (m, 2H, 5-H/6-H), 2.07 (ddd, J=7.1/6.9/14.0 Hz, 1H, 1’’-H),

2.40 (dddd, J=1.6/2.8/6.0/16.9 Hz, 1H, 4-H), 2.54 2.66 (m, 3H, 4-H/7-H/

1’’-H), 3.73 (td, J=7.0/9.7 Hz, 1H, 1’-H), 3.77 (td, J=7.0/9.7 Hz, 1H, 1’-

H), 4.96 (dddd, J=1.0/1.0/2.9/10.2 Hz, 1H, 3’’-H), 5.01 (dddd, J=1.4/1.5/

2.9/17.1 Hz, 1H, 3’’-H), 5.34 (m, 1H, 2-H), 4.96 (dddd, J=5.8/7.9/10.2/

17.1 Hz, 1H, 2’’-H); ¹³C NMR (125 MHz, CDCl₃, ref.: CDCl₃): d=14.13

(C-2’), 23.29 (C-5), 28.17 (C-6), 33.02 (C-4), 35.29 (C-1’’), 48.80 (C-7),

63.89 (C-1’), 105.80 (C-2), 115.94 (C-3’’), 136.94 (C-2’’), 176.30 (C-3),

202.51 (C-1); IR (film): n˜ = 3079, 2940, 2942, 1871, 1650, 1608, 1476,

1444, 1377, 1360, 1305, 1241, 1184, 1158, 1112, 1033, 997, 911, 845, 808,

754 cm^À1; GC-MS (70 eV): m/z (%): 195 (8) [M ⁺+1], 194 (40) [M ⁺], 193

(12) [(MÀ1)⁺], 179 (4), 166 (10), 165 (20), 153 (3), 152 (14), 151 (27), 150

(6), 149 (5), 140 (16), 139 (8), 138 (8), 137 (13), 126 (6), 125 (44), 124

(13), 123 (14), 121 (5), 120 (3), 119 (3), 112 (23), 111 (11), 110 (7), 109

(9), 108 (3), 107 (7), 105 (4), 99 (7), 98 (26), 97 (94), 96 (7), 95 (19), 94

(4), 93 (11), 92 (4), 91 (14), 86 (8), 85 (5), 84 (31), 83 (11), 82 (23), 81

(3R*,4S*)-4-Allyl-3-hydroxy-1-cycloheptanone (26a): NMR (¹H,¹H-

1

COSY, ¹³C,¹³C-DEPT); H NMR (500 MHz, CDCl₃, ref.: CHCl₃): d=1.53

(dddd, J=1.7/11.3/11.3/13.1 Hz, 1H, 5-H), 1.57 1.67 (m, 2H, 4-H/6-H),

1.67 1.73 (m, 1H, 5-H), 1.85 (m, 1H, 6-H), 2.05 (ddddd, J=1.3/1.3/7.0/

7.0/14.0 Hz, 1H, 1’-H), 2.20 (ddddd, J=1.3/1.3/7.0/7.0/14.0 Hz, 1H, 1’-H),

2.40 (ddd, J=3.7/11.5/17.5 Hz, 1H, 7-H), 2.47 (dddd, J=1.4/3.7/5.2/

17.5 Hz, 1H, 7-H), 2.47 (d, J=4.0 Hz, 1H, 3-H (OH)), 2.71 (dd, J=7.1/

14.5 Hz, 1H, 2-H), 2.77 (dd, J=2.0/14.5 Hz, 1H, 2-H), 4.04 (dddd, J=2.0/

2.4/4.0/7.1 Hz, 1H, 3-H), 4.99 (dddd, J=1.3/1.3/2.0/10.0 Hz, 1H, 3’-H),

5.05 (dddd, J=1.3/1.3/2.0/17.1 Hz, 1H, 3’-H), 5.76 (dddd, J=7.0/7.0/10.0/

17.1 Hz, 1H, 2’-H); ¹³C NMR (125 MHz, CDCl₃, ref.: CDCl₃): d=22.85

(C-6), 29.13 (C-5), 38.27 (C-1’), 44.04 (C-7), 46.32 (C-4), 49.93 (C-2),

68.20 (C-3), 116.48 (C-3’), 137.06 (C-2’), 213.59 (C-1); IR (film): n˜

=

3453, 3080, 2933, 2867, 1691, 1640, 1451, 1414, 1352, 1256, 1157, 1076,

1018, 996, 914, 873, 839, 790 cm^À1; GC-MS (70 eV): m/z (%): 149 (3)*,

126 (4), 111 (3), 110 (5), 109 (6), 108 (4), 107 (7), 98 (4), 97 (6), 96 (4), 95

(10), 93 (7), 91 (4), 86 (4), 85 (6), 84 (16), 83 (11), 82 (10), 81 (25), 80

(17), 79 (26), 77 (6), 71 (22), 70 (9), 69 (11), 68 (18), 67 (42), 66 (7), 65

(6), 59 (4), 58 (17), 57 (19), 56 (10), 55 (63), 54 (21), 53 (22), 52 (3), 51

(4), 50 (3), 45 (4), 44 (12), 43 (100), 42 (13), 41 (51), 40 (11), 39 (35), 32

(28), 31 (7), 29 (25), 28 (62), 27 (29); *no [M ⁺] detected; GC-MS (CI):

m/z (%): 170 (2) [MH⁺+1], 169 (15) [MH⁺], 153 (5), 152 (11), 151 (100)

[MH⁺ÀH₂O].

865

Chem. Eur. J. 2004, 10, 851 874

www.chemeurj.org

¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

J. Mattay and H. Rinderhagen

FULL PAPER

(3R*,4S*)-4-Allyl-3-hydroxy-1-cycloheptanone (26b): NMR (¹H,¹H-

5-H), 5.83 (td, J=4.2/10.0 Hz, 1H, 6-H); ¹³C NMR (50 MHz, CDCl₃, ref.:

CDCl₃): d=0.12 (C-1’), 21.71 (CH₂), 22.57 (CH₂), 102.93 (C-2), 126.40

(C-5), 129.80 (C-6), 148.07 (C-1); IR (film): n˜ =3053, 2965, 2880, 2830,

2764, 2724, 2492, 1649, 1428, 1401, 1251, 1199, 1165, 981, 954, 910, 845,

805, 755 cm^À1; GC-MS (70 eV): m/z (%): 169 (10) [M ⁺+1], 168 (80)

[M ⁺], 167 (28), 152 (40), 151 (32), 77 (29), 75 (55), 74 (10), 73 (100), 59

(10), 45 (31).

1

COSY, ¹³C,¹³C-DEPT); H NMR (500 MHz, CDCl₃, ref.: CHCl₃): d=1.23

(dddd, J=1.2/8.9/9.5/14.3 Hz, 1H, 5-H), 1.67 (ddddd, J=1.6/4.8/9.7/9.7/

14.6 Hz, 1H, 6-H), 1.76 (ddddd, J=3.4/4.8/8.0/8.1/8.2 Hz, 1H, 4-H), 1.81

(m, 1H, 6-H), 1.88 (m, 1H, 5-H), 2.02 (ddddd, J=1.3/1.7/7.8/7.8/14.2 Hz,

1H, 1’-H), 2.29 (m, 1H, 1’-H), 2.30 (ddd, J=4.6/9.6/17.1 Hz, 1H, 7-H),

2.44 (dddd, J=0.8/4.7/6.7/17.1 Hz, 1H, 7-H), 2.69 (dd, J=2.4/13.0 Hz,

1H, 2-H), 2.75 (d, J=4.3 Hz, 1H, 3-H (OH)), 2.81 (dd, J=9.1/13.0 Hz,

1H, 2-H), 3.64 (dddd, J=2.5/4.3/7.1/9.4 Hz, 1H, 3-H), 4.99 (dddd, J=1.3/

1.7/2.0/10.3 Hz, 1H, 3’-H), 5.01 (dddd, J=1.3/1.7/2.0/16.9 Hz, 1H, 3’-H),

5.37 (dddd, J=6.5/7.8/10.3/16.9 Hz, 1H, 2’-H); ¹³C NMR (125 MHz,

CDCl₃, ref.: CDCl₃): d=20.40 (C-6), 28.83 (C-5), 36.85 (C-1’), 43.78 (C-

7), 46.04 (C-4), 49.78 (C-2), 70.95 (C-3), 116.72 (C-3’), 136.41 (C-2’),

212.50 (C-1); IR (film): n˜ =3442, 3080, 2936, 1697, 1640, 1443, 1415,

1351, 1263, 1226, 1033, 996, 912, 832, 748 cm^À1; GC-MS (70 eV): m/z (%):

126 (5)*, 110 (3), 109 (5), 108 (4), 107 (6), 98 (4), 97 (5), 96 (4), 95 (9), 94

(4), 93 (6), 92 (4), 91 (5), 86 (4), 85 (4), 84 (14), 83 (9), 82 (10), 81 (21),

80 (15), 79 (24), 78 (3), 77 (6), 71 (20), 70 (5), 69 (9), 68 (17), 67 (42), 66

(6), 65 (7), 59 (3), 58 (18), 57 (15), 56 (9), 55 (57), 54 (18), 53 (20), 52 (3),

51 (5), 45 (3), 44 (7), 43 (100), 42 (12), 41 (48), 40 (7), 39 (32), 32 (3), 31

(5), 29 (21), 28 (16), 27 (24); *no [M ⁺] detected; GC-MS (CI): m/z (%):

170 (1) [MH⁺+1], 169 (12) [M ⁺], 153 (5), 152 (11), 151 (100) [MH⁺

ÀH₂O].

General procedure G (synthesis of the silyl enol ethers): Diisopropyl-

amine (360 mmol) in dry THF (500 mL) was placed in a dry apparatus

under argon atmosphere and cooled to 08C. n-Butyllithium (1.6m in n-

hexane; 206 mL, 330 mmol) were added at this temperature within

30 min and stirred for additional 30 min. After cooling to À788C the re-

spective ketone/enone (300 mmol) in dry THF (50 mL) were added.

Then the solution was stirred for 1 h and trimethylsilyl chloride

(450 mmol) were added. The mixture was warmed to room temperature

within 1 h and stirred for an additional hour at this temperature. After

evaporation of the solvent the residue was diluted in n-pentane (300 mL)

the precipitating lithium chloride was filtered off. The solvent was evapo-

rated and the residue was purified by fractional distillation. At small

scales the residue was only purified by kugelrohr distillation and immedi-

ately converted to the corresponding cyclopropyl derivative according to

GP H.

1,6-Cycloheptadienyltrimethylsilyl ether: Silylation of 2-cyclohepten-1-

one (1b; 16.0 g, 145 mmol) according to GP G yielded a colorless liquid

(230.9 g, 87%). B.p. 678C at 7.5 mbar; NMR (¹³C,¹³C-gated); ¹³C NMR

(50 MHz, CDCl₃, ref.: CDCl₃): d=0.17 (C-1’), 26.61 (CH₂), 27.12 (CH₂),

31.27 (CH₂), 112.74 (C-2), 128.16 (C-7), 133.28 (C-6), 148.01 (C-1); GC-

MS (70 eV): m/z (%): 183 (8) [M ⁺+1], 182 (43) [M ⁺], 181 (7), 168 (6),

167 (43), 165(5), 155 (3), 154 (13), 151 (17), 149 (3), 139 (3), 93 (3), 92

(5), 91 (15), 85 (3), 83 (6), 81 (3), 79 (4), 78 (3), 77 (12), 76 (13), 75 (46),

74 (9), 73 (100), 65 (6), 61 (5), 59 (9), 53 (3), 47 (5), 45 (20), 43 (4), 41

(4), 39 (4); GC-MS (CI): m/z (%): 185 (6) [MH⁺+2], 184 (17) [MH⁺

+1], 183 (100) [MH⁺], 182 (10) [M ⁺].

1,7-Cyclooctadienyl trimethylsilyl ether: Silylation of 2-cycloocten-1-one

(1c; 10.2 g, 82.1 mmol) according to GP G yielded as a colorless liquid

(12.4 g, 77%). B.p. 568C at 2 mbar; NMR (¹H,¹³C,¹³C-gated); ¹H NMR

(200 MHz, CDCl₃, ref.: CHCl₃): d=0.16 (s, 9H, 1’-H), 1.32 1.61 (m, 4H),

1.98 2.28 (m, 4H), 4.96 (t, J=8.0 Hz, H-2), 5.55 5.80 (m, 2H); ¹³C NMR

(50 MHz, CDCl₃, ref.: CDCl₃): d=0.39 (C-1’), 22.39 (CH₂), 25.13 (CH₂),

25.48 (CH₂), 29.05 (CH₂), 110.22 (C-2), 125.07 (C-8), 133.12 (C-7), 148.42

(C-1); IR (film): n˜ =3019, 2930, 2857, 1643, 1446, 1251, 1205, 1177, 1165,

1151, 903, 886, 845 cm^À1; GC-MS (70 eV): m/z (%): 197 (5) [M ⁺+1], 196

(26) [M ⁺], 195 (3), 182 (4), 181 (26), 169(4), 168 (21), 167 (34), 154 (3),

153 (4), 151 (6), 105 (3), 91 (9), 82 (4), 79 (5), 78 (4), 77 (10), 76 (4), 75

(44), 74 (9), 73 (100), 67 (3), 65 (3), 61 (4), 59 (6), 55 (4), 47 (4), 45 (16),

41 (3); GC-MS (CI): m/z (%): 199 (7) [MH⁺+2], 198 (17) [MH⁺+1],

197 (100) [MH⁺], 196 (11) [M ⁺].

(1Z,8Z)-1,8-Cyclononadienyl trimethylsilyl ether: Silylation of 2-cyclono-

nen-1-one (1d; 3.50 g, 25.4 mmol) according to GP G yielded a colorless

liquid (3.70 g, 69%). B.p. 658C at 2 mbar; NMR (¹H,¹³C,¹³C-gated):

¹H NMR (200 MHz, CDCl₃, ref.: CHCl₃): d=0.18 (s, 9H, 1’-H), 1.32 1.71

(m, 6H), 1.96 2.35 (m, 4H), 4.96 (t, J=8.6 Hz, H-2), 5.65 5.90(m, 2H);

¹³C NMR (50 MHz, CDCl₃, ref.: CDCl₃): d=0.57 (C-1’), 25.89 (CH₂),

26.95 (CH₂), 28.33 (CH₂), 29.97 (CH₂), 30.04 (CH₂), 110.90 (C-2), 125.47

(C-9), 135.32 (C-8), 147.87 (C-1); IR (film): n˜ =3008, 2925, 2853, 1650,

1634, 1454, 1406, 1251, 1207, 1172, 1157, 886, 844, 854 cm^À1; GC-MS

(70 eV): m/z (%): 211 (2) [M ⁺+1], 210 (11) [M ⁺], 195 (7), 181 (6), 169

(7), 168 (12), 167 (62), 157 (3), 156 (19), 155 (10), 154 (6), 151 (6), 127

(3), 91 (8), 79 (6), 77 (8), 76 (4), 75 (42), 74 (9), 73 (100), 67 (4), 61 (3),

59 (5), 55 (4), 47 (3), 45 (15), 43 (3), 41 (5), 39 (3); GC-MS (CI): m/z

(%): 212 (2) [MH⁺+1], 211 (12) [MH⁺], 210 (5) [M ⁺], 209 (3) [(MÀ1)⁺

], 122 (10), 121 (100); HRMS: m/z: calcd for C₁₂H₂₂OSi: 210.1440, found:

210.1438 [M ⁺].

General procedure H (cyclopropanisation of silyl enol ethers containing

additional reactive olefinic bonds): The respective silyl enol ether

(100 mmol) in dry Et₂O (250 mL) was placed in a dry apparatus under

argon atmosphere and cooled to 08C. Diethyl zinc (1.0m in n-hexane;

150 mL, 150 mmol) were added within 30 min at this temperature. Meth-

ylene iodide (100 mmol) in Et₂O (20 mL) was added within 30 min and

the mixture was warmed to room temperature and stirred for 12 24 h.

The conversion was checked by gas chromatography. (Note the low sensi-

tivity of detection of diiodo methane by gas chromatography.) If required

additional methylene iodide and eventually diethyl zinc solution was

added and the mixture was stirred again for 12 24 h. After complete con-

version the mixture was carefully hydrolyzed with saturated ammonium

chloride solution until complete dissolution of the zinc salts. The aqueous

layer was separated and extracted two times with Et₂O (50 mL). The

combined organic were washed with saturated sodium bicarbonate solu-

tion and dried over Na₂SO₄. The solvent was evaporated and the residue

was purified by fractional distillation or by fast column chromatography.

6,7-Dihydro-5H-benzo[a]cyclohepten-9-yltrimethylsilyl ether: Silylation

of benzsuberon (2; 25.0 g, 156 mmol) according to GP G yielded a color-

less liquid (31.5 g, 87%). B.p. 738C at 0.5 mbar; NMR (¹H,¹³C,¹³C-gated);

¹H NMR (200 MHz, CDCl₃, ref.: CHCl₃): d=0.17 (s, 9H, 1’-H), 1.83 2.08

(m, 4H, 6-H/7-H), 2.65 (t, J=6.3 Hz, 2H, 5-H), 5.418 (t, J=6.6 Hz, 1H,

8-H), 7.12 7.30 (m, 3H), 7.47 (m, 1H); ¹³C NMR (50 MHz, CDCl₃, ref.:

CDCl₃): d=0.24 (C-1’), 23.84 (C-6), 33.03 (CH₂), 33.30 (CH₂), 109.39 (C-

8), 125.77 (CH), 126.82 (CH), 127.46 (CH), 128.66 (CH), 138.18 (C-5a),

140.87 (C-9a), 149.50 (C-8)*, 140.35 (C-9)*; *: signal assignments are

mutual interchangeable; IR (film): n˜ =2935, 2855, 1633, 1486, 1448,

Eventually the product partially hydrolyzed during chromatography. In

these cases the corresponding alkyl alcohol can be converted into the

silyl alkyl ether by the following procedure. 2.0 Molar equivalents trie-

thylamine and 1.3 equivalents trimethylsilyl trifluoromethanesulfonate

were added to the hydrolyzed product diluted in methylene chloride

(approx. 15 mL per 5 mmol alcohol). The mixture was stirred for 2 h di-

luted with methylene chloride and washed with saturated sodium bicar-

bonate solution. The organic layer was dried over MgSO₄, the solvent

was evaporated and the residue was purified again by fast column chro-

matography.

