Nitrogen-containing tricyclic and tetracyclic compounds by stereoselective samarium diiodide promoted cyclizations of quinolyl-substituted ketones - A new access to azasteroids

Article abstract of DOI:10.1002/ejoc.200800019

In this report, we describe our experiments dealing with samarium diiodide promoted cyclizations of quinolyl-substituted ketones 6-12 and also the attempted reductive cyclization of carbazole-containing ketone 13. These precursors were prepared by Heck-ty

Full text of DOI:10.1002/ejoc.200800019

FULL PAPER
DOI: 10.1002/ejoc.200800019
Nitrogen-Containing Tricyclic and Tetracyclic Compounds by Stereoselective
Samarium Diiodide Promoted Cyclizations of Quinolyl-Substituted Ketones –
A New Access to Azasteroids
Francesca Aulenta,[a,b] Ulrike K. Wefelscheid,[a] Irene Brüdgam,[a][‡] and
Hans-Ulrich Reißig*[a]
Keywords: Samarium / Electron transfer / Quinolines / Steroids / C–C coupling
In this report, we describe our experiments dealing with
samarium diiodide promoted cyclizations of quinolyl-substi-
tuted ketones 6–12 and also the attempted reductive cycliza-
tion of carbazole-containing ketone 13. These precursors
were prepared by Heck-type coupling reactions of the corre-
diastereoselective fashion. The azatetracycles present ste-
roid-like skeletons but with unnatural cis–cis annulation of
rings B, C and D. We also describe the chemical modification
of the styrene-type double bond of these products, which
provided highly functionalized steroid-type compounds such
sponding hetaryl nonaflates with adequately substituted ole- as 29, 30 and 32.
fins as a key step. The cyclization of compounds 7–12 led to
nitrogen-containing tri- and tetracyclic compounds 23–28 in
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
moderate to good yields and generally proceeded in a highly
Germany, 2008)
high degree of diastereoselectivity mostly observed could be
explained by a six-membered transition structure during the
ketyl addition, in which the samariumalkoxy moiety occu-
pies an equatorial position for steric and electronic reasons
(Scheme 1).[3a,3f,7]
Introduction
Heteroatom-containing steroids and in particular aza-
steroids have proven to be attractive targets in pharmaceuti-
cal chemistry. The presence of a nitrogen atom confers to
these compounds interesting biological activities,[1] which
have encouraged organic chemists to provide not only ef-
ficient routes towards the synthesis of known target com-
pounds, but also to generate novel structures that could po-
tentially lead to useful drugs.[2] Our approach towards the
synthesis of nitrogen-containing polycyclic structures is
based on samarium diiodide promoted cyclizations of
hetaryl-substituted ketones. Such methodology has been
widely investigated by our group[3] and other authors,[4] and
it provides highly functionalized products with very good
diastereoselectivities.[5] The cyclizations of γ-aryl and γ-
naphthyl ketones such as 1 are promoted by the SmI2–
HMPA complex,[6] which transfers one electron to the car-
bonyl group to thus generate a samarium ketyl species
(Scheme 1). This intermediate attacks the ortho position of
the aromatic ring, which thereby forms a new six-membered
ring. A second electron transfer followed by regioselective
protonation affords the final tricyclic compound 2. The
Scheme 1. Proposed mechanism for the samarium diiodide induced
diastereoselective cyclization of γ-naphthyl-substituted ketone 1
leading to tricyclic product 2.
[a] Institut für Chemie und Biochemie, Freie Universität Berlin,
Takustr. 3, 14195 Berlin, Germany
Herein, we report the application of this method to the
stereoselective synthesis of nitrogen-containing tricyclic and
tetracyclic compounds such as 3 (Scheme 2). Starting mate-
rials 4 combine the quinoline moiety with a suitably posi-
tioned carbonyl group as a precursor of a samarium ketyl.
As a short and potentially flexible synthesis of ketones 4,
Fax: +49-30-83855367
E-mail: hans.reissig@chemie.fu-berlin.de
[b] BASF, GKT/W – B 001, Polymer Research – Biopolymers,
67056 Ludwigshafen, Germany
[‡] Responsible for X-ray crystal structure analysis
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
Eur. J. Org. Chem. 2008, 2325–2335
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FULL PAPER
we envisaged palladium-catalyzed reactions with hydroxy- the Supporting Information). The preparation of nonaflate
quinoline derivatives such as 5 as precursors. Similarly, we 14 was easily achieved from precursor 5 by a standard
attempted to introduce carbazole derivatives as components method employing sodium hydride as base followed by
in the reductive cyclization process.
treatment
with
nonafluorobutanesulfonyl
fluoride
(Scheme 4).[10] Although not yet routinely explored in cross-
coupling reactions,[11] (het)aryl nonaflates have shown to
exhibit several advantages over the corresponding triflates.
They are very stable, easily purified by crystallization or
column chromatography, and smoothly prepared[12] using
the commercially available, non-toxic and cost-effective
nonafluorobutanesulfonyl fluoride. The subsequent Heck
reaction of quinolyl nonaflate 14 with methyl vinyl ketone
15 was performed in the presence of lithium chloride, trieth-
ylamine, and 5 mol-% of palladium diacetate in DMF
smoothly affording the expected product 16 in very good
yield (Scheme 4), which was reduced to furnish target com-
pound 6.
Scheme 2. Retrosynthetic analysis for target compounds 3.
Results and Discussion
Synthesis of Hetaryl-Substituted Ketones by Heck
Couplings
We planned to investigate the cyclizations of γ-hetaryl-
substituted ketones 6–13 (Scheme 3). Their syntheses were
achieved by palladium-promoted arylations (Heck reac-
tions)[8] of quinolyl and carbazolyl nonaflates (nonafluoro-
butane sulfonates) with a series of adequately substituted
olefins.[9] Among the possible hydroxyquinoline and carb-
azole precursors to be used, we selected 8-hydroxyquinoline,
6-hydroxyquinoline and 2-hydroxy-9H-carbazole, because
they are stable and commercially available at low cost.
Scheme 4. Synthesis of β-hetaryl ketone 6 via nonaflate 14.
Coupling of quinolyl nonaflate 14 with olefin 17, in
which the double bond is not activated by a carbonyl group,
proved to be more challenging, and ketone 18 was obtained
only in moderate yield when modified Jeffery conditions
were applied Scheme 5.[13] 1,3-Diene 19 Ϫ probably formed
by dehydrogenation from 18 Ϫ was isolated as a minor
component under the reaction conditions applied. This
selectivity problem was of no consequence for our purpose,
as hydrogenation of the product mixture afforded the de-
sired saturated ketone 8 in good yield.
In Scheme 6, we present the synthesis of cyclohexanone
derivative 10. A small amount of this compound was di-
rectly formed in the Heck coupling of quinolyl nonaflate 14
with racemic homoallylic alcohol 20.[14] The major product
in this experiment was unsaturated alcohol 21, which was
smoothly transformed into the desired compound 10 by
oxidation with the Py·SO3 complex in DMSO[15] followed
by hydrogenation. The palladium-catalyzed migration of
double bonds of allylic and homoallylic alcohols in Heck
Scheme 3. The β-, γ- and δ-hetaryl-substituted ketones 6–13 to be
studied in samarium diiodide promoted cyclizations.
As examples, for the preparation of these target com- reactions is well documented in the literature.[16] It is known
pounds we describe the syntheses of ketones 6, 8 and 10 in that the stability of the possible alkene formed governs the
detail (see Schemes 4, 5 and 6; for all other precursors see outcome of the isomerization reaction. In the case of allylic
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Stereoselective SmI2 Promoted Cyclizations of Quinolyl-Substituted Ketones
ondary alcohol 22 was isolated in 24% yield along with
24% of unconsumed starting material (Scheme 7). Gratify-
ingly, the 6-trig cyclization of ketone 7 afforded the desired
tricyclic product 23 as a single diastereomer in 53% yield.
As expected, the cyclization occurred exclusively at the 7-
position of the quinoline ring and the nitrogen atom of the
heterocycle was not attacked. In agreement with previous
results,[3f] 23 contains a cis-decaline substructure. The rela-
tive configuration was proven by two-dimensional NOESY-
NMR spectroscopic analysis. This stereochemical result can
be rationalized by the transition-structure model discussed
in the introduction (Scheme 1), in which the bulky samari-
umalkoxy moiety adopts an equatorial position. Interest-
ingly, homologous ketone 8 did not lead to the desired tri-
cyclic product containing a seven-membered ring; instead,
spiro compound 24 was formed as a single diastereomer,
albeit in poor 11% yield. In this experiment, 83% of ketone
8 was recovered, which is indicative of the strong reluctance
of this system to undergo reductive cyclization.[18]
Scheme 5. Synthesis of δ-hetaryl ketone 8 starting from nonaflate
14.
alcohols (especially primary allylic alcohols), the enol is
generally the most stable alkene and the corresponding
ketone is hence formed upon work up. In the example de-
picted in Scheme 6, only a small amount of material derived
from homoallylic alcohol 20 proceeds through this route to
ketone 10, whereas the major part does not undergo mi-
gration of the double bond.
Scheme 6. Synthesis of γ-hetaryl ketone 10 starting from nonaflate
14 and rac-20.
Scheme 7. Samarium diiodide induced reactions of quinolyl-substi-
tuted ketones 6, 7 and 8.
Samarium Diiodide Induced Cyclizations of Heteroaryl-
Substituted Ketones
The successful addition of the ketyl derived from 7 onto
Studies of the SmI2–HMPA induced cyclization were the electron-deficient quinoline ring system stereoselectively
performed by employing samarium diiodide (2.5 equiv.) in leading to tricyclic compound 23 prompted us to investigate
THF along with a large excess of HMPA (18 equiv.) and precursors 9, 10 and 11 incorporating cyclic ketones. They
tert-butanol (2.2 equiv.) as a proton source. This method also bear a three-carbon spacer unit between the carbonyl
was previously optimized in our group for other sub- group and the heterocycle and should generate analogous
strates.[3,17] Acyclic ketones were initially employed as tetracyclic compounds with steroid-like skeletons
model systems, and quinolyl-substituted ketone 6 served as (Scheme 8). Actually, ketones 9 and 10 were converted in
the first substrate. Not unexpectedly,[5j] the possible 5-trig moderate yields into the corresponding tetracyclic com-
cyclization leading to a tricyclic product failed and only sec- pounds 25 and 26 containing a five- and six-membered “D-
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F. Aulenta, U. K. Wefelscheid, I. Brüdgam, H.-U. Reißig
FULL PAPER
ring”, respectively. In both cases, the diastereoselectivity the tetracyclic skeleton 28 as a single diastereomer and in
was again excellent and only the “unnatural” cis–cis annu- 54% yield (Scheme 9). The observed regioselectivity may be
lated products were isolated. Consistent with this trend, explained by the higher stabilization of the intermediates
ketone 11 afforded a single “diazasteroid” derivative 27 in (radical and anion) by the adjacent pyridine moiety.
