Cathodic cyclisation of N-(oxoalkyl)pyridinium salts - Formation of tricyclic indolizidine and quinolizidine derivatives in aqueous medium

Article abstract of DOI:10.1002/ejoc.200300180

The cathodic cyclisation of N-(oxoalkyl)pyridinium salts, derived from 4-methylpyridine and cyclic ketones, afforded functionalised tricyclic indolizidine and quinolizidine derivatives in high yields. Through systematic variation of the ring size of the k

Full text of DOI:10.1002/ejoc.200300180

FULL PAPER
Cathodic Cyclisation of N-(Oxoalkyl)pyridinium Salts ؊ Formation of
Tricyclic Indolizidine and Quinolizidine Derivatives in Aqueous Medium
Jens Heimann,[a] Hans J. Schäfer,*[a] Roland Fröhlich,[a][‡] and Birgit Wibbeling[a]
Keywords: Cyclisation / Electrochemistry / Fused-ring systems / Heterocycles / Umpolung
The cathodic cyclisation of N-(oxoalkyl)pyridinium salts, de- the cyclisation is proposed. In the key step, a hydroxyalkyl
rived from 4-methylpyridine and cyclic ketones, afforded
radical generated by reduction of the protonated ketone adds
functionalised tricyclic indolizidine and quinolizidine deriv- reversibly to the pyridinium ring. Semiempirical calculations
atives in high yields. Through systematic variation of the ring
size of the ketone and the cyclised ring, a series of four cyclo-
penta-/cyclohexa[a]indolizidines and -quinolizidines was ob-
tained. The cyclisation was also applied to the synthesis of a
indicate that only diastereomers resulting from the thermo-
dynamically more stable cyclised intermediates are obtained.
From these data and the ∆∆fHꢀ value for the transition states
of the cyclisation, thermodynamic rather than kinetic control
seems to be more likely.
cyclohexa[b]quinolizidine derivative, which represents
a
substructure of the cevanine alkaloids. There is no obvious
alternative route as short as this cathodic cyclisation to such
indolizidines and quinolizidines. A detailed mechanism of
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2003)
Introduction
A few years ago we showed that the cathodic cyclisation
of arylalkanones,[14a,18] can be extended to the cyclisation
of N-(oxoalkyl)pyridinium salts to provide hydroxyindolizi-
dine and -quinolizidine derivatives.[19] The pyridinium salts
are readily available by nucleophilic substitution of halogen
ketones with pyridine. The sequence overall provides func-
tionalised indolizidine and quinolizidine derivatives by a
shorter route than achievable by existing methods.[20] The
radical cyclisation of N-(iodoalkyl)pyridinium salts[21] and
N-alkenyl-2-bromopyridinium salts[22] is also reported to
give indolizidines and quinolizidines. In comparison with
the cathodic cyclisation, though, this method has draw-
backs such as the use of tributyltin hydride for hydrogen
atom transfer and the loss of functionality in the course of
the cyclisation.
Since the pioneering work of Kolbe, organic electrochem-
istry has emerged as a powerful tool both for functional-
group interconversions and for CϪC bond-forming reac-
tions.[1] One important method of the latter class is the in-
tramolecular cyclisation of acyclic precursors with two
functional groups of the same polarity.[2] This is achieved
by selective reversal of the reactivity (‘‘umpolung’’) of one
of these groups by electron transfer, which can render a
nucleophilic group electrophilic by oxidation (e.g., enol
ethers) or an electrophilic group nucleophilic by reduction
(e.g., carbonyl groups), thus initiating the CϪC bond coup-
ling. This unique strategy provides simple routes to carbo-
and heterocycles as documented by numerous anodic[2,3]
and cathodic cyclisations.[2,4]
The following combinations of functional groups have re-
cently been intramolecularly coupled at the cathode: alkyl
halides with alkenes,[5] two electron-deficient alkenes,[6] α,β-
unsaturated esters with allenes,[7] ketones[8] or aldehydes,[9]
diesters to give vicinal diketones,[10] esters with alkenes to
give secondary alcohols[11] or two imines to piperazines[12]
and macrocycles.[13] The coupling of ketones with al-
kenes,[14] nitriles,[15] vinylsilanes,[16] O-methyl oximes[17] and
phenyl rings[14a,18] was also studied recently.
Here we report on the extension of the cathodic cyclis-
ation to the synthesis of a series of tricyclic hydroxyindolizi-
dine and -quinolizidine derivatives.[23] The objectives were
to examine the application of the reaction to more complex
target structures and to gain a more detailed insight into
the mechanism.
Results and Discussion
[a]
Organisch-Chemisches Institut, Westfälische Wilhelms-
Universität Münster,
Preparation of the Pyridinium Salts
Corrensstraße 40, 48149 Münster, Germany
Fax: (internat.) ϩ 49-251/8336523
E-mail: schafeh@uni-muenster.de
In order to demonstrate the potential for the construc-
tion of tricyclic indolizidines and quinolizidines by the way
of cathodic cyclisation, compounds 1؊4 were chosen as tar-
get compounds (Scheme 1). It was thought that the N-(4-
[‡]
Crystal structure determination.
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
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oxoalkyl)pyridinium salts 5/6, for the synthesis of the quin- order to avoid losses due to their poor tendency to crystal-
olizidines 1/2, and the corresponding 3-oxo salts 10/11, to lise and because they are very hygroscopic. The yields and
provide the indolizidines 3/4, should be available by alky- purities of 5 and 6 and all other salts reported (except for
lation of 4-methylpyridine (9) with the 4-bromo ketones 7/ 10, 19 and 20, Table 1) were therefore determined reprodu-
1
8 and the acetals of the 3-bromo ketones 12/13, respectively. cibly by H NMR spectroscopy with methyl 3-bromopro-
Protection of the carbonyl groups of the latter, which were panoate as internal standard by integration of the NCH2
deprotected in situ by the acidic electrolyte during cathodic signals of the salts and the CH2 signals of the standard.
reduction of the salts 10/11, was necessary to prevent de- The low yield of 6 in comparison to 5 results from 4-methyl-
hydrobromination in the alkylating step.
pyridine (9) acting more as a base than as a nucleophile in
the case of the bromo ketone 8, giving 4-methylpyridinium
bromide as major product.
The alkylation precursor 13 was obtained by bromination
of the hydroxy acetal 16 by a variant of the Mitsunobu
reaction[27] described by Falck[28] with lithium bromide
(Scheme 3). Since preliminary experiments to alkylate 4-
methylpyridine (9) with 13 showed this compound to be
less reactive than 7, the corresponding tosylate 17[29] and
mesylate 18[30] were also synthesised from the alcohol 16.
Scheme 1. Retrosynthetic analysis of the [a]-anellated indolizidines
and quinolizidines 1؊4
The bromo ketone 7 was prepared by alkylation of the
β-oxo ester 14 with 1,2-dibromoethane and potassium car-
bonate in refluxing acetone, followed by decarboxylation in
hydrobromic acid[24,25] (Scheme 2). Application of the same
procedure to the synthesis of the bromo ketone 8[25,26]
failed. With sodium hydride as base in DMF[25] and sub-
sequent treatment as above, the bromo ketone 8 was ob-
tained as a rather unstable compound in 18% overall yield.
Deprotonation of cyclohexanone with LDA, followed by
the addition of dibromoethane in THF and heating until
reflux, with or without added TMEDA, mainly gave aldol
condensation products.
Scheme 3. Synthesis of alkylation precursors from 16 and alky-
lation experiments
Table 1. Yields of the pyridinium salts 10, 19 and 20
Entry
1
2
3
4
5
6
Precursor
13
17
18
18
18
18
Time [min] 20
20
20
60
180
240
Yield[a]
Ͻ 1% 10 5% 19 5% 20 19% 20 33% 20 43% 20
[a]
Yields not corrected for purity.
The alcohol 16 was obtained by aldol addition of formal-
dehyde to cyclohexanone (22),[31] followed by acetalisation
of the resulting hydroxymethyl ketone 24 with ethylene gly-
col and PPTS catalysis[32] in benzene (Scheme 4).[33] In tolu-
ene instead of benzene, the dehydration product 6-methyl-
ene-1,4-dioxaspiro[4.5]decane was predominantly formed.
Whilst the synthesis of (hydroxymethyl)cyclopentanone (23)
by the same route was possible,[31,34] the acetalisation re-
sulted in a mixture of α,β-unsaturated methylenecyclo-
pentanone and the corresponding acetal. The known pro-
cedure[35] for acetalisation of the β-oxo ester 14 and sub-
Scheme 2. Synthesis of the salts 5 and 6
For the preparation of the salts 5 and 6, the bromo ke- sequent hydride reduction to 25 was therefore employed.
tones 7 and 8 were heated to 120 °C with a 1.5-fold excess The alkylation of 4-methylpyridine (9) with 13, 17 and 18
of 4-methylpyridine (9) without added solvent, similarly to did not provide the precursor for the cyclisation in accept-
the previously described procedure[19] (Scheme 2). The re- able yields (Scheme 3, Table 1). This problem could finally
sulting oils were washed with diethyl ether and dried to give be solved by the use of triflate as a leaving group
white, powdery solids. These were not purified further, in (Scheme 5). The triflate 28 could be isolated by column
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Electrochemical Formation of Tricyclic Indolizidine and Quinolizidine Derivatives
FULL PAPER
Scheme 6. Retrosynthetic analysis of the cyclohexa[b]quinolizidine
33
Scheme 4. Synthesis of 25 and 16
ride and sodium halide (I, Cl, Br) as nucleophile in aceto-
nitrile it is possible to choose the halogen atom to be intro-
duced.[40] The intermediate trimethylsilyl ether is not iso-
lated, but is cleaved during workup with fluoride solution.
These conditions, when applied to 36, afforded the bromo
ketone 35 with trans stereochemistry, as was clearly con-
firmed by the coupling constants of the CHCOCH3 proton
(2 ϫ J ϭ 10.5 Hz and J ϭ 3.7 Hz). The alkylation of 4-
methylpyridine (9) was accomplished as for the other salts.
As in the case of 8, significant amounts of 4-methylpyridin-
ium bromide were formed as the main impurity in the
product.
chromatography and characterised, but the yield was low,
so the alkylation was performed without isolation of the
triflates. In this way, the cyclisation precursors 29 and 30
were obtained in high yields from the alcohols 25 and 16.
Some of the material was found to be deprotected, afford-
ing the salts 31 and 32, respectively. For the determination
1
of the yields by H NMR as described above, solutions of
the crude products in a mixture of D2SO4, D2O and
CD3CN were examined, resulting in the complete deprotec-
tion of the acetals to 31 and 32, which was checked by
ESI-MS.
Scheme 7. Synthesis of the pyridinium salt 34
Electrolysis
The electrolyses of the pyridinium salts were carried out
in a divided beaker-type cell at a mercury pool cathode un-
der constant current conditions, since this proved to result
in higher yields of the cyclised products than obtainable
by potential control conditions.[19] The electrolyte was 1 
aqueous sulfuric acid, from which the products were easily
extracted with diethyl ether and dichloromethane after the
Scheme 5. Synthesis of the cyclisation precursors for the indolizid-
ines from 25 and 16 via triflates
The synthesis of tricyclic [b]-anellated quinolizidines pH had been increased to about 10 with solid potassium
would be an important extension of the products accessible carbonate.
so far, because compound 33, which was targeted as shown
The cyclisation of 5 had previously been reported to af-
in Scheme 6, represents a substructure of the cevanine ster- ford two isomeric products in a total yield of 46%.[19]
oidal alkaloids.[36,37] The salt 34 should arise from alky- Meanwhile, the yield of this cyclisation was increased to
lation of 4-methylpyridine (9) with the bromo ketone 35, 73% of two out of four possible diastereomeric products 1a
which should in turn be accessible by nucleophilic ring- and 1b by increasing the amount of charge transferred to a
opening of the cyclopropyl ketone 36.
2.6-fold excess (Scheme 8). The structure of the minor iso-
The bicyclic ketone 36 was obtained by cyclopropanation mer 1b was elucidated by X-ray crystallography (Figure 1),
of 37[38] (Scheme 7). The regioselective opening of the while the X-ray structure of the major isomer 1a had been
cyclopropyl ring in 36 with trimethylsilyl iodide has been published before.[19] The cyclisation of the salt 6 provided
reported.[39] By using a combination of trimethylsilyl chlo- three diastereomeric quinolizidine[41] derivatives 2aϪ2c in a
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FULL PAPER
combined yield of 82%, with much lower diastereoselec-
tivity than seen in the case of 1 (Scheme 8). Again, the
structures of all three products were corroborated by X-
ray crystallography (Figure 1). The isomers 2a and 2b are
structural analogues of 1a and 1b, respectively, whereas in
the major isomer 2c the former cyclohexanone and the new
ring are trans-connected. (These two rings are cis-connected
in all other isomers in this series.) The six-membered rings
in all isomers 1 and 2 adopt the favoured chair confor-
mation.
Scheme 9. Electrolysis of 29 and 30 to afford the indolizidines 3
and 4
Scheme 8. Electrolysis of 5 and 6 to afford the quinolizidines 1
and 2
Figure 2. Crystal structures of the indolizidines 3a, 3b, 4a and 4b
Comparison of all crystal structures reveals that the indo-
lizidine/quinolizidine core adopts a trans conformation (ni-
trogen lone pair and hydrogen atom 9b-H, 10b-H or 11b-
H) in all cases except for the indolizidines 4 (Figure 1 and
2). This difference could also be deduced from the IR spec-
tra, since all of these except for those of compounds 4 show
strong Bohlmann absorptions[43] of the NCϪH stretch of
the hydrogen atoms trans to the lone pair of the nitrogen
atom in the 2700Ϫ2800 cmϪ1 region.