1353, 1331, 1252, 1229, 1180, 1134, 1094, 1073, 889, 844, 770, 746 cm^À1

;

GC-MS (70 eV): m/z (%): 234 (3) [M ⁺+2], 233 (13) [M ⁺+1], 232 (61)

[M ⁺], 231 (17), 219 (17), 218 (11), 217 (57), 215 (4), 205 (7), 204 (15),

203 (29), 201 (9), 189 (3), 185 (4), 143 (12), 142 (28), 141 (16), 131 (8),

130 (3), 129 (7), 128 (18), 127 (4), 116 (4), 115 (16), 101 (4), 91 (6), 89

(3), 77 (4), 76 (3), 75 (27), 74 (9), 73 (100), 59 (4), 45 (17), 43 (3); GC-

MS (CI): m/z (%): 235 (5) [MH⁺+2], 234 (21) [MH⁺+1], 233 (100)

[MH⁺], 232 (10) [M ⁺], 231 (3) [(MÀ1)⁺]; HRMS: m/z: calcd for

C₁₄H₂₀OSi: 232.1283, found: 232.1283 [M ⁺].

1,5-Cyclohexadienyltrimethylsilyl ether: Silylation of 2-cyclohexen-1-one

(1a; 28.8 g, 300 mmol) according to GP G yielded 1,5-cyclohexadienyltri-

methylsilyl ether (40.9 g, 81%) as

a colorless liquid. B.p. 618C at

16 mbar; NMR (¹H,¹H-COSY, ¹³C,¹³C-DEPT, HMQC); ¹H NMR

(500 MHz, CDCl₃, ref.: CHCl₃): d=0.16 (s, 9H, 1’-H), 2.05 (m, 2H), 2.14

(m, 2H,), 4.85 (dt, J=2.1/4.5 Hz, 1H, 2-H), 5.66 (qd, J=2.0/10.0 Hz, 1H,

6-(3-Butenyl)-1,6-cycloheptadienyltrimethylsilyl ether: Silylation of 3-(3-

butenyl)-2-cyclohepten-1-one (4a; 3.65 g, 22.2 mmol) was carried out ac-

cording to GP G. The title compound was isolated after kugelrohr distil-

866

¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemeurj.org

Chem. Eur. J. 2004, 10, 851 874

Cascade Reactions

851 874

lation as a colorless liquid (5.05 g, 96%). NMR (¹H,¹³C,¹³C-DEPT);

¹H NMR (500 MHz, CDCl₃): d=0.14 (s, 9H, 1’’-H), 1.81 (tt, J=6.3/

6.3 Hz, 2H, 4-H), 2.07 (dt, J=5.8/6.1 Hz, 2H, 3-H), 2.11 2.20 (m, 6H, 5-

H/1’-H/2’-H), 4.93 (tdd, J=1.2/2.0/10.4/13.6 Hz, 1H, 4’-H), 5.00 (tdd, J=

1.6/2.0/17.0 Hz, 1H, 4’-H), 5.14 (dt, J=1.7/5.8 Hz, 1H, 2-H), 5.44 (m, 1H,

7-H), 5.79 (tdd, J=6.3/10.4/17.0 Hz, 1H, 3’-H); ¹³C NMR (125 MHz,

CDCl₃): d=0.22 (C-1’’), 26.43 (CH₂), 28.31 (CH₂), 32.60 (CH₂), 33.63

(CH₂), 39.65 (CH₂), 111.38 (C-2), 114.66 (C-4’), 123.78 (C-7), 138.26 (C-

3’), 145.88 (C-6), 147.94 (C-1); IR (film): n˜ =2932, 1640, 1438, 1378,

1250, 1168, 1113 cm^À1; GC-MS (70 eV): m/z (%): 237 (6) [M ⁺+1], 236

(30) [M ⁺], 235 (5), 221 (15), 208 (5), 207 (9), 195 (13), 194 (18), 193 (9),

182 (3), 181 (9), 180 (5), 179 (10), 168 (4), 167 (9), 165 (5), 131 (6), 117

(4), 106 (4), 105 (5), 104 (4), 91 (13), 79 (5), 77 (4), 75 (27), 74 (10), 73

(100), 61 (3), 59 (5), 55 (3), 47 (3), 45 (18), 41 (5).

M⁺+1], 210 (5) [M⁺], 209 (2) [(MÀ1)⁺], 122 (100) [MH⁺ÀMe₃-

SiOH+1], 121 (100) [MH⁺ÀMe₃SiOH].

(2Z)-Bicyclo[7.1.0]dec-2-en-1-yl trimethylsilyl ether (8d): Cyclopropani-

sation of 1,8-cyclononadienyl trimethylsilyl ether (3.00 g, 14.3 mmol) was

carried out according to GP H. Column chromatography on silica gel

(Et₂O/n-pentane 1:200) yielded 8d as a colorless liquid (1.81 g, 56%).

NMR (¹H,¹H-COSY, ¹³C,¹³C-DEPT, HMQC); ¹H NMR (500 MHz,

CDCl₃, ref.: CHCl₃): d=0.07 (s, 9H, 1’-H), 0.08 (dd, J=5.2/6.7 Hz, 1H,

10-H), 0.47 (dddd, J=1.3/8.8/11.8/15.1 Hz, 1H, 8-H), 0.83 (dd, J=5.2/

10.1 Hz, 1H, 10-H), 1.07 1.22 (m, 3H, 6-H/7-H/9-H), 1.50 (m, 1H, 5-H),

1.62 (m, 1H, 5-H), 1.68 1.77 (m, 2H, 6-H/7-H), 1.99 2.11 (m, 2H, 4-H/8-

H), 2.88 (m, 1H, 4-H), 5.61 5.68 (m, 2H, 2-H/3-H); ¹³C NMR (125 MHz,

CDCl₃, ref.: CDCl₃): d=1.27 (C-1’), 20.15 (C-10), 26.03 (C-7), 27.29 (C-4/

C-5)*, 28.97 (C-6), 29.06 (C-9), 33.95 (C-8), 56.99 (C-1), 130.93 (C-2),

138.66 (C-3). *signal shows correlation signals with 4 protons in HMQC

2D experiment; IR (film): n˜ =3008, 2956, 2923, 2854, 1455, 1248, 1202,

1164, 1089, 1042, 1018, 974, 944, 888, 840, 750, 701 cm^À1; GC-MS (70 eV):

m/z (%): 224 (4) [M ⁺], 223 (2) [(MÀ1)⁺], 209 (3), 195 (3), 182 (4), 181

(15), 171 (3), 170 (26), 169 (17), 168 (9), 167 (35), 156 (3), 155 (10), 154

(3), 151 (6), 142 (3), 127 (4), 93 (3), 92 (3), 91 (9), 81 (3), 79 (6), 77 (5),

76 (3), 75 (31), 74 (9), 73 (100), 67 (4), 59 (4), 55 (5), 53 (3), 47 (3), 45

(20), 43 (3), 41 (8), 39 (5); GC-MS (CI): m/z (%): 226 (2) [M+H⁺+1],

225 (12) [M+H⁺], 234 (2) [M ⁺], 223 (3) [(MÀ1)⁺], 137 (4), 136 (11),

135 (100); HRMS: m/z: calcd for C₁₃H₂₄OSi: 223.1495, found: 223.1518

[(MÀ1)⁺].

(2Z)-Bicyclo[4.1.0]hept-2-en-1-yl trimethylsilyl ether (8a): Cyclopropani-

sation of 1,5-cyclohexadienyl trimethylsilyl ether (33.7 g, 200 mmol) was

carried out according to GP H. Purification by spinning band column dis-

tillation yielded 8a as a colorless liquid (27.7 g, 76%). B.p. 768C at

10 mbar; NMR (¹H,¹H-COSY,¹³C,¹³C-DEPT, HMQC); ¹H NMR

(500 MHz, CDCl₃, ref.: CHCl₃): d=0.11 (s, 9H, 1’-H), 0.72 (dd, J=5.3/

6.2 Hz, 1H, 7-H), 0.94 (dd, J=5.3/9.8 Hz, 1H, 7-H), 1.45 (ddddd, J=1.6/

2.0/4.0/6.2/9.8 Hz, 1H, 6-H), 1.51 (dddd, J=2.0/2.4/6.2/12.7 Hz, 1H, 5-H),

1.57 (m, 1H, 4-H), 1.80 (m, 1H, 5-H), 1.93 (m, 1H, 4-H), 5.33 (dddd, J=

1.4/1.6/6.2/10.2 Hz, 1H, 3-H), 6.08 (ddd, J=1.5/1.6/10.2 Hz, 1H, 2-H);

¹³C NMR (125 MHz, CDCl₃, ref.: CDCl₃): d=1.05 (C-1’), 17.42 (C-5),

17.74 (C-7), 20.21 (C-4), 22.98 (C-6), 53.85 (C-1), 121.20 (C-3), 133.42 (C-

2); IR (film): n˜ =3041, 3005, 2963, 2934, 2862, 1638, 1444, 1396, 1370,

1316, 1250, 1213, 1159, 1105, 1087, 1047, 1018, 1002, 977, 930, 863, 841,

753, 715 cm^À1; GC-MS (70 eV): m/z (%): 183 (3) [M ⁺+1], 182 (16) [M ⁺

], 181 (5), 168 (6), 167 (38), 165 (7), 154 (11), 153 (4), 152 (3), 151 (20),

149 (4), 91 (7), 77 (6), 76 (10), 75 (35), 74 (9), 73 (100), 65 (5), 61 (4), 59

(8), 55 (5), 53 (5), 51 (3), 47 (7), 45 (28), 44 (5), 43 (8), 41 (6), 39 (8), 29

(3), 28 (5), 27 (5); HRMS: m/z: calcd for C₁₀H₁₇OSi: 181.1049, found:

181.1036 [(MÀ1)⁺].

(2Z)-Bicyclo[5.1.0]oct-2-en-1-yltrimethylsilyl ether (8b): Cyclopropanisa-

tion of 1,6-cycloheptadienyl trimethylsilyl ether (20.5 g, 112 mmol) ac-

cording to GP H yielded 8b as a colorless liquid (20.0 g, 91%). B.p. 868C

at 20 mbar; NMR (¹H,¹H-COSY, ¹³C,¹³C-DEPT, HMQC); ¹H NMR

(500 MHz, CDCl₃, ref.: CHCl₃): d=0.10 (s, 9H, 1’-H), 0.39 (dd, J=4.9/

6.9 Hz, 1H, 8-H), 0.95 (dd, J=4.9/9.9 Hz, 1H, 8-H), 1.26 (ddddd, J=2.1/

4.3/9.6/9.9/14.0 Hz, 1H, 4-H), 1.41 1.49 (m, 2H, 6-H/7-H), 1.64 (ddddd,

J=2.4/3.6/6.0/9.5/14.0 Hz, 1H, 5-H), 1.98 (m, 1H, 5-H), 2.06 (m, 1H, 4-

H), 2.12 (m, 1H, 4-H), 5.37 (ddd, J=4.2/6.9/11.3 Hz, 1H, 3-H), 5.85 (dm,

J=11.3 Hz, 1H, 2-H); ¹³C NMR (125 MHz, CDCl₃, ref.: CDCl₃): d=1.17

(C-1’), 22.07 (C-8), 23.99 (C-5), 28.28 (C-7), 28.44 (C-6), 30.29 (C-4),

59.00 (C-1), 126.75 (C-3), 132.58 (C-2); IR (film): n˜ =2922, 1451, 1249,

1181, 1090, 984, 840, 753 cm^À1; GC-MS (70 eV): m/z (%): 197 (2) [M ⁺

+1], 196 (9) [M ⁺], 181 (9), 169 (3), 168 (10), 167 (49), 165 (3), 155 (2),

154 (7), 153 (2), 151 (5), 105 (3), 91 (6), 83 (2), 82 (2), 79 (4), 78 (3), 77

(7), 76 (3), 75 (29), 74 (8), 73 (100), 67 (3), 65 (2), 61 (2), 59 (5), 55 (3),

53 (2), 47 (3), 45 (16), 43 (2), 41 (3), 39 (3); GC-MS (CI): m/z (%): 197

(4) [MH⁺], 196 (5) [M ⁺], 107 (100) [MH⁺ÀMe₃SiOH]; HRMS: m/z:

calcd for C₁₁H₁₉OSi: 195.1205, found: 195.1193 [(MÀ1)⁺]; elemental

analysis calcd (%) for C₁₁H₂₀OSi (196.36): C 67.28, H 10.27; found: C

67.16, H 10.03.

2-Trimethylsilyloxy-tricyclo[6.4.0.0^2,4]dodeca-1(8),9,11-triene (9): Cyclo-

propanisation of 6,7-dihydro-5H-benzo[a]cyclohepten-9-yltrimethylsilyl

ether (14.6 g, 62.8 mmol) according to GP H yielded 9 as a colorless

liquid (14.4 g, 93%). B.p. 598C at 0.2 mbar; NMR (¹H,¹H-COSY, ¹³C,¹³C-

DEPT, HMQC, HMBC); ¹H NMR (500 MHz, CDCl₃, ref.: CHCl₃): d=

0.04 (s, 9H, 1’-H), 0.11 (dddd, J=6.5/12.1/12.3/14.2 Hz, 1H, 5-H), 0.51

(dd, J=5.3/5.8 Hz, 1H, 3-H), 1.08 (dddd, J=4.8/5.8/9.4/12.1 Hz, 1H, 4-

H), 1.18 (dd, J=5.3/9.4 Hz, 1H, 3-H), 1.49 (ddddd, J=1.1/6.4/6.5/12.6/

13.0 Hz, 1H, 6-H), 1.86 (ddddd, J=1.4/5.9/7.2/12.3/13.0 Hz, 1H, 6-H),

1.94 (dddd, J=1.1/4.8/5.9/14.2 Hz, 1H, 5-H), 2.55 (ddd, J=1.4/6.4/

13.0 Hz, 1H, 7-H), 3.36 (ddd, J=7.2/12.6/13.0 Hz, 1H, 7-H), 7.08 (dd, J=

2.0/7.0 Hz, 1H, 9-H), 7.18 (dd, J=2.0/7.0 Hz, 1H, 10-H)*, 7.20 (dd, J=

2.0/7.0 Hz, 1H, 11-H)*, 7.08 (dd, J=2.0/7.0 Hz, 1H, 12-H); ¹³C NMR

(125 MHz, CDCl₃, ref.: CDCl₃): d=1.23 (C-1’), 19.71 (C-3), 21.64 (C-4),

24.71 (C-6), 26.88 (C-5), 30.38 (C-7), 59.53 (C-2), 126.18 (C-10), 128.27

(C-11), 128.64 (C-9), 130.11 (C-12), 139.39 (C-8)*, 140.35 (C-1)*; *: signal

assignments are mutual interchangeable; IR (film): n˜ =2934, 2858, 1451,

1249, 1219, 1206, 1190, 1112, 1088, 1042, 990, 931, 840, 752 cm^À1; GC-MS

(70 eV): m/z (%): 247 (3) [M ⁺+1], 246 (22) [M ⁺], 245 (3), 231 (12), 219

(5), 218 (10), 217 (41), 205 (10), 204 (22), 203 (20), 201 (3), 157 (4), 156

(7), 155 (4), 142 (3), 141 (12), 131 (4), 130 (3), 129 (9), 128 (12), 127 (3),

117 (3), 116 (3), 115 (13), 91 (8), 77 (3), 75 (24), 74 (10), 73 (100), 59 (4),

45 (20), 43 (3), 41 (3), 39 (3); GC-MS (CI): m/z (%): 248 (1) [MH⁺+1],

247 (5) [MH⁺], 246 (7) [M ⁺], 245 (3) [(MÀ1)⁺], 159 (4), 158 (13), 157

(100); HRMS: m/z: calcd for C₁₅H₂₂OSi: 246.1440, found: 246.1439 [M ⁺

]; elemental analysis calcd (%) for C₁₅H₂₂OSi (246.42): C 73.11, H 9.00;

found: C 73.41, H 8.96.

