Enantioselective synthesis of (-)-(1R,2R)-1,2-dihydrochrysene-1,2-diol

Article abstract of DOI:10.1016/j.tet.2014.10.016

A general chiral building block containing the 1R,2R-trans-diol moiety was constructed utilizing the stereoselective Shi-epoxidation reaction on a tetralone scaffold assembled by a Negishi cross-coupling on N,N-diethylbenzamide. Further elaboration of thi

Full text of DOI:10.1016/j.tet.2014.10.016

Tetrahedron 70 (2014) 9041e9051
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Enantioselective synthesis of (ꢀ)-(1R,2R)-1,2-dihydrochrysene-
1,2-diol
*
ꢀ
Marianne Lorentzen, Magne O. Sydnes, Kare B. Jørgensen
Department of Mathematic and Natural Science, Faculty of Science and Technology, University of Stavanger, N-4036 Stavanger, Norway
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 5 August 2014
Received in revised form 25 September 2014
Accepted 6 October 2014
Available online 13 October 2014
A general chiral building block containing the 1R,2R-trans-diol moiety was constructed utilizing the
stereoselective Shi-epoxidation reaction on a tetralone scaffold assembled by a Negishi cross-coupling on
N,N-diethylbenzamide. Further elaboration of this chiral building block into polycyclic aromatic com-
pounds was demonstrated with the total synthesis of the precursor for the most carcinogenic metabolite
of chrysene, (ꢀ)-(1R,2R)-1,2-dihydrochrysene-1,2-diol in 87% ee.
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
Cross-coupling
FriedeleCrafts acylation
PAH-metabolites
Shi-epoxidation
trans-Dihydrodiol
1. Introduction
a general method for making the desired enantiomers of trans-
dihydrodiols in a few steps from a general chiral building block
Polycyclic aromatic hydrocarbons (PAHs), either found naturally
in coal tars and oil1 or formed by incomplete combustion of organic
materials, such as tobacco,2 and fuel,3 or in charred meat,4 are all
well-known pollutants in the environment. When digested by
mammals or fish these compounds go through several enzymatic
catalyzed oxidation steps forming different metabolites.5 Initial
enzymatic oxidation form epoxides, which undergo ring opening to
trans-diols (Fig. 1). Further oxidation form metabolites that essen-
tially bind covalently to DNA6 and proteins6a,7 in cells forming
adducts, which leads to mutagenesis and cancer.1b,8 Analysis of
DNA adducts and protein adducts has a great potential as a new tool
in environmental monitoring of oil contamination.6a,b,7a The pres-
ence in oil and the properties of chrysene, e.g., the toxicity of the
metabolites formed in vivo, makes it an excellent starting point for
the study of DNA and protein adduct formation. (1R,2R)-1,2-Dihy-
drochrysene-1,2-diol (1) has been found to be the precursor of the
most carcinogenic chrysene metabolites formed.9 It is believed that
by subjecting fish (Atlantic cod) to chrysene metabolite 1, instead of
chrysene itself, higher amount of DNA and protein adducts will be
formed in vivo, which will enable studies to a better understanding
of the further metabolism of chrysene and other PAHs. Other PAHs
can also form similar carcinogenic trans-dihydrodiols. Thus,
would be desirable as an alternative to the synthesis of the racemic
compound, which was followed by separation of the two enantio-
mers as described by Harvey.10 Here we report our search for such
a general chiral building block that led to the first enantioselective
synthesis of (ꢀ)-(1R,2R)-1,2-dihydrochrysene-1,2-diol (1) starting
from readily available N,N-diethylbenzamide, where the chirality
was installed utilizing the Shi-epoxidation reaction.11
It was envisioned that trans-dihydrodiols like 1 could be pre-
pared from a general chiral building block by the two strategies
outlined in the retrosynthetic analysis depicted in Scheme 1. The
first approach includes an amide reduction,12 a Wittig reaction13
and a photocyclization reaction.14 The double bond was envi-
sioned to be introduced either before the amide reduction or after
the photocyclization reaction. The second approach includes a di-
rected ortho metalation (DoM) reaction,15
a SuzukieMiyaura
cross-coupling reaction,16 and a directed remote metalation (DreM)
reaction17 followed by a protection/cleavage protocol to generate
the trans-dihydrodiol 1. Other ring systems may be introduced by
using other coupling partners in the Wittig reaction or Suzu-
kieMiyaura reaction.
2. Results and discussion
The total synthesis of (1R,2R)-1,2-dihydrochrysene-1,2-diol (1)
began by coupling readily available N,N-diethylbenzamide 3 with
ethyl-4-bromobutyrate utilizinga Negishicross-coupling reaction.18
* Corresponding author. Tel.: þ47 51832306; fax: þ47 51831750; e-mail address:
kare.b.jorgensen@uis.no (K.B. Jørgensen).
http://dx.doi.org/10.1016/j.tet.2014.10.016
0040-4020/Ó 2014 Elsevier Ltd. All rights reserved.

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M. Lorentzen et al. / Tetrahedron 70 (2014) 9041e9051
Fig. 1. Metabolism of polycyclic aromatic hydrocarbons.
Table 1
Negishi cross-coupling reaction and ester hydrolysis
Entry
Catalyst (mol %)
Additive
(mol %)
Temperature
(ꢁC)
Time
(h)
Yield of
5 (%)
1
2
3
4
5
6
7
8
9
Pd2(dba)3
d
Reflux
Reflux
Reflux
0/rt
50
Reflux
Reflux
Reflux
Reflux
19
19
19
19
2
2
2
2
2
nr
nr
nr
Pd(dppf)Cl2 (5)
Pd(dppf)Cl2 (5),
Ni(acac)2 (5)
Ni(acac)2 (5)
Ni(acac)2 (5)
Ni(acac)2 (5)
NiCl2(PCy3)2 (2)
NiCl2(dppe) (5)
d
DIBALH (10)
PPh3 (5)
PPh3 (5)
PPh3 (5)
PPh3 (10)
d
23a
40b
67
44
61
20c
DIBALH (10)
a
Homocoupling product of 40% was isolated.
Homocoupling product observed by TLC but not isolated.
Homocoupling product of 38% was isolated.
b
c
However, raising the temperature improved the reaction outcome,
and the best result was obtained at reflux for 2 h giving product 5 in
67% isolated yield (entry 6, Table 1). At this temperature no traces of
homocoupled benzamide were observed by TLC or 1H NMR
analysis. In all the reactions where the cross-coupling of ethyl-4-
bromobutyrate and N,N-diethylbenzamide 3 occurred a small
amount of unreacted benzamide 3 coeluted with the desired prod-
uct 4 in the chromatographic purification. The ester 4 was, therefore,
hydrolyzed with potassium hydroxide where the butanoic acid 5
was obtained in the respective yields shown in Table 1.
Scheme 1. Retrosynthetic analysis for the formation of compound
diethylbenzamide.
1 from N,N-
N,N-diethylbenzamide 3 was ortho-lithiated with sec-butyl lithium
(s-BuLi),15 followed by an in situ transmetalation with zinc chloride
(ZnCl2), and an in situ cross-coupling with ethyl-4-bromobutyrate.18
Palladium catalysis was found not to promote the desired trans-
formation (entries 1e3, Table 1). However, switching to a nickel
catalyst improved matters. Different conditions were tested using
Ni(acac)2/PPh3 as the catalyst.19 At low temperature a significant
amount of homocoupled benzamide and a low yield of the desired
cross-coupling product was isolated (entries 4 and 5, Table 1).20
The amount of PPh3 was found to have an effect on the reaction
outcome. Adding 2 equiv of PPh3 (10 mol %) compared to Ni(acac)2
(5 mol %) resulted in a lower yield of compound 5 (entry 7, Table 1).
Other nickel catalysts were also tested (entries 8 and 9, Table 1), but
the reaction outcome did not improve.
From butanoic acid 5, tetralone 6 was prepared by an intra-
molecular FriedeleCrafts acylation reaction.21 Transformation of
butanoic acid 5 to its corresponding acyl chloride, followed by
treatment with a catalytic amount of aluminum trichloride (AlCl3)

M. Lorentzen et al. / Tetrahedron 70 (2014) 9041e9051
9043
Table 3
Shi-epoxidation reaction
resulted in only trace amounts of tetralone 6, as observed by TLC
analysis (entry 1, Table 2). Methane sulfonic acid (MsOH), known to
directly transform carboxylic acids to tetralones,22 did not promote
the reaction in any way (entry 2, Table 2). However, with Eaton’s
reagent (7.7 wt % of P2O5 in MsOH)23 at elevated temperatures
tetralone 6 could be obtained in the respective yields shown in
Table 2. The best overall conditions were found to be 100 ꢁC for 2 h
giving tetralone 6 in 61% isolated yield (entry 10, Table 2). Worth
noting, 2 equiv of P2O5 was necessary in order to obtain this yield.
When 1 equiv was used the yield of tetralone 6 decreased signifi-
cantly (entries 13 and 14, respectively). It was also observed that
with longer reaction time (entries 6 and 12, Table 2) the yield of
tetralone 6 decreased, which might be explained by the conversion
of amides to nitriles in the presence of drying agents such as
diphosphor pentaoxide (P2O5).24
Table 2
Intramolecular FriedeleCrafts acylation of butanoic acid 5
Entry
Shi catalyst (equiv)
K2CO3 (equiv)
Yield (%) of 9
ee (%)
1
2
3
0.3
0.3
0.5
5.8
8.0
8.0
48
70
76
85
83
83
Entry
Reagent
Temperature (ꢁC)
Time (h)
Yield (%)
1
SOCl2/AlCl3, (CH2)2Cl2
MsOH
75/85
70
rt
60
60
60
80
80
100
100
100
100
100
100
120
2/19
19
19
6
19
72
1.5
4
1.5
2
3
67
1
3
Trace
nr
nr
2
3a
4
Eaton’s reagentb
Eaton’s reagent
Eaton’s reagent
Eaton’s reagent
Eaton’s reagent
Eaton’s reagent
Eaton’s reagent
Eaton’s reagent
Eaton’s reagent
Eaton’s reagent
Eaton’s reagent
Eaton’s reagent
Eaton’s reagent
26
39
30
45
52
54
61
59
13
37
31
54
The free hydroxyl group within trans-diol monosilyl ether 9 was
protected with TBDPSCl to afford trans-diol disilyl ether 10 in 94%
isolated yield (Scheme 2). With both hydroxyl groups protected,
amide 10 was reduced to aldehyde 11 using Schwartz reagent
(Cp2Zr(H)Cl)12 resulting in the formation of product 11 in 87% yield.