50% yield. NMR spectroscopic analysis of this latter com-
Unfortunately, ketone 13 containing a carbazole ring as
pound, carried out at room temperature, showed two dis- samarium ketyl acceptors did not undergo the desired cycli-
tinct amide rotamers attributable to the presence of the N- zation. Instead, only a complex mixture of decomposed ma-
Boc group. The presence of rotamers is also visible in the terial was obtained. We have to conclude that the fairly elec-
NMR spectra of precursor ketone 11 Ϫ a phenomenon typ- tron-rich carbazole system is not suitable for these cycliza-
ical of amides and carbamate groups.[19]
tions, at least when the carbonyl group is connected to C-
2. This failure has to be compared to the successful cycliza-
tions employing aniline, pyrrole and indole derivatives
studied in our group.[3d,3e,3g,3h]
Typical Subsequent Reactions of Azasteroid Derivatives
The polycyclic compounds obtained under the reductive
conditions reported above contain a styrene-type double
bond, which provides a suitable handle for subsequent syn-
thetic transformations.[3f,3i,3j] A few typical examples lead-
ing to highly functionalized compounds are presented in
Scheme 10. They involve the epoxidation of the double
bond of compound 26 to afford pentacyclic product 29 by
using meta-chloroperbenzoic acid, the dihydroxylation of
precursor 28 under standard Sharpless conditions[20] to give
polycyclic triol 30 and the stereoselective hydroboration of
28 to furnish compound 32. In the first case, the reaction
was low yielding and provided the desired epoxide in only
Scheme 8. Samarium diiodide promoted synthesis of azasteroid de-
rivatives 25 and 26 and that of diazasteroid 27.
The samarium diiodide induced cyclization smoothly oc-
curred also with precursor 12, in which the quinoline ring
bears the functionalized alkyl chain at C-6. The samarium
ketyl attacked the aromatic ring exclusively at C-7 to afford
Scheme 9. Samarium diiodide promoted reactions of quinoline de-
rivative 12 and that of carbazole derivative 13.
Scheme 10. Reactions of tetracyclic compounds 26 and 28.
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Stereoselective SmI2 Promoted Cyclizations of Quinolyl-Substituted Ketones
36% yield, possibly as a result of the concurrent oxidation ized, but just hydrolyzed to give product 31. Constitution
of the pyridine ring to the N-oxide. Nevertheless, the reac- and relative configuration of this unexpected tetracyclic
tion occurred in a stereoselective fashion and delivered product were again determined by X-ray crystallographic
compound 29 as a single diastereomer. The bowl-like shape analysis (Figure 2). A second hydroboration/oxidation ex-
of 26 and the steering effect of its hydroxy group contrib- periment employing a large excess of hydrogen peroxide fi-
uted to the observed excellent face selectivity. The consti- nally transformed precursor 28 into the expected hydroxyl-
tution and relative configuration of 29 were unequivocally ated product 32 in 71% yield (Scheme 10).[22] The regio-
assigned by X-ray crystallographic analysis (Figure 1).
and stereoselectivity of this process were supported by NOE
experiments of compound 32 and are in accordance with
the expectation.
Conclusions
We demonstrated that highly functionalized nitrogen-
containing tri- and tetracyclic compounds can be synthe-
sized in a diastereoselective fashion by samarium diiodide
induced cyclizations of appropriately substituted γ-hetaryl
ketones. The samarium diiodide induced reductive coupling
generates cis–cis annulated rings and therefore opens the
door for molecules with steroid-like frameworks but with
“unnatural configuration”. Again, the samarium ketyl cy-
clizations seem to be restricted to the formation of new six-
membered rings.[5j] The styrene-type double bond of the re-
sulting products allow a series of smooth addition reac-
tions, which generally occur in a stereoselective fashion due
to the shape of the starting materials. The potential bio-
logical activity of some of these compounds is at present
under examination,[23] and the results obtained will be re-
ported elsewhere. In addition, we demonstrated that a vari-
ety of Heck couplings can be performed with hetaryl nona-
flates in reasonable efficacy. The corresponding nonaflates
employed may also be of value for the introduction of other
substituents to the heterocycles by palladium-catalyzed pro-
cesses.
Figure 1. Structure of compound 29.
Epoxidation of the double bond of compound 27 was
also attempted; however, under the conditions reported
above complete decomposition of the starting material was
observed. Dihydroxylation of tetracycle 28 occurred
smoothly to afford product 30 in good yield (Scheme 10).
Again, only a single diastereomer was isolated, as the deliv-
ery of the hydroxy groups occurs from the sterically less-
hindered convex face of the molecule and cis to the bridge-
head hydroxy group.[21]
An attempted hydroboration of compound 28 was exe-
cuted in a first experiment only with a slight excess of hy-
drogen peroxide (with respect to the borane equivalents)
during the oxidative work-up step. As a result, the fairly
stable pyridine–borane complex 31 was isolated in high
yield (Scheme 10). Apparently, there was insufficient hydro-
gen peroxide present and hence the carbon–boron bond of
the intermediate monoalkylborane species was not oxid-
Experimental Section
General Experimental Procedure: Reactions were generally per-
formed under an atmosphere of argon in flame-dried flasks, and
solvents and reagents were added by syringes. 1,2-Diodoethane was
dried at 50 °C for 3 h in vacuo. Tetrahydrofuran and diethyl ether
were freshly distilled from sodium/benzophenone under an atmo-
sphere of argon. Hexamethylphosphoramide was distilled from cal-
cium hydride (130 °C, 12 mbar) and stored over molecular sieves
(4 Å) under an atmosphere of argon. (Warning: HMPA has been
identified as a carcinogenic reagent. Appropriate glove protection is
required during handling. Reactions and chromatography should be
performed in a well-vented hood). Argon was purged through the
solution to eliminate residual oxygen prior to use. Triethylamine
and diisopropylamine were distilled from potassium hydroxide and
stored over potassium hydroxide under an atmosphere of argon.
Dichloromethane was distilled from calcium hydride and stored
over molecular sieves (4 Å) under an atmosphere of argon. Ethanol
was distilled from magnesium oxide and stored over molecular si-
eves (4 Å) under an atmosphere of argon. Dry dimethylformamide
and dry dimethyl sulfoxide were purchased from Aldrich and used
under an atmosphere of argon. Other reagents were purchased and
were used as received without further purification unless otherwise
stated. Products were purified by flash chromatography on silica
Figure 2. Structure of tetracyclic pyridine–borane complex 31.
Eur. J. Org. Chem. 2008, 2325–2335
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2329

F. Aulenta, U. K. Wefelscheid, I. Brüdgam, H.-U. Reißig
FULL PAPER
1
gel (230–400 mesh, Merck). Preparative HPLC was carried out on 88 °C. H NMR (500 MHz, CDCl3): δ = 2.51 (s, 3 H, 1-H), 6.94
3
3
3
a nucleosil 50–5 column (diameter 16 mm, length 244 mm) and de-
tection was carried out with a Knauer variable UV-detector (λ =
255 nm) and a Knauer refractometer. Unless otherwise stated,
(d, J = 16.7 Hz, 1 H, 3-H), 7.44 (dd, J = 7.9 Hz, J = 4.3 Hz, 1
H, Ar), 7.54 (t, 3J ≈ 8 Hz, 1 H, Ar), 7.85 (d, J = 7.9 Hz, 1 H, Ar),
3
3
3
8.00 (d, J = 7.3 Hz, 1 H, Ar), 8.15 (d, J = 8.5 Hz, 1 H, Ar), 8.86
(d, 3J = 16.7 Hz, 1 H, 4-H), 8.95–8.98 (m, 1 H, Ar) ppm. 13C NMR
(126 MHz, CDCl3): δ = 26.8 (q, C-1), 121.5 (d, C-3), 126.2, 127.4
(2d, Ar), 128.4 (s, Ar), 129.4, 130.2 (2d, Ar), 133.0 (s, Ar), 136.1
(d, Ar), 139.8 (d, C-4), 146.0 (s, Ar), 150.1 (d, Ar), 199.2 (C-2)
yields refer to analytically pure samples. H and 13C NMR spectra
1
were recorded with a Bruker AC 250 (250 MHz), AC 500
(500 MHz) or Joel Eclipse 500 (500 MHz) instrument. Integrals are
in accordance with assignments; coupling constants are given in
Hz. IR spectra were measured with an FTIRD spectrometer Nico- ppm. IR (KBr): ν = 3055, 3025, 2995, 2970, 2920 (=CH, C–H),
˜
let 5 SXC or with a Nexus FTIR spectrometer equipped with a
Nicolet Smart DuraSamplIR ATR. MS and HRMS analyses were
performed with Finnigan MAT 711 (EI, 80 eV, 8 kV), MAT CH7A
(EI, 80 eV, 3 kV) and Varian Ionspec QFT-7 (ESI-FT ICRMS) in-
struments. Elemental analyses were recorded with “Elemental-Ana-
lyzer” (Perkin–Elmer). Melting points were measured with a Reich-
ert apparatus and are uncorrected. Single-crystal X-ray data were
collected with a Bruker-XPS diffractometer (CCD area detector,
Mo-Kα radiation, λ = 0.71073 A, graphite monochromator), empir-
ical absorption correction by using symmetry-equivalent reflections
(SADABS), structure solution and refinement by SHELXS-97 and
SHELXL-97 in the WINGX System. The hydrogen atoms were
located by difference Fourier syntheses. CCDC-606014 (for 29)
and -606015 (for 31) contain the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
1645 (C=O) cm–1. MS (EI, 80 eV, 60 °C): m/z (%) = 197 (3) [M]+,
182 (2) [M – CH3]+, 154 (100) [M – CH3CO]+. HRMS (EI, 80 eV,
60 °C): calcd. for C13H11NO 197.08406; found 197.08538.