Figure 1. Crystal structures of the quinolizidines 1b and 2aϪ2c
The cyclisation of the pyridinium salt 34 provided two
sets Ϫ 33 and 38 Ϫ of two diastereomers of linear anellated
The electrolysis of the pyridinium salts 29 and 30 pro- cyclohexa[b]quinolizidines[41] in a combined yield of 73%
vided two diastereomeric indolizidine[42] derivatives in com- (33a, 33b, 38a) (Scheme 10). The two major products 33a
bined yields of 83 and 65% (Scheme 9). In all isomers, the and 33b represent two out of four possible diastereomers of
former cycloalkanone and the new ring are cis-connected 33 and differ in configuration at the former carbonyl car-
(analogues to 1a and 1b), no traces of the two other pos- bon atom of compound 34. The products 38a and 38b have
sible isomers with trans-connected rings being found. The the same stereochemistry as 33a and 33b, but the position
diastereoselectivity of the cyclisation was low with respect of the remaining double bond of the former pyridinium ring
to the observed isomers. Again, all structures were con- is different. These kinds of regioisomers were observed pre-
firmed by X-ray crystallography (Figure 2). The indolizid- viously in the case of bicyclic quinolizidines.[19] The struc-
ine 4b did not give crystals as a free base, but did so as a tures of 33b and 38a were elucidated by X-ray diffraction
picrate salt (the picrate anion is omitted in Figure 2 for clar- of appropriate crystals (Figure 3), and that of 33a by NMR
ity). As in the case of the quinolizidines 1 and 2, the six- experiments demonstrating NOE effects between the
membered rings in 4 adopt the chair conformation.
C11ϪCH3 and the C10a and C11a hydrogen atoms.[44] The
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Electrochemical Formation of Tricyclic Indolizidine and Quinolizidine Derivatives
FULL PAPER
IR spectrum of 33a shows strong Bohlmann bands at 2818 in 1  aqueous sulfuric acid was obtained. The second po-
and 2745 cmϪ1 and the signal of the 10a-H in the 1H NMR tential was assigned to the pyridinium electrophore.
spectrum shows two large couplings (2 ϫ J ϭ 11.2, J ϭ
From these data, the mechanism presented in Scheme 11
2.9 Hz). These data suggest that in the case of 33a Ϫ and is proposed. The carbonyl group in the salt 5 is activated
also for 33b and 38a Ϫ all rings are trans-connected/in trans by protonation and reduced by one electron to afford the
conformation. The structure of 38b, which could not be iso- nucleophilic hydroxyalkyl radical 40 (cathodic umpolung).
lated, is suggested to be that shown, as elucidated by com- The fact that the protonated carbonyl group is reduced,
parison of the GC-MS data of the crude reaction mixture. rather than the pyridinium ring, is further supported by the
The mass spectrum of 38b is almost identical to that of observation that no reduction of 4-methylpyridinium bro-
38a, whereas the spectra of the isomers 33a and 33b are mide, present as major impurity in the salts 6 and 34, was
significantly different with respect to their peak intensities. observed during electrolysis. Only 4-methylpyridine (9), and
In addition, the GC-MS showed that the cyclisation had no reduction products thereof, was found in the crude prod-
also yielded the two other diastereomers of 33 in minor ucts in addition to the cyclised quinolizidine derivatives.
amounts (33c and 33d, about 6% of all isomers, not iso- The intermolecular coupling of acetone and N-ethylpyridin-
lated). The products 33 and 38 are of possible interest as ium bromide in sulfuric acid was also shown to proceed
they are substructures of some steroidal alkaloids of the through the reduction of acetone rather than the pyridin-
cevanine type.[36,37]
ium bromide.[46] The hydroxyalkyl radical 40 adds intramol-
ecularly to the electrophilic pyridinium ring, thus con-
verting the distonic radical cation 40 into the delocalised
radical cation 41. This is further reduced to the neutral di-
enamine 42, which Ϫ after protonation to provide 43 Ϫ
affords the indolizidine 1 after final reduction of the imin-
ium group. No intermediates of the reaction can be ob-
served by ESI-MS, which indicates that once the reaction is
initiated by the reduction of 39 it proceeds directly to the
final product, as all intermediates become reduced more an-
odically than 39.
Scheme 10. Electrolysis of 34 to afford the [b]-anellated quinolizid-
ines 33 and 38
Figure 3. Crystal structures of the [b]-anellated quinolizidines 33b
and 38a
Scheme 11. Proposed mechanism of the cathodic cyclisation, shown
for the synthesis of indolizidine 1 from the pyridinium salt 5
Mechanistic Considerations
Differential pulse polarography of N-(4-oxopentyl)pyridi-
nium chloride in aqueous sulfuric acid at pH ϭ 1Ϫ4
The diastereoselectivity of the reaction is determined in
showed one acidity-dependent potential shift from Ϫ1.91 the cyclisation step from 40 to 41, as equilibration of the
to Ϫ1.53 V (vc. SCE) and a second, acidity-independent isomers by elimination of water and rehydration of the re-
reduction potential at Ϫ1.43 V.[19,45] The first reduction was sulting alkenes was ruled out by control experiments. Stir-
attributed to the carbonyl group and the linear dependency ring of the pure diastereomeric tertiary alcohols in 1 
on the pH to activation by protonation of the carbonyl oxy- aqueous sulfuric acid for 3 d left these unchanged. From
gen atom at different acid concentrations. For 1  aqueous the electrolysis of the salt 29, only the two diastereomers
sulfuric acid, the electrolyte used in the preparative electro- with the thermodynamically strongly favoured cis connec-
lyses, the potential could not be measured directly, because tion of the two five-membered rings were isolated
the peak overlapped with that of the proton reduction from (Scheme 9). The cyclisation of the salt 6 yielded the isomer
the electrolyte. By extrapolation from the potentials at 2c with trans-connected six-membered rings as major prod-
higher pH, a value of Ϫ1.37 V for the carbonyl reduction uct, but also the isomers 2a and 2b with two cis-connected
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rings (Scheme 8). The product 2c can be compared with
trans-decalin, which is only slightly lower in energy than cis-
decalin, being analogous to 2a and 2b. These observations
suggest that the ring closure of 40 to 41 is reversible and
that the diastereoselectivity is determined by the relative
heats of formation of the isomeric intermediates 41
(thermodynamic control). Results obtained by Minisci on
the intermolecular addition of radicals of different types to
protonated heteroaromatic bases in various solvents[47] ad-
ditionally support the proposed reversible cyclisation.
To demonstrate that only isomers resulting from thermo-
dynamically favoured intermediates 41 were obtained, the
heats of formation ∆fH of all four diastereomeric intermedi-
ates I-1a to I-1d (Scheme 12) and I-2a to I-2d (Scheme 13)
were calculated by use of MOPAC 93 (AM1).[48] In the
cyclisation of salt 5, the intermediates I-1a and I-1b, with a
cis connection of the five- and the six-membered ring, are
lower in energy than the others, providing the isolated iso-
mers (Scheme 12). For the cyclisation of 6, the intermediate
I-2c affording the major product 2c is slightly lower in en-
ergy than I-2a and I-2b, thus also affording substantial por-
tions of the products. In both cases, the intermediates I-1d
and I-2d are significantly higher in energy than the corre-
sponding c isomers, due to an unfavourable twist confor-
mation that the central ring has to adopt. The fact that the
isolated products only result from those intermediates that
are lower in energy is also true for the cyclisation to the
indolizidines 3 and 4, as the cis-connected intermediates
producing the afforded isomers are significantly lower in
energy than the trans-connected ones (data not shown).[48]
Scheme 13. Calculated ∆∆fH values of the transition states TS and
the cyclised intermediates I for the reduction of the salt 6 to the
quinolizidine 2
timisation of the geometries)[48,49] (Schemes 12 and 13).
From these data, it is not possible to differentiate clearly
whether thermodynamic or kinetic control as more import-
ant, since the the transition states TS-1a, TS-1b and TS-2a
to TS-2c, producing the afforded isomers, are significantly
lower in energy than the other. However, the heat of forma-
tion of the transition state TS-2b does not agree with the
ratios of the observed diastereomers, thus suggesting that
the cyclisation might not be kinetically controlled.
Overall, with the data obtained so far, a thermo-
dynamically controlled reversible cyclisation, as also pro-
posed by Minisci for related couplings,[47] is suggested as
the key step.
The position of the double bond in the final products is
determined by the regioselectivity of the protonation of the
dienamine (42) (either β-protonation as observed for 1؊4
and 33, or δ-protonation as occurred in the case of 38),
which produces isomeric eniminium ions, which are further
reduced at the cathode. In dienamines the kinetically
favoured site for protonation is the nitrogen atom, but at
equilibrium the eniminium ions that occur by protonation
at C-β and C-δ are dominant.[50] It was deduced that
weaker acids protonate more readily at the β-carbon atom
while stronger acids afford the conjugated eniminium ions
by protonation of the δ-carbon atom to a larger extent.
However, as in the case of the related protonation of dienol-
ate anions by water, the competition is also influenced
strongly by steric and electronic factors. These are difficult
to take into account to explain why the protonation is selec-
tive in most cases but not in the cyclisation of 34.
Scheme 12. Calculated ∆∆fH values of the transition states TS and
the cyclised intermediates I for the reduction of the salt 5 to the
quinolizidine 1
Conclusion
In the case of an irreversible cyclisation, the stereoselec-
tivity should be governed by the relative energies of the
The cathodic cyclisation of N-(oxoalkyl)pyridinium salts
transition states TSs between 40 and 41 (I) (kinetic control). has successfully been extended to the synthesis of four
The heats of formation ∆fH of all transition states TS-1a cyclopenta-/cyclohexa[a]indolizidine (3, 4) and -quinolizid-
to TS-1d and TS-2a to TS-2d were therefore also calculated ine derivatives (1, 2) in high yields, from 65 to 83%. One
by use of MOPAC 93 (AM1, TS algorithm with free op- example of a cyclohexa[b]quinolizidine (33/38) is also pro-
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FULL PAPER
electrodes were connected to the outside of the cell by platinum
and copper wires that were sealed in glass to avoid contact with
the solutions. The catholyte was stirred with a conventional Teflon-
coated magnetic stirrer bar lying on top of the mercury. A Jaissle
IMP 83 served as current source.
vided. The pyridinium salts, which were completely con-
verted into cyclised products, are easily available and need
not to be purified. Another advantage of the method is the
use of aqueous sulfuric acid as solvent, so that no support-
ing electrolyte is needed, which facilitates the workup. There
is no alternative to this cathodic cyclisation that allows such Preparation of the Pyridinium Salts
a short synthesis of functionalised indolizidine and quinoli-
zidine derivatives.
A mechanism has been developed to explain the observed
diastereoselectivities, in terms of a reversible addition of an
intermediate hydroxyalkyl radical to the pyridinium ring, as
2-(2-Bromoethyl)cyclopentanone (7): A mixture of ethyl 2-oxocyclo-
pentanecarboxylate (14, 11.71 g, 75.0 mmol), potassium carbonate
(31.10 g, 225 mmol) and 1,2-dibromoethane (39.0 mL, 85.0 g,
453 mmol) was dissolved in acetone (200 mL, dried with molecular
˚
sieves 3 A) and heated at reflux for 9 h, and then stirred at room
only diastereomers resulting from the thermodynamically temperature overnight. The suspension was filtered, the filtrate was
concentrated, and excess 1,2-dibromoethane was distilled off at
10 mbar/60 °C. The residue was purified by flash chromatography
(light petroleum/diethyl ether, 3:1, Rf ϭ 0.29). Yield: 12.75 g
(48.5 mmol, 65%) ethyl 1-(2-bromoethyl)-2-oxocyclopentanecar-
boxylate as a colourless oil. IR (film): ν˜ ϭ 2979 (m), 1748 (s, Cϭ
O, ester), 1726 (s, CϭO, ketone), 1446 (m), 1404 (w), 1367 (w),
1298 (m), 1258 (s), 1235 (s), 1183 (s), 1159 (s), 1096 (m), 1028 (m),
more stable cyclised intermediates were obtained (thermo-
dynamic control). This result might be useful for qualitative
prediction, by simple semiempirical calculations, of which
diastereomers of future synthetic targets should be access-
ible. However, from the data obtained so far, kinetic control
could not be ruled out.
In due course, we will report on the extension of the
method to the cyclisation of various pyridinium salts de-
rived from aldehydes to demonstrate further the usefulness
and scope of the reaction.
860 (w) cmϪ1 1H NMR (300.1 MHz, CDCl3): δ ϭ 1.26 (t, 3J ϭ
.
