Domino C–H Activation Reactions through Proximity Effects

Article abstract of DOI:10.1002/ejoc.201801289

Proximity effects permit C–H activation reactions without directing groups. Here competitive reactions of selected substrates were investigated which allow a domino-carbopalladation/Mizoroki–Heck reaction and a domino-carbopalladation/C–H activation reaction. In the Pd-catalyzed transformation of the enantio- and diastereopure alkyne 8a the tetra-substituted alkenes 10 and 11 were formed almost exclusively through a domino carbopalladation/Mizoroki–Heck reaction. In contrast, the diastereomer 8c only led to the acenaphthylenes 12c and 13c through a domino carbopalladation/C–H activation reaction. Moreover, in the reaction of 20, 24 and 27 containing a naphthyl moiety only the tetra-substituted alkenes 23, 25/26 and 28/29, respectively were obtained, whereas in the reaction of 34, containing a phenanthrene moiety, compound 37 was the only product, formed via a C–H activation reaction.

Full text of DOI:10.1002/ejoc.201801289

DOI: 10.1002/ejoc.201801289
Full Paper
C–H Activation
Domino C–H Activation Reactions through Proximity Effects
Florian Lotz,[a][‡] Klaus Kahle,[a][‡] Mehrnoush Kangani,[a] Soundararasu Senthilkumar,[a] and
Lutz F. Tietze*[a]
Abstract: Proximity effects permit C–H activation reactions tion. In contrast, the diastereomer 8c only led to the acenaphth-
without directing groups. Here competitive reactions of se- ylenes 12c and 13c through a domino carbopalladation/C–H
lected substrates were investigated which allow a domino- activation reaction. Moreover, in the reaction of 20, 24 and 27
carbopalladation/Mizoroki–Heck reaction and a domino-carbo- containing a naphthyl moiety only the tetra-substituted alkenes
palladation/C–H activation reaction. In the Pd-catalyzed trans- 23, 25/26 and 28/29, respectively were obtained, whereas in
formation of the enantio- and diastereopure alkyne 8a the the reaction of 34, containing a phenanthrene moiety, com-
tetra-substituted alkenes 10 and 11 were formed almost exclu- pound 37 was the only product, formed via a C–H activation
sively through a domino carbopalladation/Mizoroki–Heck reac- reaction.
Introduction
The development of highly efficient synthetic procedures is one
of the major goals in organic chemistry. These methods should
permit the preparation of complex molecules starting from sim-
ple substrates in a green fashion reducing the amount of waste,
being careful with our environment, and moreover have also
economical advantages. Domino reactions, as a novel synthetic
concept, fulfill all these demands.[1] Especially useful are cata-
lytic domino reactions as Pd-catalyzed transformations.[2] An-
other important issue in synthetic chemistry is the avoidance
of prefunctionalization, which can be accomplished using C–H
activation reaction.[3] However, an often encountered draw back
in this concept is the need of directing groups, which have to
be removed or functionalized afterwards.[4] A possibility to
avoid this problem is the use of proximity effects.[5]
Scheme 1. Formation of an acenaphthylene through a domino-carbopallada-
tion/C–H activation reaction. The ligands at Pd are omitted for clarity.
Some time ago we have shown that the Pd-catalyzed reac-
tion of 2 leads to the acenaphthylene 5 via a proposed transi-
tion structure 3 and not to the tetra-substituted alkene 4 via 1
(Scheme 1).[6] The preference in the formation of 5 can be ex-
plained by a proximity effect.
groups including aromatic systems, double bonds and allyl-
silanes to allow a differentiation between domino-carbopalla-
dation/Mizoroki–Heck and domino-carbopalladation/C–H acti-
vation reactions were used.
Here we describe competitive reactions of selected sub-
strates which allow a domino-carbopalladation/Mizoroki–Heck
reaction and a domino-carbopalladation/C–H activation reac-
tion through proximity effects. The reactions lead either to heli-
cal tetra-substituted alkenes which might be useable as molec-
ular switches[7] or acenaphthylenes.
Results and Discussion
At first we investigated the Pd-catalyzed reaction of compound
8 as a mixture racemic diastereomers which contains a naphthyl
moiety allowing a domino-carbopalladation/C–H activation re-
action and a cyclohexenyl ether moiety permitting a domino-
carbopalladation/Mizoroki–Heck reaction. Compound 8 can
easily be prepared by reaction of the aldehyde 6 with the alk-
yne 7 using nBuLi for deprotonation of the alkyne with 91 %
yield. Treatment of 8 as racemic mixture of the two diastereo-
mers with the Herrmann–Beller catalyst 14[8] in CH3CN/DMF/
H2O (5:5:1) at 140 °C in a microwave oven for 45 min in the
As substrates compounds containing a bromonaphthyl, iodo-
naphthyl or a bromophenanthryl moiety with different donor
[a] Institute of Organic und Biomolecular Chemistry, Georg-August-University
of Göttingen,
Tammannstr. 2, 37077 Göttingen, Germany
E-mail: ltietze@gwdg.de
http://www.tietze.chemie.uni-goettingen.de
[‡] These authors have contributed equally to this work.
Supporting information and ORCID(s) from the author(s) for this article are
available on the WWW under https://doi.org/10.1002/ejoc.201801289.
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presence of LiOAc and nBu4NOAC gave the two tetra-substi-
tuted alkenes 10 and 11 and the acenaphthylenes 12 and 13
as an almost 1:1 mixture (Scheme 2). The ratio of 10/11 is about
55:45 and the ratio of 12/13 is about 35:65. In the formation of
10 and 11, it can be supposed that 10 is the primarily formed
product, from which 11 is obtained by re-addition of PdHL3 and
elimination. In the case of the acenaphthelenes, we assume that
12 is formed first, which is then partly transformed into 13 by
cleavage of the cyclohexenyl ether moiety. However, it cannot
be excluded that at least to some extent the cyclohexenyl ether
moiety in 8 is cleaved first which then would lead to 13 directly.
The ratio of 12 and 13 varies considerably, depending on the
reaction conditions. Noteworthy, in the formation of 10 and 11
only the cis-fused compounds are obtained as single diastereo-
mers.
Scheme 3. Intermediates in the formation of 10/11 and 12/13. The ligands
at Pd are omitted for clarity.
It can be anticipated that as the primary step a coordination
of the Pd-atom with the hydroxyl group takes place to form a
Pd complex 15 which leads to the vinyl-Pd intermediate 16.
This could then yield the acenaphthylene 12, but also by
overlap of the Pd-atom with the π-system of the double bond
the helical tetra-substituted alkene 10. Since only 10a and 11a
are formed from 8a in a domino-carbopalladation/Mizoroki–
Heck reaction, it can be assumed that the double bond in the
cyclohexene moiety is more reactive than the naphthyl group.
On the other hand, reaction of the diastereomeric alkyne 8c
with the Herrmann–Beller catalyst 14 led almost exclusively to
the acenathylenes 12c and 13c in a domino-carbopalladation/
C–H activation reaction in 58 % and 30 % yield, respectively. As
intermediates the Pd complex 17 and the vinyl-Pd 18 can be
supposed, in which an overlap of the Pd-atom with the double
bond of the cyclohexene moiety is not possible. Therefore, only
the acenaphthylenes 12c and 13c were obtained as products
(Scheme 3).