Substrate 11 was further subjected to a Wittig reaction13 with
benzyltriphenylphosphonium chloride and NaOH (50%-solution) in
DCM, thus forming stilbene 12 in 98% yield as a ca. 2:3 mixture of E-
and Z-isomers. The mixture of E- and Z-stilbene was further
5
6
7
8
9
10
11
12
13c
14c
15
1.5
a
P2O5 (2 equiv) was used if not otherwise specified.
Eaton’s reagent¼7.7 wt % of P2O5 dissolved in MsOH.
P2O5 (1 equiv).
b
c
From tetralone 6, tert-butyldiphenylsilyl enol ether 7 was ob-
tained in 92% yield by deprotonation with potassium hexame-
thyldisilazide (KHMDS), followed by in situ trapping of the formed
enol with tert-butyldiphenylsilyl chloride (TBDPSCl).25 With com-
pound 7 in hand, the key step in the synthesis of target molecule 1,
namely the Shi-epoxidation reaction,11,25 could be performed. Silyl
enol ether 7 was first transformed to silyloxy epoxide 8, followed by
regio- and stereospecific addition of hydride to give trans-diol
monosilyl ether 9. This specific transformation of tetralones has
been demonstrated to give trans-diols in high yields and high en-
antiomeric excess.25
However, the Shi-epoxidation reaction is a rather sensitive re-
action, and the outcome of the reaction depends on several factors,11
especially the pH of the reaction mixture. Following literature pro-
cedures,25 trans-diol monosilyl ether 9 was only obtained in 48%
yield (entry 1, Table 3). However, the pH was measured to be only 9,
while at ideal conditions the pH should be 10.5 or higher.11 By in-
creasing the amount of potassium carbonate from 5.8 equiv to
8 equiv, trans-diol monosilyl ether 9 was obtained in 70% isolated
yield (entry 2, Table 3). In attempts to further increase the yield, the
reaction was performed with 0.5 equiv of Shi catalyst, but the yield
only increased slightly (entry 3, Table 3). The enantiomeric excess
was shown to be 85% for the lower yielding reaction (entry 1, Table
3) and 83% for the higher yielding reactions (entries 2 and 3, Table 3),
as evident from chiral HPLC analysis (Lux 3u Cellulose-2 column).
Scheme 2. Reagents and conditions: (a) (i) NaH (1.95 equiv), THF, 0 ꢁC, 40 min; (ii)
TBDPSCl (1.2 equiv), rt, 19 h, 94%; (b) Cp2Zr(H)Cl (1.5 equiv), THF, rt, 30 min, 87%; (c)
benzyltriphenylphosphonium chloride, NaOH (50%-solution), DCM, rt, 30 min, 98%; (d)
h
n
, I2 (1.5 equiv), 1,2-epoxybutane (15 equiv), toluene, 1.5 h, 96%; (e) (i) NBS (1.5 equiv),
AIBN (0.1 equiv), CCl4, 65 ꢁC, 2 h; (ii) t-BuOK (1.05 equiv), THF, 45 ꢁC, 10 min, trace.

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M. Lorentzen et al. / Tetrahedron 70 (2014) 9041e9051
subjected to a Mallory photochemical cyclization reaction14 to af-
ford compound 13 in 96% isolated yield, as shown in Scheme 2.
From tetrahydrochrysene-1,2-diol 13 installation of the final
double bond was attempted by utilizing the bromination/elimina-
tion strategy.26 Unfortunately, the bromination reaction gave
a range of products, which were inseparable by flash column
chromatography. Subjecting the mixture to DBU resulted in for-
mation of only trace amounts of the desired dihydrochrysene-1,2-
diol 14 as evident by 1H NMR analysis, along with a mixture of
products, such as formation of mono-substituted chrysene with the
loss of tert-butyldiphenylsilanol. Bromination of mono-substituted
chrysene, along with bromination of the desired product 1, due to
the excess N-bromosuccinimide (NBS), may also occur. In spite of all
efforts put into trying to separate these compounds, these products
were not separable from one another by flash column chroma-
tography on silica gel.
Installation of the double bond was also attempted by using
DDQ, a reagent used by Harvey for the dehydrogenation of the
benzo[a]anthracene-metabolite.27 However, subjecting substrate
13 to DDQ only resulted in recovery of starting material. In-
troduction of the double bond was attempted at an earlier stage,
but, as for substrate 13 DDQ was found not to promote the for-
mation of the double bond in neither substrate 9, 10 nor 11 (as
indicated in Scheme 3).
Scheme 4. Reagents and conditions: (a) (i) s-BuLi (1.2 equiv), TMEDA (1.2 equiv), THF,
ꢀ78 ꢁC, 10e20 min; (ii) I2 (1.2 equiv), ꢀ78 ꢁC to rt, 1.5 h, 83% of 18 (X¼I).
Scheme 5. Reagents and conditions: (a) NBS (1.2 equiv), AIBN (0.1 equiv), CCl4, 65 ꢁC,
4 h, 67%; (b) DBU (1.2 equiv), THF, reflux, 3 days, 73%; (c) Cp2Zr(H)Cl (1.2 equiv), THF, rt,
30 min, 76%; (d) benzyltriphenylphosphonium chloride, NaOH (50%-solution), DCM, rt,
20 min, 99%; (e) h
76%.
n, I2 (cat.), Et2O/DCM (35:1), 3 h, 28%; (f) TBAF (2.6 equiv), THF, rt, 3 h,
Scheme 3. Attempted introduction of double bond upon treatment with DDQ.
Utilization of the amide functionality within substrate 10 as
a directing group was attempted in order to introduce a halogen in
the more acidic benzylic position.28 Neither LDA nor n-BuLi pro-
moted the desired transformation and with s-BuLi the ortho-
metalated product was formed instead of the desired compound 17
(Scheme 4). This may indicate that the amide group in this par-
ticular compound is a stronger directing group toward deprotona-
tion in the ortho-position rather than the more acidic benzylic
position. The relative large protecting groups on both hydroxyl
groups may also affect the regioselectivity of the metalation
reaction.
Since both treatment with DDQ and the metalation strategy
failed, substrate 10 was subjected to the more typical bromina-
tion,26 followed by an elimination reaction. Fortunately, the bro-
mination/elimination strategy was more successful compared to
tetrahydrochrysene-1,2-diol 13 and benzyl bromide 17 (X¼Br) was
obtained in 67% isolated yield (Scheme 5). In addition 26% of sub-
strate 10 could be recovered from the reaction mixture. From
benzyl bromide 17 (X¼Br) an elimination reaction was performed.
Using DBU the reaction reached completion after 3 days giving the
desired compound 2 in 73% yield, while with t-BuOK the reaction
was finished after only 1 h and compound 2 was obtained in 66%
isolated yield.
Amide 2 was reduced to aldehyde 16 (76% yield) using Schwartz
reagent,12 and further subjected to a Wittig reaction13 to afford a ca.
2:3 mixture of E- and Z-stilbene 20 in 96% yield. The E- and Z-
stilbene was further subjected to a Mallory photochemical cycli-
zation reaction as previously described.14 Unfortunately, the re-
action gave a mixture of products and only trace amounts of the
desired product were detected by 1H NMR analysis. GCeMS anal-
ysis of the product mixture detected one major product with a mass
of 864 Da, indicating that iodine had been added to the compound
after cyclization.
Since stoichiometric amount of iodine was found to be a prob-
lem, the photochemical transformation was tested with a catalytic
amount of iodine,29 and the desired compound 14 was finally ob-
tained in 28% isolated yield. With compound 14 in hand, the final
deprotection with tetrabutylammonium fluoride (TBAF) went

M. Lorentzen et al. / Tetrahedron 70 (2014) 9041e9051
9045
smoothly, resulting in the isolation of (ꢀ)-(1R,2R)-1,2-
dihydrochrysene-1,2-diol (1) in 76% yield. The product was found
two strategies outlined in Scheme 1 the best approach was found to
be alternative 1, utilizing amide reduction, a Wittig reaction, and
a photochemical cyclization reaction. The analytical data of target
molecule 1 were in full accordance with data reported in the lit-
erature. Compound 1 is now undergoing biological studies in order
to shed light on the further fate of the metabolite in vivo.
to have 87% ee as measured by chiral HPLC (Lux 3u Cellulose-2
20
column) and the optical rotation was found to be [
a
]
ꢀ85.4 (c
D
23
0.58, acetone/DMSO 4:1) (lit.21
[
a
]
D
ꢀ105 (c 0.37, THF)). The
spectroscopic data obtained for compound 1 were in full accor-
dance with data reported in the literature.10aed,30
The synthesis of target compound 1 was also attempted utilizing
the directed ortho metalation (DoM)15 and directed remote met-
alation (DreM)17 strategy, outlined in Scheme 1. Amide 2 was ortho
lithiated with s-BuLi, followed by in situ trapping of the formed
lithiated species with iodine to afford product 21 in 78% yield
(Scheme 6). The ortho-metalated product 21 was further subjected
to a SuzukieMiyaura cross-coupling reaction16 with o-tolylboronic
acid forming biphenyl 22 in 97% isolated yield. From biphenyl 22
a directed remote metalation reaction with LDA was conducted and
the transformation went quantitatively as observed by TLC analysis.
However, when subjecting the cyclized product 23 to 2,6-lutidine
and triflic anhydride17 only a 7% yield of product 24 could be iso-
lated. DreM product 23 suffers from rapid oxidation as observed by
a rapid color change on the TLC plate. The product was kept under
nitrogen as much as possible during work-up procedures. However,
due to steric hindrance between 2,6-lutidine and the compound
itself, protection with triflic anhydride did not go to completion and
upon purification most of compound 23 was lost. A change to
pyridine (stirred overnight) as base resulted in mostly an aroma-
tization of product 24, with the loss of tert-butyldiphenylsilanol,
and only trace amounts of the desired product 24 were observed by
TLC and 1H NMR analysis.
4. Experimental
4.1. General
Tetrahydrofuran (THF) was distilled under nitrogen atmosphere
from Na/benzophenone. N,N,N0,N0-tetramethylethylenediamine
(TMEDA) was distilled and stored over potassium hydroxide (KOH).