2-Trimethylsilyloxy-tricyclo[6.3.0.0^2,4]undec-1(8)-ene (10): Silylation of bi-

cyclo[5.3.0]dec-1(7)-en-2-one (3; 3.24 g, 21.6 mmol) was carried out ac-

cording to GP G. The crude product was purified by kugelrohr distilla-

tion and treated according to GP H. The cyclopropanisation product was

purified by column chromatography (cyclohexane/ethyl acetate 98:2)

yielding 10 (3.47 g, 68%) as a colorless oil. NMR (¹H,¹H-COSY, ¹³C,¹³C-

DEPT, HMQC, HMBC); ¹H NMR (500 MHz, CDCl₃, ref.: CHCl₃): d=

0.09 (s, 9H, 1’-H), 0.24 (dd, J=4.8/6.8 Hz, 1H, 3-H), 0.92 (dd, J=4.8/

10.1 Hz, 1H, 3-H), 1.10 (dddd, J=1.7/7.5/9.4/14.3 Hz, 1H, 5-H), 1.42

(dddd, J=6.8/7.5/7.0/10.1 Hz, 1H, 4-H), 1.49 (ddddd, J=1.6/5.1/5.4/8.9/

14.2 Hz, 1H, 6-H), 1.66 1.81 (m, 3H, 6-H/10-H), 2.02 (ddddd, J=1.3/2.6/

5.1/10.0/17.7 Hz, 1H, 7-H), 2.14 (dddd, J=1.9/6.9/8.9/14.3 Hz, 1H, 5-H),

2.14 2.30 (m, 3H, 7-H/11-H), 2.42 (m, 1H, 9-H), 2.67 (m, 1H, 9-H);

¹³C NMR (125 MHz, CDCl₃, ref.: CDCl₃): d=1.06 (C-1’), 21.90 (C-10),

22.10 (C-3), 24.33 (C-6), 27.65 (C-4), 29.39 (C-5), 31.95 (C-7), 35.67 (C-

9), 39.61 (C-11), 57.13 (C-2), 134.62 (C-8), 136.16 (C-1); IR (film): n˜ =

3078, 3000, 2931, 2844, 1671, 1449, 1369, 1346, 1324, 1305, 1260, 1248,

(2Z)-Bicyclo[6.1.0]non-2-en-1-yl trimethylsilyl ether (8c): Cyclopropani-

sation of 1,7-cyclooctadienyl trimethylsilyl ether (4.20 g, 21.4 mmol) ac-

cording to GP H yielded 8c as a colorless liquid (3.56 g, 77%). B.p. 648C

at 4 mbar; NMR (¹H,¹H-COSY, ¹³C,¹³C-gated); ¹H NMR (500 MHz,

CDCl₃, ref.: CHCl₃): d=0.05 (dd, J=5.1/6.9 Hz, 1H, 9-H), 0.12 (s, 9H,

1’-H), 0.82 (dddd, J=4.0/11.0/11.0/14.3 Hz, 1H, 7-H), 0.83 (dd, J=5.1/

10.0 Hz, 1H, 9-H), 1.05 (dddd, J=3.3/6.9/10.0/11.4 Hz, 1H, 8-H), 1.38 (m,

1H, 5-H), 1.58 1.70 (m, 2H, 6-H), 1.87 1.98 (m, 3H, 4-H/5-H/7-H), 2.56

(m, 1H, 4-H), 5.59 (d, J=10.5 Hz, 1H, 2-H), 5.74 (ddd, J=5.0/7.4/

10.7 Hz, 1H, 3-H); ¹³C NMR (50 MHz, CDCl₃, ref.: TMS): d=1.56 (C-

1’), 18.92 (C-9), 24.80 (CH₂), 27.32 (C-8), 29.15 (CH₂), 29.28 (CH₂), 30.08

(CH₂), 57.03 (C-1), 127.76 (C-3), 136.73 (C-2); GC-MS (70 eV): m/z (%):

211 (2) [M ⁺+1], 210 (12) [M ⁺], 209 (4), 195 (4), 181 (7), 169 (6), 168

(11), 167 (47), 156 (7), 155 (7), 154 (6), 151 (4), 91 (7), 79 (5), 77 (6), 76

(4), 75 (33), 74 (9), 73 (100), 67 (3), 59 (5), 55 (4), 53 (3), 45 (14), 43 (4),

41 (5), 39 (3); GC-MS (CI): m/z (%): 212 (2) [MH⁺+1], 211 (15) [MH⁺/

1182, 1137, 1121, 1096, 1079, 1054, 1020, 995, 943, 930, 842, 749, 688 cm^À1

GC-MS (70 eV): m/z (%): 237 (4) [M ⁺+1], 236 (27) [M ⁺], 221 (12), 209

;

867

Chem. Eur. J. 2004, 10, 851 874

www.chemeurj.org

¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

J. Mattay and H. Rinderhagen

FULL PAPER

(8), 208 (25), 207 (79), 205 (6), 195 (4), 194 (23), 193 (6), 191 (7), 180 (5),

179 (3), 166 (10), 165 (3), 151 (3), 131 (8), 118 (4), 117 (7), 115 (5), 105

(7), 93 (6), 92 (3), 91 (16), 79 (9), 78 (4), 77 (9), 76 (3), 75 (33), 74 (10),

73 (100), 67 (4), 65 (4), 59 (7), 55 (4), 53 (5), 45 (20), 43 (3), 41 (13), 39

(6), 29 (4), 28 (3), 27 (4); GC-MS (CI): m/z (%): 237 (8) [MH⁺+1], 236

(8) [M ⁺], 235 (6) [M ⁺ÀH], 149 (4), 148 (13), 147 (100); HRMS: m/z:

calcd for C₁₄H₂₄OSi: 236.1596, found: 236.1596 [M ⁺].

(C-7), 25.29/25.31 (C-4’’), 28.41/28.44 (C-6), 28.99/29.28 (C-6’’), 30.55/

30.90 (C-4), 33.21 (C-1’’), 46.19/46.24 (C-1’), 57.53/57.58 (C-1), 127.01/

127.02 (C-3’’)*, 127.11/127.14 (C-2)*, 131.48/131.76 (C-2’’), 139.09/139.20

(C-3); *: signal assignments are mutual interchangeable; IR (film): n˜ =

3075, 3021, 2932, 2863, 1745, 1648, 1450, 1379, 1309, 1249, 1219, 1184,

1127, 1090, 1050, 1000, 973, 944, 926, 840, 750, 720 cm^À1; GC-MS (70 eV):

m/z (%): 291 (2) [M ⁺+1], 291 (7) [M ⁺], 262 (3), 261 (13), 248 (5), 247

(4), 211 (5), 210 (28), 209 (21), 196 (6), 195 (29), 182 (6), 181 (29), 169

(4), 168 (19), 167 (10), 119 (6), 117 (3), 105 (4), 91 (9), 80 (3), 79 (16), 77

(4), 75 (17), 74 (8), 73 (100), 53 (5), 45 (8), 41 (6); GC-MS (CI): m/z (%):

292 (2) [MH⁺+1], 291(8) [MH⁺/M ⁺+1], 290 (5) [M ⁺], 289 (3) [M ⁺

ÀH], 203 (6), 202 (18), 201 (100); HRMS: m/z: calcd for C₁₈H₃₀OSi:

290.2066, found: 290.2056 [M ⁺].

3-(3-Butenyl)bicyclo[5.1.0]oct-2-en-1-yltrimethylsilyl ether (11a): Cyclo-

propanisation of 6-(3-butenyl)-1,6-cycloheptadienyltrimethylsilyl ether

(4.63 g, 19.6 mmol) was carried out according to GP H. Column chroma-

tography on silica gel (cyclohexane/ethyl acetate 99:1) yielded 11a as a

colorless oil (3.83 g, 78%). NMR (¹H,¹H-COSY, ¹³C,¹³C-DEPT, HMQC,

HMBC); ¹H NMR (500 MHz, CDCl₃): d=0.09 (s, 9H, 1’’-H), 0.24 (dd,

J=4.9/6.6 Hz, 1H, 8-H), 0.88 (dd, J=4.9/9.9 Hz, 1H, 8-H), 1.00 (dddd,

J=4.7/8.0/9.7/14.2 Hz, 1H, 6-H), 1.19 (ddddd, J=1.6/5.0/6.6/8.0/9.9 Hz,

1H, 7-H), 1.26 (ddddd, J=4.7/4.8/6.5/11.3/13.6 Hz, 1H, 5-H), 1.63

(ddddd, J=4.7/4.7/5.4/9.7/13.6 Hz, 1H, 5-H), 1.91 (ddd, J=4.7/4.8/

14.9 Hz, 1H, 4-H),1.96 (dddd, J=4.7/5.0/6.5/14.2 Hz, 1H, 6-H), 1.99 2.05

(m, 2H, 1’-H), 2.06 2.19 (m, 2H, 2’-H), 2.42 (dddd, J=2.1/5.4/11.3/

14.9 Hz, 1H, 4-H), 4.92 (dddd, J=1.2/1.2/2.0/10.3 Hz, 1H, 4’-H), 4.99

(dddd, J=1.7/1.7/2.0/17.0 Hz, 1H, 4’-H), 5.63 (dddd, J=1.6/1.6/1.6/2.1 Hz,

1H, 2-H), 5.77 (dddd, J=6.5/6.5/10.3/17.0 Hz, 1H, 3’-H); ¹³C NMR

(125 MHz, CDCl₃): d=1.31 (C-1’’), 20.92 (C-8), 22.57 (C-5), 25.07 (C-7),

28.33 (C-6), 30.99 (C-4), 32.11 (C-1’), 38.67 (C-2’), 57.45 (C-1), 114.53 (C-

4’), 125.62 (C-2), 138.42 (C-3’), 140.27 (C-3); IR (film): n˜ =3081, 2935,

3-(3-Butenyl)bicyclo[6.1.0]non-2-en-1-yl trimethylsilyl ether (11b): Silyla-

tion of 3-(3-butenyl)-2-cycloocten-1-one (4b; 1.70 g, 4.65 mmol) was car-

ried out according to GP G. The crude product was purified by kugelrohr

distillation and treated according to GP H. The cyclopropanisation prod-

uct was purified by column chromatography (cyclohexane/ethyl acetate

99:1) yielding 11b (1.41 g, 56%) as a colorless oil. NMR (¹H,¹H-COSY,

¹³C,¹³C-DEPT, HMQC); ¹H NMR (500 MHz, CDCl₃): d=0.03 (dd, J=

5.0/6.8 Hz, 1H, 9-H), 0.08 (s, 9H, 1’’-H), 0.71 (dddd, J=1.9/11.4/11.6/

14.0 Hz, 1H, 7-H), 0.78 (dd, J=5.0/10.1 Hz, 1H, 9-H), 1.062 (dddd, J=

3.2/6.8/10.1/10.6 Hz, 1H, 8-H), 1.29 (m, 1H, 5-H), 1.58 (m, 1H, 6-H),

1.670 (m, 1H, 6-H), 1.77 1.90 (m, 3H, 4-H/5-H/7-H), 2.015 2.255 (m,

4H, 1’-H/2’-H), 2.72 (m, 1H, 4-H), 4.94 (dddd, J=1.4/1.4/1.9/10.2 Hz, 1H,

4’-H), 5.01 (dddd, J=1.6/1.6/1.9/17.1 Hz, 1H, 4’-H), 5.39 (m, 1H, 2-H),

5.81 (dddd, J=6.6/6.6/10.2/17.1 Hz, 1H, 3’-H); ¹³C NMR (125 MHz,

CDCl₃): d=1.52 (C-1’’), 18.75 (C-9), 25.91 (C-5), 28.46 (C-8), 29.66 (C-7),

30.17 (C-6), 31.25 (C-4), 32.16 (C-2’), 36.35 (C-1’), 57.57 (C-1), 114.48 (C-

4’), 123.69 (C-2), 138.55 (C-3’), 148.48 (C-3); IR (film): n˜ =3080, 2926,

2856, 1658, 1641, 1448, 1383, 1317, 1295, 1249, 1204, 1188, 1159, 1095,

1079, 1020, 995, 976, 952, 910, 894, 844, 752, 709, 687 cm^À1; GC-MS

(70 eV): m/z (%): 264 (2) [M ⁺], 223 (8), 222 (6), 221 (24), 211 (3), 210

(10), 209 (52), 208 (5), 207 (4), 193 (5), 181 (6), 180 (4), 179 (5), 167 (7),

156 (5), 155 (3), 133 (3), 131 (3), 119 (3), 117 (3), 105 (4), 93 (3), 91 (12),

79 (6), 77 (4), 75 (20), 74 (9), 73 (100), 67 (4), 59 (3), 55 (4), 45 (9), 41

(7), 39 (3); GC-MS (CI): m/z (%): 266 (3) [MH⁺+1], 265 (10) [MH⁺/

2864, 1641, 1452, 1251, 1218, 1187, 1091, 1050, 1000, 926, 846, 751 cm^À1

;

GC-MS (70 eV): m/z (%): 250 (6) [M ⁺], 235 (7), 222 (4), 221 (24), 209

(8), 208 (11), 207 (4), 195 (19), 194 (3), 193 (10), 181 (12), 180 (4), 179

(5), 167 (6), 119 (4), 117 (3), 105 (5), 91 (10), 79 (4), 75 (18), 74 (8), 73

(100), 59 (3), 55 (4), 45 (17), 41 (5); GC-MS (CI): m/z (%): 252 (2)

[MH⁺+1], 251(10) [MH⁺], 250(11) [M ⁺], 249(3) [M ⁺ÀH], 162 (13), 161

(100), 133 (7), 119 (5); elemental analysis calcd (%) for C₁₅H₂₆OSi

(250.45): C 71.93, H 10.46; found: C 71.80, H 10.22.

3-(3-Butynyl)bicyclo[5.1.0]oct-2-en-1-yl trimethylsilyl ether (12a): Silyla-

tion of 3-(2-butynyl)-2-cyclohepten-1-one (2.17 g, 13.4 mmol) was carried

out according to GP G. The crude product was purified by kugelrohr dis-

tillation and treated according to GP H. The cyclopropanisation product

was purified by column chromatography (cyclohexane/ethyl acetate 99:1)

yielding 12a as a colorless oil (2.39 g, 72%). NMR (¹H,¹H-COSY, ¹³C-

APT, HMQC, HMBC); ¹H NMR (500 MHz, CDCl₃): d=0.09 (s, 9H, 1’’-

H), 0.26 (dd, J=4.9/6.7 Hz, 1H, 8-H), 0.89 (dd, J=4.9/9.9 Hz, 1H, 8-H),

1.04 (dddd, J=4.6/8.0/9.7/14.2 Hz, 1H, 6-H), 1.20 (ddddd, J=1.3/4.8/6.7/

8.0/9.9 Hz, 1H, 7-H), 1.27 (ddddd, J=4.5/4.6/6.5/11.3/13.7 Hz, 1H, 5-H),

1.63 (ddddd, J=4.6/4.7/5.4/9.7/13.7 Hz, 1H, 5-H), 1.91 (ddd, J=4.5/4.7/

14.8 Hz, 1H, 4-H), 1.91 (dd, J=2.6/2.6 Hz, 1H, 4’-H), 1.96 (dddd, J=4.6/

4.8/6.5/14.2 Hz, 1H, 6-H), 2.14 2.29 (m, 4H, 1’-H; 2’-H), 2.42 (dddd, J=

2.1/5.4/11.3/14.8 Hz, 1H, 4-H), 5.63 (dd, J=1.3/2.1 Hz, 1H, 2-H);

¹³C NMR (125 MHz, CDCl₃): d=1.29 (C-1’’), 17.29 (C-2’), 20.93 (C-8),

22.57 (C-5), 25.13 (C-7), 28.21 (C-6), 30.85 (C-4), 38.00 (C-1’), 57.32 (C-

1), 68.62 (C-4’), 83.94 (C-3’), 126.64 (C-2), 138.74 (C-3); IR (film): n˜ =

3317, 3077, 2934, 2865, 2122, 1450, 1249, 1218, 1186, 1088, 1050, 995, 927,

840, 754, 628 cm^À1; GC-MS (70 eV): m/z (%): 248 (0.41) [M ⁺], 233 (3),

219 (6), 206 (3), 195 (5), 143 (4), 129 (4), 105 (3), 91 (7), 79 (4), 77 (7), 75

(18), 74 (9), 73 (100), 59 (36), 45 (15), 43 (3), 41 (4), 39 (4); GC-MS (CI):

m/z (%): 250 (2) [MH⁺+1], 249 (6) [MH⁺], 248 (5) [M⁺], 247 (3)

[(MÀ1)⁺], 160 (13), 159 (100), 131 (11), 117 (14); HRMS: m/z: calcd for

C₁₅H₂₃OSi: 247.1518, found: 247.1510 [(MÀ1)⁺].

3-(2-Cyclohexenylmethyl)bicyclo[5.1.0]oct-2-en-1-yl trimethylsilyl ether

(13a): Silylation of 3-(2-cyclohexenylmethyl)-2-cyclohepten-1-one

(950 mg, 4.65 mmol) was carried out according to GP G. The crude prod-

uct was purified by kugelrohr distillation and treated according to GP H.

The cyclopropanisation product was purified by column chromatography

(cyclohexane/ethyl acetate 99:1) yielding of 13a (640 mg, 47%) as a col-

orless oil. NMR (¹H,¹H-COSY, ¹³C,¹³C-DEPT, HMQC, HMBC);

¹H NMR (500 MHz, CDCl₃): d=0.097/0.099 (s, 9H, 1’’’-H), 0.24 0.28 (m,

1H, 8-H), 0.86 0.91 (m, 1H, 8-H), 0.97 1.08 (m, 1H, 6-H), 1.12 1.30 (m,

3H, 5-H/7-H/6’’-H), 1.42 1.54 (m, 1H, 5’’-H), 1.58 1.74 (m, 3H, 5-H/5’’-

H/6’’-H), 1.84 2.01 (m, 6H, 4-H/6-H/1’-H/4’’-H), 2.36 2.45 (m, 1H, 4-H),

2.14 2.23 (m, 1H, 1’’-H), 5.46 5.55 (m, 1H, 2’’-H), 5.5871/5.570 (s, 1H, 2-

H), 5.61 5.67 (m, 1H, 3’’-H); ¹³C NMR (125 MHz, CDCl₃): d=1.29 (C-

1’’’), 21.00/21.06 (C-8), 21.24/21.36 (C-5’’), 22.53/22.69 (C-5), 25.05/25.24

M

⁺+1], 264 (4) [M ⁺], 176 (16), 175 (100); HRMS: m/z: calcd for

C₁₆H₂₈OSi: 264.1909, found: 264.1890 [M ⁺]; elemental analysis calcd (%)

for C₁₆H₂₈OSi (264.48): C 72.66, H 10.67; found: C 71.61, H 10.52.