To get further information on the importance of the stereo-
chemistry of the substrates in the cyclisation reactions, we pre-
pared the alkyne rac-20 with only one stereogenic center con-
taining an allylsilane moiety as donor (Scheme 4). For the syn-
thesis of rac-20, which was obtained in 71 %, the aldehyde 6
was treated with the alkyne 19 using nBuLi for the deprotona-
tion. For the Pd-catalyzed reaction again the Hermann–Beller
catalyst 14 (10 mol-%) in the presence of LiOAc and nBu4NOAc
in a solvent mixture of CH3CN/DMF/H2O (5:5:1) at 120 °C for 4 h
was used (Scheme 4). As the major product the tetra-substi-
tuted alkene rac-23 was obtained in 64 % yield via a domino-
carbopalladation/Mizoroki–Heck reaction. The also expected
two acenaphthylenes rac-21 and rac-22 were found only in
traces (< 5 %).
In a similar way, also compound 24 containing a long chain
aliphatic allylsilane can be treated with the Herman–Beller cata-
lyst 14 to give exclusively the tetra-substituted alkenes 25 and
26 in an overall yield of 66 % in a ratio of 1:5.3 (Scheme 5). In
this case due to the employed iodide also a desilylated product
26 was formed. We then replaced the oxygene in the chain in
24 by a NAc group using 27 as substrate. Again tetra-substi-
tuted alkenes 28 and 29 were obtained exclusively in a Pd-
catalyzed domino-carbopalladation/Mizoroki–Heck-reaction in
an overall yield of 82 % with a ratio of 1:5.3.
Scheme 2. Formation of tetra-substituted alkenes 10/11 through a domino-
carbopalladation/Mizoroki–Heck reaction and acenaphthylenes 12/13
through a domino-carbopalladation/C–H activation reaction. The ligands at
Pd are omitted for clarity.
For clarifying the selectivity in the product formation, the
four stereoisomers of 8 were separated by preparative chroma-
tography on a stationary IB-Phase. Separate reactions of the
stereoisomers allowed an unambiguous identification of the
mode of action and moreover a precise explanation of the for-
mation of the two different types of products.
Reaction of alkyne 8a with the Herrmann–Beller catalyst 14
led to the almost exclusive formation of the enantio- and dia-
Also in these two transformations only one diastereomer is
stereopure helical tetrasubstituted alkenes 10a and 11a in 44 % found, though two new stereogenic elements are created.
and 36 % yield, respectively (Scheme 2 and Scheme 3).
Moreover, in the elimination step of a Pd-H species from the
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Scheme 4. Synthesis and Pd-catalyzed reaction of rac-20.
Figure 1. Proposed intermediate Pd complex K1.
tronic reasons. Obviously, the question arises, whether a C–H
activation reaction is always discriminated when an intermedi-
ate vinyl-Pd complex could react with a double bond system.
To get further insight in this aspect, we designed a molecule,
where proximity of the aromatic system is increased.
Thus, we prepared compound 34 where the naphthyl moiety
in 24 has been replaced by a phenanthrene group (Scheme
6). The synthesis is rather simple. The commercially available
phenanthrene derivative 30 with a hydroxyl group was acetyl-
ated and then nitrated to give 31 allowing a selective brom-
ination after hydrolysis of the acetate. It followed an alkyl-
ation with 2-bromethanol and oxidation with Dess–Martin-
Periodinane to give the corresponding aldehyde 32.
In the next step the alkyne 33 containing an allylsilane moi-
ety was introduced using nBuLi for deprotonation followed by
addition to the aldehyde 32 to give the substrate 34 for the
domino reaction in 68 % yield. Compound rac-34 contains a
phenanthrene moiety, where a C–H activation reaction could
take place and an allylsilane suitable for a Mizoroki–Heck reac-
Scheme 5. Synthesis and Pd-catalyzed reaction of rac-24 and rac-27.
intermediately formed Pd complex only the products with a
vinyl or a vinylsilane moiety are obtained. This phenomenon
has been described by us earlier.[9, 2u]
The high diastereoselectivity in the formation of the new
stereogenic center and the helical double bond can be ex-
plained by assuming an intermediate Pd complex K-1 of which
the formation is governed by the hydroxyl group in the starting
material (Figure 1).
In the so far performed transformations the Mizoroki–Heck- tion (Scheme 6). Treatment of 34 with 10 mol-% Pd(PPh3)4 in
reactions was favored although a C–H activation was always the presence of LiOAc and nBu4NCl in CH3CN at 110 °C for
principally possible. Merely in the case of 8c a C–H activation 17 h gave exclusively compound 37 in 73 % yield via a domino-
reaction was observed, but only due to the fact that the carbopalladation/C–H activation reaction. It can be assumed
Mizoroki Heck-reaction was not feasible because of stereoelec- that the Pd-intermediate 36 or the corresponding complex with
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Scheme 6. Synthesis and Pd-catalyzed reaction of rac-34.
the hydroxyl group is an intermediate. The tetra-substituted alk- sons or the donor is a phenanthrene moiety the C–H activation
ene 35 was not found. The formation of 37 is clearly due to a reaction wins.
proximity effect.
The determination of the structures of the new compounds
is mainly based on 1H- and 13C-NMR spectra and mass spec-
trometry. For further confirmation a crystal structure determina-
tion of rac-10 was performed, which could be obtained in crys-
talline form.[10] For the determination of the absolute configura-
tion of 10a/11a obtained from 8a, a CD-spectra of the mixture
was measured and compared with a calculated spectra[11,12] of
(S,S,S)-10 showing good identity.
Experimental Section
rac-(2S,1′′′R)- and rac-(2S,1′′′S)-1-(1-Bromonaphthalin-2-yloxy)-
4-[2-(cyclohex-2-enylmethyl)-phenyl]-but-3-yne-2-ol
and (rac-8c): To a solution of rac-1-cyclohex-2-enyloxy-2-ethinyl-
benzyne 7 in anhydrous THF (24 mL) was slowly given with stirring
at –60 °C nBuLi (2.5 M, 3.02 mL, 7.54 mmol, 2.00 equiv.). Stirring was
continued at –60 °C for 1 h, then at –20 °C for 1.5 h and then the
mixture was cooled down again to –60 °C. The mixture was trans-
ferred via a big transfer cannula dropwise to a solution of (1-bromo-
naphthalin-2-yloxy)acetaldehyde 6 (1.00 g, 3.77 mmol, 1.00 equiv.)