(5E)-6-Quinolin-8-ylhex-5-en-2-one (18) and (3E,5E)-6-Quinolin-8-
ylhexa-3,5-dien-2-one (19): A high-pressure tube was loaded with
sodium hydrogencarbonate (0.504 g, 6.00 mmol), triethylbenzyl-
ammonium chloride (0.547 g, 2.40 mmol), compound 14 (0.855 g,
2.00 mmol), palladium(II) acetate (45 mg, 0.20 mmol) and DMF
(4 mL). The suspension was stirred at room temperature under an
atmosphere of argon for 10 min. A solution of 5-hexen-2-one (17)
(0.925 mL, 8.00 mmol) in DMF (2 mL) was then added, and the
vessel was sealed and heated to 90 °C for 48 h. The mixture was
cooled to room temperature, distilled water was added and the two
phases were separated. The product was extracted with CH2Cl2
(3ϫ10 mL), and the combined organic layers were washed with
brine (2ϫ10 mL) and dried with MgSO4. The solvent was removed
under reduced pressure to leave the crude product, which was puri-
fied by column chromatography on silica gel (hexane/ethyl acetate,
Quinolin-8-yl Nonafluorobutane-1-sulfonate (14): To a suspension
of sodium hydride (60 wt.-%, 2.48 g, 62.0 mmol) in THF (80 mL) from 4:1 to 2:1) to afford a 5:1 mixture of 18 and 19 as a colourless
at room temperature was slowly added a solution of 8-hydroxy-
quinoline (5; 5.00 g, 34.4 mmol) in THF (20 mL). The mixture was
stirred at room temperature for 20 min. Nonafluorobutanesulfonyl
fluoride (18.5 mL, 31.1 g, 103 mmol) was then added, and the mix-
ture was stirred for an additional 4 h. At 0 °C, the mixture was
quenched by dropwise addition of distilled water. The product was
extracted from the aqueous phase with CH2Cl2, and the combined
organic layer was washed with brine, dried with MgSO4 and fil-
tered. The solvent was removed under reduced pressure. The crude
product was purified by column chromatography on silica gel (hex-
ane/ethyl acetate, 7:1) and subsequent recrystallisation from hexane
solid (0.198 g, 44%). Data for 18 (mixture with 19): 1H NMR
(500 MHz, CDCl3): δ = 2.16 (s, 3 H, 1-H), 2.32–2.64 (m, 2 H, 4-
H), 2.67–2.70 (m, 2 H, 3-H), 6.42 (dt, J = 16.3 Hz, J = 6.7 Hz, 1
3
3
3
3
3
H, 5-H), 7.36 (dd, J = 8.1 Hz, J = 4.1 Hz, 1 H, Ar), 7.46 (dd, J
= 8.1 Hz, 3J = 7.1 Hz, 1 H, Ar), 7.66 (dd, 3J = 8.1 Hz, 4J = 1.2 Hz,
3
3
1 H, Ar), 7.68 (d, J = 16.3 Hz, 1 H, 6-H), 7.82 (dd, J = 7.1 Hz,
4J = 1.2 Hz, 1 H, Ar), 8.09 (dd, 3J = 8.1 Hz, 4J = 1.2 Hz, 1 H, Ar),
8.91 (dd, 3J = 4.1 Hz, 4J = 1.2 Hz, 1 H, Ar) ppm. 13C NMR
(126 MHz, CDCl3): δ = 27.5 (t, C-4), 29.9 (q, C-1), 43.2 (t, C-3),
120.9, 125.3, 126.3, 126.4 (4 d, Ar), 126.8 (d, C-6), 129.1 (s, Ar),
131.1 (d, C-5), 136.2 (d, Ar), 144.4, 145.4 (2s, Ar), 149.3 (d, Ar),
to furnish 14 as a colourless solid (10.7 g, 73%). M.p. 84 °C. 1H
208.2 (C-2) ppm. Data for 19 (mixture with 18): 1H NMR
3
3
NMR (250 MHz, CDCl3): δ = 7.39–7.56 (m, 3 H, Ar), 7.75 (d, J (500 MHz, CDCl3): δ = 2.32 (s, 3 H, 1-H), 6.26 (d, J = 15.7 Hz,
= 9.1 Hz, 1 H, Ar), 8.12 (d, 3J = 8.2 Hz, 1 H, Ar), 8.95 (d, 3J =
1 H, 3-H), 7.15 (ddd, 3J = 15.7 Hz, 3J = 10.9 Hz, 4J = 0.5 Hz, 1
4.6 Hz, 1 H, Ar) ppm. 13C NMR (63 MHz, CDCl3): δ = 121.0, H, 4-H), 7.42 (dd, 3J = 8.2 Hz, 3J = 4.1 Hz, 1 H, Ar), 7.44–7.50
3
3
122.7, 126.0, 128.3 (4 d, Ar), 129.9 (s, Ar), 135.8 (d, Ar), 141.2,
(m, 1 H, 5-H), 7.53 (t, J ≈ 8 Hz, 1 H, Ar), 7.77 (dd, J = 7.9 Hz,
3 3
146.5 (2 s, Ar), 151.7 (d, Ar) ppm. IR (KBr): ν = 3075 (=CH, C–
4J = 1.2 Hz, 1 H, Ar), 7.98 (d, J = 7.3 Hz, 1 H, Ar), 8.13 (dd, J
˜
H), 1630, 1600, 1570 (C=C) cm–1. MS (EI, 80 eV, 50 °C): m/z (%)
= 427 (26) [M]+, 144 (52), 116 (100), 89 (30). HRMS (EI, 80 eV,
50 °C): calcd. for C13H6F9NO3S 426.99246; found 426.99422.
= 8.2 Hz, J = 1.7 Hz, 1 H, Ar), 8.29 (d, J = 15.7 Hz, 1 H, 6-H),
8.94 (dd, 3J = 4.2 Hz, 4J = 1.7 Hz, 1 H, Ar) ppm. 13C NMR
(126 MHz, CDCl3): δ = 26.8 (q, C-1), 121.9, 126.2, 126.3, 128.3,
128.4 (5 d, Ar), 129.0 (d, C-4) 131.4 (d, C-3), 134.7 (s, Ar), 137.2
(d, Ar), 137.9 (d, C-6), 145.5 (d, C-5), 145.6, 145.7 (2 s, Ar), 150
4
3
(3E)-4-Quinolin-8-ylbut-3-en-2-one (16): A high-pressure tube was
loaded with triethylamine (0.43 mL, 3.0 mmol), lithium chloride
(0.127 g, 3.00 mmol), compound 14 (0.855 g, 2.00 mmol), palladi-
um(II) acetate (23 mg, 0.10 mmol) and DMF (4 mL). The suspen-
sion was stirred at room temperature under an atmosphere of argon
for 10 min. A solution of methyl vinyl ketone (15) (0.245 mL,
3.00 mmol) in DMF (2 mL) was then added, and the vessel was
sealed and heated to 100 °C for 24 h. The mixture was cooled to
room temperature, distilled water was added and the two phases
were separated. The product was extracted with CH2Cl2
(3ϫ10 mL), the combined organic layer was washed with brine
(2ϫ10 mL), dried with MgSO4 and the solvent was removed under
reduced pressure to afford the crude product, which was purified
by column chromatography on silica gel (hexane/ethyl acetate,
3.5:1) to furnish 16 as a colourless solid (0.347 g, 88%). M.p. 86–
(d, Ar), 198.7 (s, C-2) ppm. Data for 18/19: IR (KBr): ν = 3045,
˜
3000, 2920, 2850 (=CH, C–H), 1710 (C=O), 1660–1555 (C=C)
cm–1. MS (EI, 80 eV, 80 °C): m/z (%) = 225 (28) [M]+, 182 (61) [M –
CH3CO]+, 154 (100) [M – C4H7O]+, 43 (21) [CH3CO]+. HRMS (EI,
80 eV, 80 °C): calcd. for C15H15NO 225.11537; found 225.11486.