3-(3-Butynyl)bicyclo[6.1.0]non-2-en-1-yl trimethylsilyl ether (12b): Silyla-

tion of 3-(3-butynyl)-2-cycloocten-1-one (5b; 1.95 g, 13.4 mmol) was car-

ried out according to GP G. The crude product was purified by kugelrohr

distillation and treated according to procedure H. The cyclopropanisation

product was purified by column chromatography (cyclohexane/ethyl ace-

tate 99:1) yielding 12b (1.21 g, 41%) as a colorless oil. NMR (¹H,¹H-

COSY, ¹³C,¹³C-DEPT, HMQC); ¹H NMR (500 MHz, CDCl₃): d=0.05

(dd, J=5.1/6.8 Hz, 1H, 9-H), 0.07 (s, 9H, 1’’-H), 0.72 (dddd, J=1.9/11.4/

11.5/14.3 Hz, 1H, 7-H), 0.79 (dd, J=5.1/10.1 Hz, 1H, 9-H), 1.062 (ddddd,

J=0.7/3.3/6.8/10.2/11.4 Hz, 1H, 8-H), 1.29 (m, 1H, 5-H), 1.59 (m, 1H, 6-

H), 1.68 (m, 1H, 6-H), 1.77 1.90 (m, 3H, 4-H/5-H/7-H), 1.93 (dd, J=2.5/

2.5 Hz, 1H, 4’-H), 2.17 2.37 (m, 4H, 1’-H/2’-H), 2.72 (m, 1H, 4-H), 5.41

(m, 1H, 2-H); ¹³C NMR (125 MHz, CDCl₃): d=1.52 (C-1’’), 17.32 (C-2’),

18.72 (C-9), 25.84 (C-5), 28.42 (C-8), 29.57 (C-7), 30.16 (C-6), 31.15 (C-

4), 36.85 (C-1’), 57.41 (C-1), 68.62 (C-4’), 84.20 (C-3’), 124.44 (C-2),

147.15 (C-3); IR (film): n˜ =3316, 3074, 2995, 2927, 2857, 2122, 1661,

1445, 1383, 1316, 1294, 1249, 10204, 1189, 1157, 1139, 1094, 1079, 1047,

1021, 978, 951, 893, 840, 753 cm^À1; GC-MS (70 eV): m/z (%): 262 (1)

[M ⁺], 261 (1) [(MÀ1)⁺], 247 (3), 233 (4), 223 (3), 221 (4), 220 (5), 219

(21), 210 (8), 209 (39), 207 (3), 206 (4), 205 (9), 181 (3), 179 (4), 167 (4),

165 (3), 157 (3), 156 (6), 155 (3), 143 (3), 131 (3), 129 (5), 117 (3), 115

(3), 105 (4), 91 (11), 79 (5), 77 (6), 75 (20), 74 (9), 73 (100), 67 (3), 59 (3),

55 (3), 45 (11), 41 (4), 39 (4); GC-MS (CI): m/z (%): 264 (5) [MH⁺+1],

263 (19) [MH⁺/M⁺+1], 262 (4) [M ⁺], 174 (13), 173 (100); HRMS: m/z:

calcd for C₁₆H₂₅OSi: 261.1675, found: 261.1659 [(MÀ1)⁺]; elemental

analysis calcd (%) for C₁₆H₂₆OSi (262.46): C 73.22, H 9.98; found: C

70.85, H 10.60.

3-(2-Cyclohexenylmethyl)bicyclo[6.1.0]non-2-en-1-yl trimethylsilyl ether

(13b): Silylation of 3-(2-cyclohexenylmethyl)-2-cycloocten-1-one (6b;

1.48 g, 6.77 mmol) was carried out according to GP G. The crude product

was purified by kugelrohr distillation and treated according to GP H.

868

¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemeurj.org

Chem. Eur. J. 2004, 10, 851 874

Cascade Reactions

851 874

The cyclopropanisation product was purified by column chromatography

(cyclohexane/ethyl acetate 99:1) yielding 13b (1.10 g, 53%) as a colorless

oil. NMR (¹H,¹H-COSY, ¹³C,¹³C-DEPT, HMQC, HMBC); ¹H NMR

(500 MHz, CDCl₃): d=0.01 0.07 (m, 1H, 9-H), 0.084/0.086 (s, 9H, 1’’’-

H), 0.68 0.77 (m, 1H, 7-H), 0.78 0.83 (m, 1H, 9-H), 1.03 1.10 (m, 8-H),

1.13 1.25 (m, 1H, 6’’-H), 1.25 1.34 (m, 1H, 5-H), 1.45 1.77 (m, 5H),

1.77 2.09 (m, 7H), 2.21 2.34 (m, 1H, 1’’-H), 2.62 2.72 (m, 1H, 4-H),

5.366/5.378 (s, 1H, 2-H), 5.51 5.59 (m, 1H, 2’’-H), 5.62 5.69 (m, 1H, 3’’-

H); ¹³C NMR (125 MHz, CDCl₃): d=1.52 (C-1’’’), 18.73/18.83 (C-9),

21.12/21.50 (C-5’’), 25.33/25.34 (C-4’’), 25.56/25.72 (C-5), 28.43/28.52 (C-

8), 28.87/29.60 (C-6’’), 29.69/29.73 (C-7), 30.17/30.20 (C-6), 30.90/31.44

(C-4), 33.18/33.29 (C-1’’), 43.97/44.18 (C-1’), 57.65 (C-1), 125.10/125.30

(C-2), 126.87/127.11 (C-3’’), 131.54/131.89 (C-2’’), 146.89/147.04 (C-3); IR

(film): n˜ =3072, 3022, 2926, 2857, 1656, 1446, 1314, 1293, 1248, 1204,

1188, 1095, 1079, 1017, 953, 893, 839, 752, 720 cm^À1; GC-MS (70 eV): m/z

(%): 304 (5) [M ⁺], 223 (14), 222 (5), 221 (9), 210 (10), 209 (25), 208 (5),

207 (9), 181 (12), 168 (8), 167 (13), 155 (8), 134 (5), 133 (8), 131 (8), 129

(4), 117 (7), 115 (4), 91 (11), 81 (21), 80 (5), 79 (25), 77 (5), 75 (25), 74

(8), 73 (100), 67 (7), 59 (5), 55 (5), 53 (5), 45 (8), 41 (8), 39 (10); GC-MS

(CI): m/z (%): 306 (30) [MH⁺+1], 305 (100) [MH⁺]; HRMS: m/z: calcd

for C₁₉H₃₂OSi: 304.2222, found: 304.2211 [M ⁺].

General procedure I (PET oxidative reaction): The respective cyclopro-

pylsilyl ether and sensitizer (10 40 mol%) were dissolved in dry acetoni-

trile. The solution was either poured into an immersion well reactor or

apportioned to pyrex irradiation tubes (12 mL, 1 cm diameter). Note,

that DCA is only slightly soluble in acetonitrile leading to a suspension

of the sensitizer at the beginning of the irradiation. The tubes or the reac-

tor were sealed with a septum. The solution was deoxygenated with

argon and ultrasound irradiation (1 h: pyrex tubes/3 h: immersion well

reactor) and irradiated in a Rayonet photochemical reactor using lamps

of the appropriate wavelength (DCN: 350 nm/DCA: 420 nm) for at least

24 h. The reaction was monitored by GC. The solvent was removed and

the residue was purified (generally by column chromatography and/or

HPLC).

PET oxidative reaction of bicyclo[4.1.0]hept-2-en-1-yl trimethylsilyl ether

(8a): Bicyclo[4.1.0]hept-2-en-1-yl trimethylsilyl ether (8a; 993 mg,

5.45 mmol) and DCN (422 mg, 2.37 mmol) were dissolved in acetonitrile

(215 mL), apportioned to 12 pyrex tubes and irradiated according to

GP I for 48 h. The crude product was purified by kugelrohr distillation

yielding 6-methylcyclohex-2-enone (27; 91 mg, 15%). NMR (¹H, ¹³C,¹³C-

DEPT); ¹H NMR (500 MHz, CDCl₃, ref.: CHCl₃): d=1.09 (d, J=6.8 Hz,

3H, 1’-H), 1.68 (dddd, J=6.7/8.4/11.9/13.4 Hz, 1H, 5-H), 2.02 (ddddd,

J=1.2/4.4/4.5/4.6/13.4 Hz, 1H, 5-H), 2.30 2.39 (m, 3H, 4-H/6-H), 5.928

(ddd, J=2.0/2.0/10.0 Hz, 1H, 2-H), 6.88 (dddd, J=1.2/3.3/4.6/10.0 Hz,

1H, 3-H); ¹³C NMR (125 MHz, CDCl₃, ref.: CDCl₃): d=14.80 (C-1’),

25.27 (C-5), 30.57 (C-4), 41.35 (C-6), 129.03 (C-2), 149.71 (C-3), 202.23

(C-1); IR (film): n˜ =2936, 2877, 1678, 1455, 1427, 1389, 1376, 1215, 1130,

1056, 951, 801 cm^À1; GC-MS (70 eV): m/z (%): 110 (17) [M⁺], 68 (100),

41 (15), 40 (20), 39 (43), 27 (15).

4-(2-Propenyl)bicyclo[5.1.0]oct-2-en-1-yl trimethylsilyl ether (14a,b): Si-

lylation of 4-(2-propenyl)-2-cyclohepten-1-one (7; 650 mg, 4.33 mmol)

was carried out according to GP G. The crude product was purified by

kugelrohr distillation and treated according to procedure H. The cyclo-

propanisation product was purified by HPLC (cyclohexane/ethyl acetate

130:1) yielding a mixture of the isomeric 4-(2-propenyl)bicyclo[5.1.0]oct-

2-en-1-yl trimethylsilyl ethers (14a,b) as a colorless oil (480 mg, 47%).

For identification and for mechanistic reasons the isomers were separated

by preparative gas chromatography.

PET oxidative reaction of bicyclo[5.1.0]oct-2-en-1-yl trimethylsilyl ether

(8b): Bicyclo[5.1.0]oct-2-en-1-yl trimethylsilyl ether (8b; 1.31 g,

6.68 mmol) and DCN (422 mg, 2.37 mmol) were dissolved in acetonitrile

(400 mL) and irradiated in an immersion well reactor according to GP I

for 72 h. The crude product was filtered over silica (cyclohexane/ethyl

acetate 80:20) and purified by HPLC (cyclohexane/ethyl acetate 85:15)

yielding (3aR*, 6aS*)-hexahydro-2(1H)pentalenone (28; 489 mg, 57%).

NMR (¹H,¹³C,¹³C-gated); ¹H NMR (300 MHz, CDCl₃, ref.: CHCl₃): d=

1.26 1.40 (m, 2H), 1.48 1.77 (m, 2H), 1.80 2.02 (m, 4H), 2.33 2.49 (m,

2H), 2.55 2.71 (m, 2H); ¹³C NMR (75 MHz, CDCl₃, ref.: TMS): d=25.19

(C-5), 33.13 (C-4/6), 39.31 (C-3a/6a), 44.39 (C-1/3), 220.88 (C-2). *The

stereochemical assignment was carried out by direct comparison with the

original spectra of the cis-compound: IR (film): n˜ =2935, 2842, 1725,

1440 cm^À1; GC-MS (CI): m/z (%): 126 (9) [MH⁺+1] 125 (100) [MH⁺].

(1S*,4R*,7S*)-4-(2-Propenyl)bicyclo[5.1.0]oct-2-en-1-yl

trimethylsilyl

ether (14a): NMR (¹H,¹H-COSY, ¹³C,¹³C-DEPT, HMQC, HMBC,

NOESY); ¹H NMR (500 MHz, CDCl₃, ref.: CHCl₃): d=0.10 (s, 9H, 1’’-

H), 0.36 (dd, J=4.9/7.1 Hz, 1H, 8-H^A), 0.93 (dd, J=4.9/10.2 Hz, 1H, 8-

H^B), 0.96 (dddd, J=3.5/9.4/10.6/13.9 Hz, 1H, 5-H^B), 1.37 (m, 1H, 7-H),

1.46 (dddd, J=3.5/6.0/8.0/14.0 Hz, 1H, 6-H^A), 1.59 (dddd, J=3.6/3.8/7.4/

13.9 Hz, 1H, 5-H^A), 1.91 (dddd, J=3.8/4.0/9.7/14.0 Hz, 1H, 6-H^B), 2.02

2.13 (m, 2H, 1’-H), 2.29 (m, 1H, 4-H), 4.99 (dm, J=10.2 Hz, 3’-H^A),

5.002 (dm, J=17.0 Hz, 3’-H^B), 5.26 (ddd, J=0.9/3.8/11.2 Hz, 1H, 3-H),

5.75 (dddd, J=6.9/6.9/10.2/17.0 Hz, 1H, 2’-H), 5.83 (ddd, J=1.4/2.6/

11.2 Hz, 1H, 2-H); ¹³C NMR (125 MHz, CDCl₃, ref.: CDCl₃): d=1.16 (C-

1’’), 21.17 (C-8), 27.12 (C-6), 27.13 (C-7), 29.28 (C-5), 38.69 (C-4), 41.25

(C-1’), 58.62 (C-1), 116.12 (C-3’), 131.45 (C-2), 132.47 (C-3), 136.98 (C-

2’); IR (film): n˜ =3081, 3014, 2962, 2853, 1656, 1640, 1441, 1415, 1378,

1250, 1190, 1125, 1095, 1015, 991, 955, 912, 840, 750 cm^À1; GC-MS

(70 eV): m/z (%): 236 (1) [M ⁺], 235 (<1) [(MÀ1)⁺], 221 (5), 207 (6),

195 (7), 194 (8), 193 (6), 182 (3), 181 (4), 180 (4), 179 (5), 168 (7), 167

(27), 154 (3), 151 (3), 105 (3), 91 (4), 79 (4), 77 (5), 75 (18), 74 (9), 73

(100), 59 (3), 45 (7), 41 (3); GC-MS (CI): m/z (%): 237 (9) [MH⁺], 236

(8) [M ⁺], 149 (4), 148 (13), 147 (100); HRMS: m/z: calcd for C₁₄H₂₃OSi:

235.1518, found: 235.1513 [(MÀ1)⁺].

PET oxidative reaction of bicyclo[6.1.0]non-2-en-1-yl trimethylsilyl ether

(8c): Bicyclo[6.1.0]non-2-en-1-yl trimethylsilyl ether (8c; 1.20 g,

5.70 mmol) and DCN (500 mg, 2.81 mmol) were dissolved in acetonitrile

(400 mL) and irradiated in an immersion well reactor according to GP I

for 90 h. The crude product was first prepurified by kugelrohr distillation

and secondly by HPLC (cyclohexane/ethyl acetate 90:10) yielding

(3aR*,7aS*)-octahydro-2H-inden-2-one (29; 385 mg, 49%) as a colorless

oil. NMR (¹H,¹³C,¹³C-gated); ¹H NMR (300 MHz, CDCl₃, ref.: CHCl₃):

d=1.33 1.68 (m, 8H), 2.05 2.35 (m, 6H); ¹³C NMR (75 MHz, CDCl₃,

ref.: TMS): d=22.39 (C-5/6), 27.37 (C-4/7), 35.46 (C-3a/7a), 43.23 (C-1/

3), 220.35 (C-2); IR (film): n˜ =2930, 2857, 1744, 1462, 1449, 1405, 1366,

1235, 1161, 1140, 1119, 1073, 916, 732 cm^À1; GC-MS (70 eV): m/z (%):

139 (8) [M ⁺+1], 138 (63) [M ⁺], 120 (4), 110 (4), 109 (9), 96 (14), 95

(39), 94 (95), 93 (3), 92 (3), 91 (5), 83 (4), 82 (37), 81 (100), 80 (9), 79

(31), 78 (4), 77 (16), 70 (4), 68 (11), 68 (52), 67 (97), 66 (12), 65 (15), 57

(6), 56 (8), 55 (36), 54 (48), 53 (43), 52 (5), 51 (6), 43 (9), 42 (12), 41 (86),

40 (12), 39 (53), 29 (23), 28 (12), 27 (30); GC-MS (CI): m/z (%): 140 (1)

[MH⁺+2], 139 (10) [MH⁺+1] 138 (100) [MH⁺]. *The stereochemical as-

signment was carried out by direct comparison with the original spectra

of the analogous trans-compound.

(1S*,4S*,7S*)-4-(2-Propenyl)bicyclo[5.1.0]oct-2-en-1-yl

trimethylsilyl

ether (14b): NMR (¹H,¹H-COSY, ¹³C,¹³C-DEPT, HMQC, HMBC,

NOESY); ¹H NMR (500 MHz, CDCl₃, ref.: CHCl₃): d=0.12 (s, 9H, 1’’-

H), 0.39 (dd, J=4.8/6.8 Hz, 1H, 8-H^A), 0.95 (dd, J=4.8/10.1 Hz, 1H, 8-

H^B), 1.09 (dddd, J=3.0/7.1/7.6/14.9 Hz, 1H, 6-H^A), 1.44 (ddddd, J=1.6/

6.8/6.9/7.1/10.1 Hz, 1H, 7-H), 1.55 1.67 (m, 2H, 5-H), 2.06 2.21 (m, 3H,

4-H/1’-H), 2.25 (dddd, J=2.2/6.4/8.7/14.7 Hz, 1H, 6-H^B), 4.99 (dm, J=

10.1 Hz, 3’-H^A), 5.02 (dm, J=17.1 Hz, 3’-H^B), 5.23 (dd, J=4.4/12.1 Hz,

1H, 3-H), 5.76 (dddd, J=7.0/7.0/10.1/17.1 Hz, 1H, 2’-H), 5.84 (ddd, J=

2.6/1.6/12.3 Hz, 1H, 2-H); ¹³C NMR (125 MHz, CDCl₃, ref.: CDCl₃): d=

1.48 (C-1’’), 23.91 (C-8), 26.65 (C-6), 27.95 (C-7), 30.10 (C-5), 40.03 (C-

1’), 42.19 (C-4), 58.02 (C-1), 116.03 (C-3’), 129.88 (C-3), 131.01 (C-2),

137.15 (C-2’); IR (film): n˜ =3081, 3004, 2962, 2861, 1658, 1640, 1451,

1413, 1379, 1250, 1182, 993, 912, 840, 751 cm^À1; GC-MS (70 eV): m/z (%):

236 (2) [M ⁺], 235 (3) [(MÀ1)⁺], 221 (5), 207 (5), 195 (9), 194 (7), 193

(7), 182 (3), 181 (4), 180 (4), 179 (5), 168 (6), 167 (21), 154 (3), 151 (3),

105 (4), 91 (4), 79 (4), 77 (5), 75 (18), 74 (9), 73 (100), 59 (3), 45 (7), 41

(3); GC-MS (CI): m/z (%): 237 (9) [MH⁺], 236 (6) [M ⁺], 149 (4), 148

(13), 147 (100); HRMS: m/z: calcd for C₁₄H₂₃OSi: 235.1518, found:

235.1523 [(MÀ1)⁺].