in anhydrous THF (12 mL) at –60 °C. Stirring was continued at this
temperature for 1 h and then the mixture was warmed up to room
temp. within 1 h. Concentrated aqueous ammonium chloride solu-
tion (50 mL) was added and the mixture extracted with dichloro-
methane (3 × 50 mL). After drying over MgSO4 and removal of the
solvent in vacuo, the remaining residue was purified by chromatog-
raphy (pentane/Et2O, 4:1) on silica gel to give the desired com-
pound 8 (1.42 g, 3.08 mmol, 82 %) as a colorless oil. Rf = 0.41 (pent-
(rac-8a)
Conclusions
In summary, proximity effects can be used to allow C–H activa-
tion reactions without the need of directing groups. In the de-
scribed experiments we have designed molecules where a com-
petition between a domino-carbopalladation/Mizoroki–Heck re-
action and a domino-carbopalladation/C–H activation reaction
exists with the result that a double bond or an allylsilane to
allow a Mizoroki–Heck reaction is a better donor than a
naphthyl moiety. However, in the cases where the Mizoroki–
ane/Et2O = 2:1). IR (Film): ν = 2926 (C–H), 1596, 1503, 1350, 1271
˜
(Ar–O), 1077 (CH2–O), 801, 758 cm–1. UV (CH3CN): λmax (ε) =
Heck reaction is less appropriate due to stereo electronic rea- 231.5 nm (4.865), 252.5 (4.275), 272.5 (3.715), 282.0 (3.802), 294.5
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1
(3.675), 322.5 (3.271), 334.5 (3.316). H NMR (300 MHz, CDCl3): δ = rac-(P)-(2S,4′aS,9′aS)-(Z)-1-(1,4,4a,9a-Tetrahydroxanthen-9-yl-
1.21–1.36 (m, 1 H, 6′′′-Ha), 1.48 (mc, 1 H, 5′′′-Hb), 1.61–1.77 (m, 2 H, iden)-2,3-dihydro-1H-benzo[f]chromen-2-ol (11): Rf = 0.24 (DCM/
5′′′-Ha, 6′′′-Hb), 1.95 (mc, 2 H, 4′′′-H2), 2.50 (mc, 1 H, 1′′′-H), 2.71 (ddd, pentane, 5:1). IR (KBr): ν = 2931 (C–H), 1594, 1454 (CH2), 1344 (CH),
˜
J = 13.1, 8.1, 2.1 Hz, 1 H, 1′′′′-Hb), 2.82 (ddd, J = 13.1, 6.9, 3.7 Hz, 1
H, 1′′′′-Ha), 2.96 (d, J = 5.3 Hz, 1 H, OH), 4.36 (ddd, J = 9.5, 7.0,
0.7 Hz, 1 H, 1-Ha), 4.45 (dd, J = 9.5, 3.4 Hz, 1 H, 1-Hb), 5.10 (mc, 1 H,
2-H), 5.57 (dq, J = 10.2, 2.1 Hz, 1 H, 3′′′-H), 5.62–5.70 (m, 1 H,
1232 (Ar–O), 1084 (CH2–O), 817, 655 cm–1. UV (CH3CN): λmax (lg ε) =
213.5 nm (4.652), 243.0 (4.458), 318.5 (4.068), 351.5 (4.114). 1H NMR
(600 MHz, CDCl3): δ = 1.95 (dbr, J = 6.2 Hz, 1 H, OH), 2.03–2.16 (m,
2 H, 1′-Hb, 4′-Hb), 2.25–2.31 (m, 1 H, 4′-Ha), 2.47 (ddd, J = 10.9, 6.1,
2′′′-H), 7.15 (dt, J = 7.3, 1.6 Hz, 1 H, 5′′-H), 7.18 (mc, 1 H, 3′′-H), 7.26 1.5 Hz, 1 H, 9′a-H), 2.58 (dt, J = 17.6, 5.5 Hz, 1 H, 1′-Ha), 4.28 (dd,
(mc, 1 H, 4′′-H), 7.29 (d, J = 8.9 Hz, 1 H, 3′-H), 7.41–7.47 (m, 1 H, 6′- J = 11.9, 2.5 Hz, 1 H, 3-Hb), 4.30 (mc, 1 H, 4′a-H), 4.45 (dd, J = 11.9,
H, 6′′-H), 7.59 (ddd, J = 8.4, 6.9, 1.2 Hz, 1 H, 7′-H), 7.80 (dt, J = 8.1,
0.6 Hz, 1 H, 5′-H), 7.82 (d, J = 8.9 Hz, 1 H, 4′-H), 8.23 (dq, J = 8.5, 1 H, 2′-H), 6.89 (dd, J = 8.3, 0.9 Hz, 1 H, 5′-H), 6.98 (ddd, J = 7.6, 7.6,
0.9 Hz, 1 H, 8′-H) ppm. 13C NMR (75 MHz, CDCl3): δ = 21.20 (C-5′′′),
1.2 Hz, 1 H, 7′-H), 7.11 (d, J = 8.8 Hz, 1 H, 5-H), 7.26 (ddd, J = 8.7,
1.8 Hz, 1 H, 3-Ha), 5.41 (mc, 1 H, 2-H), 5.43 (mc, 1 H, 3′-H), 5.61 (mc,
25.33 (C-4′′′), 28.75 (C-6′′′), 36.42 (C-1′′′), 41.01 (C-1′′′′), 62.08 (C-2), 7.4, 1.6 Hz, 1 H, 6′-H), 7.36 (ddd, J = 7.9, 7.0, 1.0 Hz, 1 H, 8-H), 7.44
74.20 (C-1), 85.27 (C-4), 89.25 (C-3), 110.5 (C-1′), 115.8 (C-3′), 121.8 (ddd, J = 8.2, 6.7, 1.3 Hz, 1 H, 9-H), 7.59 (dd, J = 7.7, 1.5 Hz, 1 H,
(C-1′′), 124.9 (C-6′), 125.8 (C-5′′), 126.3 (C-8′), 127.3 (C-2′′′), 127.8 (C-
7′), 128.1 (C-5′), 128.5 (C-4′′), 129.1 (C-4′), 129.7 (C-3′′), 130.4 (C-4′a),
8′-H), 7.73 (d, J = 8.9 Hz, 1 H, 6-H), 7.79 (d, J = 8.1 Hz, 1 H, 7-H),
8.00 (d, J = 8.5 Hz, 1 H, 10-H) ppm. 13C NMR (125 MHz, CDCl3): δ =
131.3 (C-3′′′), 132.5 (C-6′′), 133.0 (C-8′a), 143.4 (C-2′′), 152.6 (C-2′) 21.80 (C-1′), 30.77 (C-4′), 36.01 (C-9′a), 66.67 (C-2), 72.86 (C-3), 74.76
ppm. MS (70 eV, EI): m/z (%) = 462.2 (1) [M]+, 381.2 (39) [M – Br]+, (C-4′a), 112.6 (C-10b), 116.5 (C-5′), 118.1 (C-5), 119.7 (C-1*), 120.2
363.2 (84) [M – H2O – Br]+, 281.1 (28) [M – C6H9 – H2O – Br]+, 222.0 (C-7′), 121.4 (C-3′), 123.8 (C-8), 124.4 (C-10), 124.8 (C-8′a*), 126.0
(50) [C17H18]+, 81.1 (100) [C6H9]+. C27H25BrO2 (461.4): calcd. C 70.29,
(C-2′), 126.3 (C-9), 128.3 (C-7), 129.4 (C-6a*), 129.8 (C-8′), 129.9
H 5.46; found C 70.66, H 5.72. HR-MS: Calculated: m/z = 460.1038 (C-6), 129.9 (C-6′), 132.8 (C-10a*), 137.6 (C-9′), 152.5 (C-4a), 154.8 (C-
[M + H]+; found m/z = 460.1038.