7.2 Hz, 3 H, CH3), 1.85Ϫ2.60 (m, 8 H), 3.31Ϫ3.40 (m, 1 H,
3
CHABr), 3.47Ϫ3.56 (m, 1 H, CHBBr), 4.18 (q, J ϭ 7.2 Hz, 2 H,
OCH2) ppm. 13C NMR (75.5 MHz, CDCl3): δ ϭ 14.0 (q, CH3),
19.6 (t), 27.5 (t), 33.4 (t), 37.0 (t), 37.5 (t), 60.2 (s), 61.6 (t, OCH2),
170.3 (s, COOEt), 213.4 (s, CO) ppm. MS (GC-MS): m/z (%) ϭ
262/264 (2/2) [Mϩ], 234/236 (52/52) [Mϩ Ϫ C2H4], 217/219 (24/24)
Experimental Section
[Mϩ Ϫ OCH2CH3], 207/209 (26/10), 205 (18), 182 (42) [Mϩ
Ϫ
HBr], 179 (22), 156 (100) [Mϩ Ϫ C2H3Br], 155 (22), 154 (64), 141
(24), 127 (14), 110 (36), 109 (52), 99 (44), 81 (70), 67 (22), 55 (34),
53 (30), 41 (25). C10H15BrO3 (263.13): calcd. C 45.65, H 5.75; found
C 45.81, H 5.67. Ethyl 1-(2-bromoethyl)-2-oxocyclopentanecarbox-
ylate (10.00 g, 38.0 mmol) was dissolved in hydrobromic acid (48%,
40 mL) and the solution was heated at reflux for 30 min until the
evolution of carbon dioxide ceased. The solution was cooled to
room temperature, diluted with water (50 mL) and extracted with
diethyl ether (100 mL). The aqueous phase was neutralised with
solid sodium hydrogen carbonate and again extracted with diethyl
ether (2 ϫ 100 mL). The combined organic phases were washed
with a saturated solution of sodium hydrogen carbonate (100 mL),
dried (MgSO4), filtered and concentrated. The residue was purified
by flash chromatography (light petroleum/diethyl ether, 5:1, Rf ϭ
0.24). Yield: 5.87 g (30.7 mmol, 81%) 7 as slightly yellow oil. IR
(film): ν˜ ϭ 2964 (m), 2875 (m), 1739 (s, CϭO), 1452 (w), 1431 (w),
1404 (w), 1274 (w), 1253 (w), 1221 (w), 1154 (m), 1086 (w), 928
General Remarks: For detailed synthetic procedures and analytical
data for the known compounds 17, 18, 23, 24, 25, 26 and 36, and
also the data for 16, see the Supporting Information (see footnote
on the first page of this article). Melting points were determined
with a Kofler hot stage microscope and are not corrected. IR spec-
tra were obtained with a Bruker IFS 28 FT-IR system. NMR spec-
tra were recorded with Bruker ARX 300, Bruker AMX 400 and
Varian Unity plus 600 instruments. Two-dimensional HH and CH
correlations, as well as DEPT spectra, were recorded if necessary
for the given assignments of the signals. A small letter ‘‘e’’ is used
to assign equatorial protons, ‘‘a’’ is used for axial. Mass spectra
(GC-MS) were recorded with a Finnigan-MAT 8230 (EI, 70 eV) in
combination with a Varian GC 3400 and with the GC-MS iontrap
system Varian Saturn II (EI, 70 eV). Data from the latter instru-
ment is marked with an asterisk (*). In both systems, HP 5 capillary
columns (25 m, 0.2 mm i.d., 0.33 µm film) were used. ESI-MS data
were recorded with a Micromass Quattro LC-Z machine equipped
with nanospray inlet (capillary: 1.20 kV; cone: 20 V). The samples
were applied as acetonitrile solutions. Exact mass (EMS) determi-
nations were made with the MAT 8230 (reference PFK) and the
Quattro LC-Z (reference PEG). Gas chromatography was carried
out with a HewlettϪPackard HP 5890 Series II equipped with an
HP5 capillary column (25 m, 0.2 mm i.d., 0.52 µm film) and an
FID detector. Preparative flash chromatography was carried out
on silica gel 60 (40Ϫ63 µm) purchased from Merck, with use of an
excess pressure of 1 bar (argon). Diethyl ether and dichloromethane
were distilled before use. Light petroleum refers to petroleum ether
1
(w), 804 (w) cmϪ1. H NMR (300.1 MHz, CDCl3): δ ϭ 1.40 -1.60
(m, 1 H), 1.70Ϫ1.94 (m, 2 H), 1.96Ϫ2.20 (m, 2 H), 2.21Ϫ2.40 (m,
4 H), 3.41Ϫ3.51 (m, 1 H, CHABr), 3.54Ϫ3.62 (m, 1 H, CHBBr)
ppm. 13C NMR (75.5 MHz, CDCl3): δ ϭ 20.6 (t), 29.4 (t), 31.6 (t),
32.9 (t), 37.8 (t), 47.7 (d), 219.7 (s, CϭO) ppm. MS (GC-MS): m/
z (%) ϭ 190/192 (4/4) [Mϩ], 161/163 (2/2) [Mϩ Ϫ C2H5], 84 (100)
[Mϩ Ϫ C2H3Br], 67 (6), 55 (50), 41 (21), 39 (10). C7H11BrO
(191.07): calcd. C 44.00, H 5.80; found C 44.24, H 5.83.
4-Methyl-N-[2-(2-oxocyclopentyl)ethyl]pyridinium Bromide (5): 4-
Methylpyridine (9, 2.92 mL, 2.79 g, 30.0 mmol) was added to 2-(2-
boiling at 30Ϫ50 °C and was purchased as p.a. quality. All other bromoethyl)cyclopentanone (7, 3.82 g, 20.0 mmol), and the flask
chemicals were used without further purification. The electrolyses
was closed with a paraffin bubbler. The mixture was heated to 120
°C for 20 min. The viscous liquid obtained was cooled to room
were carried out in a divided beaker-type cell[51] at a mercury pool
cathode (18 cm2). A round platinum grid (5 cm2) served as anode temperature, and diethyl ether was added (80 mL). The mixture
and was placed in a glass tube (i.d. 3 cm), that was sealed at one
end with a glass frit (D4) to separate the cell compartments. This
anodic chamber was centred 1 cm above the mercury cathode so
that the distance between the parallel electrodes was 1.5 cm. Both
was stirred for 10 min and decanted. This procedure was repeated
twice. Diethyl ether (80 mL) was then added, and the flask was
stoppered and placed in a freezer at Ϫ20 °C until the pasty material
solidified. The solid was pulverised under diethyl ether (because the
Eur. J. Org. Chem. 2003, 2919Ϫ2932
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 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2925

J. Heimann, H. J. Schäfer, R. Fröhlich, B. Wibbeling
FULL PAPER
pyridinium salts are very hygroscopic) and stirred for 10 min. The
diethyl ether was decanted and the salts were dried in vacuo. The
purity and the yield of the salt were determined by 1H NMR spec-
troscopy with methyl 3-bromopropanoate as internal standard by
3.57 g (purity: 25%, based on pure salt: 2.99 mmol, 15%) 6 as a
powdery, white solid. IR (KBr): ν˜ ϭ 3048 (m), 2929 (m), 1701 (m,
CϭO), 1638 (s), 1610 (m), 1508 (m), 1440 (w), 1378 (w), 1310 (w),
1257 (w), 1200 (w), 1034 (w), 794 (m) cmϪ1. 1H NMR (400.1 MHz,
integration of the NCH2 signals of the salt and the CH2 signals CD3CN): δ ϭ 1.37 (mc, 1 H), 1.50Ϫ1.90 (m, 4 H), 1.95Ϫ2.15 (m,
3
of the standard. Yield: 5.46 g (purity: 96%, based on pure salt: 2 H), 2.18Ϫ2.58 (m, 4 H), 2.59 (s, 3 H, CH3), 4.59 (t, J ϭ 7.8 Hz,
3
3
18.4 mmol, 92%) 5 as a powdery, white solid. M.p. 115 °C. IR
2 H, NCH2), 7.83 (d, J ϭ 6.6 Hz, 2 H, NCHCH), 8.84 (d, J ϭ
(KBr): ν˜ ϭ 3047 (m), 2961 (m), 2878 (m), 1729 (s, CϭO), 1643 (s), 6.6 Hz, 2 H, NCH) ppm. 13C NMR (100.6 MHz, CD3CN): δ ϭ
1519 (m), 1475 (m), 1402 (w), 1380 (w), 1312 (w), 1275 (w), 1214 23.0 (q, CH3), 26.1 (t), 29.0 (t), 32.7 (t), 35.4 (t), 43.1 (t), 48.6 (d),
(w), 1173 (m), 1041 (w), 830 (m) cmϪ1 1H NMR (400.1 MHz, 60.5 (t, NCH2), 130.1 (d, NCHCH), 145.2 (d, NCH), 161.0 (s,
.
CD3CN): δ ϭ 1.60Ϫ1.75 (m, 1 H), 1.78Ϫ1.91 (m, 1 H), 1.95Ϫ2.10 CCH3), 213.1 (s, CϭO) ppm. MS (ESIϩ-MS): m/z (%) ϭ 218 (20)
(m, 2 H), 2.11Ϫ2.43 (m, 5 H), 2.70 (s, 3 H, CH3), 4.83 (t, 3J ϭ
[Mϩ], 94 (100) [9 ϩ Hϩ]. MS-MS (ESIϩ-MS, m/z ϭ 218): m/z
7.8 Hz, 2 H, NCH2), 7.96 (d, J ϭ 6.3 Hz, 2 H, NCHCH), 9.05 (d, (%) ϭ 218 (30) [Mϩ], 125 (100) [Mϩ Ϫ 9], 94 (25) [9 ϩ Hϩ]. MS
3J ϭ 6.3 Hz, 2 H, NCH) ppm. 13C NMR (100.6 MHz, CD3CN): (ESIϪ-MS): m/z (%) ϭ 97/99 (10/10) [BrϪ ϩ H2O], 79/81 (100/100)
δ ϭ 21.7 (t), 22.6 (q, CH3), 30.6 (t), 32.7 (t), 38.6 (t), 47.0 (d), 60.3 [BrϪ]. EMS (ESIϩ-MS): calcd. (C14H20NOϩ) 218.1545; found
(t, NCH2), 130.0 (d, NCHCH), 145.3 (d, NCH), 161.1 (s, CCH3), 218.1551.
3
220.8 (s, CϭO) ppm. MS (ESIϩ-MS): m/z (%) ϭ 204 (100) [Mϩ].
1,4-Dioxaspiro[4.5]dec-6-ylmethanol (16): 1,2-Ethanediol (38.73 g,
MS-MS (ESIϩ-MS, m/z ϭ 204): m/z (%) ϭ 204 (20) [Mϩ], 111 (100)
624 mmol) and pyridinium para-toluenesulfonate (PPTS, 7.84 g,
[Mϩ Ϫ 9], 94 (35) [9 ϩ Hϩ], 83 (75), 55 (15). MS (ESIϪ-MS): m/z
31.2 mmol) were added to a solution of 2-(hydroxymethyl)cyclo-
hexanone (24, 20.00 g, 156 mmol) in benzene (400 mL) and the
mixture was heated at reflux (1 h) in a DeanϪStark apparatus.
(%) ϭ 97/99 (10/10) [BrϪ ϩ H2O], 79/81 (100/100) [BrϪ]. EMS
(ESIϩ-MS): calcd. (C13H18NOϩ) 204.1388; found 204.1391.
Saturated sodium hydrogen carbonate solution (300 mL) was ad-
2-(2-Bromoethyl)cyclohexanone (8): The alkylation was carried out
ded and the layers were separated. The aqueous layer was extracted
under argon in dried glassware. Ethyl 2-oxocyclohexanecarboxylate
with diethyl ether (2 ϫ 200 mL) and the combined organic phases
(15, 15.00 g, 88.1 mmol) was added dropwise to a suspension of
were dried (MgSO4), filtered and concentrated. The residue was
sodium hydride (60% in mineral oil, 3.60 g, 90.0 mmol) in DMF
distilled through a Vigreux column. The fraction boiling at 63 °C/
0.06 mbar was collected to yield 16 (22.02 g, 128 mmol, 82%) as a
colourless oil. Data: see Supporting Information.
˚
(100 mL, dried with molecular sieves 4 A). The reaction mixture
was stirred at room temperature until the evolution of hydrogen
had ceased. 1,2-Dibromoethane (15.0 mL, 32.66 g, 174 mmol) was
added, and the mixture was heated at reflux for 30 min. After the
reaction mixture had been cooled to room temperature, it was
poured into water (100 mL) and extracted with diethyl ether (4 ϫ
80 mL). The combined organic phases were washed with saturated
sodium hydrogen carbonate solution (150 mL) and subsequently
with brine (2 ϫ 150 mL), dried (MgSO4), filtered and concentrated.
Hydrobromic acid (48%, 50 mL) was added to the crude product,
and the solution was heated at reflux for 30 min until the evolution
of carbon dioxide had ceased. The solution was cooled to room
temperature, poured into water (100 mL) and extracted with diethyl
ether (4 ϫ 100 mL). The combined organic phases were washed
with a saturated solution of sodium hydrogen carbonate (200 mL),
dried (MgSO4), filtered and concentrated. The residue was purified
by flash chromatography (pentane/diethyl ether, 5:1, Rf ϭ 0.33) fol-
lowed by a second purification (pentane/diethyl ether, 15:1, Rf ϭ
0.16). Yield: 3.32 g (16.2 mmol, 18%) 8 as a colourless oil. IR
(film): ν˜ ϭ 2935 (s), 2861 (m), 1710 (s, CϭO), 1448 (m), 1371 (w),
1338 (w), 1312 (w), 1262 (w), 1224 (w), 1128 (m), 1065 (w), 828
6-(Bromomethyl)-1,4-dioxaspiro[4.5]decane (13): DEAD (4.42 mL,
4.95 g, 28.4 mmol) was added dropwise at 0 °C under argon, in
dried glassware, to a solution of triphenylphosphane (7.61 g,
29.0 mmol) in dry THF (100 mL). After the mixture had been
stirred for 20 min, lithium bromide (5.04 g, 58.1 mmol) was added,
followed by alcohol 16 (2.00 g, 11.6 mmol). The orange solution
was stirred at 0 °C for another hour and at room temperature for
4 h. The solvent was removed and the residue was poured into
water (50 mL) and extracted with diethyl ether (3 ϫ 50 mL). The
combined organic phases were washed with brine (100 mL), dried
(MgSO4) and concentrated. Light petroleum (100 mL) was added
to the residue, the mixture was stirred for 30 min and filtered, and
the solvents were evaporated. The crude product was purified by
flash chromatography (light petroleum/diethyl ether, 15:1, Rf
ϭ
0.38). Yield: 1.69 g (7.19 mmol, 62%) 13 as a colourless oil. IR
(film): ν˜ ϭ 2939 (s), 2883 (m), 2862 (m), 1447 (w), 1353 (w), 1324
(w), 1278 (w), 1227 (w), 1184 (m), 1159 (s), 1139 (s), 1087 (s), 1061
1
(m), 1040 (w), 1015 (m), 948 (w), 926 (s), 872 (m) cmϪ1. H NMR
1
(w), 715 (w) cmϪ1. H NMR (300.1 MHz, CDCl3): δ ϭ 1.37 (mc,
(300.1 MHz, CDCl3): δ ϭ 1.20Ϫ1.80 (m, 7 H), 1.94Ϫ2.05 (m, 1
H), 2.10Ϫ2.20 (m, 1 H), 3.15 (dd, 3J ϭ 10.5, 2J ϭ 9.8 Hz, 1 H,
CHAOH), 3.72 (dd, 2J ϭ 9.8, 3J ϭ 3.1 Hz, 1 H, CHBOH),
3.85Ϫ4.02 (m, 4 H) ppm. 13C NMR (75.5 MHz, CDCl3): δ ϭ 23.7
(t), 24.2 (t), 28.3 (t), 33.8 (t), 34.5 (t), 47.4 (d), 64.7 (2 t), 110.2 (s)
ppm. MS (GC-MS*): m/z (%) ϭ 234/236 (2/2) [Mϩ], 154 (100) [Mϩ
Ϫ HBr], 113 (15), 99 (20), 93 (5), 67 (6), 55 (30), 41 (16), 39 (20).