Glove box was used when necessary. All reactions were carried out
under nitrogen atmosphere if not otherwise specified. The photo-
chemical reactions were performed by using a Photochemical Re-
actor Ltd. equipped with a 400 W medium pressure Mercury-lamp
in a 350 mL quartz immersion well reactor fitted with a no. 3408
Pyrex glass filter sleeve. TLC was performed on Merck silica gel 60
F254 plates, using UV light at 254 nm and 5% alcoholic molybdo-
phosphoric acid for detection. Normalsil 60, 40e63 mm silica gel
was used for flash chromatography. 1H NMR and 13C NMR were
recorded on a Varian Mercury 300 MHz, all at room temperature.
Chloroform-d1 was used as solvent, unless otherwise specified.
Chemical shifts were reported in parts per million (ppm) compared
to TMS (
CDCl3 (d 77.0, triplet). The splitting pattern was recorded as a sin-
d
0, singlet, for 1H NMR), or for 13C resonance signal to
glet, s; doublet, d; triplet, t; double doublet, dd; double triplet, dt;
quartet, q; multiplet, m; broad, br. IR was recorded on a Perkin
Elmer FT-IR spectrometer, version 3.02.01. Melting points were
determined on a Stuart Scientific melting point apparatus SMP3.
Enantiomeric excess (ee) was determined using chiral Ultimate 300
HPLC with a Lux 3u Cellulose-2 column (150ꢂ4.60 mm, Phenomex
Inc.), RS pump, Autosampler and a Diode Array detector at 220 nm.
4.2. Synthesis of ethyl 4-(2-(N,N0-diethylcarbamoyl)phenyl)
butanoate (4)
N,N-Siethylbenzamide (1.68 g, 9.48 mmol) in THF (10 mL) was
added to a solution of s-BuLi (8.4 mL, 10.42 mmol, 1.4 M solution in
cyclohexane), TMEDA (1.56 mL, 10.41 mmol), and THF (14 mL) at
ꢀ78 ꢁC. After stirring for 1 h, a solution of ZnCl2 (1.43 g, 10.45 mmol,
pre-dried under vacuum) in THF (10 mL) was added and the mix-
ture was allowed to warm to room temperature over a period of
45 min.
A second round bottomed flask containing Ni(acac)2 (124 mg,
0.48 mmol, 5 mol %) and Ph3P (128 mg, 0.49 mmol, 5 mol %) in THF
(15 mL) was heated to reflux before ethyl-4-bromobutyrate (1.4 mL,
9.69 mmol) was added. After stirring the resulting reaction mixture
for 10 min, the arylzinc chloride was added slowly over a period of
15 min and the mixture was stirred at reflux for 2 h. After allowing
the mixture to cool down, it was quenched with saturated NH4Cl
(50 mL) and extracted with Et2O (3ꢂ70 mL). The organic layer was
dried over MgSO4, filtered, and concentrated to give a yellow oil.
The crude product was purified by flash column chromatography
(petroleum ether/EtOAc 1:1) to afford a ca. 9:1 mixture of product 4
and benzamide 3 (2.04 g) as a light yellow oil. 1H NMR (CDCl3,
Scheme 6. Reagents and conditions: (a) (i) s-BuLi (1.06 equiv), TMEDA (1.06 equiv),
THF, ꢀ78 ꢁC, 1 h; (ii) I2 (1.5 equiv), ꢀ78 ꢁC to rt, 5 h, 78%; (b) o-tolylboronic acid
(1.5 equiv), PdCl2dppf (5 mol %), Na2CO3 (2 M), DME, reflux, 19 h, 97%; (c) LDA
(2.5 equiv), THF, 0 ꢁC, 1 h, quant.; (d) 2,6-lutidine (1.1 equiv), Tf2O (1.1 equiv), DCM, 0 ꢁ
to rt, 2 h, 7%.
C
300 MHz):
d 7.38 (s, 5H, benzamide 3), 7.30e7.14 (m, 4H), 4.12 (q,
3. Conclusion
J¼7.1 Hz, 2H), 3.79 (app. s, 1H), 3.58 (app. s, 2H, benzamide 3), 3.35
(app. s, 1H), 3.48 (q, J¼7.0 Hz, 2H), 2.66e2.58 (br m, 2H), 2.33 (t,
J¼7.4 Hz, 2H), 1.99e1.92 (m, 2H), 1.28e1.22 (m, 6H), 1.11 (app. s, 3H,
benzamide 3), 1.04 (t, J¼7.0 Hz, 3H); 13C NMR (CDCl3, 75 MHz):
An enantioselective synthesis of (ꢀ)-(1R,2R)-1,2-dihydro-
chrysene-1,2-diol (1) has been achieved, starting from readily
available N,N-diethylbenzamide. The chirality (trans-diol) within
the structure was formed by a Shi-epoxidation reaction. From the
d
173.2 (COOEt), 170.5 (CON), 137.5 (C), 136.8 (C), 129.3 (CH), 128.6
(CH), 126.0 (CH), 125.5 (CH), 60.1 (OCH2CH3), 42.7 (NCH2), 38.5

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M. Lorentzen et al. / Tetrahedron 70 (2014) 9041e9051
(NCH2), 33.8 (CH2), 32.1 (CH2), 25.8 (CH2), 14.2 (NCH2CH3), 13.8
(OCH2CH3), 12.6 (NCH2CH3).
pentane (30 mL) and filtered through Celite. The yellow filtrate
was concentrated and purified by flash column chromatography
(petroleum ether/EtOAc 2:1) to afford 292 mg (92%) of product 7
4.3. 4-(2-(N,N0-Diethylcarbamoyl)phenyl)butanoic acid (5)
as a fluffy white foamy oil. 1H NMR (CDCl3, 300 MHz):
d 7.78 (app.
d, J¼6.8 Hz, 3H), 7.72 (app. d, J¼6.3 Hz, 2H), 7.41 (app. s, 6H), 7.30
(t, J¼7.7 Hz, 1H), 7.10 (dd, J¼1.0, 7.6 Hz, 1H), 4.79 (t, J¼4.7 Hz, 1H),
3.78e3.71 (m, 1H), 3.43e3.37 (m, 1H), 3.16 (q, J¼7.1 Hz, 2H),
2.73e2.65 (m, 1H), 2.51e2.43 (m, 1H), 2.10e1.99 (m, 2H), 1.25 (t,
J¼7.1 Hz, 3H), 1.10 (app. s, 9H), 1.04 (t, J¼7.1 Hz, 3H); 13C NMR
To a solution of phenylbutanoate 4 (2.04 g) in MeOH (65 mL) and
water (5 mL) was added KOH (0.79 g, 14.15 mmol). The reaction
mixture was heated at reflux for 2 h, before concentrated in vacuo.
The yellow residue was dissolved in water (50 mL), added 2 M
aqueous NaOH-solution (2 mL) and extracted with Et2O (2ꢂ60 mL).
The water layer was adjusted to pH 0 by the addition of 6 M HCl
(4 mL) and extracted a second time with Et2O (3ꢂ60 mL). The latter
organic layer was dried over MgSO4, filtered, and concentrated to
afford 1.68 g (67% from benzamide 3) of product 5 as a light yellow
(CDCl3, 75 MHz):
d
170.6 (CO), 147.4 (C), 135.4 (CHꢂ4), 133.9 (C),
133.0 (C), 132.9 (C), 132.3 (C), 129.8 (CHꢂ2), 127.7 (CHꢂ4), 126.3
(CH), 124.6 (CH), 122.0 (CH), 106.3 (CH¼), 42.7 (NCH2), 38.7 (NCH2),
26.6 (CH3ꢂ3), 24.6 (CH2), 21.6 (CH2), 19.5 (C), 14.1 (NCH2CH3), 12.9
(NCH2CH3); IR (KBr) 3072 (w), 2891 (w), 2932 (m), 2858 (w), 1635
(s), 1473 (w), 1428 (m), 1362 (w), 1344 (w), 1286 (w), 1255 (m),
1220 (w), 1196 (w), 1149 (m), 1113 (m), 955 (w), 921 (w), 823 (w),
736 (w), 701 (m); mass spectrum m/z (relative intensity %) 506.3
[MþNa]þ (100); HRMS (ESI) calcd for C31H37O2N1Si1þNa:
506.2491, found 506.2492.
oil. 1H NMR (CDCl3, 300 MHz):
d 9.65 (br s, 1H, OH), 7.38e7.14 (m,
4H), 3.79 (app. s, 1H), 3.37 (app. s, 1H), 3.12 (q, J¼6.9 Hz, 2H), 2.66
(app. s, 1H), 2.58 (app. s, 1H), 2.35 (t, J¼7.2 Hz, 2H), 1.94 (app. hep,
J¼7.3 Hz, 2H), 1.25 (t, J¼7.5 Hz, 3H), 1.04 (t, J¼7.5 Hz, 3H); 13C NMR
(CDCl3, 75 MHz):
d 178.0 (COOH), 170.9 (CON), 137.4 (C), 136.5 (C),
129.5 (CH), 128.8 (CH), 126.1 (CH), 125.6 (CH), 42.9 (NCH2), 38.8
(NCH2), 33.6 (CH2), 32.0 (CH2), 25.1 (CH2), 13.8 (NCH2CH3), 12.6
(NCH2CH3); IR (KBr) 2974 (m), 2936 (m),1731 (s),1630 (m),1591 (s),
1498 (w), 1460 (m), 1439 (m), 1383 (w), 1364 (w), 1292 (w), 1220
(w), 1150 (w), 1117 (w), 1085 (w), 946 (w), 752 (w); mass spec-
trometry m/z (relative intensity %) 286.1 [MþNa]þ (100); HRMS
(ESI) calcd for C15H21O3NþNa: 286.1414, found 286.1412.
4.6. trans-(5R,6R)-5-((tert-Butyldiphenylsilyl)oxy)-N,N-diethyl-
6-hydroxy-5,6,7,8-tetrahydronaphthalene-1-carboxamide (9)25
OxoneÒ (519 mg, 0.844 mmol, 1.38 equiv) in aqueous EDTA so-
lution (4.9 mL), and K2CO3 (674 mg, 4.88 mmol, 8 equiv) in water
(4.9 mL) were added simultaneously (syringe pump, 0.053 mL/min)
over a period of 90 min to a precooled mixture of silyl enol ether 7
(295 mg, 0.61 mmol), Shi catalyst (51 mg, 0.197 mmol, 0.3 equiv),
tetrabutylammonium bisulfate (5 mg, 0.015 mmol, 0.04 equiv),
acetonitrile (3.7 mL), DME (7.4 mL), and aqueous sodium bor-
ateeEDTA solution (7.4 mL) at 0 ꢁC. After stirring for an additional
30 min at 0 ꢁC, the reaction mixture was diluted with ice-cold
pentane (70 mL), and ice-cold water (40 mL). The aqueous layer
was extracted with ice-cold pentane (2ꢂ70 mL). The organic layer
was washed with brine (1ꢂ150 mL), dried over MgSO4, filtered, and
concentrated in vacuo to give a transparent oil.