4′c) ppm. MS (70 eV, EI): m/z (%) = 382.2 (100) [M]+, 364.2 (8) [M –
H2O]+, 328.2 (38) [M – C4H6]+, 311.1 (9) [M – C4H7O]+. HPLC (prep.
RP-column G): Wave length: 233 nm, flow rate 12 mL/min, eluent
acetonitrile/water = 57:43, tR = 54.49 min, portion: 45 %. C26H22O3
(382.5). Calculated: m/z = 382.1569 [M]+; found m/z = 382.1563.
Pd-Catalyzed Reaction of 8: A mixture of 8 (200 mg, 0.43 mmol,
1.0 equiv.), the palladacycle 14 (10 mol-%), lithium acetate (4 equiv.)
and tetrabutyl ammonium acetate (3 equiv.) in the solvent aceto-
nitrile/DMF/water (10 mL, 5:5:1) under argon was irradiated in a
microwave oven for 8 h at 120 °C (DC-control). The reaction mixture
was treated with 50 mL of brine and extracted with diethyl ether
(3 × 25 mL). After drying over sodium sulfate and removal of the
solvent in vacuo column chromatography on silica gel (DCM/pent-
ane = 5:1) provided the products 10/11 (66.0 mg, 0.173 mmol,
40 %) as colourless oil and 12 (47.9 mg, 0.125 mmol, 29 %) as or-
ange solid. 10 and 11 were separated by preparative HPLC. In iden-
tical reactions 8a and 8c were treated with the Pd complex 14. 8a
led to the enantiopure compounds 10a and 11a, whereas 8c gave
the enantiopure compounds 12c and 13c.
(1S,1′′S)-4-[2-(Cyclohex-2-enyloxy)-phenyl]-2,3-dihydro-1-oxa-
cyclopenta[def]phenanthren-3-ol (12): Rf = 0.35 (DCM/pentane,
5:1). IR (Film): ν = 2928 (C–H), 1667, 1484 (CH2), 1442, 1231 (Ar–O),
˜
1113 (CH–O), 1006 (CH2–O) cm–1. UV (CH3CN): λmax (lg ε) = 243.5 nm
(4.308), 309.0 (3.779), 322.5 (3.856), 362.0 (3.840), 377.5 (3.915). 1H
NMR (600 MHz, CDCl3): δ = 1.19–1.44 (m, 2 H, 5′′-H2), 1.56–1.66 (m,
2 H, 6′′-H2), 1.80–1.98 (m, 2 H, 4′′-H2), 4.16 (sbr, 1 H, OH), 4.40 (ddd,
J = 11.8, 2.6, 1.4 Hz, 1 H, 2-Hb), 4.65 (dd, J = 11.8, 4.0 Hz, 1 H, 2-Ha),
4.79 (mc, 1 H, 1′′-H), 5.08 (mc, 1 H, 3-H), 5.91–5.95 (m, 1 H, 3′′-H),
5.96–6.00 (m, 1 H, 2′′-H), 7.16 (d, J = 8.8 Hz, 1 H, 9-H), 7.18 (dt, J =
7.5, 0.8 Hz, 1 H, 5′-H*), 7.21 (d, J = 8.1 Hz, 3′-H*), 7.38 (ddd, J = 8.1,
7.5, 1.8 Hz, 1 H, 4′-H*), 7.51 (dd, J = 8.0, 6.7 Hz, 1 H, 6-H), 7.60 (dd,
J = 7.5, 1.9 Hz, 1 H, 6′-H*), 7.75 (d, J = 6.7 Hz, 1 H, 7-H*), 7.79 (d,
J = 8.8 Hz, 1 H, 8-H), 7.81 (d, J = 8.0 Hz, 1 H, 5-H*) ppm. 13C NMR
(125 MHz, CDCl3): δ = 18.07 (C-5′′), 24.88 (C-4′′), 27.59 (C-6′′), 64.60
(C-3), 74.71 (C-1′′), 75.89 (C-2), 117.5 (C-3′), 118.2 (C-9), 121.3 (C-9b),
122.2 (C-5′*), 124.1 (C-4a), 125.2 (C-3′′), 125.4 (C-7*), 126.2 (C-5*),
126.3 (C-6), 126.9, 127.4, 127.6 (C-7a*, C-9c*, C-1′*), 128.6 (C-4′*),
130.1 (C-8), 130.9 (C-4*), 132.0 (C-6′*), 134.0 (C-2′′), 140.0 (C-3a),
153.4 (C-9a), 154.8 (C-2′) ppm. MS (70 eV, EI): m/z (%) = 382.3 (13)
[M]+, 301.2 (11), [M – C6H9]+, 283.1 (55) [M – C6H9 – H2O]+, 255.1
(100) [M – C6H9 – H2O – CH2O]+, 81.1 (12) [C6H9]+. C26H22O3 (382.5).
HR-MS: Calculated: m/z = 405.1462 [M + Na]+; found m/z =
405.1461.