trans-2-[(E)-2-Quinolin-8-ylethenyl]cyclohexanol (21) and 2-(2-Quin-
olin-8-ylethyl)cyclohexanone (10): A high-pressure tube was loaded
with compound 14 (0.855 g, 2.00 mmol), sodium hydrogencarbon-
ate (0.504 g, 6.00 mmol), triethylbenzylammonium chloride
(0.547 g, 2.40 mmol), palladium(II) acetate (45 mg, 0.20 mmol) and
DMF (4 mL). The suspension was stirred at room temperature un-
der an atmosphere of argon for 10 min. A solution of trans-2-vinyl-
cyclohexanol (20) (1.01 g, 8.00 mmol) in DMF (2 mL) was then
2330
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© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 2325–2335

Stereoselective SmI2 Promoted Cyclizations of Quinolyl-Substituted Ketones
added, and the vessel was sealed and heated to 90 °C for 48 h. The
vessel was then cooled to room temperature and distilled water was
added. The product was extracted with CH2Cl2, the combined or-
ganic layer was washed with brine and dried with MgSO4 and the
solvent was removed under reduced pressure. Column chromatog-
raphy on silica gel (hexane/ethyl acetate, from 6:1 to 2:1) yielded
21 as a colourless solid (380 mg, 75%) and 10 as a colourless oil
6-Quinolin-8-ylhexan-2-one (8): A 5:1 mixture of compounds 18
and 19 (144 mg, 0.647 mmol) and Pd/C (30 mg) afforded, after pu-
rification by column chromatography on silica gel (hexane/ethyl
acetate from 4:1 to 3:1), 8 as a colourless oil (122 mg, 84%). 1H
NMR (500 MHz, CDCl3): δ = 1.63–1.70 (m, 2 H, 4-H),1.72–1.77
3
(m, 2 H, 5-H), 2.05 (s, 3 H, 1-H), 2.42 (t, J = 7.4 Hz, 2 H, 3-H),
3
3
3
3.24 (t, J = 7.6 Hz 2 H, 6-H), 7.31 (dd, J = 8.2 Hz, J = 4.2 Hz,
1
3
(43 mg, 8%). Data for 21: M.p. 139–141 °C. H NMR (500 MHz,
1 H, Ar), 7.40 (dd, 3J = 8.1 Hz, J = 7.0 Hz, 1 H, Ar), 7.49 (dd, 3J
CDCl3): δ = 1.28–1.36 (m, 4 H, 3-H, 4-H, 6-H), 1.70–1.72 (m, 1 = 7.0 Hz, 4J = 1.2 Hz, 1 H, Ar), 7.60 (dd, 3J = 8.1 Hz, 4J = 1.2 Hz,
H, 5-H), 1.79–1.81 (m, 1 H, 5-H), 1.90–1.93 (m, 1 H, 3-H), 2.08– 1 H, Ar), 8.05 (dd, 3J = 8.2 Hz, 4J = 1.8 Hz, 1 H, Ar), 8.87 (dd, 3J =
2.15 (m, 1 H, 6-H), 2.22 (s, 1 H, OH), 2.25–2.29 (m, 1 H, 2-H), 4.2 Hz, 4J = 1.8 Hz, 1 H, Ar) ppm. 13C NMR (126 MHz, CDCl3): δ
3
3
3.39–3.44 (m, 1 H, 1-H), 6.31 (dd, J = 16.1 Hz, J = 8.8 Hz, 1 H,
1Ј-H), 7.38 (dd, 3J = 8.2 Hz, 3J = 4.2 Hz, 1 H, Ar), 7.48 (t, 3J ≈ 3), 120.6, 125.8, 126.1, (3 d, Ar), 128.2 (s, Ar), 128.6, 136.1 (2 d,
7.5 Hz, 1 H, Ar), 7.69 (dd, 3J = 8.2 Hz, 4J = 1.2 Hz, 1 H, Ar), 7.80
Ar), 140.7, 146.6 (2 s, Ar), 149.0 (d, Ar), 209.0 (s, CO) ppm. IR
= 23.7 (t, C-4), 29.7 (q, C-1), 29.9 (t, C-5), 31.0 (t, C-6), 43.5 (t, C-
3
3
4
(d, J = 16.1 Hz, 1 H, 2Ј-H), 7.87 (dd, J = 7.2 Hz, J = 1.2 Hz, 1
H, Ar), 8.10 (dd, 3J = 8.2 Hz, 4J = 1.8 Hz, 1 H, Ar), 8.92 (dd, 3J =
4.2 Hz, 4J = 1.8 Hz, 1 H, Ar) ppm. 13C NMR (126 MHz, CDCl3): δ
= 24.8 (t, C-4), 25.2 (t, C-5), 31.5 (t, C-3), 34.0 (t, C-6) 50.9 (d, C-
2), 73.3 (d, C-1), 121.0, 125.5, 126.4, 127.1 (4 d, Ar), 127.9 (d, C-
2Ј), 128.5 (s, Ar), 134.6 (d, C-1Ј), 135.9 (s, Ar), 136.3 (d, Ar), 145.7
(film): ν = 3080, 3050, 3030, 3005, 2945, 2880, 2860 (=CH, CH),
˜
1710 (C=O), 1615, 1595, 1575 (C=C) cm–1. MS (EI, 80 eV, 60 °C)
m/z (%) = 227 (36) [M]+, 184 (10) [M – CH3CO]+, 170 (100) [M –
C3H5O]+, 157 (83) [M – C4H7O]+, 142 (8) [M – C5H9O]+, 43 (37)
[CH3CO]+. HRMS (EI, 80 eV, 60 °C): calcd. for C15H17NO
227.13101; found 227.13233. C15H17NO (227.3): calcd. C 79.26, H
7.54, N 6.16; found C 78.68, H 7.24, N 5.86.
(s, Ar), 149.6 (d, Ar) ppm. IR (KBr): ν = 3420 (OH), 3045, 3030,
˜
2920, 2845 (=CH, C–H), 1645, 1610, 1595, 1570 (C=C) cm–1. MS
(EI, 80 eV, 70 °C): m/z (%) = 253 (17) [M]+, 225 (7), 154 (100)
[M – C6H11O]+. HRMS (EI, 80 eV, 70 °C): calcd. for C17H19NO
253.14667; found 253.14573. Data for 10: 1H NMR (500 MHz,
CDCl3): δ = 1.42–1.45 (m, 1 H, 3-H), 1.57–1.69 (m, 3 H, 1Ј-H, 4-
H, 5-H), 1.79–1.82 (m, 1 H, 5-H), 1.97–1.99 (m, 1 H, 4-H), 2.19–
2.29 (m, 3 H, 3-H, 1Ј-H, 6-H), 2.36–2.41 (m, 2 H, 2-H, 6-H), 3.24–
trans-2-(2-Quinolin-8-ylethyl)cyclohexanol: Compound 21 (0.516 g,
2.04 mmol) and Pd/C (103 mg) afforded, after purification by col-
umn chromatography on silica gel (hexane/ethyl acetate, 3:1), the
product as colourless oil (430 mg, 83%). 1H NMR (500 MHz,
CDCl3): δ = 1.09–1.40 (m, 4 H, 4-H, 5-H), 1.61–1.90 (m, 6 H, 1Ј-
3
H, 3-H, 6-H), 2.01–2.06 (m, 1 H, 2-H), 3.08 (ddd, 2J = 12.6 Hz, J
3
2
3
= 11.0 Hz, J = 5.8 Hz, 1 H, 2Ј-H), 3.38 (ddd, J = 12.6 Hz, J =
3
3
3.29 (m, 2 H, 2Ј-H), 7.32 (dd, J = 8.2 Hz, J = 4.1 Hz, 1 H, Ar),
10.8 Hz, 3J = 5.4 Hz, 1 H, 2Ј-H), 3.51–3.59 (m, 1 H, 1-H), 5.66 (br.
s, 1 H, OH), 7.33 (dd, J = 8.1 Hz, J = 4.1 Hz, 1 H, Ar), 7.38 (t,
3
3
3
7.42 (dd, J = 8.0 Hz, J = 7.1 Hz, 1 H, Ar), 7.55 (d, J = 7.1 Hz,
3
3
1 H, Ar), 7.61 (dd, 3J = 8.0 Hz, J = 1.4 Hz, 1 H, Ar), 8.07 (dd, 3J
4
3J ≈ 7.5 Hz, 1 H, Ar), 7.49 (d, J = 6.3 Hz, 1 H, Ar), 7.60 (d, J =
8.2 Hz, 1 H, Ar), 8.09 (dd, 3J = 8.1 Hz, 4J = 1.8 Hz, 1 H, Ar), 8.84
(dd, 3J = 4.1 Hz, 4J = 1.8 Hz, 1 H, Ar) ppm. 13C NMR (126 MHz,
CDCl3): δ = 25.1, 28.0, 28.4, 31.1 34.6, 34.6 (6 t, C-3, C-4, C-5, C-
6, C-1Ј, C-2Ј), 45.0 (d, C-2), 74.5 (d, C-1), 120.6, 125.8, 126.2,
128.4, 128.8 (5 d, Ar), 136.8, 141.4, 146.0 (3 s, Ar), 148.8 (d, Ar)
3
3
= 8.2 Hz, 4J = 1.8 Hz, 1 H, Ar), 8.87 (dd, 3J = 4.1 Hz, 4J = 1.8 Hz,
1 H, Ar) ppm. 13C NMR (126 MHz, CDCl3): δ = 24.7 (t, C-5),
28.0 (t, C-4), 28.6 (t, C-2Ј), 30.2 (t, C-1Ј), 34.0 (t, C-3), 41.9 (t, C-
6), 50.4 (d, C-2), 120.6, 125.8, 126.2 (3 d, Ar), 128.2 (s, Ar), 128.6,
136.2 (2 d, Ar), 140.2, 146.7 (2 s, Ar), 149.1 (d, Ar), 213.4 (s, C-1)
ppm. IR (film): ν = 3060, 3030, 2930, 2860 (=CH, C–H), 1705
˜
ppm. IR (film): ν = 3375 (OH), 3060, 3030, 3040, 2925, 2855 (=CH,
˜
(C=O), 1615, 1595, 1575 (C=C) cm–1. C17H19NO (253.3): calcd. C
80.60, H 7.56, N 5.53; found C 80.08, H 7.74, N 4.90.
C–H), 1615, 1595, 1575 (C=C) cm–1. MS (EI, 80 eV, 80 °C): m/z
(%) = 255 (43) [M]+, 237 (11) [M – H2O]+, 156 (69) [C11H10N]+,
143 (100). HRMS (EI, 80 eV, 80 °C): calcd. for C17H21NO
255.16231; found 255.16352.
Typical Hydrogenation Procedure: Hydrogen gas was bubbled
through a suspension of Pd/C (10 wt.-%) in EtOH (5 mL/mmol)
for 2 h. Then, a solution of the corresponding olefin in EtOH or
AcOEt (3 mL/mmol) was added, and the mixture was stirred at
room temperature under an atmosphere of hydrogen. Completion
of the reaction was followed by TLC analysis (hexane/ethyl acetate,
3:1). The solid residue was filtered off through a pad of silica gel
and thoroughly washed with EtOH. The organic solvent was re-
moved under reduced pressure, and the crude product was purified
by column chromatography on silica gel.
2-(2-Quinolin-8-ylethyl)cyclohexanone (10): A solution of trans-2-
(2-quinolin-8-ylethyl)cyclohexanol (800 mg, 3.14 mmol) and trieth-
ylamine (0.80 mL, 6.0 mmol) in DMSO (30 mL) was cooled to 0 °C
and Py·SO3 complex (848 mg, 5.33 mmol) was then added. The
mixture was stirred for 20 min at this temperature and then warmed
to room temperature and stirred for another 2 h. The mixture was
quenched with distilled water, and the product was extracted with
CH2Cl2. The combined organic phase was washed with brine, dried
with MgSO4 and filtered, and the solvent was removed under re-
duced pressure. The crude product was purified by column
chromatography on silica gel (hexane/ethyl acetate, 3:1) to yield 10
as a colourless oil (447 mg, 56%). For analytical data see above.