4.4. N,N0-Diethyl-5-oxo-5,6,7,8-tetrahydronaphthalene-1-
carboxamide (6)
To butanoic acid 5 (300 mg, 1.141 mmol) was added Eaton’s
reagent (7.7 wt % P2O5 in MsOH, 6.2 mL) and the resulting reaction
mixture was quickly warmed to 100 ꢁC and stirred for 2 h. The dark
brown mixture was then cooled to room temperature and poured
into ice (40 mL). After the ice had melted the yellow aqueous so-
lution was extracted with CH2Cl2 (3ꢂ60 mL). The organic layer was
washed with saturated NaHCO3-solution (1ꢂ100 mL), dried over
MgSO4, filtered, and concentrated in vacuo to give a dark brown oil.
The crude product was purified by flash column chromatography
(petroleum ether/EtOAc 1:1) to afford 170 mg (61%) of product 6 as
a white solid. Mp 96.1e96.6 ꢁC (Et2O); 1H NMR (CDCl3, 300 MHz):
To a precooled solution of crude product in THF (12 mL) was
added boraneetetrahydrofuran complex solution (0.91 mL,
0.91 mmol, 1 M in THF) at 0 ꢁC. The reaction mixture was stirred at
0
ꢁC for 90 min, before septum was removed and the mixture di-
luted with Et2O (10 mL). An aqueous 1 M solution of tris(hydrox-
ymethyl)aminomethane hydrochloride (10 mL) was added slowly,
and the solution was warmed to room temperature and stirred for
30 min. Water (10 mL) was added, and the aqueous layer extracted
with Et2O (3ꢂ30 mL). The organic layer was washed with brine
(1ꢂ75 mL), dried over MgSO4, filtered, and concentrated in vacuo.
The crude product was purified by flash column chromatography
(petroleum ether/EtOAc 1:1) to afford 215 mg (70%) of product 9 as
a fluffy white foamy oil. 83% ee measured by a Lux 3u Cellulose-2
d
8.09e8.06 (m, 1H), 7.39e7.23 (m, 2H), 3.76 (app. s, 1H), 3.43 (app.
s, 1H), 3.14 (q, J¼7.2 Hz, 2H), 3.06 (app. s, 1H), 2.73 (app. s, 1H), 2.67
(t, J¼6.6 Hz, 2H), 2.15 (app. d, J¼6.9 Hz, 2H), 1.28 (dt, J¼0.8, 7.2 Hz,
3H), 1.06 (dt, J¼0.8, 7.5 Hz, 3H); 13C NMR (CDCl3, 75 MHz):
d 197.7
(CO), 169.5 (CON), 140.4 (C), 137.0 (C), 133.1 (C), 130.2 (CH), 127.6
(CH), 126.6 (CH), 42.7 (NCH2), 39.0 (NCH2), 38.9 (CH2), 26.4 (CH2),
22.7 (CH2), 14.1 (NCH2CH3), 12.9 (NCH2CH3); IR (KBr) 2981 (w),
2943 (m), 2874 (w), 1683 (s), 1624 (s), 1584 (m), 1478 (m), 1457 (m),
1432 (m), 1366 (w), 1327 (w), 1296 (m), 1278 (s), 1215 (m), 1192 (w),
1131 (m),1088 (m), 950 (w), 905 (w), 829 (m), 802 (m), 736 (w), 669
(w), 548 (w); mass spectrum m/z (relative intensity %) 268.1
[MþNa]þ (100); HRMS (ESI) calcd for C15H19O2NþNa: 268.1308,
found 268.1309.
HPLC column (10% i-PrOH in hexane, 218 nm, 1.0 mL/min) tR 8.9
20
(minor), tR 18.9 (major); [
(CDCl3, 300 MHz):
a]
e113.8 (c 0.21, acetone); 1H NMR
D
d
7.75e7.62 (m, 4H), 7.47e7.37 (m, 6H), 7.21e7.04
(m, 3H), 4.61 (app. d, J¼8.5 Hz, 1H), 4.02 (app. s, 1H), 3.77 (app. s,
1H), 3.36e2.89 (m, 4H), 2.58e2.53 (m, 1H), 2.23e2.18 (m, 1H), 1.93
(app. s, 1H), 1.83e1.74 (m, 1H), 1.26e1.22 (br m, 4H), 1.07 (s, 9H),
4.5. 5-((tert-Butyldiphenylsilyl)oxy)-N,N-diethyl-7,8-
0.99e0.95 (br m, 2H); 13C NMR (CDCl3, 75 MHz):
d 170.5 (CO), 137.5
dihydronaphthalene-1-carboxamide (7)
(C), 136.3 (CH), 136.2 (CH), 135.9 (CH), 135.7 (CH), 134.2 (C), 133.0
(C), 132.4 (C), 132.2 (C), 129.9 (CH), 129.8 (CH), 127.9 (CHꢂ2), 127.6
(CHꢂ2), 125.9 (CH), 125.8 (CH),124.5 (CH), 75.1 (CHeOSi), 71.2
(CHeOSi), 42.5 (NCH2), 38.6 (NCH2), 27.1 (CH3ꢂ3), 26.2 (CH2), 22.6
(CH2), 19.5 (C), 13.9 (NCH2CH3), 12.8 (NCH2CH3); IR (KBr) 3393 (br,
w), 3070 (w), 2932 (m), 2857 (m), 1614 (s), 1460 (w), 1427 (s), 1292
(w),1217 (w),1110 (s),1069 (br s), 853(w), 821 (w), 788 (w), 741 (w),
703 (m), 609 (w); mass spectrum m/z (relative intensity %) 524.3
[MþNa]þ (100); HRMS (ESI) calcd for C31H39O3NSiþNa: 524.2591,
found 524.2591.
A solution of KHMDS (213 mg, 1.07 mmol) in THF (3 mL) was
added drop wise to a stirred solution of tetralone 6 (161 mg,
0.66 mmol) in THF (8 mL) at ꢀ78 ꢁC. The brown solution was
stirred for 35 min before TBDPSCl (0.2 mL, 0.77 mmol) was added
drop wise. After stirring for 5 min at ꢀ78 ꢁC, the flask was re-
moved from the cooling bath and allowed to warm to room
temperature. The mixture was stirred at room temperature for 1 h,
and concentrated in vacuo. The brown oil was dissolved in

M. Lorentzen et al. / Tetrahedron 70 (2014) 9041e9051
9047
4.7. (5R,6R)-5,6-Bis((tert-butyldiphenylsilyl)oxy)-N,N-diethyl-
5,6,7,8-tetrahydronaphthalene-1-carboxamide (10)
4.9. (((1R,2R)-5-Styryl-1,2,3,4-tetrahydronaphthalene-1,2-
diyl)bis(oxy))bis(tert-butyldiphenylsilane) (12)
To a suspension of sodium hydride (56 mg, 1.40 mmol) in
THF (4 mL) was added trans-diol monosilyl ether 9 (365 mg,
0.728 mmol) in THF (9 mL) at 0 ꢁC. The reaction mixture was
warmed to room temperature, and stirred for 30 min before
TBDPSCl (0.23 mL, 0.886 mmol) was added drop wise. After
stirring overnight (19 h), the reaction mixture was quenched
with saturated NH4Cl (15 mL) and extracted with Et2O
(3ꢂ30 mL). The organic layer was dried over MgSO4, filtered,
and concentrated in vacuo. The crude product was purified by
flash column chromatography (petroleum ether/EtOAc 2:1) to
To a solution of aldehyde 11 (179 mg, 0.27 mmol) in CH2Cl2
(8 mL) was added benzyltriphenylphosphonium chloride
(146 mg, 0.38 mmol) and a 50%-solution of NaOH (0.8 mL). The
yellow reaction mixture was stirred at room temperature for
2.5 h. Water (20 mL) was added and the water layer was extracted
with CH2Cl2 (3ꢂ20 mL). The organic layer was washed with brine
(40 mL), dried over MgSO4, filtered, and concentrated in vacuo.
The crude product was purified by flash column chromatography
(2% EtOAc in petroleum ether) to afford 195 mg (98%) of product
12 as a fluffy white foamy oil as ca. 2:1 mixture of Z and E iso-
afford 508 mg (94%) of product 10 as fluffy white foamy oil as
mers. 1H NMR (CDCl3, 300 MHz):
d 7.56e7.18 (m, 25H), 7.02e6.88
20
a ca. 2:3 mixture of rotamers. [
NMR (CDCl3, 300 MHz):
a
]
ꢀ45.1 (c 0.26, acetone); 1H
(m, 2H), 6.76e6.59 (m, 2H), 6.45 (d, J¼7.6 Hz, 1Hdminor isomer),
6.36 (d, J¼7.6 Hz, 1Hdmajor isomer), 4.50 (app. s, 1H), 4.30 (app.
s, 1H), 3.08e2.76 (m, 2H), 2.41e2.31 (m, 1H), 1.89e1.84 (m, 1H),
D
d
7.59e7.19 (m, 20H), 7.04 (t, J¼7.4 Hz,
1H), 6.92 (t, J¼7.5 Hz, 1Hdmajor rotamer), 6.84 (t, J¼7.3 Hz,
1Hdminor rotamer), 6.51 (d, J¼7.5 Hz, 1Hdmajor rotamer), 6.32
(d, J¼7.3 Hz, 1Hdminor rotamer), 4.45 (app. d, J¼2.3 Hz, 1H),
4.28 (app. s, 1H), 3.91e3.72 (m, 2H), 3.49e2.71 (m, 3H),
2.57e231 (m, 1H), 1.87e1.82 (m, 2H), 1.29e1.24 (m, 3H),
1.11e1.02 (m, 3Hdminor rotamer), 0.94 (t, J¼6.9 Hz, 3Hdmajor
rotamer), 0.84 (s, 9H), 0.82 (s, 9H); 13C NMR (CDCl3, 75 MHz):
0.85 (s, 9H), 0.84 (s, 9H); 13C NMR (CDCl3, 75 MHz):
d 137.0 (C),
136.6 (C), 136.0 (CH), 135.9 (CHꢂ2), 135.8 (CHꢂ2), 135.6 (CHꢂ2),
135.2 (C), 134.1 (C), 134.0 (C), 133.9 (C), 133.8(4) (C), 133.8(0) (C),
131.3 (C), 130.7 (CH), 130.2 (CH), 129.9 (CH), 129.8 (C), 129.5
(CHꢂ2), 129.4 (CH), 129.3 (CH), 129.0 (CHꢂ2), 128.7 (CH), 128.1
(CH), 128.0 (CHꢂ2), 127.5(4) (CHꢂ2), 127.5(1) (CH), 127.4 (CHꢂ2),
127.2 (CHꢂ2), 126.9 (CH), 126.6 (C), 126.5 (CH), 125.3 (C), 125.1
(CH), 124.7 (C), 72.0 (CHeOSidminor isomer), 71.9
(CHeOSidmajor isomer), 70.4 (CHeOSidmajor isomer), 70.2
(CHeOSidminor isomer), 26.8 (CH3ꢂ3), 26.7 (CH3ꢂ3), 24.0 (CH2),
22.0 (CH2), 19.2 (3) (Cꢂ2dmajor isomer), 19.2 (0) (Cꢂ2dminor
isomer); IR (KBr) 3070 (m), 2930 (s), 2857 (m), 1660 (w), 1589
(w), 1472 (m), 1427 (s), 1390 (w), 1362 (w), 1189 (w), 1112 (s), 1075
(br, s), 1007 (m), 910 (w), 858 (w), 822 (m), 790 (w), 738 (m), 701
(s), 610 (m); mass spectrum m/z (relative intensity %) 765.4
[MþNa]þ (100); HRMS (ESI) calcd for C50H54O2Si2þNa: 765.3560,
found 765.3562.