rac-(P)-(2S,4′aS,9′aS)-(Z)-1-(3,4,4a,9a-Tetrahydroxanthen-9-yl-
iden)-2,3-dihydro-1H-benzo[f]chromen-2-ol (10): Rf = 0.24 (DCM/
pentane, 5:1). IR (KBr): ν = 1594 (C=C), 1454 (CH2), 1231 (Ar–O), 1075
˜
(CH2–O), 759 (H–C=C–H cis) cm–1. UV (CH3CN): λmax (lg ε) =
212.5 nm (4.568), 242.5 (4.360), 318.5 (3.974), 350.5 (4.022). 1H NMR
(600 MHz, CDCl3): δ = 1.57–1.63 (m, 1 H, 4′-Ha), 1.87–1.94 (m, 1 H,
3′-Ha), 1.99 (d, J = 7.6 Hz, 1 H, OH), 1.98–2.06 (m, 1 H, 4′-Hb), 2.22–
2.31 (m, 1 H, 3′-Hb), 3.03 (sbr, 1 H, 9′a-H), 4.26 (dd, J = 12.1, 2.4 Hz,
1 H, 3-Hb), 4.32 (mc, 1 H, 4′a-H), 4.44 (dd, J = 12.1, 1.8 Hz, 1 H, 3-
Ha), 5.35 (dt, J = 7.4, 1.8 Hz, 1 H, 2-H), 5.68–5.75 (m, 2 H, 1′-H, 2′-H),
6.84 (dd, J = 8.3, 1.0 Hz, 1 H, 5′-H), 6.94 (ddd, J = 7.6, 7.6, 1.1 Hz,
1 H, 7′-H), 7.11 (d, J = 8.8 Hz, 1 H, 5-H), 7.24 (ddd, J = 8.5, 7.3, 1.6 Hz,
1 H, 6′-H), 7.36 (ddd, J = 8.0, 6.8, 1.2 Hz, 1 H, 8-H), 7.46 (ddd, J =
8.3, 6.8, 1.2 Hz, 1 H, 9-H), 7.54 (dd, J = 7.6, 1.6 Hz, 1 H, 8′-H), 7.74
(d, J = 8.8 Hz, 1 H, 6-H), 7.79 (d, J = 8.0 Hz, 1 H, 7-H), 7.99 (d,
J = 8.5 Hz, 1 H, 10-H) ppm. 13C NMR (125 MHz, CDCl3): δ = 20.10
(C-3′), 26.36 (C-4′), 38.88 (C-9′a), 66.30 (C-2), 73.05 (C-3), 73.91
(C-4′a), 112.4 (C-10b), 116.0 (C-5′), 118.2 (C-5), 119.8 (C-7′), 120.0
(C-8′a*), 123.1 (C-1′), 123.7 (C-8), 124.4 (C-10), 125.7 (C-1*), 126.5 (C-
Pd-Catalyzed Reaction of rac-20
rac-(P)-(2S,3′S)-(Z)-(1′′E)-1-[3-(2-Trimethylsilanyl-vinyl)-chro-
man-4-yliden]-2,3-dihydro-1H-benzo[f]chromen-2-ol (23): A
mixture of rac-20 (700 mg, 1.37 mmol, 1.00 equiv.), the Pd complex
14 (10 mol-%), lithium acetate (4 equiv.) and tetrabutyl ammonium
9), 128.3 (C-7), 129.3 (C-8′), 129.4 (C-6a*), 129.9 (C-6′), 130.0 (C-6), acetate (3 equiv.) in the solvent acetonitrile/DMF/water (10 mL,
130.1 (C-2′), 132.4 (C-10a), 135.1 (C-9′), 152.7 (C-4a), 156.0 (C-4′c) 5:5:1) under argon was irradiated in a microwave oven for 4 h at
ppm. MS (70 eV, EI): m/z (%) = 382.2 (100) [M]+, 364.1 (24) [M – 120 °C (DC-control). The reaction mixture was treated with 50 mL
H2O]+. HPLC (prep. RP-column G): wave length: 233 nm, flow rate
of brine and extracted with diethyl ether (3 × 25 mL). After drying
over sodium sulfate and removal of the solvent in vacuo, column
12 mL/min, eluent: acetonitrile/water, 57:43, tR = 58.17 min, portion:
55 %. HR-MS: C26H22O3 (382.5). Calculated: m/z = 382.1569 [M]+; chromatography on silica gel (DCM/pentane = 5:1) provided the
found m/z = 382.1563.
product rac-23 (378 mg, 0.881 mmol, 64 %) as colorless solid. The
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compounds rac-21 and rac-22 were obtained in traces only. Rf =
d, J = 14.0 Hz, 1 H, 5′-Ha), 1.57–1.69 (m, 2 H, 3′-Hb, 4′-Hb), 1.95 (br.
d, J = 14.0 Hz, 1 H, 5′-Hb), 2.48 (ddd, J = 13.6, 13.6, 4.0 Hz, 1 H, 6′-
Ha), 2.83 (br. d, J = 13.6 Hz, 1 H, 6′-Hb), 3.04 (br. s, 1 H, 2′-H), 4.33
(dd, J = 11.5, 2.8 Hz, 1 H, 3-Ha), 4.57 (dd, J = 11.5, 1.2 Hz, 1 H,
3-Hb), 5.00 (ddd, J = 17.5, 1.7, 1.7 Hz, 1 H, 2′′-Ha), 5.26 (br. s, 1 H, 2-
H), 5.28 (ddd, J = 10.6, 1.7, 1.7 Hz, 1 H, 2′′-Hb), 6.08 (ddd, J = 17.5,
10.5, 5.7 Hz, 1 H, 1′′-H), 7.10 (d, J = 8.9 Hz, 1 H, 5-H), 7.27–7.38 (m,
2 H, 8-H, 9-H), 7.69 (d, J = 8.9 Hz, 1 H, 6-H), 7.72–7.78 (m, 2 H, 7-H,
10-H) ppm. 13C NMR (50.3 MHz, CDCl3): δ = 21.7, 27.2, 29.3 (C-3′,
C-4′, C-5′), 35.4 (C-6′), 44.7 (C-2′), 65.0 (C-2), 74.8 (C-3), 114.1, 116.7
(C-10b, C-2′′), 118.1 (C-5), 123.2 (C-6a), 123.4, 125.9, 127.9 (C-7, C-8,
C-9, C-10), 129.1 (C-6), 129.1 (C-10a), 132.4 (C-1), 138.4 (C-1′′), 140.7
(C-1′), 152.7 (C-4a) ppm. MS (70 eV, EI): m/z (%) = 306.1 (100) [M]+,
288.1 (16) [M – H2O]+, 181.0 (14) [M – H2O – C8H11]+. HR-MS:
0.33 (DCM/pentane = 4:1). IR (KBr): ν = 2925 (C–H), 1592, 1464 (CH2),
˜
1231 (Ar–O), 995 (C=C), 815, 764 (C=Ccis) cm–1. UV (CH3CN): λmax
(lg ε) = 212.0 nm (4.598), 242.0 (4.367), 319.0 (3.998), 351.0 (4.044).
1H NMR (600 MHz, CDCl3): δ = 0.01 (s, 9 H, SiMe3), 2.05 (sbr, 1 H,
OH), 3.04 (mc, 1 H, 3′-H), 4.04 (dd, J = 10.7, 2.3 Hz, 1 H, 2′-Hb), 4.19
(dd, J = 10.7, 1.8 Hz, 1 H, 2′-Ha), 4.26 (dd, J = 12.2, 2.2 Hz, 1 H, 3-
Hb), 4.44 (dd, J = 12.2, 1.5 Hz, 1 H, 3-Ha), 5.44 (mc, 1 H, 2-H), 5.57
(dbr, J = 19.0 Hz, 1 H, 2′′-H), 5.97 (dd, J = 19.0, 5.9 Hz, 1 H, 1′′-H),
6.84 (d, J = 8.3 Hz, 1 H, 8′-H), 6.99 (t, J = 7.5 Hz, 1 H, 6′-H), 7.10 (d,
J = 8.9 Hz, 1 H, 5-H), 7.23–7.27 (m, 1 H, 7′-H), 7.29 (mc, 1 H, 9-H),
7.33 (dd, J = 8.0, 6.9 Hz, 1 H, 8-H), 7.61 (mc, 1 H, 5′-H), 7.73 (d, J =
8.9 Hz, 1 H, 6-H), 7.76 (d, J = 8.0 Hz, 1 H, 7-H), 7.86 (d, J = 8.4 Hz, 1
H, 10-H) ppm. 13C NMR (125 MHz, CDCl3): δ = –1.37 (SiMe3), 44.46
(C-3′), 66.15 (C-2), 72.55 (C-2′), 72.60 (C-3), 112.2 (C-10b), 116.3 (C- C21H22O2 (306.4): Calculated: m/z = 306.1620, m/z = found:
8′), 118.1 (C-5), 120.2 (C-6′), 120.9 (C-4′a), 123.6 (C-8), 125.5 (C-1), 306.1620.