C9H15BrO2 (235.12): calcd. C 45.98, H 6.43; found C 46.11, H 6.68.
1 H), 1.54Ϫ1.95 (m, 4 H), 2.02Ϫ2.19 (m, 2 H), 2.27Ϫ2.44 (m, 3
H), 2.57 (mc, 1 H), 3.48 (t, 3J ϭ 6.7 Hz, 2 H, CH2Br) ppm. 13C
NMR (75.5 MHz, CDCl3): δ ϭ 25.1 (t), 27.9 (t), 32.1 (t), 32.6 (t),
33.9 (t), 42.1 (t), 48.6 (d), 211.8 (s, CϭO) ppm. MS (GC-MS):
m/z (%) ϭ 204/206 (3/3) [Mϩ], 161/163 (3/3) [Mϩ Ϫ C3H7], 98 (100)
[Mϩ Ϫ C2H3Br], 81 (6), 70 (6), 55 (30), 41 (10). C8H13BrO (205.10):
calcd. C 46.85, H 6.39; found C 48.11, H 6.75. The compound is
rather unstable, so that the exact mass had to be obtained: EMS
(GC-MS): calcd. 204.0150/206.0129; found 204.0167/206.0149.
1,4-Dioxaspiro[4.5]dec-6-ylmethyl Trifluoromethanesulfonate (28):
The reaction was carried out under argon in dried glassware. A
solution of alcohol 16 (1.00 g, 5.81 mmol) and dry pyridine
(0.52 mL, 510 mg, 6.44 mmol) in dry dichloromethane (5 mL) was
added dropwise at 0 °C over 30 min to a solution of trifluorome-
thanesulfonic anhydride (1.00 mL, 1.72 g, 6.10 mmol) in dry di-
chloromethane (20 mL). The reaction mixture was stirred at 0 °C
for a further 30 min and then poured into a mixture of ice and
4-Methyl-N-[2-(2-oxocyclohexyl)ethyl]pyridinium Bromide (6): 4-
Methylpyridine (9, 2.92 mL, 2.79 g, 30.0 mmol) was added to 2-(2-
bromoethyl)cyclohexanone (8, 4.10 g, 20.0 mmol) and the flask was
closed with a paraffin bubbler. The mixture was heated to 120 °C
for 15 min. The reaction mixture (two phases) was cooled to room
temperature and treated as described for the synthesis of 5. Yield:
2926
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Eur. J. Org. Chem. 2003, 2919Ϫ2932

Electrochemical Formation of Tricyclic Indolizidine and Quinolizidine Derivatives
FULL PAPER
saturated sodium hydrogen carbonate solution (50 mL). The layers
were separated and the aqueous layer was extracted with dichloro-
methane (2 ϫ 50 mL). The combined organic phases were dried
(MgSO4), filtered and concentrated. The resulting suspension was
filtered through a short column with silica gel (diethyl ether), then
further purified by flash chromatography (light petroleum/diethyl
ether, 1:1, Rf ϭ 0.56). Yield: 511 mg (1.68 mmol, 29%) 28 as a
N-(1,4-Dioxaspiro[4.4]non-6-ylmethyl)-4-methylpyridinium Trifluoro-
methanesulfonate (29): The reaction was carried out as described
above for the salt 30. Thus, a solution of alcohol 16 (3.16 g,
20.0 mmol) and 4-methylpyridine (9, 1.96 mL, 1.87 g, 20.1 mmol)
in dry diethyl ether (10 mL) was added dropwise at 0 °C over
30 min to
a solution of trifluoromethanesulfonic anhydride
(3.10 mL, 5.33 g, 18.9 mmol) in dry diethyl ether (50 mL). The re-
colourless oil, which decomposed rapidly at room temperature. IR sulting suspension was stirred at 0 °C for a further 30 min, and was
(film): ν˜ ϭ 2943 (s), 2887 (m), 2867 (m), 1449 (m), 1413 (s), 1356 then filtered (glass frit D4). 4-Methylpyridine (9, 2.92 mL, 2.79 g,
(w), 1339 (w), 1246 (s), 1206 (s), 1147 (s), 1098 (s), 1058 (m), 1017
(m), 987 (w), 940 (s), 867 (w), 821 (w), 762 (w) cmϪ1 1H NMR removed. The subsequent procedure was identical to that used for
(300.1 MHz, CDCl3): δ ϭ 1.20Ϫ1.85 (m, 7 H), 1.90Ϫ2.00 (m, 1 30. Yield: 6.67 g of a mixture of 29 and 31, which slowly crystallised
30.0 mmol) was added to the filtrate, and the diethyl ether was
.
2
H), 2.10Ϫ2.25 (m, 1 H), 3.85Ϫ4.08 (m, 4 H), 4.37 (dd, J ϭ 9.5,
to provide a slightly yellow solid. The purity was determined by
3J ϭ 9.5 Hz, 1 H, CHAOS), 4.75 (dd, J ϭ 9.5, J ϭ 4.3 Hz, 1 H, NMR in D2SO4/D2O/CD3CN to cleave all acetal 29 in the mixture
2
3
CHBOS) ppm. 13C NMR (75.5 MHz, CDCl3): δ ϭ 23.3 (t), 24.0 to the ketone 31: 77% 31, based on pure salt 31: 15.1 mmol, 80%.
(t), 26.8 (t), 34.2 (t), 44.1 (d), 64.4 (2 t), 77.3 (t), 108.8 (s), 118.7
IR (KBr): ν˜ ϭ 3062 (m), 2966 (m), 2892 (w), 1737 (m, CϭO), 1644
1
(q, JC,F ϭ 320 Hz, CF3) ppm. MS (GC-MS): m/z (%) ϭ 304 (4) (s), 1575 (w), 1520 (m), 1476 (m), 1263 (s), 1225 (s), 1158 (s), 1031
[Mϩ], 261 (68) [Mϩ Ϫ C3H7], 217 (8), 171 (16) [Mϩ Ϫ SO2CF3], (s), 949 (m), 906 (w), 830 (m), 756 (m), 709 (w), 639 (s) cmϪ1. H
1
155 (100) [Mϩ Ϫ SO3CF3], 125 (6), 113 (12), 99 (54), 86 (6), 55
NMR (400.1 MHz, CD3CN): δ ϭ 1.60 (mc, 1 H), 1.76 (mc, 1 H),
(14), 41 (8). EMS (GC-MS): calcd. (C10H15F3O5S) 304.0592; 1.92Ϫ1.98 (m, 1 H), 2.08Ϫ2.20 (m, 2 H), 2.25Ϫ2.34 (m, 1 H), 2.56
found 304.0604.
(s, 3 H, CH3), 2.81 (mc, 1 H, NCH2CH), 4.50 (dd, 2J ϭ 13.8, 3J ϭ
7.1 Hz, 1 H, NCHA), 4.66 (dd, 2J ϭ 13.8, 3J ϭ 6.7 Hz, 1 H,
NCHB), 7.79 (d, 3J ϭ 6.7 Hz, 2 H, NCHCH), 8.53 (d, 3J ϭ 6.7 Hz,
2 H, NCH) ppm. 13C NMR (100.6 MHz, CD3CN): δ ϭ 20.2 (t),
21.7 (q, CH3), 27.3 (t), 38.0 (t), 49.9 (d), 60.1 (t, NCH2), 120.7 (q,
1JC,F ϭ 319 Hz, CF3), 129.1 (d, NCHCH), 144.1 (d, NCH), 161.0
(s, CCH3), 219.7 (s, CϭO) ppm. MS (ESIϩ-MS): m/z (%) ϭ 234
(100) [Mϩ], 190 (10) [Mϩ 31], 122 (20), 94 (10) [9 ϩ Hϩ]. MS-MS
N-(1,4-Dioxaspiro[4.5]dec-6-ylmethyl)-4-methylpyridinium Trifluoro-
methanesulfonate (30): The reaction was carried out under argon in
dried glassware. A solution of alcohol 16 (3.00 g, 17.4 mmol) and 4-
methylpyridine (9, 1.70 mL, 1.63 g, 17.5 mmol) in dry diethyl ether
(10 mL) was added dropwise at 0 °C over 30 min to a solution of
trifluoromethanesulfonic anhydride (2.71 mL, 4.66 g, 16.5 mmol)
in dry diethyl ether (50 mL). The resulting suspension was stirred
for a further 30 min at 0 °C and then filtered (glass frit D4). 4-
Methylpyridine (9, 2.55 mL, 2.44 g, 26.2 mmol) was added to the
filtrate, and the diethyl ether was removed. The residue was heated
to 120 °C (flask closed with paraffin bubbler) for 20 min. The reac-
tion mixture was cooled to room temperature, and diethyl ether
(50 mL) was added. The mixture was stirred for 10 min and de-
canted. This procedure was repeated twice more. The residue was
dissolved in water (100 mL) and repeatedly extracted with diethyl
ether (100 mL) until the aqueous phase was only slightly yellow.
The aqueous phase was concentrated and the residue was dried
over P2O5 in vacuo. The viscous oil crystallised slowly on scratch-
ing, to provide a slightly yellow solid. Yield: 6.29 g (mixture of 30
and 32). The purity was determined by NMR in D2SO4/D2O/
CD3CN to cleave all acetal 30 in the mixture to the ketone 32: 83%
32, based on pure salt 32: 14.8 mmol, 90%. IR (KBr): ν˜ ϭ 3062
(w), 2959 (m), 2902 (w), 2870 (w), 1645 (s), 1523 (m), 1481 (m),
1268 (s), 1224 (s), 1161 (s), 1093 (m), 1052 (m), 1032 (s), 1013 (m),
(ESIϩ-MS, m/z ϭ 234): m/z (%) ϭ 234 (20) [Mϩ], 141 (70) [Mϩ
Ϫ
9], 99 (100), 69 (10). MS-MS (ESIϩ-MS, m/z ϭ 190): m/z (%) ϭ
190 (35) [Mϩ], 94 (100) [9 ϩ Hϩ], 69 (95), 55 (13), 41 (10). MS
(ESIϪ-MS): m/z (%) ϭ 149 (100) [CF3SO3Ϫ]. EMS (ESIϩ-MS):
calcd. (C14H20NO2ϩ) 234.1494; found 234.1485.
rac-(1S,2S)-1-Acetyl-2-(bromomethyl)cyclohexane (35): The reac-
tion was carried out under argon in dried glassware. Trimethylsilyl
chloride (9.14 mL, 7.86 g, 72.3 mmol) was added dropwise over a
period of 5 min to a suspension of 1-acetylbicyclo[4.1.0]heptane
(36, 5.00 g, 36.2 mmol) and sodium bromide (7.44 g, 72.3 mmol) in
˚
acetonitrile (100 mL, dried with molecular sieves 3 A). After stir-
ring at room temperature for 3 d, the mixture was poured into
sodium sulfite solution (5%, saturated with potassium fluoride,
200 mL). The layers were separated and the aqueous layer was ex-
tracted with diethyl ether (3 ϫ 100 mL). The combined organic
phases were washed with brine (200 mL), dried (MgSO4), filtered
and concentrated. The crude product was purified by flash chroma-
tography (light petroleum/diethyl ether, 20:1, Rf ϭ 0.19). Yield:
3.06 g (14.0 mmol, 39%) 35 as a colourless oil. IR (film): ν˜ ϭ 2933
(s), 2857 (s), 1710 (s, CϭO), 1448 (m), 1352 (m), 1300 (m), 1246
951 (m), 929 (m), 873 (w), 832 (m), 755 (w), 712 (w), 638 (m) cmϪ1
.
1H NMR (400.1 MHz, CD3CN): δ ϭ 1.35Ϫ1.70 (m, 3 H),
1.75Ϫ1.85 (m, 1 H), 1.95Ϫ2.05 (m, 2 H), 2.22 (mc, 1 H), 2.33 (mc,
1 H), 2.53 (s, 3 H, CH3), 3.12 (mc, 1 H, NCH2CH), 4.32 (dd, 2J ϭ
(m), 1219 (w), 1184 (w), 1159 (m), 954 (w) cmϪ1 1H NMR
.
(300.1 MHz, CDCl3): δ ϭ 1.18Ϫ1.42 (m, 4 H), 1.72Ϫ2.03 (m, 3
3
2
3
H), 2.19 (s, 3 H, CH3), 2.55 (ddd, 3J ϭ 10.5, 3J ϭ 10.5, 3J ϭ
13.8, J ϭ 5.1 Hz, 1 H, NCHA), 4.70 (dd, J ϭ 13.8, J ϭ 7.6 Hz,
3
3
2
3
1 H, NCHB), 7.75 (d, J ϭ 6.5 Hz, 2 H, NCHCH), 8.55 (d, J ϭ
6.5 Hz, 2 H, NCH) ppm. 13C NMR (100.6 MHz, CD3CN): δ ϭ
21.3 (q, CH3), 24.2 (t), 27.5 (t), 31.5 (t), 41.6 (t), 50.6 (d), 59.9 (t,
NCH2), 120.3 (q, 1JC,F ϭ 319 Hz, CF3), 128.6 (d, NCHCH), 144.1
(d, NCH), 160.3 (s, CCH3), 213.3 (s, CϭO) ppm. MS (ESIϩ-MS):
m/z (%) ϭ 248 (100) [Mϩ], 204 (28) [Mϩ 32], 122 (15), 105 (10), 94
(14) [9 ϩ Hϩ]. MS-MS (ESIϩ-MS, m/z ϭ 248): m/z (%) ϭ 248 (35)
[Mϩ], 155 (100) [Mϩ Ϫ 9], 111 (12), 99 (10), 95 (10), 94 (12) [9 ϩ
Hϩ], 93 (20), 83 (30), 73 (15), 55 (20). MS-MS (ESIϩ-MS, m/z ϭ
204): m/z (%) ϭ 204 (35) [Mϩ], 111 (10), 94 (90) [9 ϩ Hϩ], 83 (45),
3.70 Hz, 1 H, CHCOCH3), 3.34 (dd, J ϭ 10.3, J ϭ 2.6 Hz, 1 H,
CHABr), 3.43 (dd, J ϭ 10.3, J ϭ 5.0 Hz, 1 H, CHBBr) ppm. 13C
NMR (75.5 MHz, CDCl3): δ ϭ 25.2 (t), 25.6 (t), 29.4 (t), 29.5 (q,
CH3), 29.7 (t), 38.9 (d, C-2), 39.5 (t, CH2Br), 53.9 (d, C-1), 211.5
(s, CϭO) ppm. MS (GC-MS): m/z (%) ϭ 218/220 (4/6) [Mϩ], 163/
165 (4/11), 139 (100) [Mϩ Ϫ Br], 97 (20), 95 (40), 81 (24), 67 (16),
57 (10), 44 (15), 43 (16), 40 (36). C9H15BrO (219.12): calcd. C 49.33,
H 6.90; found C 49.66, H 6.90.