PET oxidative reaction of bicyclo[7.1.0]dec-2-en-1-yl trimethylsilyl ether

(8d): Bicyclo[7.1.0]dec-2-en-1-yl trimethylsilyl ether (8d; 1.01 g,

4.50 mmol) and DCN (300 mg, 1.69 mmol) were dissolved in acetonitrile

(192 mL), apportioned to 12 pyrex tubes and irradiated according to

GP I for 48 h. The crude product was purified by kugelrohr distillation

yielding 6-methlycyclohex-2-enone (27; 91 mg, 15%). The crude product

was filtered over silica gel (cyclohexane/ethyl acetate 80:20) and purified

by stepwise HPLC (cyclohexane/ethyl acetate prepurification: 90:10; fine

purification 95:5) yielding (Z)-3-cyclodecen-1-one (30; 67 mg, 10%) as

869

Chem. Eur. J. 2004, 10, 851 874

www.chemeurj.org

¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

J. Mattay and H. Rinderhagen

FULL PAPER

the major product. The corresponding E isomer was detectable in

¹H NMR of the crude product mixture but had not been isolated as pure

product.

3’-H), 1.34 1.48 (m, 3H, 1’-H/2’-H), 1.86 (m, 1H, 1’-H), 2.32 (dd, J=3.3/

19.0 Hz, 1H, 2-H), 2.81 (dd, J=7.5/19.0 Hz, 1H, 2-H), 3.33 (dddd, J=3.3/

4.2/7.5/8.3 Hz, 1H, 3-H), 7.33 (dddd, J=0.9/0.9/7.7/7.4 Hz, 1H, 6-H),

7.467 (dddd, J=0.9/0.9/0.9/7.7 Hz, 1H, 4-H), 7.56 (ddd, J=1.2/7.3/7.7 Hz,

1H, 5-H), 7.69 (ddd, J=0.9/1.2/7.7 Hz, 1H, 7-H); ¹³C NMR (125 MHz,

CDCl₃, ref.: CDCl₃): d=14.06 (C-3’), 20.72 (C-2’), 37.95 (C-3), 38.26 (C-

1’), 43.00 (C-2), 123.38 (C-7), 125.52 (C-4), 127.33 (C-6), 134.52 (C-5),

136.62 (C-7a), 158.93 (C-3a), 206.45 (C-1); IR (film): n˜ =3074, 2962,

2933, 2876, 1714, 1605, 1463, 1406, 1378, 1328, 1281, 1236, 1209, 1196,

1150, 1094, 1042, 1015, 971, 758 cm^À1; GC-MS (70 eV): m/z (%): 175 (6)

[M ⁺+1], 174 (27) [M ⁺], 145 (8), 133 (10), 132 (100), 131 (40), 129 (3),

128 (4), 118 (3), 117 (6), 116 (4), 115 (14), 104 (10), 103 (45), 102 (16), 91

(12), 90 (4), 89 (5), 78 (7), 77 (34), 65 (5), 51 (11), 50 (3), 43 (3), 41 (7),

39 (7); GC-MS (CI): m/z (%): 176 (13) [MH⁺+1], 175 (100) [MH⁺];

HRMS: m/z: calcd for C₁₂H₁₄O: 174.1045, found: 174.1039 [M⁺].

(Z)-3-Cyclodecen-1-one (30): NMR (¹H, ¹³C,¹³C-DEPT); ¹H NMR

(500 MHz, CDCl₃, ref.: TMS): d=1.33 (m, 2H), 1.39 (m, 2H), 1.46 (m,

2H), 1.688 (m, 2H), 2.16 (m, 2H, 5-H), 2.49 (m, 2H, 10-H), 3.14 (dd, J=

1.2/8.3 Hz, 1H, 2-H), 5.60 (ttd, J=1.2/8.3/10.8 Hz, 3-H)*, 5.77 (ttd, J=

1.2/8.3/10.8 Hz, 4-H)*; ¹³C NMR (125 MHz, CDCl₃, ref.: TMS): d=22.54

(CH₂), 23.66 (CH₂), 24.55 (CH₂), 25.26 (CH₂), 26.37 (CH₂), 39.04 (C-5),

43.24 (C-2), 123.79 (C-3)*, 133.81 (C-4)*, 214.42 (C-1); *: signal assign-

ments are mutual interchangeable.

PET oxidative reaction of 2-trimethylsilyloxy-tricyclo[6.3.0.0^2,4]undec-

1(8)-ene (10): Compound 10 (370 mg, 1.57 mmol) was dissolved in aceto-

nitrile (243 mL), apportioned together with DCA (119 mg, 0.52 mmol;

7 mg each tube) to 17 pyrex tubes and irradiated according to GP I for

48 h. The crude product was purified by column chromatography on

silica (cyclohexane/ethyl acetate 925:75) yielding (3aS*,5aR*,8aS*)-3-oc-

tahydrocyclopenta[c]pentalen-4(5H)-one (31; 170 mg, 66%). NMR

PET oxidative reaction of 3-(3-butenyl)bicyclo[5.1.0]oct-2-en-1-yl trime-

thylsilyl ether (11a) Compound 11a (560 mg, 2.24 mmol) and phenan-

threne (1.98 g) were dissolved in acetonitrile (164 mL), apportioned to-

gether with DCA (180 mg, 0.79 mmol) to 12 pyrex tubes and irradiated

according to GP I for 48 h. The crude product was purified by column

chromatography on silica gel (Et₂O/n-pentane 1:18) yielding 3-(3-buten-

1

(¹H,¹H-COSY, ¹³C,¹³C-DEPT, HMQC); H NMR (500 MHz, CDCl₃, ref.:

CHCl₃): d=1.35 (m, 1H, 2-H), 1.37 (m. 1H, 6-H^B), 1.58 (m, 1H, 1-H),

1.61 (m, 1H, 2-H), 1.62 (m, 1H, 7-H), 1.64 (m, 1H, 8-H), 1.65 (m, 1H, 7-

H), 1.69 (m, 1H, 1-H), 1.73 (m, 1H, 8-H), 1.79 1.87 (m, 2H, 3-H), 1.93

(m, 1H, 6-H^A), 2.08 (ddd, J=1.8/6.0/18.3 Hz, 1H, 5-H^B), 2.16 (dddd, J=

4.4/6.0/8.4/9.0 Hz, 1H, 5a-H), 2.23 (ddd, J=1.8/6.3/6.9 Hz, 1H, 3a-H),

2.49 (dd, J=9.0/18.3 Hz, 1H, 5-H^A); ¹³C NMR (125 MHz, CDCl₃, ref.:

CDCl₃): d=25.70 (C-7), 26.76 (C-2), 30.81 (C-3), 34.41 (C-6), 40.75 (C-8),

41.92 (C-1), 44.74 (C-5a), 46.40 (C-5), 58.55 (C-8a), 59.43 (C-3a), 223.70

(C-4); IR (film): n˜ =2945, 2868, 1738, 1469, 1449, 1409, 1314, 1267, 1211,

1163, 1113, 1040, 946, 924, 907, 775 cm^À1; GC-MS (70 eV): m/z (%): 165

(3) [M ⁺+1], 164 (31) [M ⁺], 146 (7), 136 (25), 135 (5), 123 (34), 122 (31),

121 (56), 120 (12), 119 (4), 117 (3), 108 (14), 107 (18), 105 (7), 104 (4), 96

(11), 95 (25), 94 (41), 93 (43), 92 (6), 91 (33), 83 (3), 82 (16), 81 (34), 80

(47), 79 (100), 78 (10), 77 (50), 76 (5), 68 (16), 67 (86), 66 (14), 65 (23),

55 (37), 54 (15), 53 (26), 52 (5), 51 (6), 42 (6), 41 (58), 40 (9), 39 (32), 29

(14), 27 (16); GC-MS (CI): m/z (%): 165 (100) [MH⁺+1], 164 (12)

[MH⁺]; HRMS: m/z: calcd for C₁₁H₁₆O: 164.1201, found: 164.1199 [M ⁺

].

yl)-7-methyl-3-cyclohepten-1-on (34a; 80 mg, 20%) and

a mixture

(133 mg, 33%) of the three isomeric cyclisation products 35a, 36a and

37a (relative amounts according to GC: 12:15:6). This mixture was sepa-

rated for spectroscopic characterizaction by reversed phase-HPLC (RP-

18, acetonitrile/water 70:30) and preparative GC (1558C isotherm/

0.38 bar).

3-(3-Butenyl)-7-methyl-3-cyclohepten-1-one (34a): NMR (¹H,¹H-COSY,

¹³C,¹³C-DEPT, HMQC); ¹H NMR (500 MHz, CDCl₃, ref.: CHCl₃MS):

d=1.07 (d, J=6.9 Hz, 3H, 1’’-H), 1.59 (dddd, J=3.7/9.9/9.9/13.7 Hz, 1H,

6-H), 1.93 (dddd, J=3.3/5.2/8.3/13.8 Hz, 1H, 6-H), 2.07 2.30 (m, 6H, 5-

H/1’-H/2’-H), 2.64 (dqd, J=5.1/6.9/9.9 Hz, 1H, 7-H), 3.07 (d, J=13.8 Hz,

1H, 2-H), 3.16 (dd, J=1.1/13.8 Hz, 1H, 2-H), 4.93 (dddd, J=0.9/0.9/1.6/

11.2 Hz, 1H, 4’-H), 4.98 (dddd, J=1.6/1.6/1.6/17.2 Hz, 1H, 4’-H), 5.53

(dd, J=5.5/5.5 Hz, 1H, 4-H), 5.74 (dddd, J=6.4/.6.4/10.3/17.2 Hz, 1H, 3’-

H); ¹³C NMR (125 MHz, CDCl₃, ref.: CDCl₃): d=16.60 (C-1’’), 26.46 (C-

5), 31.87 (C-2’), 32.39 (C-6), 39.23 (C-1’), 45.37 (C-2), 47.79 (C-7), 114.81

(C-4’), 125.67 (C-4), 133.36 (C-3), 137.97 (C-3’), 210.87 (C-1); GC-MS

(CI): m/z (%): 180 (13) [MH⁺+1], 179 (100) [MH⁺].

PET oxidative reaction of 2-trimethylsilyloxy-tricyclo[6.4.0.0^2,4]dodeca-

1(8),9,11-triene (9): Compound 9 (1.57 g, 6.37 mmol) and DCN (398 mg,

2.33 mmol)) were dissolved in acetonitrile (500 mL) and irradiated in an

immersion well reactor according to GP I for 84 h. The crude product

was filtered over silica gel (cyclohexane/ethyl acetate 85:15) and purified

by HPLC (cyclohexane/ethyl acetate 90:10) yielding 6-methyl-6,7,8,9-tet-

rahydro-5H-benzo[a]cyclohepten-5-one (32; 366 mg, 34%) and 3-propyl-

1-indanone (33; 125 mg, 11%) as colorless oils.

(3aR*,5aS*,9aR*)-Octahydro-1H-cyclopenta[c]inden-5(5aH)-one (35a):

1

NMR (¹H,¹H-COSY, ¹³C,¹³C-DEPT, HSQC, HMBC, NOESY); H NMR

(500 MHz, CDCl₃, ref.: TMS): d=1.10 (m, 1H, 7-H^B), 1.22 (m, 1H, 9-

H^A), 1.260 (m, 1H, 8-H^B), 1.41 (m, 1H, 3-H^B), 1.42 (m, 1H, 6-H^A), 1.461

(m, 1H, 9-H^B), 1.48 (m, 1H, 7-H^A), 1.53 (m, 1H, 8-H^A), 1.560 (m, 1H, 1-

H^A), 1.75 (m, 1H, 2-H^A), 1.83 (m, 1H, 2-H^B), 1.843 (m, 1H, 1-H^B), 1.99

(m, 1H, 6-H^B), 2.03 (dd, J=4.1/8.0/8.4/12.4 Hz, 1H, 3-H^A), 2.03 (m, 1H,

5a-H), 2.09 (dddd, J=2.7/8.8/8.9/9.0 Hz, 1H, 3a-H), 2.14 (ddd, J=1.6/2.7/

19.4 Hz, 1H, 4-H^B), 2.45 (dd, J=8.8/19.4 Hz, 1H, 4-H^A); ¹³C NMR

(125 MHz, CDCl₃, ref.: CDCl₃): d=21.18 (C-6), 23.18 (C-7), 23.40 (C-8),

24.68 (C-2), 32.49 (C-3), 35.64 (C-9), 36.78 (C-1), 41.41 (C-4), 44.13 (C-

3a), 50.16 (C-9a), 52.95 (C-5a), 220.05 (C-5); IR (film): n˜ =2931, 2862,

1738, 1447, 1408 cm^À1; GC-MS (70 eV): m/z (%): 179 (13) [M ⁺+1], 178

(100) [M ⁺], 163 (3), 161 (3), 150 (15), 149 (62), 137 (9), 136 (77), 135

(47), 134 (10), 133 (3), 124 (3), 123 (34), 122 (12), 121 (29), 120 (10), 119

(6), 117 (4), 110 (4), 109 (12), 108 (31), 107 (30), 106 (4), 105 (11), 97 (4),

96 (15), 95 (36), 94 (40), 93 (60), 92 (13), 91 (50), 83 (5), 82 (13), 81 (75),

80 (26), 79 (97), 78 (12), 77 (35), 69 (5), 68 (17), 67 (66), 66 (11), 65 (17),

56 (3), 55 (29), 54 (9), 53 (23), 52 (4), 51 (6), 43 (6), 42 (9), 41 (89), 40

(5), 39 (42), 29 (31); HRMS: m/z: calcd for C₁₂H₁₈O: 178.1358, found:

178.1353 [M ⁺].

6-Methyl-6,7,8,9-tetrahydro-5H-benzo[a]cyclohepten-5-one (32): NMR

1

(¹H,¹H-COSY, ¹³C,¹³C-DEPT, HMQC); H NMR (500 MHz, CDCl₃, ref.:

CHCl₃): d=1.12 (d, J=6.6 Hz, 3H, 1’-H), 1.57 (dddd, J=5.0/6.5/11.3/

13.3 Hz, 1H, 7-H), 1.68 (ddddd, J=3.3/6.5/8.5/11.8/13.3 Hz, 1H, 8-H),

1.89 (dddd, J=5.2/6.9/8.5/13.4 Hz, 1H, 7-H), 2.09 (ddddd, J=3.3/5.2/6.8/

6.8/13.8 Hz, 1H, 8-H), 2.90 (ddd, J=3.3/6.8/15.5 Hz, 1H, 9-H), 2.90 (dtd,

J=5.2/6.6/11.3 Hz, 1H, 6-H), 1.67 (ddd, J=3.3/11.0/15.5 Hz, 1H, 9-H),

7.18 (d, J=7.5 Hz, 1H, 4-H), 7.35 (ddd, J=1.5/7.5/7.5 Hz, 1H, 3-H), 7.25

(dd, J=7.7/7.5 Hz, 1H, 2-H), 7.65 (dd, J=1.5/7.7 Hz, 1H, 1-H); ¹³C NMR

(125 MHz, CDCl₃, ref.: CDCl₃): d=16.33 (C-1’), 25.38 (C-8), 31.80 (C-7),

33.47 (C-9), 43.93 (C-6), 126.15 (C-3), 128.22 (C-1), 129.65 (C-4), 131.15

(C-2), 139.46 (C-4a), 141.76 (C-9a), 207.61 (C-5); IR (film): n˜ =3069,

3025. 2937, 2867, 1679, 1598, 1481, 1448, 1375, 1348, 1322, 1276, 1251,

1223, 1204, 1160, 1122, 1106, 1091, 1072, 989, 970, 895, 852, 822, 782, 760,

737, 711 cm^À1; GC-MS (70 eV): m/z (%): 175 (10) [M ⁺+1], 174 (78)

[M ⁺], 173 (4), 159 (11), 156 (14), 147 (4), 146 (39), 145 (42), 144 (32),

143 (6), 142 (3), 141 (15), 133 (6), 132 (34), 131 (100), 130 (33), 129 (24),

128 (22), 127 (9), 120 (12), 119 (21), 118 (29), 117 (18), 116 (19), 115 (36),

105 (10), 104 (34), 103 (30), 102 (10), 92 (5), 91 (55), 90 (50), 89 (46), 79

(5), 78 (27), 77 (54), 76 (13), 75 (4), 65 (24), 64 (9), 63 (12), 55 (15), 53

(4), 52 (4), 51 (10), 50 (4), 43 (5), 41 (13), 39 (16), 29 (8); GC-MS (CI):

m/z (%): 176 (14) [MH⁺+1], 175 (100) [MH⁺]; HRMS: m/z: calcd for

C₁₂H₁₄O: 174.1045, found: 174.1037 [M⁺].