4-Quinolin-8-ylbutan-2-one (6): Compound 16 (300 mg, 1.52 mmol)
and Pd/C (60 mg) afforded, after purification by column
chromatography on silica gel (hexane/ethyl acetate, 3:1), 6 as a
colourless oil (161 mg, 53%). 1H NMR (500 MHz, CDCl3): δ =
2.11 (s, 3 H, 1-H), 2.94 (t, 3J = 7.6 Hz, 2 H, 3-H), 3.49 (t, 3J =
General Procedure for SmI2 Induced Coupling Reactions: Samarium
7.6 Hz, 2 H, 4-H), 7.34 (dd, 3J = 8.2 Hz, 3J = 4.2 Hz, 1 H, Ar), (2.6–3.0 equiv.) and 1,2-diiodoethane (2.4–2.7 equiv.) were sus-
3
3
3
7.40 (dd, J = 8.2 Hz, J = 7.0 Hz, 1 H, Ar), 7.55 (d, J = 7.0 Hz,
pended in THF (25 mL/2.20 mmol SmI2) under an atmosphere of
argon and stirred at room temperature until the colour of the sus-
pension turned to dark blue (approximately 2 h). The flask was
evacuated, purged with argon and HMPA (18 equiv.) was added.
1 H, Ar), 7.63 (dd, 3J = 8.2 Hz, J = 1.8 Hz, 1 H, Ar), 8.08 (dd, 3J
4
= 8.2 Hz, 4J = 1.8 Hz, 1 H, Ar), 8.88 (dd, 3J = 4.2 Hz, 4J = 1.8 Hz,
1 H, Ar) ppm. 13C NMR (126 MHz, CDCl3): δ = 26.2 (t, C-4),
29.8 (q, C-1), 44.5 (t, C-3), 120.8, 126.2, 126.3 (3 d, Ar), 128.3 (s, The hetaryl-substituted ketone (1 equiv.) and tBuOH (2.2 equiv.)
Ar), 129.1, 136.2 (2 d, Ar), 139.6, 146.6 (2 s, Ar), 149.2 (d, Ar),
208.4 (s, C-2) ppm.
were dissolved in THF (15 mL/mmol of ketone) and argon was
purged through for 10 min. The solution was then added to the
Eur. J. Org. Chem. 2008, 2325–2335
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2331

F. Aulenta, U. K. Wefelscheid, I. Brüdgam, H.-U. Reißig
FULL PAPER
deep-violet solution of SmI2 in THF–HMPA. The reaction was
stirred for 16 h at room temperature and then quenched by the
addition of a saturated solution of sodium hydrogencarbonate
(15 mL). The aqueous phase was extracted with Et2O (3ϫ20 mL),
and the combined organic layers were washed with distilled water
(1ϫ) and brine (2ϫ), dried with MgSO4 and filtered, and the sol-
vent was removed under reduced pressure to give the crude prod-
uct.
(2 t, C-4, C-5), 27.6 (q, CH3), 29.8 (t, C-7Ј), 34.8, 35.6 (2 t, C-3,
C-6), 46.4 (s, C-1), 73.9 (s, C-2), 121.2 (d, Ar), 122.7 (d, C-6Ј), 130.5
(s, Ar), 131.7 (d, C-5Ј), 136.7, 145.5 (2 d, Ar), 161.3 (s, Ar) ppm.
IR (film): ν = 3250 (OH), 3045, 2930, 2860 (=CH, C–H), 1670,
˜
1615, 1590, 1575 (C=C) cm–1. MS (EI, 80 eV, 30 °C) m/z (%) = 229
(60) [M]+, 228 (60) [M – H]+, 214 (2) [M – CH3]+, 144 (100) [M –
C5H8O]+, 130 (43) [M – C6H11O]+. HRMS (EI, 80 eV, 30 °C):
calcd. for C15H19NO 229.14667; found 229.14588.
4-Quinolin-8-ylbutan-2-ol (22): Compound 6 (110 mg, 0.552 mmol),
samarium (0.226 g, 1.50 mmol), 1,2-diiodoethane (0.386 g,
1.38 mmol), HMPA (1.76 mL, 9.90 mmol) and tBuOH (0.11 mL,
1.2 mmol) afforded, after purification by column chromatography
on silica gel (hexane/ethyl acetate from 3:1 to 1:1), 22 as a brownish
rac-(4bR,6aS,9aR,9bR)-4b,5,6,6a,7,8,9,9b-Octahydro-9aH-indeno-
[4,5-h]quinolin-9a-ol (25): Compound 9 (0.90 g, 0.38 mmol), samar-
ium (0.154 g, 1.02 mmol), 1,2-diiodoethane (0.264 g, 0.937 mmol),
HMPA (1.2 mL, 6.8 mmol) and tBuOH (0.07 mL, 0.8 mmol) af-
forded, after purification by column chromatography on silica gel
1
3
1
oil (27 mg, 24%). H NMR (250 MHz, CDCl3): δ = 1.12 (d, J =
5.6 Hz, 3 H, 1-H), 1.75–1.95 (m, 2 H, 3-H), 2.97–3.03 (m, 1 H, 4-
(hexane/ethyl acetate, 4:1), 25 as a colourless oil (30 mg, 33%). H
NMR (500 MHz, CDCl3): δ = 1.13–1.25 (m, 2 H, 6-H, 9-H), 1.27–
H), 3.37–3.44 (m, 1 H, 4-H), 3.70–3.82 (m, 1 H, 2-H), 5.49 (br. s, 1.37 (m, 3 H, 7-H, 9-H, OH), 1.39–1.43 (m, 1 H, 8-H), 1.57–1.62
3
3
3
1 H, OH), 7.41 (dd, J = 8.5 Hz, J = 4.3 Hz, 1 H, Ar), 7.50 (t, J (m, 3 H, 5-H, 6-H, 8-H), 1.72–1.79 (m, 1 H, 6a-H), 1.98 (ddt, 2J =
3
3
3
3
≈ 7.5 Hz, 1 H, Ar), 7.60 (d, J = 7.3 Hz, 1 H, Ar), 7.69 (dd, J = 12.9 Hz, J = 11.0 Hz, J ≈ 6.5 Hz, 1 H, 7-H), 2.78–2.81 (m, 2 H,
4
3
4
7.9 Hz, J = 1.2 Hz, 1 H, Ar), 8.17 (dd, J = 8.5 Hz, J = 1.8 Hz,
1 H, Ar), 8.88 (d, 3J = 4.3 Hz, 1 H, Ar) ppm. 13C NMR (126 MHz,
CDCl3): δ = 22.7 (q, C-1), 27.0 (t, C-4), 41.2 (t, C-3), 64.6 (d, C-
5-H, 9b-H), 3.35 (quint., J ≈ 4 Hz, 1 H, 4b-H), 6.30 (dd, 3J =
9.8 Hz, 3J = 5.6 Hz, 1 H, 10-H), 6.47 (dd, 3J = 9.8 Hz, 4J = 1.0 Hz,
3
3
4
1 H, 11-H), 7.03 (ddd, J = 7.5 Hz, J = 5.0 Hz, J = 1.0 Hz, 1 H,
2), 121.0, 126.2, 126.7 (3 d, Ar), 128.2 (s, Ar), 130.1, 137.0 (2 d, Ar), 7.23 (dd, 3J = 7.5 Hz, 4J = 1.6 Hz, 1 H, Ar), 8.34 (dd, J =
3
4
Ar), 140.7, 146.8 (2 s, Ar), 149.3 (d, Ar) ppm. IR (film): ν = 3360
5.0 Hz, J = 1.6 Hz, 1 H, Ar) ppm. 13C NMR (126 MHz, CDCl3):
δ = 19.7, 23.4, 27.3, 29.2, 32.7 (5 t, C-5, C-6, C-7, C-8, C-9), 39.4
(d, C-4b), 44.7 (d, C-9b), 47.8 (d, C-6a), 84.3 (s, C-9a), 121.3 (d,
˜
(OH), 3085, 3060, 3045, 3005, 2965, 2925, 2870 (=CH, C–H), 1615,
1595, 1580 (C=C) cm–1. MS (EI, 80 eV, 50 °C) m/z (%) = 201 (19)
[M]+, 200 (5) [M – H]+, 186 (13) [M – CH3]+, 156 (100) [M – Ar), 126.7 (d, C-11), 129.6 (s, Ar), 132.0 (d, Ar), 132.2 (d, C-10),
C2H5O]+. HRMS (EI, 80 eV, 50 °C): calcd. for C13H15NO
147.1 (d, Ar), 157.7 (s, Ar) ppm. IR (film): ν = 3390 (OH), 3040,
˜
201.11537; found 201.11644.
2950, 2925, 2870 (=CH, C–H), 1665, 1635, 1580, 1560 (C=C) cm–1.
MS (EI, 80 eV, 40 °C): m/z (%) = 241 (3) [M]+, 142 (3) [M –
C6H11O]+, 130 (100) [C9H8N]+. HRMS (EI, 80 eV, 40 °C): calcd.
for C16H19NO 241.14667; found 241.14733.