126.1 (C-10), 126.4 (C-9), 128.0 (C-7), 129.2 (C-6a), 129.7 (C-5′), 129.8
Pd-Catalyzed Reaction of 27: A mixture of rac-27 (160 mg,
(C-7′), 130.0 (C-6), 132.3 (C-10a), 133.8 (C-4′), 134.4 (C-2′′), 141.4 (C-
0.292 mmol), the palladacycle 14 (10.7 mg, 4 mol-%), lithium acet-
1′′), 152.6 (C-4a), 154.7 (C-8′a) ppm. MS (70 eV, EI): m/z (%) = 428.2
ate (119 mg, 1.17 mmol, 4.0 equiv.) and tetrabutyl ammonium
(100) [M]+, 410.2 (4) [M – H2O]+, 356.3 (6) [C24H20O3]+, 302.2 (14),
chloride (67 mg, 0.29 mmol, 1.0 equiv.) in the solvent acetonitrile/
255.1 (21), 73.0 (33). C27H28O3Si (428.6). HR-MS: Calculated: m/z =
water (12 mL, 4:1) under argon was heated for 14 h at 120 °C (DC-
429.18805 [M + H]+; found m/z = 429.18817.
control). The reaction mixture was treated with 50 mL of brine and
Pd-Catalyzed Reaction of rac-24 and rac-27: A mixture of rac-24
extracted with ethyl acetate (3 × 25 mL). After drying over sodium
(100 mg, 0.197 mmol) the palladacycle 14 (5 mol-%), lithium acetate sulfate and removal of the solvent in vacuo column chromatogra-
(80 mg, 7.88 mmol, 4.0 equiv.) and tetrabutyl ammonium chloride
(90 mg, 39.4 mmol, 2.0 equiv.) in the solvent acetonitrile/water
(8 mL, 3:1) under argon was heated for 16 h at 110 °C (DC-control).
The reaction mixture was treated with 50 mL of brine and extracted
with diethyl ether (3 × 25 mL). After drying over sodium sulfate and
removal of the solvent in vacuo column chromatography on silica
gel (pentane/ethyl acetate = 10:1 to 7:1) provided the products rac-
25 (8.6 mg, 12 %) and rac-26 (36.4 mg, 60 %) as colorless oils to-
gether with starting material 24 (12.0 mg, 12 %).
phy on silica gel (pentane/ethyl acetate = 2:1 to 1:1) provided the
products rac-28 (16 mg, 13 %) and rac-29 (70 mg, 69 %) as color-
less oils.
(1E,1′′E)-N-Acetyl-1-[2-(2-trimethylsilyl-vinyl)-cyclohexyliden]-
1,2,3,4-tetrahydro-benzo[f]chinolin-2-ol (28): Rf = 0.32 (pentane/
ethyl acetate = 1:1). 1H NMR (300 MHz, CDCl3): δ = 0.11 (s, 9 H,
SiMe3), 1.09–1.32 (m, 2 H, 3′-Ha, 4′-Ha), 1.40–1.66 (m, 4 H, 3′-Hb, 4′-
Hb, 5′-Ha, δOH), 1.95 (br. d, J = 13.1 Hz, 1 H, 5′-Hb), 2.17 (s, 3 H, CH3),
2.42 (ddd, J = 13.4, 13.4, 4.2 Hz, 1 H, 6′-Ha), 2.79 (br. d, J = 13.4 Hz,
1 H, 6′-Hb), 2.91 (br. s, 1 H, 2′-H), 3.14 (br. d, J = 13.4 Hz, 1 H, 3-Ha),
4.91 (br. dd, J = 13.4, 7.4 Hz, 1 H, 3-Hb), 5.55 (dd, J = 7.4, 1.4 Hz,
1 H, 2-H), 5.63 (dd, J = 19.0, 2.0 Hz, 1 H, 2′′-H), 6.17 (dd, J = 19.0,
rac-(1E,1′′E)-1-[2-(2-Trimethylsilyl-vinyl)-cyclohexyliden]-2,3-di-
hydro-1H-benzo[f]chromen-2-ol (25): Rf = 0.28 (pentane/ethyl
acetate = 5:1). IR (Film): ν = 3374, 3055, 2951, 2921, 1595, 1512,
˜
1467, 1246, 1067, 838 cm–1. UV (CH3CN): λmax (lg ε) = 200.5 nm 5.2 Hz, 1 H, 1′′-H), 7.35 (m, 2 H, 5-H, 8-H), 7.45 (dd, J = 7.8, 7.8 Hz,
(4.536), 238.5 (4.498), 290.0 (3.730), 301.5 (3.709), 333.0 (3.602), 1 H, 9-H), 7.78–7.90 (m, 3 H, 6-H, 7-H, 10-H) ppm. 13C NMR
345.0 (3.613). 1H NMR (300 MHz, CDCl3): δ = 0.14 (s, 9 H, SiMe3), (50.3 MHz, CDCl3): δ = –1.1 (SiMe3), 21.7, 27.1, 30.1, 35.3 (C-3′, C-4′,
1.24–1.39 (m, 2 H, 3′-Ha, 4′-Ha), 1.40–1.49 (m, 1 H, 5′-Ha), 1.49–1.68
C-5′, C-6′), 22.5 (CH3), 47.1 (C-2′), 52.9 (C-3), 69.5 (C-2), 123.6, 126.0,
(m, 2 H, 3′-Hb, 4′-Hb), 1.92 (br. d, J = 11.4 Hz, 1 H, 5′-Hb), 2.46 (ddd, 126.6, 126.8, 127.9, 128.1 (C-5, C-6, C-7, C-8, C-9, C-10), 125.8
J = 13.6, 13.6, 3.5 Hz, 1 H, 6′-Ha), 2.81 (br. d, J = 13.6 Hz, 1 H, 6′-Hb), (C-10b), 129.8, 131.7, 132.0 (C-1, C-6a, C-10a), 132.2 (C-2′′), 137.2
3.03 (br. s, 1 H, 2′-H), 4.32 (dd, J = 11.6, 2.6 Hz, 1 H, 3-Ha), 4.55 (dd,
J = 11.6, 1.2 Hz, 1 H, 3-Hb), 5.29 (br. s, 1 H, 2-H), 5.71 (dd, J = 19.3,
2.0 Hz, 1 H, 2′′-H), 6.18 (dd, J = 19.3, 4.5 Hz, 1 H, 1′′-H), 7.08 (d, J =
9.0 Hz, 1 H, 5-H), 7.25–7.34 (m, 2 H, 8-H, 9-H), 7.66 (d, J = 9.0 Hz,
1 H, 6-H), 7.70–7.75 (m, 2 H, 7-H, 10-H) ppm. 13C NMR (50.3 MHz,
CDCl3): δ = –1.1 (SiMe3), 22.0, 27.4, 29.3 (C-3′, C-4′, C-5′), 35.1
(C-6′), 46.8 (C-2′), 65.0 (C-2), 74.7 (C-3), 114.2 (C-10b), 118.1 (C-5),
123.3, 125.8, 125.9, 127.8 (C-7, C-8, C-9, C-10), 123.6 (C-6a), 129.1 (C-
6), 129.0 (C-10a), 132.1 (C-2′′), 132.5 (C-1), 140.8 (C-1′), 146.7 (C-1′′),
152.7 (C-4a) ppm. MS (70 eV, EI): m/z (%) = 378.3 (100) [M]+, 306.2
(15) [M – C3H8Si]+, 287.2 (36) [M – SiMe3 – H2O]+, 261.2 (19) [M –
SiMe3 – H2O – C2H2]+, 207.1 (32), 181.1 (59) [M – SiMe3 – H2O –
C8H10]+, 144.1 (44) [C10H8O]+. HR-MS: C24H30O2Si (378.6) Calculated:
m/z = 378.2015; found m/z = 378.2015.