(3S*,3aS*,5aR*,8aS*)-3-Methyloctahydrocyclopenta[c]pentalen-4(5H)-

one (36a): NMR (¹H,¹H-COSY, ¹³C,¹³C-DEPT, HSQC, HMBC,

1

NOESY); H NMR (500 MHz, CDCl₃, ref.: TMS): d=0.91 (d, J=7.0 Hz,

3H, 1’-H), 1.16 (dddd, J=6.3/11.5/12.2/11.5 Hz, 1H, 2-H^A), 1.26 (dddd,

J=5.2/5.2/7.0/12.8 Hz, 1H, 6-H^B), 1.48 (ddddd, J=7.0/7.0/8.2/8.4/12.4 Hz,

1H, 7-H^B), 1.57 (ddddd, J=5.2/5.5/6.2/6.7/12.4 Hz, 1H, 7-H^A), 1.64 (ddd,

J=6.2/8.2/12.6 Hz, 1H, 8-H^A), 1.66 (ddd, J=5.5/7.0/12.6 Hz, 1H, 8-H^B),

1.67 (ddd, J=6.3/12.2/12.5 Hz, 1H, 1-H^B), 1.75 (ddd, J=2.1/6.3/12.5 Hz,

1H, 1-H^A), 1.78 (dddd, J=2.1/5.9/6.3/12.2 Hz, 1H, 2-H^B), 1.91 (dddd, J=

6.7/8.4/8.5/12.8 Hz, 1H, 6-H^A), 2.00 (ddd, J=2.0/3.3/18.4 Hz, 1H, 5-H^B),

2.11 (dd, J=2.0/10.5 Hz, 1H, 3a-H), 2.16 (dddd, J=3.3/5.2/8.5/10.2 Hz,

3-Propyl-1-indanone (33): NMR (¹H,¹H-COSY, ¹³C,¹³C-DEPT, HMQC);

¹H NMR (500 MHz, CDCl₃, ref.: CHCl₃): d=0.93 (dd, J=7.2/7.2 Hz, 3H,

870

¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemeurj.org

Chem. Eur. J. 2004, 10, 851 874

Cascade Reactions

851 874

1H, 5a-H), 2.25 (dqdd, J=5.9/7.0/10.5/11.5 Hz, 1H, 3-H), 2.37 (ddd, J=

0.6/10.2/18.4 Hz, 1H, 5-H^A); ¹³C NMR (125 MHz, CDCl₃, ref.: CDCl₃):

d=15.77 (C-1’), 25.90 (C-7), 35.31 (C-6), 35.60 (C-2), 39.14 (C-3), 40.98

(C-1), 41.10 (C-8), 46.00 (C-5a), 48.79 (C-5), 59.78 (C-8a), 63.19 (C-3a),

222.39 (C-4); IR (film): n˜ =2944, 2866, 1735, 1715, 1480 cm^À1; GC-MS

(70 eV): m/z (%): 179 (14) [M ⁺+1], 178 (72) [M ⁺], 163 (4), 161 (3), 150

(16), 149 (100), 137 (11), 136 (69), 135 (22), 131 (3), 124 (7), 123 (75), 122

(5), 121 (33), 120 (10), 119 (5), 110 (3), 109 (6), 108 (20), 107 (51), 106

(4), 105 (16), 96 (32), 95 (32), 94 (32), 93 (78), 92 (13), 91 (67), 82 (9), 81

(79), 80 (19), 79 (87), 78 (12), 77 (45), 69 (8), 68 (7), 67 (37), 66 (10), 65

(17), 55 (26), 54 (6), 53 (23), 52 (5), 51 (5), 43 (7), 42 (7), 41 (83), 40 (9),

39 (46), 38 (33), 29 (39); HRMS: m/z: calcd for C₁₂H₁₈O: 178.1358,

found: 178.1347 [M ⁺].

5a), 122.18 (C-6), 129.23 (C-7), 219.05 (C-5); GC-MS (70 eV): m/z (%):

177 (4) [M ⁺+1], 176 (33) [M ⁺], 158 (5), 148 (8), 147 (12), 135 (5), 134

(33), 133 (12), 132 (16), 131 (6), 130 (12), 129 (6), 121 (3), 120 (8), 119

(18), 118 (3), 117 (8), 115 (3), 107 (9), 106 (19), 105 (29), 104 (18), 103

(6), 98 (5), 95 (3), 94 (9), 93 (17), 92 (38), 91 (100), 81 (5), 80 (11), 79

(38), 78 (18), 77 (38), 67 (10), 66 (6), 65 (12), 63 (3), 55 (6), 53 (14), 52

(6), 51 (8), 43 (3), 42 (6), 41 (35), 40 (5), 39 (24), 29 (6); GC-MS (CI): m/

z (%): 178 (13) [MH⁺+1], 177 (100) [MH⁺]; HRMS: m/z: calcd for

C₁₂H₁₆O: 176.1201, found: 176.1203 [M ⁺].

(3aS*,5aR*,8aS*)-3-Methylenoctahydrocyclopenta[c]pentalen-4(5H)-one

(40a): NMR (¹H,¹H-COSY, ¹³C,¹³C-DEPT, HMQC, NOESY); ¹H NMR

(500 MHz, CDCl₃, ref.: CHCl₃): d=1.39 (dddd, J=4.5/4.7/5.0/14.7 Hz,

1H, 6-H^B), 1.55 1.72 (m, 3H, 7-H/8-H), 1.72 1.81 (m, 3H, 8-H/1-H), 1.96

(m, 1H, 6-H^A), 2.023 (ddd, J=1.9/4.5/18.8 Hz, 1H, 5-H^B), 2.27 (dddd, J=

4.2/4.5/8.9/9.7 Hz, 1H, 5a-H), 2.30 2.43 (m, 2H, 2-H), 2.63 (dd, J=9.7/

18.8 Hz, 1H, 5-H^A), 2.76 (dddd, J=1.9/2.0/2.2/2.2 Hz, 1H, 3a-H), 4.95

(ddd, J=2.2/2.2/2.2 Hz, 1H, 1’-H), 5.02 (ddd, J=2.2/2.2/2.2 Hz, 1H, 1’-

H); ¹³C NMR (125 MHz, CDCl₃, ref.: CDCl₃): d=25.43 (C-7), 33.63 (C-

2), 34.35 (C-6), 39.16 (C-8)*, 39.19 (C-1)*, 44.03 (C-5a), 45.39 (C-5),

59.56 (C-8a), 64.66 (C-3a), 108.40 (C-1’), 149.33 (C-3), 218.09 (C-4); *:

signal assignments are mutual interchangeable; IR (film): n˜ =2947, 2866,

2163, 1737, 1650, 1447, 1407, 1222, 1167, 1042, 888 cm^À1; GC-MS (70 eV):

m/z (%): 177 (8) [M ⁺+1], 176 (58) [M ⁺], 161 (10), 149 (3), 148 (18), 147

(37), 135 (9), 134 (84), 133 (35), 132 (15), 131 (4), 121 (4), 120 (14), 119

(32), 117 (8), 115 (4), 107 (10), 106 (45), 105 (38), 104 (5), 103 (8), 95 (3),

94 (18), 93 (21), 92 (31), 91 (100), 82 (5), 81 (6), 80 (12), 79 (55), 78 (22),

77 (46), 67 (8), 66 (4), 65 (17), 63 (3), 55 (8), 54 (3), 53 (18), 52 (7), 51

(9), 42 (4), 41 (33), 40 (5), 39 (27), 29 (8), 27(11); GC-MS (CI): m/z (%):

178 (13) [MH⁺+1], 177 (100) [MH⁺], 176 (7) [M ⁺]; HRMS: m/z: calcd

for C₁₂H₁₆O: 176.1201, found: 176.1193 [M ⁺].

(3R*,3aS*,5aR*,8aS*)-3-Methyloctahydrocyclopenta[c]pentalen-4(5H)-

one (37a): NMR (¹H,¹H-COSY, ¹³C,¹³C-DEPT, HSQC, HMBC,

1

NOESY); H NMR (500 MHz, CDCl₃, ref.: TMS): d=1.04 (d, J=6.9 Hz,

3H, 1’-H), 1.27 (m, 1H, 6-H^B), 1.29 (m, 1H, 2-H^B), 1.58 (m, 1H, 7-H^A),

1.61 (m, 1H, 7-H^B), 1.63 (m, 1H, 1-H^A), 1.65 (m, 1H, 8-H^A), 1.69 (m,

1H, 2-H^A), 1.69 (m, 1H, 8-H^B), 1.76 (m, 1H, 1-H^B), 1.80 (dd, J=1.8/

5.5 Hz, 1H, 3a-H), 1.91 (dddd, J=6.8/7.2/8.6/13.4 Hz, 1H, 6-H^A), 2.02

(ddd, J=1.9/4.9/18.5 Hz, 1H, 5-H^B), 2.05 (m, 1H, 3-H), 2.16 (dddd, J=

4.9/5.3/8.6/9.2 Hz, 1H, 5a-H), 2.56 (ddd, J=0.6/9.2/18.5 Hz, 1H, 5-H^A);

¹³C NMR (125 MHz, CDCl₃, ref.: CDCl₃): d=20.78 (C-1’), 25.90 (C-7),

34.48 (C-6), 35.53 (C-2), 40.14 (C-3), 40.81 (C-1), 41.76 (C-8), 44.95 (C-

5a), 45.69 (C-5), 59.22 (C-8a), 67.44 (C-3a), 222.68 (C-4); IR (film): n˜ =

2942, 2865, 1735, 1701 cm^À1; GC-MS (70 eV): m/z (%): 179 (13) [M ⁺+1],

178 (88) [M ⁺], 163 (5), 151 (5), 150 (35), 149 (53), 137 (3), 136 (34), 135

(30), 134 (8), 133 (3), 123 (17), 122 (8), 121 (36), 120 (4), 119 (6), 117 (3),

110 (3), 109 (8), 108 (37), 107 (90), 106 (5), 105 (17), 103 (3), 97 (3), 96

(8), 95 (27), 94 (89), 93 (91), 92 (12), 91 (74), 83 (4), 82 (11), 81 (100), 80

(20), 79 (88), 78 (13), 77 (51), 69 (11), 68 (12), 67 (42), 66 (11), 65 (18),

55 (26), 54 (5), 53 (22), 52 (3), 51 (5), 43 (5), 42 (6), 41 (87), 40 (6), 39

(48), 29 (41); HRMS: m/z: calcd for C₁₂H₁₈O: 178.1358, found: 178.1352

[M ⁺].

PET oxidative reaction of 3-(2-cyclohexenylmethyl)bicyclo[5.1.0]oct-2-

en-1-yl trimethylsilyl ether (13a): Compound 13a (268 mg, 0.93 mmol)

was dissolved in acetonitrile (128 mL), apportioned together with DCA

(100 mg, 0.44 mmol) to 14 pyrex tubes and irradiated according to GP I

for 96 h. The crude product was filtered over silica (cyclohexane/ethyl

acetate 75:25) and purified by HPLC (cyclohexane/ethyl acetate 95:5)

yielding 3-(2-cyclohexenylmethyl)-7-methyl-3-cyclohepten-1-one (41a;

38 mg, 19%), (3aR*,5aS*,5bS*,9aS*,10aS*)-dodecahydropentaleno[1,6a-a]-

inden-5(1H)-one (42a; 22 mg, 11%) and (3aR*,5aS*,5bR*,9aR*,10aS*)-

dodecahydropentaleno[1,6a-a]inden-5(1H)-one (43a; 24 mg, 12%) as col-

orless oils.

PET oxidative reaction of 3-(3-butynyl)bicyclo[5.1.0]oct-2-en-1-yl trime-

thylsilyl ether (12a): Compound 12a (580 mg, 2.33 mmol) was dissolved

in acetonitrile (205 mL), apportioned together with DCA (100 mg,

0.44 mmol) to 14 pyrex tubes and irradiated according to GP I for 96 h.

The crude product was filtered over silica (cyclohexane/ethyl acetate

90:10) and purified by HPLC (cyclohexane/ethyl acetate 95:5) yielding 3-

(3-butynyl)-7-methyl-3-cyclohepten-1-one

(38a;

62 mg,

15%),

(3aR*,5aS*,9aS*)-2,3,3a,4,8,9-hexahydro-1H-cyclopenta[c]inden-5(5aH)-

one (39a; 25 mg, 15%) and (3aS*,5aR*,8aS*)-3-methylenoctahydrocyclo-

penta[c]pentalen-4(5H)-one (40a; 123 mg, 30%) as colorless oils.

3-(2-Cyclohexenylmethyl)-7-methyl-3-cyclohepten-1-one (41a): NMR

1

(¹H,¹H-COSY, ¹³C,¹³C-DEPT, HMQC); H NMR (500 MHz, CDCl₃, ref.:

CHCl₃MS): d=1.063/1.061 (d, J=6.8 Hz, 3H, 1’’’-H), 1.09 1.17 (m, 1H,

6’’-H), 1.44 1.53 (m, 1H, 5’’-H), 1.55 1.68 (m, 3H, 6-H/5’’-H/6’’-H), 1.90

2.05 (m, 5H, 6-H/1’-H/4’’-H), 2.14 2.32 (m, 3H, 5-H/1’’-H), 2.59 2.68 (m,

1H, 7-H), 3.03 3.09 (m, 1H, 2-H), 3.12 3.19 (m, 1H, 2-H), 5.45 5.53 (m,

2H, 4-H/2’’-H), 5.61 5.67 (m, 1H, 3’’-H); ¹³C NMR (125 MHz, CDCl₃,

ref.: CDCl₃): d=16.57/16.66 (C-1’’’), 21.22 (C-5’’), 25.26 (C-4’’), 26.50/

26.57 (C-5), 28.71/28.90 (C-6), 32.30/32.34 (C-6’’), 32.54/32.56 (C-1’’),

45.04/45.13 (C-2), 46.73 (C-1’). 47.82/47.89 (C-7), 127.06/127.07 (C-4),

127.22 (C-3’’), 131.03/131.16 (C-2’’), 132.16/132.22 (C-3), 210.82 (C-1); IR

(film): n˜ =3022, 2933, 1708, 1662, 1448, 1376, 1324, 1279, 1214, 1137,

1051, 957, 862, 784, 721 cm^À1; GC-MS (70 eV): m/z (%): 218 (11) [M ⁺],

175 (7), 138 (21), 123 (3), 121 (4), 110 (19), 109 (5), 107 (3), 105 (6), 96

(5), 95 (15), 94 (4), 93 (5), 92 (3), 91 (13), 82 (8), 81 (100), 80 (19), 79

(44), 78 (3), 77 (12), 69 (4), 68 (4), 67 (10), 66 (4), 65 (6), 55 (10), 53 (17),

43 (4), 42 (3), 41 (31), 39 (10), 29 (4); GC-MS (CI): m/z (%): 220 (17)

[MH⁺+1], 219 (100) [MH⁺]; HRMS: m/z: calcd for C₁₅H₂₂O: 218.1671,

found: 218.1672 [M ⁺].

3-(3-Butynyl)-7-methyl-3-cyclohepten-1-one (38a): NMR (¹H,¹H-COSY,

¹³C,¹³C-DEPT, HMQC); ¹H NMR (500 MHz, CDCl₃, ref.: CHCl₃): d=

1.063 (d, J=6.9 Hz, 3H, 1’’-H), 1.600 (dddd, J=3.5/9.8/10.1/13.4 Hz, 1H,

6-H), 1.92 (dd, J=2.5/2.5 Hz, 1H, 4’-H), 1.94 (dddd, J=3.3/5.2/8.6/

13.4 Hz, 1H, 6-H), 2.16 2.32 (m, 6H, 5-H/1’-H/2’-H), 2.665 (dqd, J=5.2/

6.9/10.1 Hz, 1H, 7-H), 3.08 (dd, J=1.0/14.0 Hz, 1H, 2-H), 3.17 (dddd, J=

1.0/1.1/1.2/14.0 Hz, 1H, 2-H), 5.60 (dddd, J=1.0/1.0/5.1/6.1 Hz, 1H, 4-H);

¹³C NMR (125 MHz, CDCl₃, ref.: CDCl₃): d=16.57 (C-1’’), 17.33 (C-2’),

26.44 (C-5), 32.33 (C-6), 38.51 (C-1’), 45.21 (C-2), 47.71 (C-7), 68.76 (C-

4’), 83.61 (C-3’), 126.81 (C-4), 132.22 (C-3), 210.57 (C-1); IR (film): n˜ =

3293, 2936, 2119, 1706, 1458, 1376, 1169, 1049 cm^À1; GC-MS (70 eV): m/z

(%): 176 (1) [M ⁺], 161 (25), 143 (3), 134 (9), 133 (7), 132 (3), 119 (11),

118 (3), 109 (3), 107 (4), 106 (14), 105 (30), 104 (5), 103 (3), 98 (9), 95

(6), 93 (9), 92 (16), 91 (100), 82 (5), 81 (8), 80 (5), 79 (40), 78 (25), 77

(29), 69 (8), 67 (16), 66 (7), 65 (20), 56 (3), 55 (16), 54 (5), 53 (6), 52 (13),

43 (5), 42 (11), 41 (78), 40 (4), 39 (48), 29 (16); GC-MS (CI): m/z (%):

178 (12) [MH⁺+1], 177 (100) [MH⁺].