2
3
rac-N-{[(1S,2S)-2-Acetylcyclohexyl]methyl}-4-methylpyridinium
69 (15), 55 (100). MS (ESIϪ-MS): m/z (%) ϭ 149 (100) [CF3SO3Ϫ]. Bromide (34): 4-Methylpyridine (9, 1.46 mL, 1.40 g, 15.0 mmol)
EMS (ESIϩ-MS): calcd. (C15H22NO2ϩ) 248.1651; found 248.1677.
was added to 1-acetyl-2-(bromomethyl)cyclohexane (35, 2.19 g,
2927
Eur. J. Org. Chem. 2003, 2919Ϫ2932
www.eurjoc.org
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

J. Heimann, H. J. Schäfer, R. Fröhlich, B. Wibbeling
FULL PAPER
10.0 mmol), and the flask was closed with a paraffin bubbler. The
mixture was heated to 120 °C for 20 min. The reaction mixture was
cooled to room temperature and treated as described for the syn-
thesis of the salt 5. Yield: 2.55 g (purity: 65%, based on pure salt:
5.30 mmol, 53%) 34 as a powdery, white solid. IR (KBr): ν˜ ϭ 3048
(m), 2932 (s), 2858 (m), 1698 (s, CϭO), 1640 (s), 1518 (m), 1475
(m), 1449 (m), 1360 (m), 1307 (w), 1249 (m), 1203 (w), 1175 (m),
HA), 2.24Ϫ2.36 (m, 2 H, 3-HB, 4-HA), 2.48 (s, 1 H, 10b-H), 2.70
2
3
3
(ddd, J ϭ 11.5, J ϭ 4.1, J ϭ 2.6 Hz, 1 H, 6-HB), 2.79Ϫ2.83 (m,
1 H, 4-HB), 5.50 (s, 1 H, 1-H) ppm. 13C NMR (150.6 MHz,
CDCl3): δ ϭ 20.5 (t, C-9), 22.9 (q, CH3), 29.4 (t, C-8), 29.8 (t, C-
7), 30.55 (t, C-3/C-10), 30.58 (t, C-3/C-10), 47.6 (d, C-7a), 52.4 (t,
C-4), 55.1 (t, C-6), 67.6 (d, C-10b), 82.9 (s, C-10a), 119.6 (d, C-1),
133.0 (s, C-2) ppm. MS (GC-MS*): m/z (%) ϭ 206 (12) [Mϩ Ϫ H],
1041 (w), 828 (m), 804 (m) cmϪ1. 1H NMR (400.1 MHz, CD3CN): 192 (6), 122 (16) [Mϩ Ϫ C5H9O], 110 (18) [Mϩ Ϫ C6H9O], 96 (100)
δ ϭ 1.05Ϫ1.20 (m, 3 H), 1.25Ϫ1.35 (m, 1 H), 1.40Ϫ1.50 (m, 1 H), [Mϩ Ϫ C7H11O], 94 (18), 81 (10), 80 (10), 67 (8), 55 (10), 41 (20),
1.65Ϫ1.80 (m, 2 H), 2.05Ϫ2.13 (m, 1 H), 2.15 (s, 3 H, COCH3), 39 (20). Because of the low quantity of slightly impure material
3
3
3
2.16Ϫ2.25 (m, 1 H), 2.54 (ddd, J ϭ 11.6, J ϭ 10.7, J ϭ 3.8 Hz, obtained, the exact mass was determined instead of an elemental
2
3
1 H, CHCOCH3), 2.61 (s, 3 H, pyCH3), 4.20 (dd, J ϭ 13.3, J ϭ
analysis. EMS (GC-MS): calcd. (C13H21NO) 207.1623; found
8.9 Hz, 1 H, NCHA), 4.44 (dd, 2J ϭ 13.3, 3J ϭ 4.6 Hz, 1 H, 207.1635.
NCHB), 7.82 (d, 3J ϭ 6.7 Hz, 2 H, NCHCH), 8.61 (d, 3J ϭ 6.7 Hz,
rac-(7aR,10aS,10bS)-2-Methyl-3,4,6,7,7a,8,9,10,10a,10b-deca-
2 H, NCH) ppm. 13C NMR (100.6 MHz, CD3CN): δ ϭ 22.6 (q,
pyCH3), 25.8 (t), 26.5 (t), 29.2 (q, COCH3), 29.7 (t), 30.8 (t), 40.6
(d, CHCH2N), 54.6 (d, CHCOCH3), 65.7 (t, NCH2), 130.1 (d,
NCHCH), 145.3 (d, NCH), 162.1 (s, CCH3), 212.5 (s, CϭO) ppm.
MS (ESIϩ-MS): m/z (%) ϭ 232 (100) [Mϩ], 94 (10) [9 ϩ Hϩ]. MS-
MS (ESIϩ-MS, m/z ϭ 232): m/z (%) ϭ 232 (25) [Mϩ], 139 (100)
[Mϩ Ϫ 9], 121 (12), 94 (30) [9 ϩ Hϩ], 81 (22), 57 (10), 43 (14). MS
(ESIϪ-MS): m/z (%) ϭ 97/99 (20/20) [BrϪ ϩ H2O], 79/81 (100/100)
[BrϪ]. EMS (ESIϩ-MS): calcd. (C15H22NOϩ) 232.1701; found
232.1734.
hydrocyclopenta[a]quinolizin-10a-ol (1a): M.p. 103 °C. IR (KBr):
ν˜ ϭ 3552 (s), 3416 (s), 3345 (s), 2961 (s), 2927 (s), 2903 (s), 2878
(s), 2815 (s, NCϪH), 2767 (s, NCϪH), 1638 (w), 1618 (m), 1445
(m), 1398 (w), 1379 (m), 1365 (m), 1333 (s), 1315 (s), 1288 (s), 1215
(m), 1202 (m), 1128 (s), 1065 (s), 1037 (m), 1007 (m), 966 (m), 906
1
(m), 875 (s) cmϪ1. H NMR (300.1 MHz, CDCl3): δ ϭ 1.44Ϫ2.10
(m, 10 H), 1.72 (s, 3 H, CH3), 2.25Ϫ2.40 (m, 3 H), 2.55Ϫ2.67 (m,
2 H), 2.75Ϫ2.85 (m, 1 H), 5.39 (s, 1 H, 1-H) ppm. 13C NMR
(75.5 MHz, CDCl3): δ ϭ 19.5 (t), 23.2 (q, CH3), 23.6 (t), 26.1 (t),
30.4 (t), 33.5 (t), 43.8 (d, C-7a), 51.3 (t), 52.5 (t), 63.2 (d, C-10b),
78.5 (s, C-10a), 118.5 (d, C-1), 135.8 (s, C-2) ppm. MS (GC-MS*):
m/z (%) ϭ 207 (12) [Mϩ], 206 (16) [Mϩ Ϫ H], 192 (7), 164 (3), 122
Electrolyses
(21) [Mϩ Ϫ C5H9O], 110 (33) [Mϩ Ϫ C6H9O], 96 (100) [Mϩ
Ϫ
General Procedure: The pyridinium salt was dissolved in 1  aque-
ous sulfuric acid and the solution was placed in the cathode com-
partment. The anode compartment was charged with 1  aqueous
sulfuric acid such that the levels of the liquids were equal. The
electrolysis was carried out under constant current conditions
(0.072 A, 4 mA/cm2) at 20 °C. Typically, the cell voltage increased
from 3.4 to 4.1 V during electrolysis. At the anode, the constant
evolution of oxygen was clearly visible, at the cathode the evolution
of hydrogen increased towards the end of the electrolysis. The
catholyte was removed from the cell, made alkaline (pH Ն 10) and
extracted with dichloromethane (3 ϫ 60 mL) and diethyl ether (3
ϫ 60 mL). The combined organic phases were dried (MgSO4) and
concentrated by rotary evaporation. To determine the isomeric ra-
tios, a sample of the crude product was passed through a short pad
of silica gel with diethyl ether/triethylamine (10:1) and analysed by
gas chromatography.
C7H11O], 94 (31), 80 (13), 67 (10), 55 (13), 41 (24), 39 (24).
C13H21NO (207.32): calcd. C 75.32, H 10.21, N 6.76; found C
75.19, H 10.19, N 6.74.
Electrolysis of 4-Methyl-1-[2-(2-oxocyclohexyl)ethyl]pyridinium Bro-
mide (6): The pyridinium salt 6 (3.57 g, 2.99 mmol based on pure
salt) was dissolved in aqueous sulfuric acid (1 , 30 mL) and elec-
trolysed according to the General Procedure until 2975 C (2.6-fold
excess) had been transferred. The crude product was analysed by
GC: 2a/2b/2c ϭ 1.0:2.1:2.6 and subjected to flash chromatography
(diethyl ether/triethylamine, 10:1) to give a mixture (544 mg,
2.46 mmol, 82%) of the three isomers. The diastereomers were
separated by flash chromatography (light petroleum/triethylamine,
10:1): 2c (Rf ϭ 0.72, slowly crystallising white solid), 2a (Rf ϭ 0.50,
white crystalline solid) and 2b (Rf ϭ 0.41, white crystalline solid).
rac-(7aS,11aS,11bS)-2-Methyl-3,4,6,7,7a,8,9,10,11a,11b-decahydro-
[11H]-cyclohexa[a]quinolizin-11a-ol (2c):[41] M.p. 69 °C. IR (KBr):
ν˜ ϭ 3422 (s), 3038 (w), 2924 (s), 2851 (s), 2809 (s, NCϪH), 2758
(m, NCϪH), 1681 (w), 1638 (m), 1618 (m), 1457 (m), 1382 (m),
1350 (m), 1310 (m), 1276 (s), 1254 (m), 1208 (s), 1149 (m), 1132
(m), 1105 (s), 1079 (m), 1039 (m), 1008 (m), 986 (m), 968 (m), 883
(s), 849 (m), 805 (w), 773 (w), 755 (w) cmϪ1. 1H NMR (599.0 MHz,
CDCl3): δ ϭ 1.08 (ddd, 2J ϭ 13.2, 3Jaa ϭ 13.2, Jae ϭ 4.6 Hz, 1 Ha,
11-H), 1.14Ϫ1.28 (m, 3 H, 7a-H, 8-He, 9-HA), 1.31 (mc, 1 H, 7-
He), 1.39 (dddd, 2J ϭ 12.9, 3Jaa ϭ 12.9, 3Jaa ϭ 12.9, 3Jae ϭ 3.7 Hz,
Electrolysis of 4-Methyl-N-[2-(2-oxocyclopentyl)ethyl]pyridinium
Bromide (5): The pyridinium salt 5 (1.71 g, 5.76 mmol based on
pure salt) was dissolved in aqueous sulfuric acid (1 , 30 mL) and
electrolysed according to the General Procedure until 5789 C (2.6-
fold excess) had been transferred. The crude product was analysed
by GC: 1a/1b ϭ 13.0:1.0 and subjected to flash chromatography
(diethyl ether/triethylamine, 10:1) to give two fractions of isomeric
products 1b (Rf ϭ 0.80, 49 mg, slowly crystallising solid) and 1a
(Rf ϭ 0.54, 827 mg, white crystalline solid). Combined yield:
876 mg (4.23 mmol, 73%).
2
3
3
3
1 H, 8-Ha), 1.52 (dddd, J ϭ 13.2, Jaa ϭ 13.2, Jaa ϭ 13.2, Jae
ϭ
rac-(7aS,10aR,10bS)-2-Methyl-3,4,6,7,7a,8,9,10,10a,10b-deca-
hydrocyclopenta[a]quinolizin-10a-ol (1b): IR (KBr): ν˜ ϭ 3419 (s),
2930 (s), 2889 (s), 2809 (m, NCϪH), 2745 (m, NCϪH), 1638 (s),
4.7 Hz, 1 H, 7-Ha), 1.55Ϫ1.66 (m, 3 H, 9-HB, 10-H), 1.67 (s, 3 H,
CH3), 1.71 (mc, 1 H, 3-HA), 1.87 (mc, 1 H, 11-He), 2.22 (ddd, 3Jaa ϭ
2
3
13.2, J ϭ 11.2, Jae ϭ 3.1 Hz, 1 H, 6-Ha), 2.20Ϫ2.90 (m, 1 H, 3-
1466 (s), 1444 (s), 1390 (m), 1346 (m), 1326 (s), 1282 (m), 1223 (w), HB), 2.31 (mc, 1 H, 11b-H), 2.38 (ddd, 2J ϭ 11.1, Jaa ϭ 11.1,
3
1188 (w), 1153 (m), 1139 (m), 1105 (s), 1071 (w), 1040 (m), 978
3Jae ϭ 3.90 Hz, 1 H, 4-Ha), 2.72 (ddd, 2J ϭ 11.1, 3Jee ϭ 5.8, 3Jea ϭ
(m), 963 (m), 911 (m), 881 (w), 860 (w) cmϪ1
.