d
170.9 (CO), 136.6 (C), 136.3 (C), 135.9 (CHꢂ2), 135.8 (CHꢂ2),
135.7 (CHꢂ2), 135.5 (CHꢂ2), 133.8 (C), 133.7 (C), 133.5 (C), 132.9
(C), 131.7 (Cdmajor rotamer), 131.5 (Cdminor rotamer), 129.6
(CH), 129.5(3) (CH), 129.5(0) (CH), 129.3 (CH), 127.5 (CHꢂ4),
127.4 (CHꢂ4), 127.3 (CHdmajor rotamer), 127.1 (CHdminor
rotamer), 125.3 (CH), 124.5 (CH), 71.7 (CHeOSidminor rotamer),
71.4 (CHeOSidmajor rotamer), 70.3 (CHeOSidmajor rotamer),
67.9 (CHeOSidminor rotamer), 42.7 (NCH2dminor rotamer),
42.4 (NCH2dmajor rotamer), 38.7 (NCH2dminor rotamer), 38.5
(NCH2dmajor rotamer), 26.7 (CH3x6), 24.1 (CH2dminor
rotamer), 23.5 (CH2dmajor rotamer), 21.1 (CH2dminor
rotamer), 20.4 (CH2dmajor rotamer), 19.1 (C), 14.0 (NCH2CH3),
12.8 (NCH2CH3); IR (KBr) 3071 (w), 2931 (m), 2857 (m), 1637 (s),
1590 (w), 1473 (w), 1460 (w), 1427 (m), 1290 (w), 1221 (w), 1111
(s), 1080 (br m), 1008 (w), 822 (w), 740 (w), 701 (s), 609 (w);
mass spectrum m/z (relative intensity %) 762.4 [MþNa]þ (100);
4.10. (((1R,2R)-1,2,3,4-Tetrahydrochrysene-1,2-diyl)bis(oxy))
bis(tert-butyldiphenylsilane) (13)
To a solution of stilbene 12 (173 mg, 0.23 mmol) in degassed
toluene (350 mL) were added iodine (68 mg, 0.27 mmol) and
1,2-epoxybutane (7 mL). The pink mixture was irradiated for
1.5 h before concentrated to a volume of 50 mL. The residue
was washed with 10% aqueous sodium thiosulfate solution
(20 mL) and brine (20 mL), dried over MgSO4, filtered, and
concentrated in vacuo. The crude product was purified by flash
column chromatography (5% EtOAc in petroleum ether) to af-
ford 166 mg (96%) of product 13 as a fluffy white foamy oil. 1H
HRMS (ESI) calcd for
762.3777.
C
47H57O3N1Si2þNa: 762.3775, found
4.8. (5R,6R)-5,6-Bis((tert-butyldiphenylsilyl)oxy)-5,6,7,8-
tetrahydronaphthalene-1-carbaldehyde (11)
Amide 10 (282 mg, 0.38 mmol) in THF (4 mL) was added to
a suspension of Cp2Zr(H)Cl (148 mg, 0.57 mmol) in THF (2 mL) at
room temperature. After 30 min of stirring the yellow solution
was concentrated in vacuo and the orange residue was purified
by flash column chromatography (petroleum ether/EtOAc 4:1) to
afford 221 mg (87%) of product 11 as a fluffy white foamy oil. 1H
NMR (CDCl3, 300 MHz):
d
8.63 (d, J¼7.9 Hz, 1H), 8.29 (d,
J¼8.5 Hz, 1H), 8.08 (d, J¼9.2 Hz, 1H), 7.90 (d, J¼7.4 Hz, 1H), 7.80
(d, J¼9.2 Hz, 1H), 7.63e7.49 (m, 4H), 7.42e7.12 (m, 18H), 6.82 (d,
J¼8.5 Hz, 1H), 4.69 (app. d, J¼1.9 Hz, 1H), 4.39 (app. s, 1H),
3.35e3.32 (m, 2H), 2.51e2.47 (m, 1H), 2.06e2.01 (m, 1H), 0.86
NMR (CDCl3, 300 MHz):
d
10.33 (s, 1H), 7.69 (d, J¼6.4 Hz, 1H),
7.53e7.17 (m, 20H), 7.02 (t, J¼7.6 Hz, 1H), 6.61 (d, J¼6.7 Hz, 1H),
4.49 (app. d, J¼2.8 Hz, 1H), 4.32 (s, 1H), 3.48e3.23 (m, 2H),
2.41e2.31 (m, 1H), 1.95e1.90 (m, 1H), 0.84 (s, 9H), 0.81 (s, 9H);
(s, 9H), 0.79 (s, 9H); 13C NMR (CDCl3, 75 MHz):
d
135.9 (CHꢂ2),
136.0 (CHꢂ2), 135.6(2) (CHꢂ2), 135.6(0) (CHꢂ2), 134.1 (C), 134.0
(C), 133.8(2) (C), 133.8(0) (C), 133.7 (C), 133.2 (C), 131.6 (C), 130.7
(C), 130.1 (CH), 129.6 (CH), 129.5 (CH), 129.4 (CHꢂ2), 129.3 (CH),
128.4 (CH), 127.6 (CHꢂ2), 127.5 (CHꢂ2), 127.4 (CHꢂ2), 127.2
(CHꢂ2), 126.4 (CH), 126.2 (CH), 123.0 (CH), 122.5 (CH), 120.1
(CH), 72.1 (CHeOSi), 70.4 (CHeOSi), 26.8 (CH3ꢂ3), 26.7 (CH3ꢂ3),
24.1 (CH2), 21.4 (CH2), 19.3 (C), 19.2 (C); IR (KBr) 3070 (m), 2930
(s), 2857 (m), 1589 (w), 1471 (m), 1427 (m), 1390 (w), 1361 (m),
1189 (w), 1112 (s), 1085 (br, s), 1068 (br, s), 1007 (m), 908 (m),
841 (m), 822 (m), 790 (w), 771 (w), 739 (m), 701 (s), 610 (m);
mass spectrum m/z (relative intensity %) 763.3 [MþNa]þ (100);
13C NMR (CDCl3, 75 MHz):
d 193.1 (CO), 140.0 (C), 137.4 (CH), 137.2
(C), 135.8 (CHꢂ4), 135.6 (CHꢂ2), 135.5 (CHꢂ2), 133.9 (C), 133.6
(C), 133.4 (Cꢂ2), 133.3 (C), 132.2 (CH), 129.7 (CH), 129.6 (CH),
129.5 (CH), 129.4 (CH), 127.7 (CHꢂ2), 127.6 (CHꢂ2), 127.5 (CHꢂ2),
127.3 (CHꢂ2), 125.5 (CH), 71.5 (CHeOSi), 69.7 (CHeOSi), 26.7
(CH3ꢂ6), 23.4 (CH2), 21.2 (CH2), 19.2 (Cꢂ2); IR (KBr) 3071 (w),
2931 (m), 2857 (m), 1698 (m), 1590 (w), 1472 (w), 1427 (m), 1184
(w), 1113 (s), 1079 (br s), 1008 (w), 822 (w), 740 (w), 701 (s), 610
(w); mass spectrum m/z (relative intensity %) 691.3 [MþNa]þ
(100); HRMS (ESI) calcd for C43H48O3Si2þNa: 691.3040, found
691.3039.
HRMS (ESI) calcd for
763.3406.
C
50H52O2Si2þNa: 763.3404, found

9048
M. Lorentzen et al. / Tetrahedron 70 (2014) 9041e9051
4.11. (((1R,2R)-1,2-Dihydrochrysene-1,2-diyl)bis(oxy))bis(tert-
butyldiphenylsilane) (14)
[MþNa]þ (100); HRMS (ESI) calcd for C47H55O3N1Si2þNa: 760.3618,
found 760.3617.
To a solution of compound 13 (399 mg, 0.54 mmol) in CCl4
(10 mL) were added N-bromosuccinimide (NBS, 144 mg,
0.81 mmol) and azobisisobutyronitrile (AIBN, 12 mg, 0.06 mmol).
The solution was quickly warmed to reflux, stirred for 2 h before it
was allowed to cool down. Succinimide was filtered off, and the
filtrate was diluted in CH2Cl2 (100 mL), washed with brine (70 mL),
dried over MgSO4, filtered, and concentrated to a yellow oil. The
crude product was purified by flash column chromatography (2%
EtOAc in petroleum ether) to afford an intractable mixture of
products.
4.13. (5R,6R)-5,6-Bis((tert-butyldiphenylsilyl)oxy)-5,6-
dihydronaphthalene-1-carbaldehyde (16)
Amide 2 (1.976 g, 2.68 mmol) in THF (50 mL) was added to
a suspension of Schwartz’ reagent (Cp2Zr(H)Cl, 834 mg, 3.23 mmol)
in THF (21 mL) at room temperature. After 20 min of stirring, silica
was added to the yellow solution and stirred for 3 min before it was
concentrated in vacuo and purified by flash column chromatogra-
phy (petroleum ether/EtOAc 10:1) to afford 1.356 g (76%) of product
16 as a fluffy white foamy oil. 1H NMR (CDCl3, 300 MHz):
d 10.23 (s,
To a solution of this product mixture and benzyl bromide
(306 mg) in THF (5 mL) was added DBU (3.6 mL, 0.54 mmol) at
room temperature. The solution was stirred for 1 h and quenched
with saturated NH4Cl (10 mL). The aqueous layer was extracted
with Et2O (3ꢂ15 mL), washed with brine (30 mL), dried over
MgSO4, filtered, and concentrated. The crude product was purified
by flash column chromatography (5% EtOAc in petroleum ether) to
afford an intractable mixture of products.