rac-(6aR,10aR)-7-Methyl-6a,7,8,9,10,10a-hexahydrobenzo[h]-
quinolin-7-ol (23): Compound 7 (0.087 g, 0.41 mmol), samarium
(0.168 g, 1.12 mmol), 1,2-diiodoethane (0.288 g, 1.03 mmol),
HMPA (1.31 mL, 7.38 mmol) and tBuOH (0.08 mL, 0.9 mmol) af-
forded, after purification by column chromatography on silica gel
rac-(4bR,6aS,10aR,10bR)-4b,6,6a,7,8,9,10,10b-Octahydronaphtho-
[1,2-h]quinolin-10a(5H)-ol (26): Compound 10 (0.342 g, 1.35
mmol), samarium (0.602 g, 4.00 mmol), 1,2-diiodoethane (1.02 g,
(hexane/ethyl acetate from 4:1 to 1:1), 23 as a brownish oil (47 mg,
1
53%). H NMR (500 MHz, CDCl3): δ = 1.34 (s, 3 H, CH3), 1.40– 3.65 mmol), HMPA (4.31 mL, 24.3 mmol) and tBuOH (0.26 mL,
1.55, 1.60–1.63, 1.80–1.84 (3 m, 4 H, 1 H, 1 H, 8-H, 9-H, 10-H), 3.0 mmol) afforded, after purification by column chromatography
2.64 (mc, 1 H, 6a-H), 2.97 (br. s, 1 H, OH), 3.45–3.48 (m, 1 H, 10a- on silica gel (hexane/ethyl acetate, 4:1) and preparative HPLC (hex-
3
3
3
H), 5.78 (dd, J = 9.8 Hz, J = 1.2 Hz, 1 H, 6-H), 6.38 (dd, J =
ane/2-propanol, 95:5), 26 as a colourless oil (115 mg, 33%). 1H
3
3
3
3
9.8 Hz, J = 3.2 Hz, 1 H, 5-H), 7.02 (dd, J = 7.5 Hz, J = 4.3 Hz, NMR (500 MHz, CDCl3): δ = 0.74 (td, J ≈ 13.5 Hz, J = 4.1 Hz,
3
4
3
1 H, Ar), 7.25 (dd, J = 7.5 Hz, J = 1.6 Hz, 1 H, Ar), 8.27 (d, J
= 4.3 Hz, 1 H, Ar) ppm. 13C NMR (126 MHz, CDCl3): δ = 19.8,
25.5 (2 t, C-9, C-10), 28.6 (q, CH3), 35.2 (t, C-8), 39.0 (d, C-10a),
46.7 (d, C-6a), 70.5 (s, C-7), 121.7 (d, Ar), 126.3 (d, C-5), 128.1 (s,
1 H, 10-H), 1.14–1.31 (m, 7 H, 7-H, 8-H, 9-H, 10-H, OH), 1.40–
1.44 (m, 1 H, 6-H), 1.53–1.60 (m, 1 H, 6a-H), 1.62 (ddd, 2J =
3
3
13.2 Hz, J = 5.3 Hz, J = 3.4 Hz, 1 H, 5-H), 1.73 (qd, J ≈ 13 Hz,
3J = 3.4 Hz, 1 H, 6-H), 1.86 (tt, J ≈ 13.5 Hz, J ≈ 4.5 Hz, 1 H, 7-
3
Ar), 129.8 (d, C-6), 132.8, 147.1 (2 d, Ar), 160.7 (s, Ar) ppm. IR H), 2.55 (dd, 3J = 7.7 Hz, J = 6.1 Hz, 1 H, 10b-H), 2.94 (dq, 2J =
3
(film): ν = 3360 (OH), 3040, 2930, 2855 (=CH, C–H), 1630, 1580,
13.2 Hz, 3J ≈ 2 Hz, 1 H, 5-H), 3.31 (t, 3J ≈ 6.5 Hz, 1 H, 4b-H),
6.22 (dd, 3J = 9.8 Hz, 3J = 6.1 Hz, 1 H, 11-H), 6.53 (d, 3J = 9.8 Hz,
˜
1565 (C=C) cm–1. MS (EI, 80 eV, 50 °C) m/z (%) = 215 (3) [M]+,
214 (2) [M – H]+, 130 (100) [M – C5H9O]+. HRMS (EI, 80 eV, 1 H, 12-H), 7.01 (ddd, J = 7.5 Hz, J = 4.9 Hz, J = 1.0 Hz, 1 H,
3
3
4
3
50 °C): calcd. for C14H17NO 215.13101; found 215.13099.
Ar), 7.20 (dd, 3J = 7.5 Hz, 4J = 1.6 Hz, 1 H, Ar), 8.34 (dd, J =
4
4.9 Hz, J = 1.6 Hz, 1 H, Ar) ppm. 13C NMR (126 MHz, CDCl3):
rac-(1R,2S)-2-Methyl-7ЈH-spiro[cyclohexane-1,8Ј-quinolin]-2-ol (24):
Compound 8 (0.095 g, 0.42 mmol), samarium (0.171 g, 1.14 mmol),
1,2-diiodoethane (0.293 g, 1.04 mmol), HMPA (1.33 mL,
7.52 mmol) and tBuOH (0.08 mL, 0.9 mmol) afforded, after purifi-
cation by column chromatography on silica gel (hexane/ethyl ace-
tate, 3.5:1), 24 as a brownish oil (11 mg, 11%). 1H NMR
(500 MHz, CDCl3): δ = 1.38, 1.53–1.61, 1.78, 2.01–2.16, 2.43 (mc,
δ = 20.2, 21.3, 24.0, 25.3, 27.0, 27.3 (6 t, C-5, C-6, C-7, C-8, C-9,
C-10), 39.8 (d, C-4b), 43.8 (d, C-6a), 48.4 (d, C-10b), 74.0 (s, C-
10a), 121.1 (d, Ar), 128.0 (d, C-12), 130.0 (s, Ar), 131.4 (d, C-11),
132.0, 146.9 (2 d, Ar), 157.9 (s, Ar) ppm. IR (film): ν = 3400 (OH),
˜
3040, 2930, 2860 (=CH, C–H), 1635, 1615, 1595, 1580, 1560 (C=C)
cm–1. MS (EI, 80 eV, 70 °C): m/z (%) = 255 (9) [M]+, 130 (100).
HRMS (EI, 80 eV, 70 °C): calcd. for C17H21NO 255.16231; found
255.16165.
3
1 H; m, 4 H; td, J = 13.8 Hz, J = 4.1 Hz, 1 H; m, 1 H; td, J =
3
12.8 Hz, J = 4.9 Hz, 1 H; 3-H, 4-H, 5-H, 6-H), 3.40 (mc, 2 H, 7Ј-
3
3
3
H), 5.92 (dt, J = 10.5 Hz, J = 3.6 Hz, 1 H, 6Ј-H), 6.24 (dt, J =
10.5 Hz, 3J = 2.0 Hz, 1 H, 5Ј-H), 7.12 (dd, 3J = 7.7 Hz, 3J = 4.8 Hz,
1 H, Ar), 7.46 (ddt, 3J = 7.7 Hz, 4J = 1.6 Hz, 4J = 0.8 Hz, 1 H,
rac-tert-Butyl (3aS,3bR,9bR,11aR)-3a-Hydroxy-1,3,3a,3b,9b,10,-
11,11a-octahydro-2H-isoindolo[4,5-h]quinoline-2-carboxylate (27):
Compound 11 (60 mg, 0.18 mmol), samarium (0.079 g,
0.53 mmol), 1,2-diiodoethane (0.122 g, 0.433 mmol), HMPA
(0.56 mL, 3.2 mmol) and tBuOH (0.03 mL, 0.4 mmol) afforded, af-
Ar), 7.65 (s, 1 H, OH), 8.37 (ddt, J = 4.8 Hz, 4J = 1.6 Hz, 4J =
3
0.8 Hz, 1 H, Ar) ppm. 13C NMR (126 MHz, CDCl3): δ = 21.0, 21.1
2332
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 2325–2335

Stereoselective SmI2 Promoted Cyclizations of Quinolyl-Substituted Ketones
ter purification by column chromatography on silica gel (hexane/
ethyl acetate from 3:1 to ethyl acetate 100%) and repeated washing
of the solid with cold Et2O, 27 as a colourless solid (30 mg,
2.5 Hz, 4J = 0.6 Hz, 1 H, 11c-H), 7.12 (ddd, 3J = 7.6 Hz, 3J =
5
3
4
4.9 Hz, J = 1.0 Hz, 1 H, Ar), 7.63 (dd, J = 7.6 Hz, J = 1.7 Hz,
1 H, Ar), 8.53 (dd, 3J = 4.9 Hz, 4J = 1.7 Hz, 1 H, Ar) ppm. 13C
50%).[24] M.p. 201–205 °C. 1H NMR (500 MHz, CD3OD): δ = NMR (126 MHz, CDCl3): δ = 20.0, 21.2, 24.2, 25.2, 27.0, 28.6 (6
1.20–1.25 (m, 2 H, 11-H), 1.30 (s, 4 H, tBu), 1.38 (s, 5 H, tBu), t, C-6, C-7, C-8, C-9, C-10, C-11), 35.2 (d, C-5b), 44.8 (d, C-7a),
1.63 (mc, 1 H, 10-H), 1.72 (mc, 1 H, 10-H), 2.03 (mc, 1 H, 11a-H),
46.2 (d, C-11b), 53.4 (d, C-1a), 55.1 (d, C-11), 73.8 (s, C-11a), 120.9
2.70–2.81 (m, 2 H, 3-H, OH), 2.85 (mc, 1 H, 3b-H), 3.08–3.10 (m, (d, Ar), 128.8 (s, Ar), 136.4, 148.8 (2 d, Ar), 157.7 (s, Ar) ppm. IR
2 H, 1-H, 3-H), 3.38 (mc, 1 H, 9b-H), 3.56 (mc, 1 H, 1-H), 6.28 (KBr): ν = 3490 (OH), 3065, 3045, 3005, 2945, 2930, 2850 (=CH,
˜
(mc, 1 H, 4-H), 6.59 (mc, 1 H, 5-H), 7.19 (mc, 1 H, Ar), 7.44 (mc,
1 H, Ar), 8.29 (mc, 1 H, Ar) ppm. 13C NMR (126 MHz, CD3OD):
δ = 23.5, 23.6, 26.4, 26.6 (4 t, C-10, C-11), 28.6, 28.7 (2 q, tBu),
40.4, 44.9, 46.1, 46.8 (4 d, C-3b, C-9b, C-11a), 51.5, 52.0, 54.0, 54.6
(4 t, C-1, C-3), 80.6, 80.7, 80.8 (3 q, tBu, C-3a), 123.29, 123.32,
128.01, 128.04 (4 d, Ar, C-5), 131.16, 131.24 (2 s, Ar), 131.8, 131.9,
134.4, 134.6 (4 d, C-4, Ar), 148.1 (d, Ar), 156.7, 156.8, 158.2, 158.3
C–H), 1595, 1575 (C=C) cm–1. C17H21NO2 (271.4): calcd. C 75.25,
H 7.80, N 5.16; found C 75.61, H 7.58, N 5.03.
rac-(4aR,6aR,7S,12aR,12bS)-2,3,4,4a,5,6,12,12a-Octahydronaph-
tho[2,1-g]quinoline-6a,7,12b(1H,7H)-triol (30): To a solution of
compound 28 (70 mg, 0.27 mmol) in tBuOH (1.35 mL) was added
distilled water (1.35 mL), potassium carbonate (112 mg,
0.810 mmol), quinuclidine (5 mg, 0.04 mmol), methylsulfonamide
(26 mg, 0.27 mmol), potassium osmate(VI) dihydrate (2.5 mg,
0.0068 mmol) and potassium hexacyanoferrate(III) (267 mg,
0.810 mmol), and the mixture was stirred vigorously overnight.