1H NMR 1.0 Hz, 1 H, 4-He), 2.74 (ddd, J ϭ 11.2, 3Jea ϭ 4.7, 3Jee ϭ 2.1 Hz,
2
(599.0 MHz, CDCl3): δ ϭ 1.30Ϫ1.40 (m, 3 H, 7-HA, 8-HA, 10-HA), 1 H, 6-He), 2.80 (s, 1 H, OH), 5.38 (s, 1 H, 1-H) ppm. 13C NMR
1.53 (mc, 1 H, 7-HB), 1.60Ϫ1.64 (m, 1 H, 7a-H), 1.65 (s, 3 H, CH3), (150.6 MHz, CDCl3): δ ϭ 21.7 (t, C-10), 23.5 (q, CH3), 25.9 (t, C-
1.68Ϫ1.80 (m, 3 H, 3-HA, 9-H), 1.86 (mc, 1 H, 10-HB), 2.05 (mc, 1 9), 28.5 (t, C-8), 28.7 (t, C-7), 30.4 (t, C-3), 33.2 (t, C-11), 43.6 (d,
H, 8-HB), 2.13 (ddd, 3J ϭ 12.7, 2J ϭ 11.5, 3J ϭ 2.6 Hz, 1 H, 6-
C-7a), 52.1 (t, C-4), 55.8 (t, C-6), 69.3 (d, C-11b), 69.8 (s, C-11a),
2928
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Eur. J. Org. Chem. 2003, 2919Ϫ2932

Electrochemical Formation of Tricyclic Indolizidine and Quinolizidine Derivatives
FULL PAPER
117.8 (d, C-1), 153.3 (s, C-2) ppm. MS (GC-MS*): m/z (%) ϭ 221 H), 5.49 (s, 1 H, 1-H) ppm. 13C NMR (75.5 MHz, CDCl3): δ ϭ
(6) [Mϩ], 220 (11) [Mϩ Ϫ H], 206 (3), 122 (15) [Mϩ Ϫ C6H11O], 23.1 (q, CH3), 26.5 (t), 30.2 (t), 34.0 (t), 37.0 (t), 48.4 (t, C-4), 51.2
110 (23) [Mϩ Ϫ C7H11O], 96 (100) [Mϩ Ϫ C8H13O], 94 (23), 81 (d, C-6a), 58.4 (t, C-6), 71.5 (d, C-9b), 90.5 (s, C-9a), 119.3 (d, C-
(11), 67 (8), 55 (12), 41 (20), 39 (18). C14H23NO (221.34): calcd. C 1), 134.3 (s, C-2) ppm. MS (GC-MS*): m/z (%) ϭ 194 (9) [Mϩ
ϩ
75.97, H 10.47, N 6.33; found C 75.73, H 10.64, N 6.34.
H], 192 (10) [Mϩ Ϫ H], 178 (5), 109 (100) [Mϩ Ϫ C5H8O], 96 (20)
[Mϩ Ϫ C6H9O], 94 (19), 81 (21), 67 (6), 55 (6), 41 (18), 39 (20).
C12H19NO (193.29): calcd. C 74.57, H 9.91, N 7.25; found C 74.38,
H 10.04, N 7.24.
rac-(7aR,11aS,11bS)-2-Methyl-3,4,6,7,7a,8,9,10,11a,11b-deca-
hydro[11H]-cyclohexa[a]quinolizin-11a-ol (2a):[41] M.p. 90 °C. IR
(KBr): ν˜ ϭ 3412 (s), 3036 (w), 2956 (s), 2928 (s), 2908 (s), 2859 (s),
2816 (s, NCϪH), 2772 (m, NCϪH), 1638 (w), 1618 (w), 1465 (m),
rac-(6aR,9aS,9bS)-2-Methyl-3,4,6,6a,7,8,9a,9b-octahydro-9H-
1447 (m), 1398 (w), 1380 (w), 1349 (m), 1317 (s), 1288 (m), 1268 cyclopenta[a]indolizin-9a-ol (3a): M.p. 85 °C. IR (KBr): ν˜ ϭ 3470
(m), 1229 (w), 1198 (m), 1171 (w), 1130 (s), 1112 (m), 1047 (s), (m), 3407 (m), 3356 (s), 3232 (s), 3042 (w), 2937 (s), 2921 (s), 2905
1011 (m), 952 (w), 923 (w), 880 (m), 859 (m), 809 (w), 762 (w) (s), 2886 (s), 2869 (s), 2852 (s), 2794 (m, NCϪH), 2776 (s, NCϪH),
cmϪ1
.
1H NMR (300.1 MHz, CDCl3): δ ϭ 1.20 Ϫ1.50 (m, 5 H), 2724 (m, NCϪH), 1638 (w), 1618 (w), 1467 (m), 1445 (m), 1395
1.55Ϫ1.82 (m, 5 H), 1.71 (s, 3 H, CH3), 2.02Ϫ2.08 (m, 1 H),
(m), 1372 (m), 1329 (m), 1311 (s), 1290 (s), 1262 (m), 1244 (m),
2.23Ϫ2.40 (m, 2 H), 2.41Ϫ2.52 (m, 2 H), 2.60 (mc, 1 H), 2.78 (mc, 1217 (m), 1196 (m), 1174 (m), 1149 (s), 1128 (m), 1079 (s), 1064
1
1 H), 3.05 (s, 1 H, 11b-H), 3.63 (s, 1 H, OH), 5.39 (s, 1 H, 1-H) (s), 1044 (m), 911 (m), 875 (s), 836 (m), 694 (m) cmϪ1. H NMR
ppm. 13C NMR (75.5 MHz, CDCl3): δ ϭ 22.7 (t, C-10), 23.5 (q, (300.1 MHz, CDCl3): δ ϭ 1.30Ϫ1.40 (m, 1 H), 1.50Ϫ1.70 (m, 2
CH3), 26.3, 27.4, 28.4 (3 t, C-7, C-8, C-9), 30.4 (t, C-3), 34.2 (t, C-
H), 1.72 (s, 3 H, CH3), 1.73Ϫ2.00 (m, 5 H), 2.25Ϫ2.42 (m, 4 H, 4-
11), 42.7 (d, C-7a), 51.5, 52.3 (2 t, C-4, C-6), 60.4 (d, C-11b), 71.2 H, 6-HA, 6a-H), 2.75 (s, 1 H, OH), 3.00Ϫ3.10 (m, 1 H, 9b-H), 3.26
(s, C-11a), 117.7 (d, C-1), 135.8 (s, C-2) ppm. MS (GC-MS*): m/z
(dd, 3J ϭ 8.6, 2J ϭ 8.6 Hz, 1 H, 6-HB), 5.49 (s, 1 H, 1-H) ppm.
13C NMR (75.5 MHz, CDCl3): δ ϭ 23.0 (q, CH3), 25.5 (t), 30.1
(%) ϭ 221 (6) [Mϩ], 220 (11) [Mϩ Ϫ H], 206 (3), 122 (16) [Mϩ
Ϫ
C6H11O], 110 (23) [Mϩ Ϫ C7H11O], 96 (100) [Mϩ Ϫ C8H13O], 94 (t), 30.9 (t), 36.2 (t), 48.5 (t, C-4), 51.6 (d, C-6a), 59.6 (t, C-6), 70.1
(25), 81 (11), 67 (10), 55 (13), 41 (20), 39 (21). C14H23NO (221.34): (d, C-9b), 89.8 (s, C-9a), 118.1 (d, C-1), 135.9 (s, C-2) ppm. MS
calcd. C 75.97, H 10.47, N 6.33; found C 76.02, H 10.57, N 6.45.
(GC-MS*): m/z (%) ϭ 192 (6) [Mϩ Ϫ H], 178 (4), 150 (3), 109
(100) [Mϩ Ϫ C5H8O], 96 (30) [Mϩ Ϫ C6H9O], 94 (25), 81 (31), 67
(10), 55 (10), 41 (24), 39 (25). C12H19NO (193.29): calcd. C 74.57,
H 9.91, N 7.25; found C 74.50, H 9.98, N 7.59.
rac-(7aS,11aR,11bS)-2-Methyl-3,4,6,7,7a,8,9,10,11a,11b-deca-
hydro[11H]-cyclohexa[a]quinolizin-11a-ol (2b):[41] M.p. 146 °C. IR
(KBr): ν˜ ϭ 3413 (s), 3029 (w), 2932 (s), 2914 (s), 2858 (s), 2814 (s,
NCϪH), 2742 (w, NϪCH), 1638 (m), 1618 (m), 1464 (m), 1439 Electrolysis of N-(1,4-Dioxaspiro[4.5]dec-6-ylmethyl)-4-methylpyrid-
(m), 1397 (w), 1350 (m), 1321 (m), 1271 (m), 1207 (s), 1186 (m), inium Trifluoromethanesulfonate (30): The pyridinium salt 30
1142 (m), 1130 (m), 1113 (s), 1085 (w), 1068 (w), 1043 (m), 1014
(m), 992 (m), 962 (w), 891 (s), 865 (w) cmϪ1. 1H NMR (300.1 MHz, sulfuric acid (1 , 30 mL) and electrolysed according to the General
CDCl3): δ ϭ 1.26Ϫ1.60 (m, 9 H), 1.69 (s, 3 H, CH3), 1.70Ϫ1.85 Procedure until 5775 C (2.6-fold excess) had been transferred. The
(m, 2 H), 1.90Ϫ2.05 (m, 2 H), 2.12Ϫ2.38 (m, 4 H), 2.75Ϫ2.90 (m, crude product was analysed by GC (4a/4b ϭ 1.7:1.0) and subjected
2 H), 5.49 (s, 1 H, 1-H) ppm. 13C NMR (75.5 MHz, CDCl3): δ ϭ
to short path flash chromatography (diethyl ether/triethylamine,
(2.41 g, 5.69 mmol based on pure salt 32) was dissolved in aqueous
20.3, 21.4, 23.0 (q, CH3), 26.8, 26.9, 27.8, 30.5 (6 t, C-3, C-7, C-8 10:1) to give a mixture (771 mg, 3.72 mmol, 65%) of the two iso-
to C-11), 42.8 (d, C-7a), 52.5, 56.1 (2 t, C-4, C-6), 71.4 (d, C-11b), mers. The diastereomers were separated over a longer column (di-
72.2 (s, C-11a), 119.1 (d, C-1), 133.4 (s, C-2) ppm. MS (GC-MS*):
m/z (%) ϭ 221 (6) [Mϩ], 220 (15) [Mϩ Ϫ H], 206 (3), 122 (21) [Mϩ
Ϫ C6H11O], 110 (28) [Mϩ Ϫ C7H11O], 96 (100) [Mϩ Ϫ C8H13O],
94 (26), 81 (10), 80 (11), 67 (8), 55 (12), 41 (21), 39 (20). C14H23NO
(221.34): calcd. C 75.97, H 10.47, N 6.33; found C 75.69, H 10.74,
N 6.55.
ethyl ether/triethylamine, 10:1): 4a (Rf ϭ 0.30, white crystalline
solid), 4b (Rf ϭ 0.13, white amorphous solid).
rac-(6aR,10aS,10bS)-2-Methyl-3,4,6,6a,7,8,9,10,10a,10b-deca-
hydrocyclohexa[a]indolizin-10a-ol (4a):[42] M.p. 119 °C. IR (KBr):
ν˜ ϭ 3416 (m), 3052 (s), 2971 (s), 2928 (s), 2853 (s), 2825 (m,
NCϪH), 1638 (w), 1618 (w), 1492 (m), 1441 (s), 1377 (w), 1345
(m), 1306 (s), 1262 (m), 1224 (m), 1212 (m), 1200 (w), 1160 (s),
Electrolysis of N-(1,4-Dioxaspiro[4.4]non-6-ylmethyl)-4-methylpyri-
dinium Trifluoromethanesulfonate (29): The pyridinium salt 29 1141 (s), 1078 (m), 1047 (m), 1032 (m), 1003 (m), 984 (m), 963 (w),
1
(2.55 g, 5.77 mmol based on pure salt 30) was dissolved in aqueous 842 (m), 801 (m), 717 (m) cmϪ1. H NMR (300.1 MHz, CDCl3):
sulfuric acid (1 , 30 mL) and electrolysed according to the General
Procedure until 5160 C (2.3-fold excess) had been transferred. The 2.10Ϫ2.25 (m, 1 H, 6a-H), 2.39 (dd, J ϭ 9.3, J ϭ 3.3 Hz, 1 H,,
δ ϭ 1.18Ϫ1.43 (m, 3 H), 1.50Ϫ2.00 (m, 7 H), 1.76 (s, 3 H, CH3),
2
3
crude product was analysed by GC (3a/3b ϭ 1.0:2.8) and subjected
to flash chromatography (diethyl ether/triethylamine, 10:1) to give
two fractions of isomeric products 3b (Rf ϭ 0.73, 659 mg, slowly
crystallising white solid) and 3a (Rf ϭ 0.40, 267 mg, white crystal-
line solid). Combined yield: 926 mg (4.79 mmol, 83%).