1H), 7.59 (dd, J¼1.4, 7.8 Hz, 1H), 7.52 (d, J¼9.9 Hz, 1H), 7.47e7.18 (m,
19H), 7.13 (d, J¼7.1 Hz, 1H), 6.97 (t, J¼7.6 Hz, 1H), 6.61 (d, J¼7.4 Hz,
1H), 5.94 (ddd, J¼1.2, 5.5, 9.9 Hz, 1H), 4.60 (app. q, J¼1.2 Hz, 1H),
4.27 (dd, J¼2.4,5.5 Hz, 1H), 0.76 (s, 9H), 0.73 (s, 9H); 13C NMR
(CDCl3, 75 MHz):
d
192.3 (CHO), 136.0 (C), 135.8 (CHꢂ2), 135.6
(CHꢂ6), 135.4 (CH), 133.9 (C), 133.7 (C), 133.6 (C), 133.5 (C), 133.4 (C),
131.7 (CH), 131.1 (CH), 130.7 (C), 129.7 (CHꢂ2), 129.6 (CH), 129.4
(CH), 127.7 (CHꢂ2), 127.6 (CHꢂ2), 127.5 (CHꢂ2), 127.3 (CHꢂ2), 127.0
(CH), 123.7 (CH), 72.8 (CHeOSi), 67.9 (CHeOSi), 26.7 (CH3ꢂ3), 26.6
(CH3ꢂ3), 19.2 (C), 19.1 (C); IR (KBr) 3070 (w), 2930 (m), 2856 (m),
1697 (m), 1590 (w), 1569 (w), 1471 (w), 1427 (m), 1390 (w), 1361
(w), 1195 (w), 1112 (s), 1074 (br s), 886 (w), 821 (w), 780 (w), 739
(m), 701 (s), 611 (w); mass spectrum m/z (relative intensity %) 689.3
[MþNa]þ (100); HRMS (ESI) calcd for C43H46O3Si2þNa: 689.2883,
found 689.2885.
4.12. (5R,6R)-5,6-Bis((tert-butyldiphenylsilyl)oxy)-N,N-di-
ethyl-5,6-dihydronaphthalene-1-carboxamide (2)
NBS (53 mg, 0.299 mmol) and AIBN (3 mg, 0.012 mmol) were
added to a solution of amide 10 (188 mg, 0.254 mmol) in CCl4
(7 mL). The reaction mixture was heated to 65 ꢁC, stirred for 4 h,
and cooled down before N-succinimine was filtered of. The filtrate
was diluted in CH2Cl2 (50 mL), washed with brine (1ꢂ30 mL), dried
over MgSO4, filtered, and concentrated. The crude product was
purified by flash column chromatography (petroleum ether/EtOAc
4:1) to afford 136 mg (67%) of the benzyl bromide 17 as a yellow oil.
DBU (0.035 mL, 0.231 mmol) was added to a solution of the
benzyl bromide 17 (136 mg, 0.166 mmol) in THF (4 mL) at room
temperature. The reaction mixture was heated to reflux, and stirred
for 67 h, cooled down, quenched with saturated NH4Cl (15 mL), and
extracted with Et2O (3ꢂ30 mL). The organic layer was dried over
MgSO4, filtered, and concentrated. The crude product was purified
by flash column chromatography (petroleum ether/EtOAc 3:1) to
4.14. (((1R,2R)-5-Styryl-1,2-dihydronaphthalene-1,2-diyl)bi-
s(oxy))bis(tert-butyldiphenylsilane) (20)
To a solution of aldehyde 16 (1.326 g, 1.99 mmol) in CH2Cl2
(50 mL) were added benzyltriphenylphosphonium chloride
(1.084 g, 2.80 mmol) and a 50% aqueous NaOH-solution (5 mL). The
orange reaction mixture was stirred at room temperature for
20 min (until the mixture turned yellow). Water (90 mL) was added
and the water layer was extracted with CH2Cl2 (3ꢂ150 mL). The
organic layer was washed with brine (25 mL), dried over MgSO4,
filtered, and concentrated. The crude product was purified by flash
column chromatography (2% EtOAc in petroleum ether) to afford
1.462 g (99%) of product 20 as a transparent oil as a ca. 2:3 mixture
afford 92 mg (73%) of product 2 as a fluffy white foamy oil as a ca.
20
3:2 mixture of rotamers. [
a
]
ꢀ169.8 (c 0.43, acetone); 1H NMR
D
(CDCl3, 300 MHz):
d
7.52e7.22 (m, 20H), 7.12 (d, J¼7.5 Hz, 1H), 6.96
of Z and E isomers. 1H NMR (CDCl3, 300 MHz):
d 7.48e7.40 (m, 8H),
(t, J¼7.3 Hz,1H), 6.59 (d, J¼9.4 Hz,1H, H-7dmajor rotamer), 6.52 (d,
J¼7.7 Hz, 1H, H-4), 6.46 (d, J¼7.5 Hz, 1H, H-7dminor rotamer),
5.94e5.82 (m,1H, H-3), 4.61 (app. s,1H, H-1), 4.31 (dd, J¼1.8, 4.8 Hz,
1H, H-2), 3.82e3.72 (m, 1H), 3.53e3.39 (m, 1H), 3.21 (app. d,
J¼6.2 Hz, 2Hdminor rotamer), 3.05 (app. d, J¼7.0 Hz, 2Hdmajor
rotamer), 1.30 (t, J¼7.0 Hz, 3H), 1.05e1.01 (br m, 3Hdminor
rotamer), 0.97e0.92 (br m, 3Hdmajor rotamer), 0.86 (s, 9Hdminor
rotamer), 0.83 (s, 9Hdmajor rotamer), 0.80 (s, 9Hdmajor rotamer),
7.37e7.12 (m, 15H), 7.09e7.01 (m, 3H), 6.95e6.84 (m, 2H),
6.76e6.57 (m, 2H), 6.45 (d, J¼7.3 Hz, 1Hdminor isomer), 6.37 (d,
J¼7.3 Hz, 1Hdmajor isomer), 5.76e5.65 (m, 1H), 4.59e4.58 (m,
1Hdminor isomer), 4.56e4.55 (m, 1Hdmajor isomer), 4.24e4.21
(m, 1H), 0.78 (s, 9Hdmajor isomer), 0.77 (s, 9Hdminor isomer),
0.75 (s, 9H); 13C NMR (CDCl3, 75 MHz):
d 137.6 (C), 136.7 (C), 135.9
(CHꢂ2dmajor), 135.8 (CHꢂ2dminor), 135.7 (3) (CHꢂ2dmajor),
135.7 (1) (CHꢂ2dminor isomer), 135.7 (0) (CHꢂ2), 135.3
(Cdminor), 135.2 (Cdmajor), 134.7 (C), 134.2(0) (Cdminor),
134.2(0) (Cdmajor), 133.9 (CHdmajor), 133.8(5) (CHdminor),
133.8(0) (Cdmajor), 133.7 (Cdminor) 131.4 (CH), 131.0 (CH), 130.3
(C), 130.0 (C), 129.7 (CHdminor), 129.6 (CH), 129.5 (CHdmajor),
129.4 (CHdmajor), 129.3 (CHdminor), 129.2(4) (CHdminor),
129.2(0) (CHdmajor), 129.1(1) (CHꢂ2), 129.1(0) (CH), 128.7
(CHdmajor), 128.6 (CHdminor), 128.1 (CH), 127.6 (CHꢂ4), 127.4
(CHdmajor), 127.3(5) (CHꢂ2), 127.3(0) (CHꢂ2dmajor), 127.2
(CHꢂ2dminor), 127.1 (CHdminor), 127.0(4) (CH), 127.0(0) (CH),
126.5 (CH), 126.3 (CHdmajor), 126.2 (CHdminor), 125.7
(CHdmajor), 125.4 (CHdminor), 73.5 (CHeOSidminor), 73.3
(CHeOSidmajor), 68.7 (CHeOSidminor), 68.5 (CHeOSidmajor),
0.77 (s, 9Hdminor rotamer); 13C NMR (CDCl3, 75 MHz):
d 170.1
(CO),135.7 (CHx6),135.6 (CHꢂ2),135.4 (C), 135.1 (C), 134.3 (C), 133.9
(C), 133.7 (C), 133.3 (C), 130.2 (CH, C-4dmajor rotamer), 130.0 (CH,
C-4dminor rotamer), 129.6 (CHꢂ2), 129.4 (C), 129.3 (C), 128.9 (CH,
C-3dmajor rotamer), 128.7 (CH, C-3dminor rotamer), 128.6 (C),
127.6 (CHx6), 127.5 (CHꢂ2), 127.3 (CHꢂ2), 127.0 (CH), 125.8 (CH),
125.7, 125.5 (CH, C-7dmajor rotamer), 125.0 (CH, C-7dminor
rotamer), 73.0 (CHeOSidminor rotamer), 72.6 (CHeOSidmajor
rotamer), 68.7 (CHeOSidminor rotamer), 68.3 (CHeOSidmajor
rotamer), 42.9 (NCH2), 39.0 (NCH2), 26.6 (CH3x6), 19.2 (C), 19.0 (C),
14.0 (NCH2CH3), 13.1 (NCH2CH3); IR (KBr) 3071 (w), 3048 (w), 2961
(m), 2931 (m), 2857 (m), 1634 (s), 1589 (w), 1473 (m), 1462 (m),
1428 (s), 1381 (w), 1362 (m),1290 (w),1216 (w), 1112 (s), 1073 (br s),
1007 (w), 910 (w), 887 (w), 822 (m), 771 (w), 738 (m), 701 (s), 610
(m), 504 (m); mass spectrum m/z (relative intensity %) 760.4
26.7(2)
(CH3ꢂ6dminor),
26.7(0)
(CH3ꢂ6,dminor), 19.2
(Cꢂ2dminor), 19.1 (Cꢂ2dmajor); IR (KBr) 3069 (w), 2930 (m),
2856 (m), 1472 (w), 1427 (m), 1361 (w), 1112 (s), 1075 (br, s), 888

M. Lorentzen et al. / Tetrahedron 70 (2014) 9041e9051
9049
(w), 822 (w), 769 (m), 739 (m), 701 (s), 611 (w); mass spectrum m/z
(relative intensity %) 763.3 [MþNa]þ (100); HRMS (ESI) calcd for
for 45 min before I2 in THF (0.437 M, 0.85 mL, 0.372 mmol) was
introduced. The orange solution was warmed to room temperature
overnight (20 h), quenched with sodium thiosulfate (10 mL), and
extracted with Et2O (3ꢂ20 mL). The organic layer was dried over
MgSO4, filtered, and concentrated in vacuo. The crude product was
purified by flash column chromatography (petroleum ether/EtOAc
5:1) to afford 167 mg (78%) of product 21 as a fluffy white foamy oil
as a ca. 3:2 mixture of rotamers. 1H NMR (CDCl3, 300 MHz):
C
50H52O2Si2þNa: 763.3404, found 763.3407.