Then, saturated solution of NaHSO3 (3 mL) was added, and the
reaction mixture was stirred for 1 h. The aqueous phase was sepa-
rated and extracted with CH2Cl2 (3ϫ5 mL). The organic phase
was dried with MgSO4 and filtered, and the solvent was removed
under reduced pressure. The crude product was purified by column
chromatography on silica gel (ethyl acetate/MeOH, 1:0 to 7:3) to
(4 s, C=O, Ar) ppm. IR (KBr): ν = 3345 (OH), 3050, 2985, 2935,
˜
2885 (=CH, C–H), 1665, 1655 (C=O), 1565 (C=C) cm–1. MS (EI,
80 eV, 120 °C): m/z (%) = 342 (26) [M]+, 286 (7) [M – C4H8]+, 130
(100) [C9H8N]+, 57 (91) [C4H9]+. HRMS (EI, 80 eV, 120 °C): calcd.
for C20H26N2O3 342.19434; found 342.19544.
rac-(4aR,12aS,12bS)-2,3,4,4a,5,6,12,12a-Octahydronaphtho[2,1-g]-
quinolin-12b(1H)-ol (28): Compound 12 (0.300 g, 1.19 mmol),
samarium (0.464 g, 3.09 mmol), 1,2-diiodoethane (0.835 g,
2.96 mmol), HMPA (3.2 mL, 21 mmol) and tBuOH (0.22 mL,
2.6 mmol) afforded, after purification by column chromatography
on silica gel (hexane/ethyl acetate, 3:1) and repeated washing of the
solid with cold Et2O, 28 as a colourless solid (125 mg, 54%). M.p.
1
afford 30 as a colourless solid (56 mg, 72%). M.p. 210–215 °C. H
3
NMR (500 MHz, CDCl3): δ = 0.91 (td, J ≈ 13 Hz, J = 3.1 Hz, 1
3
3
H, 1-H), 1.02 (br. d, J ≈ 13 Hz, 1 H, 1-H), 1.14 (td, J ≈ 13 Hz, J
= 3.8 Hz, 1 H, 6-H), 1.15–1.28, 1.37–1.45, 1.63–1.70 (3 m, 2 H, 3
H, 3 H, 2-H, 3-H, 4-H, 5-H, 4a-H), 2.16 (mc, 1 H, 4-H), 2.44 (dt,
J = 13.0 Hz, 3J = 2.3 Hz, 1 H, 6-H), 2.62 (d, 3J = 9.2 Hz, 1 H, 12a-
H), 2.63 (br. s, 1 H, OH), 3.28 (br. s, 1 H, OH), 3.49–3.58 (m, 2 H,
12-H), 4.64 (s, 1 H, 7-H), 4.90 (br. s, 1 H, OH), 7.11 (dd, 3J =
1
193–195 °C. H NMR (500 MHz, CDCl3): δ = 1.23–1.44 (m, 7 H,
1-H, 2-H, 3-H, 4-H), 1.62–1.68 (m, 1 H, 5-H), 1.69–1.75 (m, 2 H,
2
3
3
4a-H, 5-H), 1.95 (dddd, J = 14.5 Hz, J = 14.5 Hz, J = 3.9 Hz,
3J = 3.9 Hz, 1 H, 4-H), 2.06 (br. s, 1 H, OH), 2.25 (ddd, 2J =
11.6 Hz, 3J = 11.6 Hz, 3J = 5.2 Hz, 1 H, 6-H), 2.40 (mc, 1 H, 6-H),
3
2
3
3
3
4
2.57 (br. d, J = 11.1 Hz, 1 H, 12a-H), 3.16 (dd, J = 18.1 Hz, J
7.8 Hz, J = 4.8 Hz, 1 H, Ar), 7.91 (dd, J = 7.8 Hz, J = 1.4 Hz,
2
3
3
4
= 11.1 Hz, 1 H, 12-H), 3.40 (dd, J = 18.1 Hz, J = 1.8 Hz, 1 H,
12-H), 6.11 (s, 1 H, 7-H), 6.97 (ddd, J = 7.5 Hz, J = 5.0 Hz, J
1 H, Ar), 8.19 (dd, J = 4.8 Hz, J = 1.4 Hz, 1 H, 1 H, Ar) ppm.
13C NMR (126 MHz, CDCl3): δ = 20.5, 21.7, 25.6, 26.8, 27.3, 30.1,
36.8 (7 t, C-1, C-2, C-3, C-4, C-5, C-6, C-12), 44.0 (d, C-4a), 54.7
3
3
5
3
4
= 0.6 Hz, 1 H, Ar), 7.13 (dd, J = 7.5 Hz, J = 1.5 Hz, 1 H, Ar),
8.20 (dd, 3J = 5.0 Hz, 4J = 1.5 Hz, 1 H, Ar) ppm. 13C NMR (d, C-12a), 68.9 (d, C-7), 71.3, 74.6 (2 s, C-6a, C-12b), 121.9 (d,
(126 MHz, CDCl3): δ = 19.9, 21.1, 25.7, 27.0, 29.1, 29.9, 35.1 (7 t,
Ar), 134.6 (s, Ar), 137.9 (d, Ar), 146.8 (d, Ar), 156.2 (s, Ar) ppm.
IR (KBr): ν = 3465, 3415, 3175 (OH), 3065, 3010, 2935, 2865, 2850
C-1, C-2, C-3, C-4, C-5, C-6, C-12), 43.6 (d, C-4a), 49.9 (d, C-12a),
˜
76.0 (s, C-12b), 119.3 (d, C-7), 121.4 (d, Ar), 128.8 (s, Ar), 131.7 (=CH, C–H), 1585 (C=C) cm–1. C17H23NO3 (289.4): calcd. C
(d, Ar), 143.0 (s, C-6a), 146.5 (d, Ar), 155.2 (s, Ar) ppm. IR (KBr):
70.56, H 8.01, N 4.84; found C 70.06, H 7.77, N 5.01.
ν = 3310 (OH), 3070, 3045, 3010, 2920, 2910, 2860, 2850 (=CH,
˜
rac-(4aR,6aR,12aS,12bS)-2,3,4,4a,5,6,6a,7,12,12a-Decahydronaph-
tho[2,1-g]quinolin-12b(1H)-ol-borane Complex (31): To a solution of
compound 28 (60 mg, 0.23 mmol) in THF (3 mL) was added
BH3·THF (ca. 1  sol. in THF, 0.94 mL, 0.94 mmol, 4.1 equiv.)
dropwise. The mixture was stirred at 0 °C for 2 h and then 2 h at
room temperature. Then, an aqueous solution of NaOH (2.5 ,
1.22 mL, 3.06 mmol, 13 equiv.) and H2O2 (30 wt.-%, 0.115 mL,
1.13 mmol, 4.9 equiv.) were added with cooling, and the mixture
was stirred for another 2 h at room temperature. The two phases
were separated, and the product was extracted from the aqueous
layer with ethyl acetate (3ϫ5 mL). The combined organic layer was
washed with brine (3ϫ3 mL), dried with MgSO4 and filtered, and
the solvent was removed under reduced pressure. The crude prod-
uct was purified by column chromatography on silica gel (hexane/
ethyl acetate, 7:1) to afford 31 as a colourless solid (54 mg, 87%).
C–H), 1660, 1570 (C=C) cm–1. C17H21NO (255.4): calcd. C 79.96,
H 8.29, N 5.49; found C 79.83, H 7.94, N 5.80.
rac-(1aS,5bR,7aS,11aR,11bS,11cR)-5b,6,7,7a,8,9,10,11,11b,11c-De-
cahydronaphtho[1,2-h]oxireno[f]quinolin-11a(1aH)-ol (29): To
a
solution of compound 26 (60 mg, 0.23 mmol) in CH2Cl2 (5 mL) at
0 °C was slowly added m-chloroperbenzoic acid (44 mg,
0.26 mmol), and the mixture was stirred at room temperature for
16 h. An aqueous solution of NaOH (10%, 1 mL) was added, and
the two phases were separated. The product was extracted from the
aqueous layer with CH2Cl2 (3ϫ3 mL), the combined organic layer
was washed with brine (3ϫ3 mL), dried with MgSO4 and filtered.
The solvent was removed under reduced pressure to leave the crude
product, which was purified by column chromatography on silica
gel (hexane/ethyl acetate, 3:1) to afford 29 as a colourless solid
(23 mg, 36%). M.p. 170–175 °C. 1H NMR (500 MHz, CDCl3): δ =
1
3
M.p. 135–140 °C. H NMR (500 MHz, CDCl3): δ = 0.98 (br. d, J
3
3
1.66 (td, J = 13.8 Hz, J = 4.5 Hz, 1 H, 11-H), 1.10–1.43 (m, 7 H,
= 13.4 Hz, 1 H, 1-H), 1.17 (td, J = 13.4 Hz, J = 4.1 Hz, 1 H, 1-
7-H, 8-H, 9-H, 10-H, 11-H), 1.48–1.69 (m, 4 H, 6-H, 7-H, 7a-H,
H), 1.26–1.50 (m, 6 H, 2-H, 3-H, 4-H, 5-H), 1.58* (mc, 1 H, 4a-
3
3
OH), 1.88 (tt, J ≈ 13.5 Hz, J ≈ 4.5 Hz, 1 H, 8-H), 2.63 (dd, J = H), 1.60* (br. s, 1 H, OH), 1.64–1.70 (m, 1 H, 6-H), 1.75–1.85 (m,
7.0 Hz, 3J = 2.5 Hz, 1 H, 11b-H), 3.00 (dq, 2J = 13.1 Hz, 3J ≈
2.5 Hz, 1 H, 6-H), 3.17 (br. t, 3J ≈ 5.5 Hz, 1 H, 5b-H), 3.85 (dd, 3J
= 3.9 Hz, 5J = 1.0 Hz, 1 H, 1a-H), 4.00 (ddd, 3J = 3.9 Hz, 3J =
2 H, 5-H, 6-H), 1.93 (tt, J ≈ 13 Hz, 3J ≈ 4.5 Hz, 1 H, 4-H), 2.14
(ddd, 3J = 7.8 Hz, 3J = 6.1 Hz, 3J = 1.1 Hz, 1 H, 12a-H), 2.30–2.35
2
3
(m, 1 H, 6a-H), 2.55 (br. s, 3 H, BH3), 2.75 (dd, J = 17.9 Hz, J
Eur. J. Org. Chem. 2008, 2325–2335
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2333

F. Aulenta, U. K. Wefelscheid, I. Brüdgam, H.-U. Reißig
FULL PAPER
2
3
877–880; c) C. Lange, N. Holzhey, B. Schönecker, R. Beckert,
U. Möllmann, H.-M. Dahse, Bioorg. Med. Chem. 2004, 12,
3357–3362.