(3aR*,5aS*,5bS*,9aS*,10aS*)-Dodecahydropentaleno[1,6a-a]inden-

5(1H)-one (42a): NMR (¹H,¹H-COSY, ¹³C,¹³C-DEPT, HSQC, HMBC,

(3aR*,5aS*,9aS*)-2,3,3a,4,8,9-Hexahydro-1H-cyclopenta[c]inden-5(5aH)-

one (39a): NMR (¹H,¹H-COSY, ¹³C,¹³C-DEPT, HMQC); ¹H NMR

(500 MHz, CDCl₃, ref.: TMS): d=1.43 (dddd, J=2.2/7.0/13.7/15.6 Hz,

1H, 3-H^B), 1.44 1.49 (m, 2H, 9-H), 1.67 1.83 (m, 3H, 1-H/2-H), 1.55 (m,

1H, 1-H), 1.97 2.06 (m, 3H, 3-H/8-H), 2.11 (ddd, J=1.6/3.8/18.9 Hz, 1H,

4-H^B), 2.18 (dddd, J=3.8/7.0/8.2/9.0 Hz, 1H, 3a-H), 2.51 (dd, J=9.0/

18.9 Hz, 1H, 3-H^A), 2.53 (m, 1H, 5a-H), 5.69 (dddd, J=2.1/2.1/4.3/9.9 Hz,

1H, 6-H), 5.85 (dddd, J=2.3/3.9/3.9/3.9 Hz, 1H, 7-H); ¹³C NMR

(125 MHz, CDCl₃, ref.: CDCl₃): d=22.90 (C-8), 24.07 (C-2), 31.11 (C-9),

33.06 (C-3), 37.78 (C-1), 42.72 (C-4), 43.25 (C-3a), 49.08 (C-9a), 55.31 (C-

1

NOESY); H NMR (500 MHz, CDCl₃, ref.: TMS): d=0.95 (dddd, J=3.2/

12.0/12.9/12.9 Hz, 1H, 6-H^A), 1.11 (ddddd, J=3.1/3.3/12.0/12.9/12.9 Hz,

1H, 7-H^B), 1.27 (m, 1H, 3-H^B), 1.32 (ddddd, J=3.3/4.4/12.8/12.8/13.1 Hz,

1H, 8-H^A), 1.46 (dddddd, J=1.6/3.3/3.3/3.3/4.8/13.1 Hz, 1H, 8-H^B), 1.52

(m, 1H, 6-H^B), 1.56 (dddd, J=4.8/4.8/13.5/13.6 Hz, 1H, 9-H^A), 1.57 (dd,

J=7.0/12.6 Hz, 1H, 10-H^B), 1.59 (m, 1H, 2-H), 1.63 (dm, J=13.5 Hz, 1H,

9-H^B), 1.64 (m, 1H, 2-H), 1.64 (m, 1H, 7-H^A), 1.66 (m, 1H, 1-H^B), 1.73

(m, 1H, 1-H^A), 2.01 (dd, J=12.3/13.0 Hz, 1H, 10-H^A), 2.04 (m, 1H, 3-

H^A), 2.10 (ddd, J=2.1/4.6/19.2 Hz, 1H, 4-H^B), 2.22 (m, 1H, 9a-H), 2.24

871

Chem. Eur. J. 2004, 10, 851 874

www.chemeurj.org

¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

J. Mattay and H. Rinderhagen

FULL PAPER

(ddddd, J=1.2/5.0/5.9/8.2/12.0 Hz, 1H, 5b-H), 2.33 (dddd, J=4.6/5.8/8.5/

10.1 Hz, 1H, 3a-H), 2.48 (dd, J=2.1/8.2 Hz, 1H, 5a-H), 2.64 (ddd, J=

0.8/9.9/19.2 Hz, 1H, 4-H^A); ¹³C NMR (125 MHz, CDCl₃, ref.: TMS): d=

21.02 (C-8), 24.35 (C-6), 25.70 (C-7), 26.15 (C-2), 26.51 (C-9), 35.26 (C-

3), 40.96 (C-9a), 42.11 (C-5b), 43.86 (C-1), 44.16 (C-10), 46.35 (C-3a),

(3R*,3aS*,5aR*,9aS*)-3-Methyldecahydro-4H-cyclopenta[c]inden-4-one

(36b): NMR (¹H,¹H-COSY, ¹³C,¹³C-DEPT, HMQC, HMBC, NOESY);

¹H NMR (500 MHz, CDCl₃, ref.: CHCl₃): d=0.99 (m, 1H, 6-H), 1.05 (d,

J=6.9 Hz, 3H, 1’-H), 1.15 (dddd, J=9.0/10.7/11.3/13.0 Hz, 1H, 2-H^A),

1.22 1.32 (m, 2H, 7-H/8-H), 1.37 (m, 1H, 9-H), 1.47 1.55 (m, 2H, 7-H/8-

H), 1.54 (ddd, J=8.2/10.7/13.6 Hz, 1H, 1-H^B), 1.64 (m, 1H, 9-H), 1.65

(m, 1H, 6-H), 1.813 (dddd, J=2.1/6.4/8.2/13.0 Hz, 1H, 2-H^B), 1.84 (ddd,

J=2.1/9.0/13.6 Hz, 1H, 1-H^A), 1.95 (dddd, J=4.0/5.3/7.1/9.8 Hz, 1H, 5a-

H), 2.03 (ddd, J=1.8/4.0/17.1 Hz, 1H, 5-H^B), 2.11 (dd, J=1.8/9.2 Hz, 1H,

3a-H), 2.23 (dqdd, J=6.4/6.9/9.2/11.3 Hz, 1H, 3-H), 2.31 (dd, J=7.1/

17.1 Hz, 1H, 5-H^A); ¹³C NMR (125 MHz, CDCl₃, ref.: CDCl₃): d=16.02

(C-1’), 23.39 (C-7)*, 23.70 (C-8)*, 30.00 (C-6), 34.65 (C-2), 36.34 (C-9),

38.27 (C-3), 40.67 (C-1), 40.69 (C-5a), 47.19 (C-5), 51.14 (C-9a), 58.40 (C-

3a), 221.91 (C-4); *: signal assignments are mutual interchangeable; IR

(film): n˜ =2928, 2861, 1735, 1449, 1413, 1380, 1257, 1193, 1165, 1114,

1034, 934 cm^À1; GC-MS (70 eV): m/z (%): 193 (3) [M ⁺+1], 192 (14)

[M ⁺], 149 (10), 138 (11), 137 (100), 136 (11), 135 (5), 134 (3), 121 (4),

108 (5), 107 (12), 95 (9), 94 (6), 93 (9), 92 (8), 91 (15), 82 (4), 81 (24), 80

(5), 79 (27), 78 (4), 77 (12), 69 (5), 68 (3), 67 (19), 66 (3), 65 (4), 55 (15),

53 (7), 51 (3), 43 (4), 42 (3), 41 (30), 40 (5), 39 (9), 29 (9); GC-MS (CI):

m/z (%): 194 (14) [MH⁺+1], 193 (100) [MH⁺]; HRMS: m/z: calcd for

C₁₃H₂₀O: 192.1514, found: 192.1517 [M ⁺].

49.09 (C-4), 58.43 (C-10a), 65.52 (C-5a), 222.95 (C-5); IR (film): n˜

=

2931, 2863, 1730, 1467, 1447, 1407, 1316, 1270, 1248, 1166, 1039 cm^À1

;

GC-MS (70 eV): m/z (%): 218 (6) [M⁺], 190 (3), 189 (12), 176 (7), 175

(4), 147 (4), 138 (6), 137 (9), 136 (3), 133 (7), 124 (16), 123 (100), 122

(14), 121 (4), 119 (6), 117 (3), 108 (3), 107 (5), 106 (4), 105 (10), 97 (4),

96 (43), 95 (28), 94 (11), 93 (14), 92 (8), 91 (33), 82 (3), 81 (23), 80 (8), 79

(34), 78 (6), 77 (18), 67 (19), 66 (4), 65 (5), 55 (15), 53 (9), 52 (5), 43 (6),

42 (3), 41 (35), 39 (6), 29 (6); GC-MS (CI): m/z (%): 220 (17) [MH⁺+1],

219 (100) [MH⁺]; HRMS: m/z: calcd for C₁₅H₂₂O: 218.1671, found:

218.1674 [M ⁺].

(3aR*,5aS*,5bR*,9aR*,10aS*)-Dodecahydropentaleno[1,6a-a]inden-

5(1H)-one (43a): NMR (¹H,¹H-COSY, ¹³C,¹³C-DEPT, ¹³C-gated, HSQC,

HMBC, NOESY); ¹H NMR (500 MHz, CDCl₃, ref.: TMS): d=1.24 (m,

1H, 7-H), 1.36 1.42 (m, 2H, 8-H), 1.36 (dddd, J=3.0/10.4/13.1/15.2 Hz,

1H, 6-H), 1.38 (dddd, J=4.5/5.8/6.2/12.7 Hz, 1H, 3-H^B)*, 1.49 1.54 (m,

2H, 9-H), 1.567 (m, 1H, 6-H), 1.587 (m, 1H, 7-H), 1.63 (m, 1H, 2-H),

1.680 (m, 1H, 2-H), 1.69 (m, 1H, 10-H^A), 1.77 (ddd, J=6.4/8.3/12.6 Hz,

1H, 1-H^A), 1.82 (dddd, J=6.3/6.3/12.6 Hz, 1H, 1-H^B), 1.919 (m, 1H, 9a-

H), 1.93 (m, 1H, 10-H^B), 1.96 (dddd, J=6.6/8.2/8.3/12.7 Hz, 1H, 3-H^A),

2.01 (dd, J=1.8/3.0 Hz, 1H, 5a-H), 2.08 (ddd, J=1.8/6.1/18.4 Hz, 1H, 4-

H^B), 2.09 (dddd, J=3.0/5.2/5.2/10.4 Hz, 1H, 5b-H), 2.22 (dddd, J=4.5/6.1/

8.3/9.3 Hz, 1H, 3a-H), 2.56 (ddd, J=0.7/9.3/18.4 Hz, 1H, 4-H^A);

¹³C NMR (125 MHz, CDCl₃, ref.: TMS): d=21.58 (C-8), 24.76 (C-7),

26.13 (C-2), 26.61 (C-9), 27.86 (C-6), 34.54 (C-3), 39.07 (C-9a), 43.08 (C-

1), 44.84 (C-10), 45.08 (C-5b), 46.59 (C-4), 46.70 (C-3a), 57.26 (C-10a),

65.99 (C-5a), 223.42 (C-5); IR (film): n˜ =2929, 2862, 1736, 1659, 1529,

1465, 1446, 1407, 1252, 1166, 1061 cm^À1; GC-MS (70 eV): m/z (%): 218

(6) [M ⁺], 189 (6), 176 (4), 175 (3), 161 (3), 149 (3), 148 (5), 147 (13), 134

(6), 133 (7), 124 (15), 123 (100), 121 (10), 120 (3), 119 (7), 117 (4), 108

(3), 107 (4), 106 (4), 105 (12), 96 (13), 95 (12), 94 (9), 93 (17), 92 (9), 91

(34), 81 (17), 80 (9), 79 (39), 78 (6), 77 (19), 67 (21), 66 (4), 65 (5), 55

(15), 53 (4), 52 (6), 51 (3), 43 (5), 42 (3), 41 (25), 39 (10), 29 (8); GC-MS

(CI): m/z (%): 220 (16) [MH⁺+1], 219 (100) [MH⁺]; HRMS: m/z: calcd

for C₁₅H₂₂O: 218.1671, found: 218.1673 [M ⁺].

(3R*,3aS*,5aR*,9aS*)-3-Methyldecahydro-4H-cyclopenta[c]inden-4-one

(37b): NMR (¹H,¹H-COSY, ¹³C,¹³C-DEPT, HMQC*, HMBC, NOESY);

¹H NMR (500 MHz, CDCl₃, ref.: CHCl₃): d=1.08 (d, J=6.8 Hz, 3H, 1’-

H), 1.35 (m, 1H, 8-H), 1.38 (dddd, J=8.4/8.9/8.9/12.4 Hz, 1H, 2-H^B), 1.38

(m, 1H, 6-H^B), 1.40 (m, 1H, 7-H), 1.41 (m, 1H, 9-H^A), 1.42 (m, 1H, 7-

H), 1.45 (m, 1H, 8-H), 1.57 (m, 1H, 1-H^B), 1.59 (ddd, J=4.4/8.4/13.1 Hz,

1H, 9-H^B), 1.64 (dddd, J=5.4/5.4/8.0/13.3 Hz, 1H, 6-H^A), 1.71 (ddd, J=

7.8/8.9/13.1 Hz, 1H, 1-H^A), 1.79 (dd, J=1.5/7.4 Hz, 1H, 3a-H), 1.90

(dddd, J=4.4/7.7/7.8/12.4 Hz, 1H, 2-H^A), 2.02 (dddd, J=5.0/5.0/7.5/

9.4 Hz, 1H, 5a-H), 2.10 (qddd, J=6.7/7.4/7.4/8.9 Hz, 1H, 3-H), 2.22 (ddd,

J=1.5/9.4/17.9 Hz, 1H, 5-H^B), 2.31 (dd, J=7.5/17.9 Hz, 1H, 5-H^A);

¹³C NMR (125 MHz, CDCl₃, ref.: CDCl₃): d=20.80 (C-1’), 21.70 (C-7),

23.18 (C-8), 26.64 (C-6), 34.77 (C-9), 35.30 (C-2), 37.73 (C-1), 38.19 (C-

3), 39.25 (C-5a), 43.25 (C-5), 51.42 (C-9a), 66.59 (C-3a), 221.45 (C-4); IR

(film): n˜ =2928, 2858, 1736, 1450, 1413, 1375, 1346, 1315, 1234, 1197,

1156, 1123 cm^À1; GC-MS (70 eV): m/z (%): 193 (9) [M ⁺+1], 192 (50)

[M ⁺], 165 (6), 164 (49), 163 (23), 150 (11), 149 (36), 148 (5), 147 (3), 138

(6), 137 (45), 136 (21), 135 (28), 134 (4), 133 (3), 131 (3), 123 (3), 122

(11), 121 (23), 119 (3), 110 (5), 109 (9), 108 (23), 107 (74), 105 (12), 97

(5), 96 (6), 95 (28), 94 (61), 93 (50), 92 (11), 91 (42), 83 (7), 82 (14), 81

(92), 80 (20), 79 (79), 78 (11), 77 (35), 69 (13), 68 (13), 67 (59), 66 (15),

65 (15), 55 (44), 54 (9), 53 (11), 51 (8), 43 (7), 42 (12), 41 (100), 40 (9), 39

(34), 29 (20); GC-MS (CI): m/z (%): 194 (13) [MH⁺+1], 193 (100)

[MH⁺]; HRMS: m/z: calcd for C₁₃H₂₀O: 192.1514, found: 192.1514 [M ⁺

].

PET oxidative reaction of 3-(3-butenyl)bicyclo[6.1.0]non-2-en-1-yl trime-

thylsilyl ether (11b): Compound 11b (650 mg, 2.45 mmol) was dissolved

in acetonitrile (205 mL), apportioned together with DCA (160 mg,

0.70 mmol) to 15 pyrex tubes and irradiated according to GP I for 96 h.

The crude product was filtered over silica gel (cyclohexane/ethyl acetate

75:25) and purified by HPLC (cyclohexane/ethyl acetate 95:5) yielding

(3R*,3aS*,5aR*,9aS*)-3-methyldecahydro-4H-cyclopenta[c]inden-4-one

(36b; 43 mg, 9%) and a mixture (175 mg, 37%; relative amount accord-

ing to GC 22:17) of the two isomeric cyclisation products

PET oxidative reaction of 3-(3-butynyl)bicyclo[6.1.0]non-2-en-1-yl trime-

thylsilyl ether (12b): Compound 12b was dissolved in acetonitrile

(172 mL), apportioned together with DCA (200 mg, 0.88 mmol) to 12

pyrex tubes and irradiated according to GP I for 134 h. The crude prod-

uct was filtered over silica gel (cyclohexane/ethyl acetate 95:5) and puri-

(4aS*,6aR*,10aS*)-decahydrobenzo[c]inden-5(1H)-one

(35b)

and

(3R*,3aS*,5aR*,9aS*)-3-methyldecahydro-4H-cyclopenta[c]inden-4-one

(37b). The mixture was separated by preparative GC (1908C isotherm/

0.45 bar) for spectroscopic characterization.

fied

by

HPLC

(cyclohexane/ethyl

acetate

95:5)

yielding

(4aS*,6aR*,10aS*)-Decahydrobenzo[c]inden-5(1H)-one (35b): NMR

(¹H,¹H-COSY, ¹³C,¹³C-DEPT, HMQC, HMBC, NOESY); ¹H NMR

(500 MHz, CDCl₃, ref.: CHCl₃): d=1.06 1.33 (m, 6H), 1.34 1.48 (m,

5H), 1.51 1.67 (m, 3H), 1.80 1.99 (m, 3H, 4-H/6a-H/10-H), 1.94 (ddd,

J=1.4/2.9/19.5 Hz, 1H, 6-H), 2.22 (m, 1H, 4a-H), 2.40 (dd, J=8.3/

19.5 Hz, 1H, 6-H); ¹³C NMR (125 MHz, CDCl₃, ref.: CDCl₃): d=20.99

(C-8/C-9)*, 21.29 (C-4), 23.35 (C-3), 24.30 (C-2), 28.69 (C-7), 32.84 (C-

10), 35.79 (C-1), 37.72 (C-6a), 39.70 (C-10a), 42.57 (C-6), 49.66 (C-4a),

221.19 (C-5); *signal shows correlation signals with 4 protons in HMQC

2D experiment; IR (film): n˜ =2929, 2860, 1737, 1449, 1413, 1356, 1296,

1262, 1230, 1196, 1184, 1154, 1107, 1070, 1040, 1002, 909, 892, 878,

850 cm^À1; GC-MS (70 eV): m/z (%): 193 (5) [M ⁺+1], 192 (34) [M ⁺], 163

(3), 150 (9), 149 (21), 138 (14), 137 (100), 136 (17), 135 (14), 134 (6), 122

(7), 121 (10), 110 (5), 109 (8), 108 (10), 107 (15), 105 3), 98 (3), 97 (4), 96

(8), 95 (18), 94 (14), 93 (18), 92 (4), 91 (12), 83 (7), 82 (15), 81 (33), 80

(10), 79 (32), 78 (4), 77 (12), 69 (5), 68 (16), 67 (45), 66 (5), 65 (8), 55

(32), 54 (11), 53 (18), 52 (4), 51 (5), 43 (4), 42 (3), 41 (37), 40 (4), 39 (17),

29 (11), 28 (6), 27 (15).

(4aS*,6aR*,10aS*)-2,4a,6,6a,7,8,9,10-octahydrobenzo[c]inden-5(1H)-one

(39b; 139 mg, 32%) and (3aS*,5aR*,9aS*)-3-methylendecahydro-4H-cy-

clopenta[c]-inden-4-one (40b; 52 mg, 12%) as colorless oils.