4.15. (((1R,2R)-1,2-Dihydrochrysene-1,2-diyl)bis(oxy))bis(tert-
butyldiphenylsilane) (14)
Air was bubbled through a solution of stilbene 20 (84 mg,
0.113 mmol) in Et2O (245 mL) and CH2Cl2 (7 mL) for 5 min. A cat-
alytic amount of iodine (2 mg) was added to the solution and the
reaction mixture was irradiated for 3 h before washing with 10%
aqueous sodium thiosulfate solution (1ꢂ100 mL) and brine
(1ꢂ250 mL), dried over MgSO4, filtered, and concentrated. The
crude product was purified by flash column chromatography (2%
EtOAc in petroleum ether) to afford 23 mg (28%) of product 14 as
d
7.55e7.20 (m, 21H), 6.56 (d, J¼9.7 Hz, 1Hdmajor rotamer), 6.47
(d, J¼9.8 Hz, 1Hdminor rotamer), 6.12 (app. t, J¼7.8 Hz, 1H), 5.97
(dd, J¼9.7, 5.4 Hz, 1Hdmajor rotamer), 5.84 (dd, J¼9.8, 5.3 Hz,
1Hdminor rotamer), 4.58 (app. s,1Hdminor rotamer), 4.54 (app. s,
1Hdmajor rotamer), 4.32 (dd, J¼5.4, 2.5 Hz, 1Hdmajor rotamer),
4.29 (dd, 5.3, 2.4 Hz, 1Hdminor rotamer), 3.93e3.73 (m,
2Hdminor rotamer), 3.52e3.36 (m, 2Hdmajor rotamer), 3.19 (q,
J¼7.2 Hz, 2Hdminor rotamer), 3.08e3.00 (m, 2Hdmajor rotamer),
1.34 (t, J¼7.2 Hz, 3Hdminor rotamer), 1.33 (t, J¼7.1 Hz, 3Hdmajor
rotamer), 1.06 (t, J¼7.2 Hz, 3Hdminor rotamer), 1.02 (t, J¼7.1 Hz,
3Hdmajor rotamer), 0.86 (s, 9Hdminor rotamer), 0.83 (s,
9Hdmajor rotamer), 0.79 (s, 9Hdmajor rotamer), 0.77 (s,
a fluffy white foamy oil. 1H NMR (CDCl3, 300 MHz):
d
8.62 (d, J¼7.8
Hz, 1H), 8.35 (d, J¼8.4 Hz, 1H), 8.11 (d, J¼9.3 Hz, 1H), 7.9 (dd, J¼1.8,
7.8 Hz, 1H), 7.78 (d, J¼9.3 Hz, 1H), 7.69e7.08 (m, 23H), 6.95 (d,
J¼8.4 Hz, 1H), 5.96 (dd, J¼5.4, 9.8 Hz, 1H), 4.87 (app. s, 1H), 4.42 (dd,
J¼2.2, 5.4 Hz, 1H), 0.82 (s, 9H), 0.81 (s, 9H); 13C NMR (CDCl3,
75 MHz):
d
135.9 (CHꢂ2), 135.7(4) (CHꢂ2), 135.7(1) (CHꢂ2),
9Hdminor rotamer); 13C NMR (CDCl3, 75 MHz):
d 168.9 (CO), 139.3
135.7(0) (CHꢂ2), 135.3 (C), 134.2 (C), 134.0 (C), 133.9 (C), 133.6 (C),
133.3 (C), 131.5 (C), 130.6 (C), 130.5 (C), 129.6(1) (CH), 129.6(0) (CH),
129.4 (CH), 129.3 (CH), 128.7 (CH), 128.5 (C), 128.4 (CH), 128.0 (CH),
127.6 (CHꢂ4), 127.3 (CHꢂ2), 127.2 (CHꢂ2), 126.8 (CH), 126.6 (CH),
126.5 (CH), 124.6 (CH), 122.9 (CH), 121.7(3) (CH), 121.7(0) (CH), 73.7
(CHeOSi), 68.7 (CHeOSi), 26.7(2) (CH3ꢂ3), 26.7(0) (CH3ꢂ3), 19.3
(C), 19.1 (C); IR (KBr) 3071 (w), 3049 (w), 2930 (m), 2857 (m), 1718
(w), 1589 (w), 1472 (m), 1428 (m),1389 (w), 1361 (w), 1190 (w), 1112
(s), 1074 (s), 999 (w), 908 (m), 891 (w), 822 (m), 751 (m), 736 (m),
701 (s), 611 (m), 506 (m); mass spectrum m/z (relative intensity %)
761.3 [MþNa]þ (100); HRMS (ESI) calcd for C50H50O2Si2þNa:
761.3247, found 761.3249.
(C), 139.2 (C), 137.4 (CH), 137.2 (CH), 135.8 (CH), 135.7(4) (CH),
135.7(1) (CH), 135.7(0) (CH), 135.6 (CH), 135.6(0) (CH), 135.5 (CH),
135.4 (C), 135.0 (C), 133.7 (C), 133.6 (C), 133.5(3) (C), 133.5(0) (C),
133.4(2) (C), 133.4(0) (C), 133.4(0) (C), 133.0 (C), 131.2 (CH), 131.0
(CH), 130.7 (C), 130.4 (C), 129.7 (CH), 129.6(3) (CH), 129.6(0) (CH),
129.3 (CH), 127.6(2) (CH), 127.6(0) (CH), 127.5 (CH), 127.4 (CH), 137.3
(CH), 125.8 (CH), 125.2 (CH), 92.9 (CeIdmajor rotamer), 92.8 (
Idminor rotamer), 72.6 (CHeOSidminor rotamer), 72.2
(CHeOSidmajor rotamer), 68.4 (CHeOSidminor rotamer), 68.0
(CHeOSidmajor rotamer), 42.9 (NCH2dmajor rotamer), 42.8
(NCH2dminor rotamer), 39.0 (1) (NCH2dmajor rotamer), 39.0 (0)
(NCH2dminor rotamer), 26.8 (CH3ꢂ3dminor rotamer), 26.6
(CH3ꢂ3dmajor rotamer), 26.6(0) (CH3ꢂ3dmajor rotamer), 26.5
(CH3ꢂ3dminor rotamer), 19.2 (Cdminor rotamer), 19.1 (Cdmajor
rotamer), 19.0(4) (Cdminor rotamer), 19.0(1) (Cdmajor rotamer),
13.8 (NCH2CH3), 12.5 (NCH2CH3); IR (KBr) 3070 (w), 3048 (w), 2960
(m), 2931 (m), 2894 (m), 2857 (m), 1641 (s), 1589 (w), 1560 (w),
1473 (m), 1460 (m), 1428 (m), 1389 (w), 1362 (w), 1314 (w), 1283
(m), 1212 (w), 1188 (w), 1112 (s), 1073 (br s), 1007 (w), 890 (m), 823
(m), 741 (m), 701 (s), 660 (w), 611 (m), 505 (m); mass spectrum m/z
(relative intensity %) 864.3 [M]þ (100); HRMS (ESI) calcd for
4.16. (L)-(1R,2R)-1,2-Dihydrochrysene-1,2-diol (1)
To a solution of protected 1,2-dihydrochrysene-1,2-diol 14
(23 mg, 0.031 mmol) in THF (2.5 mL) was added TBAF (0.08 mL,
0.08 mmol,1 M in THF) at 0 ꢁC. The reaction mixture was warmed to
room temperature and stirred for 3 h before water (8 mL) was
added. The mixture was extracted with Et2O (3ꢂ10 mL). The or-
ganic layer was dried over MgSO4, filtered, and concentrated. The
crude product was purified by flash column chromatography (pe-
troleum ether/EtOAc 1:2) to afford 6 mg (76%) of product 1 as
a white solid. 87% ee measured by a Lux 3u Cellulose-2 HPLC col-
umn (10% i-PrOH in hexane, 254 nm, 0,5 mL/min) tR 27.2 (minor), tR
C50H52O2Si2: 864.2767, found 864.2767.
4.18. (5R,6R)-5,6-Bis((tert-butyldiphenylsilyl)oxy)-N,N-di-
ethyl-2-(o-tolyl)-5,6-dihydronaphthalene-1-carboxamide (22)
20
23
33.1 (major); [
a
]
ꢀ85.4 (c 0.58, acetone/DMSO 4:1) (lit.2a
[a]
D
D
ꢀ105 (c 0.37, THF)); 1H NMR (acetone-d6/DMSO-d6 4:1, 300 MHz):
All solution was degassed prior to use. A solution of 21 (740 mg,
0.857 mmol) and Pd(dppf)Cl2 (35 mg, 0.04 mmol) in DME (15 mL)
was stirred at room temperature for 7 min. o-Tolylboronic acid in
DME (10 mL) was introduced, followed by sodium carbonate so-
lution (2 M, 2.4 mL, 4.8 mmol). The orange solution was warmed
to reflux and stirred overnight (19 h). After allowing the black
reaction mixture to cool down, it was quenched with water
(30 mL) and extracted with Et2O (3ꢂ40 mL). The organic layer was
dried over MgSO4, filtered, and concentrated in vacuo. The crude
product was purified by flash column chromatography (petroleum
ether/EtOAc 5:1) to afford 685 mg (97%) of product 22 as a fluffy
white foamy oil as a mixture of rotamers. 1H NMR (CDCl3,
d
8.83 (d, J¼8.2 Hz, 1H), 8.78 (d, J¼8.6 Hz, 1H), 8.20 (d, J¼9.2 Hz, 1H),
8.00 (d, J¼8.6 Hz, 1H), 7.97 (dd, J¼1.6, 7.7 Hz, 1H), 7.86 (d, J¼9.2 Hz,
1H), 7.72e7.60 (m, 2H), 7.32 (dd, J¼2.5, 10.2 Hz, 1H), 6.20 (dd, J¼2.2,
10.2 Hz, 1H), 5.47 (br s, 1H, OH), 5.07 (br s, 1H, OH), 4.84 (d,
J¼11.5 Hz, 1H), 4.45 (d, J¼11.5 Hz, 1H); 13C NMR (CDCl3, 75 MHz):
d
137.9 (C), 135.1 (CH), 132.1 (C), 131.0 (C), 130.2 (C), 129.1(4) (C),
129.1(0) (CH), 128.0 (C), 127.8 (CH), 127.6 (CH), 127.3 (CH), 124.7
(CH), 123.6 (CH), 122.5 (CH), 122.4 (CH), 75.6 (CHOH), 73.3 (CHOH).