= 7.9 Hz, 1 H, 7-H), 2.90 (dd, J = 20.0 Hz, J = 7.8 Hz, 1 H, 12-
2
3
2
H), 2.95 (dd, J = 17.9 Hz, J = 12.2 Hz, 1 H, 7-H), 3.86 (d, J =
3
3
20.0 Hz, 1 H, 12-H), 7.16 (dd, J = 7.5 Hz, J = 5.9 Hz, 1 H, Ar),
[2]
[3]
For selected examples, see: a) F. Cachoux, M. Ibrahim-Ouali,
M. Santelli, Tetrahedron Lett. 2001, 42, 843–845; b) K. Oumzil,
M. Ibrahim-Ouali, M. Santelli, Synlett 2005, 1695–1698; c)
H. W. Sünnemann, A. Hofmeister, J. Magull, A. de Meijere,
Chem. Eur. J. 2006, 12, 8336–8344; d) A. Jacob von Wangelin,
H. Neumann, D. Gordes, S. Huber, C. Wendler, S. Klaus, D.
Strubing, A. Spannenberg, H. J. Jiao, L. El Firdoussi, K. Thu-
row, N. Stoll, M. Beller, Synthesis 2005, 2029–2038.
a) C. U. Dinesh, H.-U. Reißig, Angew. Chem. 1999, 111, 874–
876; Angew. Chem. Int. Ed. 1999, 38, 789–791; b) E. Nandanan,
C. U. Dinesh, H.-U. Reißig, Tetrahedron 2000, 56, 4267–4277;
c) M. Berndt, H.-U. Reißig, Synlett 2001, 1290–1291; d) S.
Gross, H.-U. Reißig, Synlett 2002, 2027–2030; e) S. Gross, H.-
U. Reißig, Org. Lett. 2003, 5, 4305–4307; f) M. Berndt, I. Hlob-
ilová, H.-U. Reißig, Org. Lett. 2004, 6, 957–960; g) V. Blot, H.-
U. Reißig, Eur. J. Org. Chem. 2006, 4989–4992; h) V. Blot, H.-
U. Reißig, Synlett 2006, 2763–2766; i) F. Aulenta, M. Berndt,
I. Brüdgam, H. Hartl, S. Sörgel, H.-U. Reißig, Chem. Eur. J.
2007, 13, 6047–6062; j) U. K. Wefelscheid, H.-U. Reißig, Adv.
Synth. Catal. 2008, 350, 65–69.
For related aryl carbonyl couplings, see: a) H. Ohno, S. Maeda,
M. Okumura, R. Wakayama, T. Tanaka, Chem. Commun.
2002, 316–317; b) H. Ohno, R. Wakayama, S. Maeda, H. Iwa-
saki, M. Okumura, C. Iwata, H. Mikamiyama, T. Tanaka, J.
Org. Chem. 2003, 68, 5909–5916; c) H. Ohno, M. Okumura, S.
Maeda, H. Iwasaki, R. Wakayama, T. Tanaka, J. Org. Chem.
2003, 68, 7722–7732; d) C.-W. Kuo, J.-M. Fang, Synth. Com-
mun. 2001, 31, 877–892; e) J.-S. Shiue, M.-H. Lin, J.-M. Fang,
J. Org. Chem. 1997, 62, 4643–4649; f) H.-G. Schmalz, S. Siegel,
J. W. Bats, Angew. Chem. 1995, 107, 2597–2599; Angew. Chem.
Int. Ed. Engl. 1995, 34, 2383–2385.
Selected reviews dealing with samarium-promoted reactions: a)
G. A. Molander, C. R. Harris, Chem. Rev. 1996, 96, 307–338;
b) F. A. Khan, R. Zimmer, J. Prakt. Chem. 1997, 339, 101–
104; c) G. A. Molander, C. R. Harris, Tetrahedron 1998, 54,
3321–3354; d) A. Krief, A.-M. Laval, Chem. Rev. 1999, 99,
745–777; e) H. B. Kagan, J. L. Namy in Topics in Organometal-
lic Chemistry Vol. 2: Lanthanides – Chemistry and Use in Or-
ganic Synthesis (Ed.: S. Kobayashi), Springer, Berlin, 1999, pp.
155–198; f) P. G. Steel, J. Chem. Soc. Perkin Trans. 1 2001,
2727–2751; g) A. Hölemann, Synlett 2001, 1497–1498; h) B. K.
Banik, Eur. J. Org. Chem. 2002, 2431–2444; i) H. B. Kagan,
Tetrahedron 2003, 59, 10351–10372; j) M. Berndt, S. Gross, A.
Hölemann, H.-U. Reißig, Synlett 2004, 422–438; k) D. J. Ed-
monds, D. Johnston, D.-J. Procter, Chem. Rev. 2004, 104, 3371–
3404; l) J. M. Concellón, H. Rodriguez-Solla, Chem. Soc. Rev.
2004, 33, 599–609.
7.58 (d, 3J = 7.5 Hz, 1 H, Ar), 8.62 (d, J = 5.9 Hz, 1 H, Ar) ppm.
3
*Overlapping signals. 13C NMR (126 MHz, CDCl3): δ = 20.9, 21.8,
24.5, 27.9, 28.9, 29.8, 30.3, 31.1, 31.2 (8 t, d, C-1, C-2, C-3, C-4,
C-5, C-6, C-7, C-12, C-6a), 44.4, 45.2 (2 d, C-4a, C-12a), 73.3 (s,
C-12b), 121.4 (d, Ar), 134.7 (s, Ar), 139.9, 147.0 (2 d, Ar), 156.6
(s, Ar) ppm. IR (KBr): ν = 3485 (OH), 3100, 3055, 3035, 2960,
˜
2930, 2860 (=CH, C–H), 2370, 2315, 2275 (B–H), 1605, 1585
(C=C) cm–1. MS (EI, 80 eV, 100 °C): m/z (%) = 271 (14) [M]+, 270
(61), 269 (31), 268 (46), 257 (53), 240 (100), 214 (25), 142 (25), 132
(87), 130 (47), 118 (27), 73 (24), 69 (27), 60 (37), 57 (33), 55 (45),
43 (59), 41 (45), 29 (27), 28 (24). HRMS (EI, 80 eV, 100 °C): calcd.
for C17H2411BNO 269.19509; found 269.19522. HRMS (EI, 80 eV,
100 °C): calcd. for C17H23NO 257.17796; found 257.17775.
C17H26BNO (271.2): calcd. C 75.29, H 9.66, N 5.16; found C 75.26,
H 9.62, N 5.16.
rac-(4aR,6aS,7R,12aS,12bS)-2,3,4,4a,5,6,6a,7,12,12a-Decahydro-
naphtho[2,1-g]quinoline-7,12b(1H)-diol (32): To a solution of com-
pound 28 (10.5 mg, 0.041 mmol) in THF (1 mL) was added
BH3·THF (ca. 1  sol. in THF, 0.41 mL, 0.41 mmol, 10 equiv.) at
0 °C. The mixture was stirred at 0 °C for 1.5 h and then 2 h at
room temperature. An aqueous solution of NaOH (2.5 , 0.62 mL,
1.56 mmol, 38 equiv.) and H2O2 (30 wt.-%, 0.15 mL, 1.48 mmol,
36 equiv.) were added with cooling. The mixture was stirred for 2 h
at room temperature and diluted with Et2O (15 mL). The two
phases were separated, and the product was extracted from the
aqueous layer with Et2O (1ϫ15 mL). The combined organic layer
was dried with Na2SO4 and filtered, and the solvent was removed
under reduced pressure. The crude product was purified by column
chromatography on silica gel (hexane/ethyl acetate, 1:2) to afford 32
as a colourless solid (8.0 mg, 71%). M.p. 220–224 °C.[22] 1H NMR
[4]
[5]
2
(500 MHz, CD3OD): δ = 0.91, 1.07, 1.25–1.69 (br. d, J ≈ 12 Hz,
3
1 H; td, J ≈ 13 Hz, J = 4.4 Hz, 1 H; m, 8 H; 1-H, 2-H, 3-H, 4-H,
3
5-H, 6-H, 4a-H), 1.90 (q d, J = 13.2 Hz, J = 3.0 Hz, 1 H, 5-H),
2
1.97–2.07 (m, 1 H, 4-H), 2.08–2.15 (m, 1 H, 6a-H), 2.18 (dq, J =
12.9 Hz, 3J ≈ 2 Hz 1 H, 6-H), 2.25 (t, 3J ≈ 6.5 Hz, 1 H, 12a-H),
2.50 (br. s, 2 H, OH), 2.94 (dd, 2J = 19.9 Hz, J = 7.7 Hz, 1 H, 12-
3
2
3
H), 3.88 (d, J = 19.9 Hz, 1 H, 12-H), 4.80 (d, J = 10.9 Hz, 1 H,
7-H), 7.40 (dd,3J = 7.8 Hz, 3J = 5.7 Hz, 1 H, Ar), 8.20 (d, 3J =
7.8 Hz, 1 H, Ar), 8.68 (d, J = 5.7 Hz, 1 H, Ar) ppm. 13C NMR
3
(126 MHz, CD3OD): δ = 21.6, 22.7, 25.6, 27.4, 28.8, 29.4, 31.1 (7
t, C-1, C-2, C-3, C-4, C-5, C-6, C-12), 41.9, 45.5, 47.2 (3 d, C-4a,
C-6a, C-12a), 67.5 (d, C-7), 74.4 (s, C-12b), 123.2 (d, Ar), 139.7 (s,
Ar), 141.2, 149.0 (2 d, Ar), 157.5 (s, Ar) ppm. IR (ATR): ν = 3350
˜
[6]
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(ESI): calcd. for C17H23NO2·H+ 274.1807; found 274.1792.
Supporting Information (see also the footnote on the first page of
this article): Synthesis and analytical data for compounds 7, 9, 11,
12 and 13 and their precursors.
[7]
[8]
Acknowledgments
Support of this work by the Deutsche Forschungsgemeinschaft, the
European Community (Marie Curie fellowship for F. A.), the
Fonds der Chemischen Industrie and the Bayer Schering Pharma
AG is most gratefully acknowledged. We thank Dr. R. Zimmer for
his help during preparation of this manuscript.
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Received: January 7, 2008
Published Online: March 10, 2008
Eur. J. Org. Chem. 2008, 2325–2335
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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