6-HA), 2.64Ϫ2.73 (mc, 1 H, 4-HA), 2.88Ϫ2.95 (mc, 1 H, 4-HB), 3.15
(dd, 2J ϭ 9.3, 3J ϭ 7.2 Hz, 1 H, 6-HB), 3.24 (mc, 1 H, 10b-H), 5.39
(s, 1 H, 1-H) ppm. 13C NMR (75.5 MHz, CDCl3): δ ϭ 22.4 (t),
23.6 (q, CH3), 23.8 (t), 29.4 (t), 30.2 (t), 31.9 (t), 45.0 (d, C-6a),
48.2 (t, C-4), 57.3 (t, C-6), 62.9 (d, C-10b), 78.3 (s, C-10a), 117.5
(d, C-1), 138.0 (s, C-2) ppm. MS (GC-MS*): m/z (%) ϭ 207 (2)
[Mϩ], 206 (5) [Mϩ Ϫ H], 159 (4), 109 (100) [Mϩ Ϫ C6H10O], 96
(20) [Mϩ Ϫ C7H11O], 94 (22), 81 (36), 67 (8), 55 (8), 41 (20), 39
(25). C13H21NO (207.32): calcd. C 75.32, H 10.21, N 6.76; found
C 75.11, H 10.38, N 6.91.
rac-(6aR,9aS,9bR)-2-Methyl-3,4,6,6a,7,8,9a,9b-octahydro-9H-
cyclopenta[a]indolizin-9a-ol (3b): M.p. 35 °C. IR (KBr): ν˜ ϭ 3409
(s), 3322 (s), 2944 (s), 2906 (s), 2862 (m), 2806 (s, NCϪH), 2727
(m, NCϪH), 1666 (w), 1638 (w), 1618 (w), 1446 (m), 1377 (m),
1321 (s), 1281 (s), 1209 (m), 1187 (s), 1132 (m), 1102 (m), 1085 (m),
1041 (m), 1017 (s), 980 (m), 936 (m), 915 (w), 865 (s), 835 (w) cmϪ1
.
rac-(6aR,10aS,10bR)-2-Methyl-3,4,6,6a,7,8,9,10,10a,10b-deca-
1H NMR (300.1 MHz, CDCl3): δ ϭ 1.22Ϫ1.38 (m, 1 H), 1.55Ϫ1.68 hydrocyclohexa[a]indolizin-10a-ol (4b):[42] M.p. 104 °C. IR (KBr):
(m, 4 H), 1.69 (s, 3 H, CH3), 1.80Ϫ1.91 (m, 1 H), 2.05Ϫ2.20 (m, 2 ν˜ ϭ 3412 (m), 3097 (s), 2971 (s), 2925 (s), 2836 (s, NCϪH), 1638
H), 2.22Ϫ2.45 (m, 3 H), 2.50Ϫ2.65 (m, 3 H), 2.95 (mc, 1 H, 9b-
(w), 1618 (w), 1449 (s), 1427 (s), 1374 (m), 1350 (s), 1319 (s), 1282
Eur. J. Org. Chem. 2003, 2919Ϫ2932
www.eurjoc.org
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2929

J. Heimann, H. J. Schäfer, R. Fröhlich, B. Wibbeling
FULL PAPER
(m), 1217 (m), 1201 (m), 1164 (m), 1150 (s), 1119 (s), 1080 (m), (300.1 MHz, CDCl3): δ ϭ 0.80Ϫ1.30 (m, 6 H), 1.06 (s, 3 H,
1053 (s), 1031 (m), 1015 (m), 980 (m), 929 (w), 891 (w), 841 (m), C11ϪCH3), 1.45Ϫ1.85 (m, 5 H), 1.71 (s, 3 H, C2ϪCH3), 1.86Ϫ2.00
797 (m), 769 (m), 698 (m) cmϪ1 1H NMR (599.0 MHz, CDCl3): (m, 1 H), 2.01Ϫ2.10 (m, 1 H), 2.30Ϫ2.47 (m, 2 H), 2.69 (mc, 1 H),
.
δ ϭ 1.28Ϫ1.49 (m, 7 H, 7-HA, 8-H, 9-H, 10-H), 1.61Ϫ1.65 (m, 1 2.79 (dd, J ϭ 11.2, J ϭ 3.8 Hz, 1 H), 3.22 (mc, 1 H), 5.33 (m, 1 H,
H, 7-HB), 1.66 (s, 3 H, CH3), 1.91Ϫ2.05 (m, 2 H, 3-H), 2.08Ϫ2.12 3-H) ppm. 13C NMR (75.5 MHz, CDCl3): δ ϭ 20.4 (q, C11ϪCH3),
(m, 1 H, 6a-H), 2.58 (dd, 3J ϭ 9.2, 2J ϭ 9.2 Hz, 1 H, 6-HA), 22.9 (q, C2ϪCH3), 24.7, 25.6, 26.5 (3 t, C-8, C-9, C-10), 30.0, 31.0
3
2
2.68Ϫ2.76 (m, 2 H, 4-H), 2.93 (dd, J ϭ 9.2, J ϭ 9.2 Hz, 1 H, 6-
HB), 3.16 (mc, 1 H, 10b-H), 5.40 (mc, 1 H, 1-H) ppm. 13C NMR (t, C-6), 65.4 (d, C-11a), 70.9 (s, C-11), 117.1 (d, C-3), 132.3 (s, C-
(150.6 MHz, CDCl3): δ ϭ 20.9, 21.1 (2 t, C-8, C-9), 23.5 (q, CH3),
2) ppm. MS (GC-MS*): m/z (%) ϭ 235 (40) [Mϩ], 234 (95) [Mϩ Ϫ
24.0 (t, C-7), 29.1 (t, C-3), 30.7 (t, C-10), 43.6 (d, C-6a), 48.3 (t, C- H], 220 (22) [Mϩ Ϫ CH3], 216 (8), 202 (8), 192 (10), 190 (9), 136
4), 54.8 (t, C-6), 69.1 (d, C-10b), 77.1 (s, C-10a), 118.8 (d, C-1), (8), 124 (11), 120 (7), 110 (100) [Mϩ Ϫ C8H13O], 96 (95) [Mϩ
134.2 (s, C-2) ppm. MS (GC-MS*): m/z (%) ϭ 206 (5) [Mϩ Ϫ H], C9H15O], 94 (80), 81 (32), 67 (42), 55 (20), 43 (80), 41 (60), 39
192 (4), 187 (5), 159 (7), 144 (3), 109 (100) [Mϩ Ϫ C6H10O], 96
(45). Due to the low quantity of the material the exact mass was
(15) [Mϩ Ϫ C7H11O], 94 (21), 81 (27), 67 (10), 55 (10), 41 (20), 39 determined instead of an elemental analysis. EMS (GC-MS): calcd.
(2 t, C-1, C-7), 35.5 (d, C-6a), 50.5 (d, C-10a), 54.9 (t, C-4), 62.8
Ϫ
(23). C13H21NO (207.32): calcd. C 75.32, H 10.21, N 6.76; found
C 74.95, H 10.21, N 6.60.
(C15H25NO) 235.1936; found 235.1934.
rac-(6aS,10aS,11R,11aS)-2,11-Dimethyl-3,4,6,6a,7,8,9,10,11,11a-
decahydro-10aH-cyclohexa[b]quinolizin-11-ol (33b):[41] M.p. 132 °C.
Electrolysis of rac-N-{[(1S,2S)-2-Acetylcyclohexyl]methyl}-4-meth-
ylpyridinium Bromide (34): The pyridinium salt 34 (1.87 g, IR (KBr): ν˜ ϭ 3412 (s), 3327 (s), 2932 (s), 2857 (s), 2801 (s,
3.90 mmol based on pure salt) was dissolved in aqueous sulfuric
acid (1 , 30 mL) and electrolysed according to the General Pro-
cedure until 5789 C (3.8-fold excess) had been transferred. The
crude product was analysed by GC: 33a/33b/33c/33d/38a/38b ϭ
10.1:4.3:0.2:0.7:1.3:1.0 and subjected to short path flash chroma-
NCϪH), 2741 (m, NCϪH), 1638 (w), 1618 (w), 1463 (m), 1450
(m), 1405 (m), 1371 (m), 1354 (m), 1323 (m), 1298 (m), 1276 (s),
1242 (m), 1224 (m), 1179 (m), 1165 (m), 1154 (m), 1122 (s), 1108
(s), 1063 (m), 1045 (w), 930 (s), 883 (m) cmϪ1 1H NMR
.
(300.1 MHz, CDCl3): δ ϭ 0.85Ϫ1.95 (m, 13 H), 1.01 (s, 3 H,
tography (light petroleum/triethylamine, 10:1) to give a mixture of C11ϪCH3), 1.71 (s, 3 H, C2ϪCH3), 2.18Ϫ2.38 (m, 3 H), 2.70 (dd,
isomers (672 mg, 2.86 mmol, 73%). Isomers 33a, 33b and 38a were
isolated by repeated flash chromatography (light petroleum/tri-
ethylamine, 10:1): 33a (Rf ϭ 0.60, slowly solidifying colourless oil),
J ϭ 11.0, J ϭ 4.1 Hz, 1 H), 2.78 (mc, 1 H), 5.53 (s, 1 H, 1-H) ppm.
13C NMR (75.5 MHz, CDCl3): δ ϭ 16.9 (q, C11ϪCH3), 23.0 (q,
C2ϪCH3), 25.0, 25.9, 26.4 (3 t, C-8, C-9, C-10), 30.4 (t, C-3), 30.8
38a (Rf ϭ 0.54, white crystalline solid), 33b (Rf ϭ 0.38, white crys- (t, C-7), 38.2 (d, C-6a), 52.3 (t, C-4), 53.7 (d, C-10a), 62.9 (t, C-6),
talline solid).
71.6 (d, C-11a), 73.2 (s, C-11), 119.4 (d, C-1), 133.5 (s, C-2) ppm.
MS (GC-MS*): m/z (%) ϭ 234 (12) [Mϩ Ϫ H], 220 (5) [Mϩ
Ϫ
rac-(6aS,10aS,11S,11aS)-2,11-Dimethyl-3,4,6,6a,7,8,9,10,11,11a-
decahydro-10aH-cyclohexa[b]quinolizin-11-ol (33a):[41] M.p. 61 °C.
IR (KBr): ν˜ ϭ 3466 (s), 3403 (s), 3036 (w), 2993 (m), 2914 (s), 2852
(s), 2818 (m, NCϪH), 2745 (m, NCϪH), 1682 (w), 1638 (w), 1618
(w), 1459 (m), 1449 (m), 1381 (m), 1356 (m), 1334 (m), 1304 (m),
CH3], 136 (6), 110 (36) [Mϩ Ϫ C8H13O], 96 (100) [Mϩ Ϫ C9H15O],
94 (20), 81 (12), 67 (10), 55 (6), 43 (22), 41 (17), 39 (15). C15H25NO
(235.37): calcd. C 76.55, H 10.71, N 5.95; found C 76.16, H 10.67,
N 5.76.
1287 (s), 1220 (m), 1176 (m), 1152 (m), 1121 (s), 1102 (m), 1058 X-ray Crystallographic Studies: Data sets were collected with Enraf
1
(s), 1025 (m), 980 (m), 952 (m), 867 (s), 845 (w), 702 (w) cmϪ1. H Nonius CAD4 and Nonius Kappa CCD diffractometers. Programs
3
3
NMR (599.0 MHz, CDCl3): δ ϭ 0.80 (ddd, Jaa ϭ 11.2, Jaa
ϭ
used: data collection EXPRESS (Nonius B. V., 1994) and COL-
LECT (Nonius B.V., 1998), data reduction MolEN (K. Fair,
3
11.2, Jae ϭ 2.9 Hz, 1 H, 10a-H), 0.83Ϫ0.92 (m, 1 H, 7-HA), 1.11
(s, 3 H, C11ϪCH3), 1.17Ϫ1.22 (m, 3 H, 8-HA, 9-HA, 10-HA), EnrafϪNonius B. V., 1990) and Denzo-SMN (Z. Otwinowski, W.
1.44Ϫ1.59 (m, 2 H, 6a-H, 7-HB), 1.60Ϫ1.63 (m, 1 H, 8-HB), 1.67 Minor, Methods Enzymol., 1997, 276, 307Ϫ326), absorption correc-
(s, 3 H, C2ϪCH3), 1.72 (mc, 1 H, 3-HA), 1.74Ϫ1.80 (m, 2 H, 9-HB, tion for CCD data SORTAV (R. H. Blessing, Acta Crystallogr.
10-HB), 1.90 (dd, 2J ϭ 12.3, 3Jaa ϭ 12.3 Hz, 1 H, 6-Ha), 2.20Ϫ2.28 1995, A51, 33Ϫ37; R. H. Blessing, J. Appl. Crystallogr. 1997, 30,
2
3
3
(m, 1 H, 3-HB), 2.28 (ddd, J ϭ 11.3, Jaa ϭ 11.3, Jae ϭ 4.0 Hz, 1
421Ϫ426), structure solution SHELXS-97 (G. M. Sheldrick, Acta
2
H, 4-Ha), 2.28 (s, 1 H, 11a-H), 2.60 (s, 1 H, OH), 2.63 (dd, J ϭ Crystallogr. 1990, A46, 467Ϫ473), structure refinement SHELXL-
12.3, Jea ϭ 3.9 Hz, 1 H, 6-He), 2.73 (ddd, J ϭ 11.3, Jea ϭ 6.0,
3Jee ϭ 1.2 Hz, 1 H, 4-He), 5.44 (s, 1 H, 1-H) ppm. 13C NMR
3
2
3
97 (G. M. Sheldrick, Göttingen, 1997), graphics SCHAKAL (E.
Keller, Freiburg, 1997). CCDC-204763 (1b), -204762 (2a), -204761
(150.6 MHz, CDCl3): δ ϭ 20.4 (q, C11ϪCH3), 23.5 (q, C2ϪCH3), (2b), -204760 (2c), -204767 (3a), -204766 (3b), -204764 (4a), -204765
24.9, 25.7, 26.5 (3 t, C-8, C-9, C-10), 30.3 (t, C-3), 30.7 (t, C-7), (4b), -204768 (33b) and -204769 (38a) contain the supplementary
37.0 (d, C-6a), 50.9 (d, C-10a), 52.1 (t, C-4), 62.5 (t, C-6), 69.6 (d,
crystallographic data for this paper. These data can be obtained
C-11a), 70.7 (s, C-11), 118.7 (d, C-1), 135.5 (s, C-2) ppm. MS (GC- free of charge at www.ccdc.cam.ac.uk/conts/retrieving.html [or
MS*): m/z (%) ϭ 234 (10) [Mϩ Ϫ H], 220 (3) [Mϩ Ϫ CH3], 138 from the Cambridge Crystallographic Data Centre, 12 Union
(6), 110 (35) [Mϩ Ϫ C8H13O], 96 (100) [Mϩ Ϫ C9H15O], 94 (20), Road, Cambridge CB2 1EZ, UK; Fax: (internat.) ϩ 44-1223/336-
81 (12), 67 (10), 55 (8), 43 (25), 41 (18), 39 (15). C15H25NO 033; E-mail: deposit@ccdc.cam.ac.uk].
(235.37): calcd. C 76.55, H 10.71, N 5.95; found C 76.70, H 10.82,
X-ray Crystal Structure Analysis of 1b: Formula C13H21NO, M ϭ
N 5.96.