The spectroscopic data for (ꢀ)-(1R,2R)-1,2-dihydrochrysene-1,2-
diol (1) were in full accordance with the data reported in the
literature.
300 MHz):
d 7.55e7.02 (m, 23H), 6.92e6.65 (m, 2H), 6.57e6.39 (m,
4.17. (5R,6R)-5,6-Bis((tert-butyldiphenylsilyl)oxy)-N,N-di-
ethyl-2-iodo-5,6-dihydronaphthalene-1-carboxamide (21)
2H), 6.00e5.77 (br m, 1H), 4.73e4.62 (br m, 1H), 4.42e4.37 (m,
1H), 3.81e3.68 (m, 1H), 3.31e2.62 (br m, 3H), 2.17 (s, 3Hdminor
rotamer), 2.15 (s, 3Hdmajor rotamer), 0.89 (s, 9Hdminor
rotamer), 0.86 (app. s, overlapping signal, 3H), 0.80 (s, 9Hdminor
To a solution of amide 2 (182 mg, 0.247 mmol) and TMEDA
(0.04 mL, 0.267 mmol) in THF (4 mL) was added s-BuLi (0.29 mL,
0.261 mmol) drop wise at ꢀ78 ꢁC. The yellow solution was stirred
rotamer), 0.64 (app. s, 3H); 13C NMR (CDCl3, 75 MHz):
d
168.5,
135.9 (CHꢂ2dminor rotamer), 135.8 (CHꢂ2dminor rotamer),

9050
M. Lorentzen et al. / Tetrahedron 70 (2014) 9041e9051
135.7 (CHꢂ2dmajor rotamer), 135.6 (CHꢂ2dmajor rotamer),
134.4 (C), 133.8 (C), 133.8 (Cꢂ6), 131.4 (CHdminor rotamer), 130.8
(CHdmajor rotamer), 129.9 (CH), 129.7 (CH), 129.6(4) (CH),
129.6(0) (CH), 129.5 (CH), 129.2 (CH), 128.7 (CH), 128.6 (Cꢂ2), 127.9
(CH), 127.6 (CHꢂ4), 127.5 (CHꢂ2), 127.3 (CHꢂ2), 126.9 (CH), 126.3
(CH), 125.9 (CH), 125.4 (CH), 124.4 (CH), 120.2 (CH), 114.9 (CH), 73.1
(CHeOSidminor rotamer), 72.6 (CHeOSidmajor rotamer), 69.0
(CHeOSidminor rotamer), 68.6 (CHeOSidmajor rotamer), 42.6
(NCH2dmajor rotamer), 42.2 (NCH2dminor rotamer), 37.7 (NCH2),
26.8 (CH3ꢂ3dminor rotamer), 26.7 (CH3ꢂ3dmajor rotamer), 26.6
(CH3ꢂ3), 20.2 (CH3, br), 19.2(3) (Cdmajor rotamer), 19.2(0)
(Cdminor rotamer), 13.7 (NCH2CH3), 11.6 (NCH2CH3); IR (KBr)
3049 (w), 2931 (m), 2857 (m), 1637 (s), 1473 (m), 1428 (m), 1383
(w), 1362 (w), 1283 (w), 1112 (s), 1073 (br s), 892 (m), 822 (m), 741
(m), 701 (s), 611 (m), 506 (m); mass spectrum m/z (relative in-
tensity %) 828.3 [M]þ (100); HRMS (ESI) calcd for C50H52O2Si2:
828.4268, found 828.4267.
Supplementary data
1H NMR and 13C NMR spectra of all new compounds and HPLC
chromatogram for compounds 10 and 1. Supplementary data as-
sociated with this article can be found in the online version, at
http://dx.doi.org/10.1016/j.tet.2014.10.016. These data include MOL
files and InChiKeys of the most important compounds described in
this article.
References and notes
1. (a) Harvey, R. G. Polycyclic Aromatic Hydrocarbons; Wiley-VCH: New York, NY,
1997; (b) Pampanin, D. M.; Sydnes, M. O. Polycyclic Aromatic Hydrocarbons A
Constituent of Petroleum: Presence and Influence in the Aquatic Environment
In Hydrocarbons; Kutcherov, V., Kolesnikov, A., Eds.; InTech: Rijeka, Croatia,
2013; pp 83e118.
2. (a) Hoffmann, D.; Djordjevic, M. V.; Hoffmann, I. Prev. Med. 1997, 26, 427e434;
(b) Merivmsky, O.; Inbar, M. Clin. Dermatol. 1998, 16, 585e588; (c) Nock, N. L.;
Tang, D.; Rundle, A.; Neslund-Dudas, C.; Savera, A. T.; Bock, C. H.; Monaghan, K.
G.; Koprowski, A.; Mitrache, N.; Yang, J. J.; Rybicki, B. A. Cancer Epidemiol.
Biomarkers Prev. 2007, 16, 1236e1245.
4.19. (1R,2R)-1,2-Bis((tert-butyldiphenylsilyl)oxy)-1,2-
dihydrochrysen-5-yl trifluoromethanesulfonate (24)
3. Oanh, N. T. K.; Reutergardh, L. B.; Dung, N. T. Environ. Sci. Technol. 1999, 33,
2703e2709.
4. (a) Sinha, R.; Peters, U.; Cross, A. J.; Kulldorff, M.; Weissfeld, J. L.; Pinsky, P. F.;
Rothman, N.; Hayes, R. B. Cancer Res. 2005, 65, 8034e8041; (b) Phillips, D. H.
Mutat. Res. 1999, 44, 139e147.
To
a precooled solution of diisopropylamine (0.28 mL,
5. (a) Daly, J. W.; Jerina, D. M.; Witkop, B. Experientia 1972, 28, 1129e1149; (b)
Jerina, D. M.; Daly, J. W. Science 1974, 185, 573e582; (c) Xue, W.; Warshawsky,
D. Toxicol. Appl. Pharmacol. 2005, 206, 73e93.
2.0 mmol) in THF (2 mL) was added n-BuLi (1.3 M, 1.54 mL,
2.0 mmol) at ꢀ10 ꢁC. After stirring for 15 min, biphenyl 22
(663 mg, 0.801 mmol) in THF (3 mL) was added. The black reaction
mixture was stirred for 1 h before quenched with saturated NH4Cl
(10 mL). The layers were separated and the water layer extracted
with Et2O (3ꢂ15 mL). The organic layer was kept under nitrogen
atmosphere as much as possible, dried over MgSO4, filtered, and
concentrated in vacuo. The yellow/orange oil was dissolved in
CH2Cl2 (10 mL) and cooled to 0 ꢁC before 2,6-lutidine (0.11 mL,
0.95 mmol) was added. After stirring for 5 min, triflic anhydride
(0.16 mL, 0.95 mmol) was added slowly and the red reaction
mixture was stirred for 45 min at 0 ꢁC and 1 h at room temper-
ature. Water (10 mL) was added to the reaction mixture and
extracted with CH2Cl2 (3ꢂ15 mL). The organic layer was dried over
MgSO4, filtered, and concentrated in vacuo. The crude product was
purified by flash column chromatography twice (petroleum ether/
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24 as a transparent oil. 1H NMR (CDCl3, 300 MHz):
d
8.54 (d, J¼8.1
Hz, 1H), 8.27 (d, J¼8.4 Hz, 1H), 7.88 (d, J¼7.2 Hz, 1H), 7.76 (s, 1H),
7.66e7.19 (m, 21H), 7.08 (d, J¼7.2 Hz, 2H), 6.87 (d, J¼8.4 Hz, 1H),
6.08 (dd, J¼5.4, 9.9 Hz, 1H), 4.8 (app. s, 1H), 4.40 (dd, J¼5.4, 2.4 Hz,
1H), 0.84 (s, 9H), 0.79 (s, 9H); 13C NMR (CDCl3, 75 MHz):
d 145.1
(C), 135.8(2) (CHꢂ2), 135.8(0) (CHꢂ2), 135.7 (CHꢂ2), 135.6 (CHꢂ2),
133.9 (C), 133.8 (C), 133.7 (C), 133.5 (C), 133.1 (C), 130.1 (CH), 130.0
(C), 129.9 (C), 129.6(2) (CH), 129.6(2) (CH), 129.6(0) (CH), 129.2
(CH), 128.5(2) (CH), 128.5(1) (CH), 128.2 (C), 128.0 (CH), 127.6(2)
(CHꢂ2), 127.6(0) (CHꢂ3), 127.5 (CHꢂ2), 127.2 (CHꢂ2), 126.9 (CH),
123.0 (CH), 121.8 (CH), 121.7 (C), 120.0 (CH), 73.8 (CHeOSi), 67.6
(CHeOSi), 26.7 (CH3ꢂ3), 26.6 (CH3ꢂ3), 19.2 (C), 19.0 (C); IR (KBr)
3072 (m), 2858 (m), 2930 (s), 1590 (w), 1472 (m), 1427 (s), 1362
(w), 1244 (m), 1213 (s), 1141 (m), 1112 (s), 1078 (m), 1007 (w), 973
(w), 898 (m), 869 (w), 846 (w), 821 (m), 808 (m), 756 (m), 739 (m),
701 (s), 612 (m), 506 (m), 459 (m); mass spectrum m/z (relative
intensity %) 909.3 [MþNa]þ (100); HRMS (ESI) calcd for
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Acknowledgements
We thank the University of Stavanger for financial support and
the provision of a PhD fellowship to M.L., and the research program
Green Production Chemistry for additional financial support.
Thanks are also due to Dr. Bjarte Holmelid, University of Bergen, for
recording HRMS spectra.

M. Lorentzen et al. / Tetrahedron 70 (2014) 9041e9051
9051
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