(4aS*,6aR*,10aS*)-2,4a,6,6a,7,8,9,10-Octahydrobenzo[c]inden-5(1H)-one

(39b): NMR (¹H,¹H-COSY, ¹³C,¹³C-DEPT, HMQC, HMBC, NOESY);

¹H NMR (500 MHz, CDCl₃, ref.: CHCl₃): d=1.16 1.40 (m, 4H, 7-H/8-H/

9-H/10-H), 1.23 (ddd, J=6.4/6.7/13.3 Hz, 1H, 1-H^B), 1.47 1.57 (m, 2H, 8-

H/9-H), 1.63 (m, 1H, 7-H), 1.65 (m, 1H, 10-H), 1.80 (ddd, J=5.7/7.6/

13.3 Hz, 1H, 1-H^A), 1.95 (ddddd, J=2.1/3.8/6.4/7.6/18.3 Hz, 1H, 2-H),

1.99 2.09 (m, 2H, 2-H/6a-H), 2.08 (ddd, J=1.2/6.1/18.6 Hz, 1H, 6-H^B),

2.41 (dd, J=7.7/18.6 Hz, 1H, 6-H^A), 2.55 2.59 (m, 1H, 4a-H), 5.58 (dddd,

J=2.1/2.2/4.4/9.9 Hz, 1H, 4-H), 5.74 (dddd, J=2.4/3.6/3.8/9.9 Hz, 1H, 3-

H); ¹³C NMR (125 MHz, CDCl₃, ref.: CDCl₃): d=21.23 (C-2)*, 21.39 (C-

9)*, 22.65 (C-8)*, 27.17 (C-7), 29.65 (C-1), 32.56 (C-10), 36.24 (C-6a),

38.71 (C-10a), 41.73 (C-6), 53.75 (C-4a), 122.28 (C-4), 128.29 (C-3),

219.17 (C-5); *: signal assignments are mutual interchangeable; IR (film):

n˜ =3032, 2928, 2855, 1741, 1449, 1412, 1343, 1280, 1256, 1240, 1225, 1200,

1163, 1146, 1128, 1100, 1065, 1010, 949, 921, 902, 872, 834, 816, 774, 744,

872

¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemeurj.org

Chem. Eur. J. 2004, 10, 851 874

Cascade Reactions

851 874

713 cm^À1; GC-MS (70 eV): m/z (%): 191 (10) [M ⁺+1], 190 (59) [M ⁺],

172 (9), 163 (3), 162 (21), 161 (8), 149 (7), 148 (50), 147 (31), 146 (10),

145 (8), 144 (6), 143 (4), 135 (3), 134 (19), 133 (29), 132 (3), 131 (6), 130

(11), 129 (5), 121 (5), 120 (12), 119 (16), 118 (4), 117 (10), 115 (4), 108

(6), 107 (8), 106 (14), 105 (29), 104 (31), 103 (6), 96 (3), 95 (30), 94 (16),

93 (22), 92 (37), 91 (100), 81 (17), 80 (23), 79 (65), 78 (26), 77 (48), 68

(3), 67 (19), 66 (7), 65 (16), 55 (11), 54 (3), 53 (13), 52 (4), 51 (7), 43 (4),

42 (4), 41 (39), 40 (4), 39 (21), 29 (8); GC-MS (CI): m/z (%): 192 (13)

[MH⁺+1], 191 (100) [MH⁺], 190 (5) [M ⁺]; HRMS: m/z: calcd for

C₁₃H₁₈O: 190.1358, found: 190.1352 [M ⁺].

1H, 3-H), 1.09 (m, 1H, 2-H), 1.13 (m, 1H, 10-H), 1.15 (m, 1H, 9-H), 1.20

(m, 1H, 4-H), 1.21 (dd, J=6.0/13.1 Hz, 1H, 11-H^B), 1.23 1.35 (m, 2H, 1-

H), 1.23 (m, 1H, 3-H), 1.26 (m, 1H, 8-H), 1.30 (m, 1H, 2-H), 1.33 (m,

1H, 10-H), 1.35 (m, 1H, 4-H), 1.35 (m, 1H, 9-H), 1.413 (m, 1H, 8-H),

1.43 (m, 1H, 7-H^B), 1.48 (dd, J=7.3/13.1 Hz, 1H, 11-H^A), 1.62 (dddd, J=

3.6/5.3/7.0/12.3 Hz, 1H, 4a-H), 1.69 (m, 1H, 7-H^A), 1.82 (ddddd, J=0.6/

5.9/6.0/7.3/12.8 Hz, 1H, 10a-H), 1.96 (dd, J=6.9/17.0 Hz, 1H, 5-H^A), 2.04

(d, J=7.7 Hz, 1H, 6a-H), 2.07 (m, 1H, 6b-H), 2.1 (ddd, J=1.3/12.3/

17.0 Hz, 1H, 5-H^B); ¹³C NMR (125 MHz, CDCl₃, ref.: TMS): d=20.98

(C-3), 22.94 (C-8), 23.72 (C-2), 23.94 (C-9), 25.30 (C-4), 26.98 (C-7),

28.75 (C-10), 36.52 (C-1), 40.38 (C-10a), 40.77 (C-4a), 41.86 (C-6b), 43.17

(C-11), 43.26 (C-5), 49.20 (C-11a), 62.97 (C-6a), 217.73 (C-6); IR (film):

n˜ =2927, 2856, 1733, 1446, 1415, 1362, 1332, 1232, 1199, 1158, 1129,

1020 cm^À1; GC-MS (70 eV): m/z (%): 233 (2) [M ⁺+1], 232 (10) [M ⁺],

189 (4), 162 (4), 161 (4), 149 (3), 147 (9), 138 (13), 137 (100), 136 (30),

134 (4), 133 (4), 121 (10), 120 (3), 119 (4), 109 (3), 108 (4), 107 (4), 105

(8), 96 (4), 95 (8), 94 (6), 93 (16), 92 (6), 91 (25), 81 (12), 80 (6), 79 (22),

77 (10), 67 (18), 66 (3), 65 (4), 55 (16), 53 (5), 43 (3), 42 (4), 41 (27), 39

(9), 29 (5); GC-MS (CI): m/z (%): 234 (18) [MH⁺+1], 233 (100) [MH⁺];

HRMS: m/z: calcd for C₁₆H₂₄O: 232.1827, found: 232.1826 [M ⁺].

(3aS*,5aR*,9aS*)-3-Methylendecahydro-4H-cyclopenta[c]-inden-4-one

(40b): NMR (¹H,¹H-COSY, ¹³C,¹³C-DEPT, HMQC); ¹H NMR (500 MHz,

CDCl₃, ref.: CHCl₃): d=1.27 (dddd, J=3.7/6.9/7.4/13.0 Hz, 1H, 6-H),

1.37 1.48 (m, 5H, 7-H/8-H/9-H), 1.48 (ddd, J=7.0/8.9/13.0 Hz, 1H, 1-H),

1.63 1.73 (m, 2H, 6-H/9-H), 1.91 (ddd, J=6.9/8.2/13.0 Hz, 1H, 1-H), 2.03

(dddd, J=6.0/6.2/7.4/7.7 Hz, 1H, 5a-H), 2.17 (ddd, J=1.5/7.7/18.2 Hz,

1H, 5-H), 2.39 (dd, J=7.4/18.2 Hz, 1H, 5-H), 2.36 2.49 (m, 2H, 2-H),

2.74 (d, J=1.5 Hz, 1H, 3a-H), 4.95 (ddd, J=2.3/2.4/2.4 Hz, 1H, 1’-H),

5.07 (ddd, J=2.4/2.4/2.4 Hz, 1H, 1’-H); ¹³C NMR (125 MHz, CDCl₃, ref.:

CDCl₃): d=22.31 (C-7)*, 22.81 (C-8)*, 27.52 (C-6), 31.76 (C-2), 33.27 (C-

9), 36.00 (C-1), 36.63 (C-5a), 42.85 (C-5), 51.35 (C-9a), 62.97 (C-3a),

109.23 (C-1’), 148.10 (C-3), 217.57 (C-4); *: signal assignments are mutual

interchangeable; GC-MS (70 eV): m/z (%): 191 (8) [M ⁺+1], 190 (59)

[M ⁺], 175 (3), 163 (3), 162 (22), 161 (12), 149 (8), 148 (70), 147 (46), 146

(12), 135 (3), 134 (22), 133 (39), 132 (3), 131 (6), 121 (6), 120 (16), 119

(30), 118 (3), 117 (10), 115 (5), 108 (4), 107 (13), 106 (24), 105 (42), 104

(6), 103 (7), 95 (8), 94 (17), 93 (30), 92 (31), 91 (100), 82 (6), 81 (15), 80

(28), 79 (71), 78 (25), 77 (67), 69 (3), 68 (4), 67 (20), 66 (7), 65 (23), 63

(3), 55 (18), 54 (5), 53 (24), 52 (5), 51 (8), 43 (3), 42 (4), 41 (40), 40 (4),

39 (20), 29 (10); GC-MS (CI): m/z (%): 192 (3) [MH⁺+2], 192 (13)

[MH⁺+1], 191 (100) [MH⁺], 190 (4) [M ⁺].

PET oxidative reaction of 4-(2-propenyl)bicyclo[5.1.0]oct-2-en-1-yl trime-

thylsilyl ether (14a,b): The two isomeric trimethylsilyl ether 14a and 14b

(overall 277 mg) and DCA (90 mg; 10 mg/tube) were apportioned in dif-

ferent isomer ratios to 9 pyrex tubes and dissolved in acetonitrile (12 mL

each) and irradiated according to GP I for 72 h. The GC analysis of each

tube showed that irrespective of the isomeric ratio (3aR*,4R*,6aR*)-4-al-

lylhexahydro-2(1H)pentalenone (44) was formed as the major product.

The contents of the tubes were combined and the solvent was evaporat-

ed. The crude product was purified by column chromatography (cyclo-

hexane/ethyl acetate 925:75) yielding (3aR*,4R*,6aR*)-4-allylhexahydro-

2(1H)pentalenone (44; 78 mg, 40%) as a colorless oil. NMR (¹H,¹H-

COSY, ¹³C,¹³C-DEPT, HMQC, HMBC, NOESY); ¹H NMR (500 MHz,

CDCl₃, ref.: CHCl₃): d=1.26 1.40 (m, 2H, 5-H/6-H), 1.65 (ddddd, J=7.0/

7.3/7.5/7.6/7.7 Hz, 1H, 4-H), 1.91 (dddd, J=4.0/6.8/7.0/12.3 Hz, 1H, 5-H),

1.97 (ddd, J=2.1/5.6/19.1 Hz, 1H, 1-H^B), 1.97 2.06 (m, 2H, 1’-H/6-H),

2.06 (ddd, J=2.1/4.6/18.8 Hz, 1H, 3-H^B), 2.15 (ddddd, J=1.1/1.5/6.8/7.0/

13.8 Hz, 1H, 1’-H), 2.25 (dddd, J=4.8/7.6/9.2/9.2 Hz, 1H, 3a-H), 2.43

(ddd, J=1.5/9.2/18.8 Hz, 1H, 3-H^A), 2.45 (ddd, J=1.5/10.1/19.2 Hz, 1H,

1-H^A), 2.692 (m, 1H, 6a-H), 4.95 (dddd, J=1.1/1.1/2.2/10.1 Hz, 1H, 3’-H),

4.97 (dddd, J=1.5/1.5/2.2/17.1 Hz, 1H, 3’-H), 5.75 (dddd, J=7.0/7.0/10.1/

17.1 Hz, 1H, 2’-H); ¹³C NMR (125 MHz, CDCl₃, ref.: CDCl₃): d=32.54

(C-6)*¹, 32.56 (C-5)*¹, 39.24 (C-1’)*², 39.26 (C-6a)*², 43.88 (C-3), 44.86

(C-1), 45.56 (C-3a), 46.73 (C-4), 115.59 (C-3’), 137.35 (C-2’), 220.89 (C-2);

*: signal assignments are mutual interchangeable; IR (film): n˜ =3080,

2950, 2866, 1740, 1700, 1678, 1660, 1640, 1547, 1438, 1404, 1242, 1159,

994, 911 cm^À1; GC-MS (70 eV): m/z (%): 164 (<1) [M ⁺], 123 (7), 122

(58), 121 (3), 96 (6), 95 (94), 94 (13), 93 (28), 92 (4), 91 (11), 82 (7), 81

(100), 80 (84), 79 (63), 78 (11), 77 (26), 68 (8), 67 (45), 66 (11), 65 (9), 55

(21), 54 (14), 53 (35), 51 (5), 43 (5), 42 (11), 41 (98), 40 (8), 39 (55), 29

(7); GC-MS (CI): m/z (%): 166 (12) [MH⁺+1], 165 (100) [MH⁺];

HRMS: m/z: calcd for C₁₁H₁₆O: 164.1201, found: 164.1198 [M ⁺].

PET oxidative reaction of 3-(2-cyclohexenylmethyl)bicyclo[6.1.0]non-2-

en-1-yl trimethylsilyl ether (13b): Compound 13b (470 mg, 1.54 mmol)

was dissolved in acetonitrile (211 mL), apportioned together with DCA

(150 mg, 0.66 mmol) to 15 pyrex tubes and irradiated according to GP I

for 68 h. The crude product was filtered over silica (cyclohexane/ethyl

acetate 95:5) and purified by HPLC (cyclohexane/ethyl acetate 95:5)

yielding (4aR*,6aS*,6bS*,10aS*,11aS*)-tetradecahydro-6H-indeno[1,7a-a]-

inden-6-one (42b; 36 mg, 10%) and (4aR*,6aS*,6bR*,10aR*,11aS*)-tetra-

decahydro-6H-indeno[1,7a-a]inden-6-one (43b; 43 mg, 12%) as colorless

oils.

(4aR*,6aS*,6bS*,10aS*,11aS*)-Tetradecahydro-6H-indeno[1,7a-a]inden-

6-one (42b): NMR (¹H,¹H-COSY, ¹³C,¹³C-DEPT, HSQC, HMBC,

NOESY); ¹H NMR (500 MHz, C₆D₆(trace of CDCl₃)*, ref.: TMS): d=

0.81 (dddd, J=3.4/12.7/12.8/12.9 Hz, 1H, 7-H^A), 0.99 (ddddd, J=3.3/3.3/

12.8/12.8/12.8 Hz, 1H, 8-H^B), 1.061 (m, 1H, 1-H^B), 1.08 (m, 1H, 3-H),

1.09 (m, 1H, 2-H), 1.19 (m, 1H, 1-H^A), 1.22 (m, 1H, 9-H), 1.27 (m, 1H,

4-H^B), 1.29 (m, 1H, 3-H), 1.32 (ddd, J=0.6/7.5/12.6 Hz, 1H, 11-H^B), 1.36

(m, 1H, 9-H), 1.36 1.44 (m, 2H, 10-H), 1.37 (m, 1H, 4-H^A), 1.39 (m, 1H,

2-H), 1.45 (dd, J=12.8/12.9 Hz, 1H, 11-H^A), 1.55 (dddddd, J=1.3/3.4/3.4/

3.4/3.4/12.8 Hz, 1H, 8-H^A), 1.77 (m, 1H, 7-H^B)*, 1.790 (m, 1H, 4a-H)*,

1.93 (ddddd, J=2.7/5.3/5.4/7.5/12.9 Hz, 1H, 10a-H), 1.98 (ddd, J=1.0/7.0/

16.9 Hz, 1H, 5-H^A)*, 2.02 (dddd, J=5.4/5.4/7.5/12.7 Hz, 1H, 6b-H), 2.13

(ddd, J=1.0/1.4/7.6 Hz, 1H, 6a-H), 2.19 (ddd, J=1.4/13.5/16.9 Hz, 1H, 5-

H^B); *For better signal separation the NMR measurements was carried

out in benzene containing traces of chloroform. In pure benzene the

chemical slightly differ from the stated above. This is important for the

*marked signal, because these signals overlap and change their sequence;

¹³C NMR (125 MHz, CDCl₃, ref.: TMS): d=20.06 (C-3), 21.22 (C-9),

23.82 (C-2), 25.56 (C-4), 25.69 (C-7), 25.85 (C-8), 26.84 (C-10), 36.04 (C-

1), 40.72 (C-11), 40.85 (C-10a), 41.26 (C-6b), 43.67 (C-4a), 45.31 (C-5),

49.01 (C-11a), 66.87 (C-6a), 216.70 (C-6); IR (film): n˜ =2924, 2857, 1732,

1446, 1411, 1249, 1227, 1196, 1164, 1080 cm^À1; GC-MS (70 eV): m/z (%):

232 (4) [M ⁺], 189 (3), 138 (14), 137 (100), 136 (30), 119 (3), 109 (3), 107

(3), 105 (5), 96 (7), 95 (8), 94 (5), 93 (10), 92 (4), 91 (17), 81 (10), 80 (4),

79 (20), 77 (7), 67 (10), 65 (4), 55 (9), 53 (4), 43 (5), 41 (14), 39 (6), 29

(4); GC-MS (CI): m/z (%): 234 (17) [MH⁺+1], 233 (100) [MH⁺];

HRMS: m/z: calcd for C₁₆H₂₄O: 232.1827, found: 232.1825 [M ⁺].

Acknowledgement

H.R. acknowledges the Studienstiftung des deutschen Volkes for a pre-

doctoral fellowship. We are indebted to Dr. Christian Wolff (NMR facili-

ty, Institute of Organic Chemistry, University of Kiel) for excellent theo-

retical and practical support concerning all kinds of NMR problems. Fi-

nancial support was provided by the DFG.

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(4aR*,6aS*,6bR*,10aR*,11aS*)-Tetradecahydro-6H-indeno[1,7a-

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873

Chem. Eur. J. 2004, 10, 851 874

www.chemeurj.org

¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

J. Mattay and H. Rinderhagen

FULL PAPER

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Article Doi

Synthetic Applications in Radical/Radical Cationic Cascade Reactions

DOI: 10.1002/chem.200304827

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