207.31, colourless crystal 0.15 ϫ 0.10 ϫ 0.10 mm, a ϭ 32.050(6),
3
˚
˚
rac-(6aS,10aS,11S,11aS)-2,11-Dimethyl-1,6,6a,7,8,9,10,10a,11,11a-
decahydro-4H-cyclohexa[b]quinolizin-11-ol (38a):[41] M.p. 132 °C.
b ϭ 5.373(1), c ϭ 20.653(2) A, V ϭ 3556.5(10) A , ρcalcd. ϭ 1.161 g
cmϪ3, µ ϭ 5.60 cmϪ1, empirical absorption correction through ψ-
IR (KBr): ν˜ ϭ 3383 (s), 2956 (s), 2921 (s), 2854 (s), 2812 (m, scan data (0.921 Յ T Յ 0.946), Z ϭ 4, orthorhombic, space group
˚
NCϪH), 2762 (m, NCϪH), 1638 (w), 1444 (m), 1403 (w), 1380
Pna21 (no. 33), λ ϭ 1.54178 A, T ϭ 223 K, ω/2θ scans, 3743 reflec-
(m), 1351 (m), 1338 (m), 1320 (m), 1301 (m), 1290 (m), 1252 (m), tions collected (Ϫh, Ϫk, ϩl), [(sinθ)/λ] ϭ 0.62 AϪ1, 3743 indepen-
˚
1229 (w), 1216 (w), 1178 (m), 1152 (m), 1122 (s), 1060 (m), 1027 dent (Rint ϭ 0.000) and 2267 observed reflections [I Ն 2 σ(I)], 413
(m), 998 (m), 967 (m), 792 (s), 605 (m) cmϪ1
2930
.
1H NMR refined parameters, R ϭ 0.048, wR2 ϭ 0.102, max. residual electron
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2003, 2919Ϫ2932

Electrochemical Formation of Tricyclic Indolizidine and Quinolizidine Derivatives
FULL PAPER
density 0.20 (Ϫ0.20) e·AϪ3, Flack parameter 0.0(4), three indepen-
dent molecules in the asymmetric unit, ratio of enantiomers 2:1,
hydrogen atoms calculated and refined as riding atoms.
b ϭ 6.342(1), c ϭ 10.264(1) A, β ϭ 91.98(1)°, V ϭ 1128.0(2) A ,
ρ
tion via ψ-scan data (0.799 Յ T Յ 0.891), Z ϭ 4, monoclinic, space
3
˚
˚
˚
calcd. ϭ 1.221 g cmϪ3, µ ϭ 5.88 cmϪ1, empirical absorption correc-
˚
group P21/c (no. 14), λ ϭ 1.54178 A, T ϭ 223 K, ω/2θ scans, 2428
X-ray Crystal Structure Analysis of 2a: Formula C14H23NO, M ϭ
221.33, colourless crystal 0.20 ϫ 0.15 ϫ 0.10 mm, a ϭ 7.027(1),
reflections collected (Ϯh, Ϫk, Ϫl), [(sinθ)/λ] ϭ 0.62 AϪ1, 2287 inde-
˚
pendent (Rint ϭ 0.054) and 2111 observed reflections [I Ն 2 σ(I)],
˚
b ϭ 9.445(1), c ϭ 9.852(1) A, α ϭ 96.08(1), β ϭ 102.76(1), γ ϭ
138 refined parameters, R ϭ 0.057, wR2 ϭ 0.170, max. residual
3
99.50(1)°, V ϭ 622.06(13) A , ρcalcd. ϭ 1.182 g cmϪ3, µ ϭ 5.63
˚
electron density 0.30 (Ϫ0.38) e·AϪ3, hydrogen atoms calculated and
˚
cmϪ1, no absorption correction (0.896 Յ T Յ 0.946), Z ϭ 2, tri-
refined as riding atoms.
˚
¯
clinic, space group P1 (no. 2), λ ϭ 1.54178 A, T ϭ 223 K, ω/2θ
scans, 2748 reflections collected (ϩh, Ϯk, Ϯl), [(sinθ)/λ] ϭ 0.62
A
X-ray Crystal Structure Analysis of 4b: Formula C13H22NO ϫ
C6H2N3O7, M ϭ 436.42, yellow crystal 0.40 ϫ 0.10 ϫ 0.05 mm,
Ϫ1, 2533 independent (Rint ϭ 0.063) and 2031 observed reflec-
˚
tions [I Ն 2 σ(I)], 148 refined parameters, R ϭ 0.045, wR2 ϭ 0.126,
3
˚
˚
a ϭ 7.283(1), b ϭ 25.682(1), c ϭ 10.658(1) A, V ϭ 1993.5(3) A ,
max. residual electron density 0.25 (Ϫ0.18) e·AϪ3, hydrogen atoms
˚
ρ
calcd. ϭ 1.454 g cmϪ3, µ ϭ 9.73 cmϪ1, empirical absorption correc-
calculated and refined as riding atoms.
tion via SORTAV (0.697 Յ T Յ 0.953), Z ϭ 4, orthorhombic, space
˚
group Pna21 (no. 33), λ ϭ 1.54178 A, T ϭ 223 K, ω and scans,
X-ray Crystal Structure Analysis of 2b: Formula C14H23NO, M ϭ
221.33, colourless crystal 0.50 ϫ 0.40 ϫ 0.20 mm, a ϭ 5.420(1),
7516 reflections collected (Ϯh, Ϯk, Ϯl), [(sinθ)/λ] ϭ 0.59 AϪ1, 3092
˚
˚
independent (Rint ϭ 0.025) and 2531 observed reflections [I Ն 2
b ϭ 6.612(1), c ϭ 18.136(1) A, α ϭ 81.79(1), β ϭ 85.03(1), γ ϭ
σ(I)], 282 refined parameters, R ϭ 0.037, wR2 ϭ 0.088, Flack par-
3
73.20(1)°, V ϭ 615.12(15) A , ρcalcd. ϭ 1.195 g cmϪ3, µ ϭ 5.69
˚
Ϫ3
˚
cmϪ1, empirical absorption correction through ψ-scan data (0.764
ameter 0.5(2), max. residual electron density 0.14 (Ϫ0.19) e·A
hydrogen atoms calculated and refined as riding atoms.
,
¯
Յ T Յ 0.895), Z ϭ 2, triclinic, space group P1 (no. 2), λ ϭ 1.54178
˚
A, T ϭ 223 K, ω/2θ scans, 2722 reflections collected (Ϯh, Ϫk, Ϯl),
X-ray Crystal Structure Analysis of 33b: Formula C15H25NO, M ϭ
235.36, colourless crystal 0.50 ϫ 0.40 ϫ 0.30 mm, a ϭ 5.372(1),
[(sinθ)/λ] ϭ 0.62 AϪ1, 2493 independent (Rint ϭ 0.023) and 2366
˚
observed reflections [I Ն 2 σ(I)], 148 refined parameters, R ϭ 0.045,
3
˚
˚
b ϭ 11.295(1), c ϭ 22.434(1) A, β ϭ 96.37(1)°, V ϭ 1352.8(3) A ,
Ϫ3
wR2 ϭ 0.147, max. residual electron density 0.31 (Ϫ0.19) e·A
,
˚
ρ
calcd. ϭ 1.156 g cmϪ3, µ ϭ 5.45 cmϪ1, empirical absorption correc-
hydrogen atoms calculated and refined as riding atoms.
tion through ψ scan data (0.772 Յ T Յ 0.854), Z ϭ 4, monoclinic,
˚
X-ray Crystal Structure Analysis of 2c: Formula C14H23NO, M ϭ
221.33, colourless crystal 0.30 ϫ 0.20 ϫ 0.10 mm, a ϭ 7.792(1),
space group P21/n (No. 14), λ ϭ 1.54178 A, T ϭ 223 K, ω/2θ scans,
3055 reflections collected (ϩh, Ϫk, Ϯl), [(sinθ)/λ] ϭ 0.62 AϪ1, 2754
˚
˚
b ϭ 15.819(2), c ϭ 10.550(1) A, β ϭ 104.05(1)°, V ϭ 1261.5(3)
independent (Rint ϭ 0.027) and 2440 observed reflections [I Ն 2
3
A , ρcalcd. ϭ 1.165 g cmϪ3, µ ϭ 5.55 cmϪ1, empirical absorption
˚
σ(I)], 158 refined parameters, R ϭ 0.045, wR2 ϭ 0.139, max. re-
sidual electron density 0.31 (Ϫ0.17) e·AϪ3, hydrogens calculated
˚
correction through ψ-scan data (0.851 Յ T Յ 0.947), Z ϭ 4, mono-
˚
clinic, space group P21/n (no. 14), λ ϭ 1.54178 A, T ϭ 223 K, ω/
and refined as riding atoms.
2θ scans, 5414 reflections collected (Ϫh, Ϯk, Ϯl), [(sinθ)/λ] ϭ 0.62
Ϫ1, 2573 independent (Rint ϭ 0.038) and 1683 observed reflec-
˚
X-ray Crystal Structure Analysis of 38a: Formula C15H25NO, M ϭ
235.36, colourless crystal 0.30 ϫ 0.30 ϫ 0.20 mm, a ϭ 8.895(1),
A
tions [I Ն 2 σ(I)], 148 refined parameters, R ϭ 0.048, wR2 ϭ 0.123,
3
˚
˚
max. residual electron density 0.26 (Ϫ0.24) e·AϪ3, hydrogens calcu-
˚
b ϭ 11.849(2), c ϭ 12.710(1) A, β ϭ 93.94(1)°, V ϭ 1336.4(3) A ,
ρ
calcd. ϭ 1.170 g cmϪ3, µ ϭ 5.51 cmϪ1, empirical absorption correc-
lated and refined as riding atoms.
tion through ψ-scan data (0.852 Յ T Յ 0.898), Z ϭ 4, monoclinic,
X-ray Crystal Structure Analysis of 3a: Formula C12H19NO, M ϭ
˚
space group P21/n (no. 14), λ ϭ 1.54178 A, T ϭ 223 K, ω/2θ scans,
193.28, colourless crystal 0.20 ϫ 0.20 ϫ 0.20 mm, a ϭ 19.521(1),
2839 reflections collected (Ϯh, ϩk, Ϫl), [(sinθ)/λ] ϭ 0.62 AϪ1, 2718
˚
3
˚
˚
b ϭ 12.832(1), c ϭ 9.425(1) A, β ϭ 113.01(1)°, V ϭ 2173.1(3) A ,
ρ
independent (Rint ϭ 0.028) and 2331 observed reflections [I Ն 2
calcd. ϭ 1.182 g cmϪ3, µ ϭ 5.77 cmϪ1, empirical absorption correc-
σ(I)], 158 refined parameters, R ϭ 0.038, wR2 ϭ 0.107, max. re-
tion via ψ-scan data (0.893 Յ T Յ 0.893), Z ϭ 8, monoclinic, space
sidual electron density 0.23 (Ϫ0.16) e·AϪ3, hydrogen atoms calcu-
˚
˚
group C2/c (no. 15), λ ϭ 1.54178 A, T ϭ 223 K, ω/2θ scans, 2365
lated and refined as riding atoms.
reflections collected (Ϯh, Ϫk, ϩl), [(sinθ)/λ] ϭ 0.62 AϪ1, 2223 inde-
˚
pendent (Rint ϭ 0.032) and 1829 observed reflections [I Ն 2 σ(I)],
130 refined parameters, R ϭ 0.045, wR2 ϭ 0.118, max. residual
[1]
[1a] Rodd’s Chemistry of Carbon Compounds, vol. 5 (Topical Vol-
umes, ‘‘Organic Electrochemistry’’) (Ed.: M. Sainsbury), 2nd
ed., Elsevier, Amsterdam, Boston, London, New York, Oxford,
electron density 0.32 (Ϫ0.23) e·AϪ3, hydrogen atoms calculated and
˚
refined as riding atoms.
Paris, San Diego, San Francisco, Singapore, Sydney, Tokyo,
X-ray Crystal Structure Analysis of 3b: Formula C12H19NO, M ϭ
193.28, colourless crystal 0.30 ϫ 0.20 ϫ 0.10 mm, a ϭ 9.849(1),
[1b]
2002.
Organic Electrochemistry (Eds.: H. Lund, O. Ham-
[1c]
3
˚
˚
merich), 4th ed., Marcel Dekker, New York, Basel, 2001.
H. J. Schäfer, in Radicals in Organic Synthesis, vol. 1 (Basic
Principles) (Eds.: P. Renaud, M. P. Sibi), Wiley-VCH,
b ϭ 12.794(2), c ϭ 17.851(1) A, V ϭ 2249.4(2) A , ρcalcd. ϭ 1.141 g
cmϪ3, µ ϭ 5.58 cmϪ1, empirical absorption correction via ψ-scan
data (0.851 Յ T Յ 0.946), Z ϭ 8, orthorhombic, space group
Weinheim, New York, Chichester, Brisbane, Singapore, To-
˚
P212121 (no. 19), λ ϭ 1.54178 A, T ϭ 223 K, ω/2θ scans, 5034
[1d]
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J. Grimshaw, Electrochemical Reactions and
reflections collected (ϩh, ϩk, Ϯl), [(sinθ)/λ] ϭ 0.62 AϪ1, 4565 inde-
˚
Mechanisms in Organic Chemistry, Elsevier, Amsterdam, Laus-
anne, New York, Oxford, Shannon, Singapore, Tokyo, 2000.
pendent (Rint ϭ 0.025) and 3104 observed reflections [I Ն 2 σ(I)],
257 refined parameters, R ϭ 0.055, wR2 ϭ 0.141, Flack parameter
[1e]
Novel Trends in Electroorganic Synthesis (Ed.: S. Torii),
0.3(3), max. residual electron density 0.32 (Ϫ0.25) e·AϪ3, two al-
˚
Springer-Verlag, Tokyo, Berlin, Heidelberg, New York, 1998.
[1f]
J. Volke, F. Liska, Electrochemistry in Organic Synthesis,
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Springer-Verlag, Berlin, Heidelberg, New York, London, Paris,
[1g]
Tokyo, Hong Kong, Barcelona, Budapest, 1994.
D. Kyria-
X-ray Crystal Structure Analysis of 4a: Formula C13H21NO, M ϭ
207.31, colourless crystal 0.40 ϫ 0.40 ϫ 0.20 mm, a ϭ 17.339(1),
cou, Modern Electroorganic Chemistry, Springer-Verlag, Berlin,
Heidelberg, New York, 1994.
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2931

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Received March 17, 2003
2932
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2003, 2919Ϫ2932