(C-1′), 143.9 (C-4a), 146.4 (C-1′′), 169.7 (C=O) ppm. MS (200 eV, DCI):
m/z (%) = 437.4 (67) [M + NH4]+, 420.3 (100) [M + H]+, 365.3 (22)
[M – C3H8Si + NH4]+, 348.3 (27) [M – C3H8Si + H]+. C26H23NO2Si
(419.6). HR-MS: Calculated: m/z = 419.2281; found m/z = 419.2281.
(E)-N-Acetyl-1-(2-vinyl-cyclohexyliden)-1,2,3,4-tetrahydro-
benzo[f]chinolin-2-ol (29): Rf = 0.25 (pentane/ethyl acetate = 1:1).
1H NMR (300 MHz, CDCl3): δ = 1.09–1.35 (m, 2 H, 3′-Ha, 4′-Ha), 1.43–
1.71 (m, 4 H, 3′-Hb, 4′-Hb, 5′-Ha, OH), 1.98 (br. d, J = 12.6 Hz, 1 H, 5′-
Hb), 2.20 (s, 3 H, CH3), 2.42 (ddd, J = 13.6, 13.6, 4.1 Hz, 1 H, 6′-Ha),
2.81 (br. d, J = 13.6 Hz, 1 H, 6′-Hb), 2.93 (br. s, 1 H, 2′-H), 3.16 (br. d,
J = 13.6 Hz, 1 H, 3-Ha), 4.90 (br. d, J = 13.6 Hz, 1 H, 3-Hb), 4.93 (ddd,
J = 17.5, 1.7, 1.7 Hz, 1 H, 2′′-Ha), 5.21 (ddd, J = 10.6, 1.7, 1.7 Hz, 1 H,
2′′-Hb), 5.55 (dd, J = 7.3, 2.0 Hz, 1 H, 2-H), 6.08 (ddd, J = 17.5, 10.6,
6.2 Hz, 1 H, 1′′-H) 7.37 (d, J = 8.9 Hz, 1 H, 5-H), 7.42–7.51 (m, 2 H,
8-H, 9-H), 7.78–7.93 (m, 3 H, 6-H, 7-H, 10-H) ppm. 13C NMR
(50.3 MHz, CDCl3): δ = 21.4, 26.8, 30.1, 35.3 (C-3′, C-4′, C-5′, C-6′),
27.4 (CH3), 44.8 (C-2′), 52.8 (C-3), 69.2 (C-2), 114.2, 116.5 (C-10b, C-
rac-(E)-1-(2-Vinyl-cyclohexyliden)-2,3-dihydro-1H-benzo[f]-
chromen-2-ol (26): Rf = 0.20 (pentane/ethyl acetate = 5:1). IR (KBr):
ν = 3357, 3073, 3053, 2927, 2850, 1593, 1511, 1341, 1234, 1078,
˜
997, 908 cm–1. UV (CH3CN): λmax (lg ε) = 201.0 nm (4.540), 241.0 2′′), 123.4, 125.9, 126.5, 126.8, 127.8, 128.0 (C-5, C-6, C-7, C-8, C-9,
(4.653), 290.0 (3.824), 301.0 (3.812), 334.5 (3.695), 344.5 (3.727). 1H C-10), 125.3, 131.6, 131.8 (C-1, C-6a, C-10a), 137.0 (C-1′), 138.3
NMR (300 MHz, CDCl3): δ = 1.24–1.41 (m, 2 H, 3′-Ha, 4′-Ha), 1.47 (br. (C-1′′), 143.6 (C-4a), 169.6 (C=O) ppm. MS (200 eV, DCI): m/z (%) =
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365.3 (50) [M + NH4]+, 348.3 (100) [M + H]+. HR-MS: C23H25NO2 8.4 Hz, 1 H, 1-H), 8.37 (d, J = 8.2 Hz, 1 H, 7-H), 8.67 (s, 1 H, 11-H),
(347.5): Calculated: m/z = 347.1885; found m/z = 347.1885.
8.83 (d, J = 8.2 Hz, 1 H, 9-H) ppm. 13C NMR (50.3 MHz, CDCl3): δ =
–1.8 (SiMe3), 18.6 (C-7′), 26.8 (C-4′), 28.1, 30.3, 30.7 (C-1′, C-2′, C-3′),
63.9 (C-5), 72.1 (C-4), 114.9 (C-2a1), 115.9 (C-2), 121.4, 123.1 (C-1, C-
11), 121.8, 123.3, 125.6, 125.9 (C-6a, C-6a1, C-9a, C-11a), 126.1, 126.9
(C-5′, C-6′), 127.1, 127.6, 128.9 (C-7, C-8, C-9), 130.9 (C-6), 134.9 (C-
5a, C-11a1), 143.8 (C-10), 154.0 (C-2a) ppm. MS (70 eV, EI): m/z (%) =
473.2 (100) [M]+, 443.2 (15) [M – CH2O]+, 384.1 (13) [M – C2HNO2],
300.0 (14) [M – CHO – C2HNO2 – SiMe3]+, 254.0 (20) [M – C2HNO2
– C2H4O2 – C4H11Si – H]+, 73.0 (50) [SiMe3]+. HR-MS: C28H31NO4Si
(473.6). Calculated: m/z = 473.2022; found m/z = 473.2022.
Synthesis and Pd-Catalyzed Reaction of rac-34
rac-(Z)-1-(4-Brom-9-nitro-3-phenanthryloxy)-11-trimethylsilyl-
9-undecen-3-yne-2-ol (34): To a solution of the 2-ethyne 33
(378 mg, 1.94 mmol, 1.50 equiv.) in anhydrous THF (6 mL) was
slowly given with stirring at –50 °C nBuLi (2.45 mL, 6.14 mmol,
2.0 equiv., 2.5
M in hexane). Stirring was continued at –50 °C for
1 h, then at –20 °C for 1.5 h and then the mixture was cooled
down again to –50 °C. The mixture was transferred via a big transfer
cannula dropwise to a solution of phenanthrene aldehyde 32
(467 mg, 1.30 mmol, 1.0 equiv.) in anhydrous THF (5 mL) at –50 °C.
Stirring was continued at this temperature for 30 min and then the
mixture was warmed up to room temp. within 2 h. Concentrated
aqueous ammonium chloride solution (50 mL) was added and the
mixture extracted with dichloromethane (3 × 50 mL). After drying
over Na2SO4 and removal of the solvent in vacuo, the remaining
residue was purified by chromatography (pentane/ethyl acetate =
5:1) on silica gel to give the desired compound rac-34 (492 mg,
68 %) as yellowish oil. Rf = 0.23 (pentane/ethyl acetate = 5:1). IR
Conflict of interest
The authors declare no conflict of interest
Acknowledgments
We thank the Deutsche Forschungsgemeinschaft (DFG), the
State of Lower Saxony, the Volkswagen Foundation for their
generous support. M. K. and S. S. thank the Georg-August-
University Göttingen for a post-doctoral fellowship.
(KBr): ν = 3520, 3085, 3005, 2936, 2231, 1596, 1526, 1446, 1280,
˜
1084, 856 cm–1. UV (CH3CN): λmax (lg ε) = 256.5 nm (4.525), 364.0
(3.919). 1H NMR (300 MHz, CDCl3): δ = –0.02 (s, 9 H, SiMe3), 1.42–
1.58 (m, 6 H, 6-H2, 7-H2, 11-H2), 1.95 (dt, J = 7.0, 7.0 Hz, 2 H, 8-H2),
2.25 (dt, J = 7.0, 1.9 Hz, 2 H, 5-H2), 2.68 (br. s, 1 H, OH), 4.27 (dd, J =
9.2, 7.6 Hz, 1 H, 1-Ha), 4.38 (dd, J = 9.2, 3.6 Hz, 1 H, 1-Hb), 4.90 (mc,
1 H, 2-H), 5.18–5.26 (m, 1 H, 9-H), 5.34–5.43 (m, 1 H, 10-H), 7.38 (d,
J = 8.7 Hz, 1 H, 2′-H), 7.68–7.80 (m, 2 H, 6′-H, 7′-H), 7.94 (d, J =
8.7 Hz, 1 H, 1′-H), 8.34 (s, 1 H, 10′-H), 8.45 (dd, J = 8.1, 1.6 Hz, 1 H,
8′-H), 9.94 (dd, J = 8.3, 1.6 Hz, 1 H, 5′-H) ppm. 13C NMR (50.3 MHz,
CDCl3): δ = –1.8 (SiMe3), 18.4, 18.6 (C-5, C-11), 26.4 (C-8), 28.1, 28.9
(C-6, C-7), 61.5 (C-2), 74.1, 76.6 (C-3, C-4), 87.7 (C-1), 109.4 (C-4′),
114.5 (C-2′), 123.1 (C-10), 124.7, 125.8 (C-8′a, C-10′a), 125.1, 125.8,
126.0, 126.9, 127.8, 128.8 (C-1′, C-5′, C-6′, C-7′, C-8′, C-10′), 130.5,
132.4 (C-4′a, C-4′b), 131.4 (C-9), 144.6 (C-9′), 157.0 (C-3′) ppm. MS
(70 eV, EI): m/z (%) = 553.2 (6) [M]+, 474.3 (30) [M – Br]+, 374.1 (21)
[M – 179]+, 317.1 (16) [M – C14H25OSi]+, 163.2 (16) [C13H7]+,
73.0 (100) [SiMe3]+. HR-MS: C28H32NO4Si (554.6): Calculated: m/z =
553.1284; found m/z = 553.1284.
Keywords: Carbopalladation · C–H Activation · Domino
reactions · Cross-coupling · Synthetic methods
[1] For recent reviews and books on domino reactions, see: a) M. Lautens,
A. Whyte, Synfacts 2018, 14, https://doi.org/10.1055/s-0037–1610487; b)
L. F. Tietze Editor (Ed.), Domino Reactions, WILEY-VCH, Weinheim, 2014;
c) L. G. Voskressensky, A. A. Festa, A. V. Varlamov, Tetrahedron 2014, 70,
551–572; d) C. M. R. Chandra, I. Atodiresei, M. Rueping, Chem. Rev. 2014,
114, 2390–2431; e) J. Muzart, Tetrahedron 2013, 69, 6735–5785; f) L. F.
Tietze, A. Düfert in Modern Tools for the Synthesis of Complex Bioactive
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benzo[cd]pyren-5-ol (37): A mixture of rac-34 (50 mg, 0.09 mmol,
1.00 equiv.), tetrakis(triphenylphosphane)palladium (10.4 mg,
10 mol-%), lithium acetate (37 mg, 0.36 mmol, 4.0 equiv.) and tetra-
butylammonium chloride (37 mg, 0.36 mmol, 4.0 equiv.) in aceto-
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similar conditions gave rac-37 with 20 %. Rf = 0.31 (pentane/ethyl
acetate = 5:1). IR (Film): ν = 3516, 3077, 3003, 2952, 2923, 1604,
˜
1517, 1249, 1076, 981, 855 cm–1. UV (CH3CN): λmax (lg ε) = 235.5 nm
(4.675), 274.0 (4.243), 287.5 (4.102), 302.0 (4.106), 335.5 (4.092),
343.0 (4.097), 368.0 (4.019), 416.5 (3.860). 1H NMR (300 MHz, CDCl3):
δ = –0.02 (s, 9 H, SiMe3), 1.48 (d, J = 8.4 Hz, 2 H, 7′-H2), 1.57 (br. s,
1 H, OH), 1.67 (tt, J = 7.0, 7.0 Hz, 2 H, 3′-H2), 1.75–1.95 (m, 2 H, 2′-
H2), 2.12 (dt, J = 7.0, 7.0 Hz, 2 H, 4′-H2), 3.29–3.48 (m, 2 H, 1′-H2),
4.38 (dd, J = 12.0, 1.4 Hz, 1 H, 4-Ha), 4.84 (dd, J = 12.0, 2.0 Hz, 1 H,
4-Hb), 5.26–5.34 (m, 1 H, 5′-H), 5.40–5.49 (m, 2 H, 5-H, 6′-H), 7.60 (d,
J = 8.4 Hz, 1 H, 2-H), 8.09 (dd, J = 8.2, 8.2 Hz, 1 H, 8-H), 8.07 (d, J =
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Received: August 17, 2018
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C–H Activation
F. Lotz, K. Kahle, M. Kangani,
S. Senthilkumar, L. F. Tietze* .......... 1–9
Domino C–H Activation Reactions
through Proximity Effects
Proximity effects allow C–H-activation Vinly–Pd species can be assumed as in-
reactions without directing groups in termediates, which either react with a
competition with domino-carbopalla- double bond or a naphthyl or phen-
dation or Mizoroki–Heck reactions. anthryl moiety.
No Need for Directing Groups: Tietze et al. @uniGoettingen Describe Domino-C–H-activation Reactions through
Proximity Effects
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DOI: 10.1002/ejoc.201801289
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