Use of the Diels-Alder cycloaddition of tetracyclone and internal aryl acetylenes for the synthesis of functionalized atropisomeric biaryls

Article abstract of DOI:10.1002/ejoc.200901080

The Diels-Alder cycloaddition reaction of tetracyclone and functionalized, internal aryl acetylenes gave access to a number of bulky atropisomeric biaryls in good to excellent: yield. The synthesis is convenient and yields the pure biaryls without tedious work-up and purification procedures. Exemplarily the atropisomers have been resolved via the diastereomers in an easy and efficient manner to yield the enantiomers.

Full text of DOI:10.1002/ejoc.200901080

FULL PAPER
DOI: 10.1002/ejoc.200901080
Use of the Diels–Alder Cycloaddition of Tetracyclone and Internal Aryl
Acetylenes for the Synthesis of Functionalized Atropisomeric Biaryls
Marko Hapke,*[a] Andrey Gutnov,[a] Nico Weding,[a] Anke Spannenberg,[a]
Christine Fischer,[a] Christian Benkhäuser-Schunk,[b] and Barbara Heller[a]
Dedicated to the memory of Prof. Dr. Peter Köll
Keywords: Atropisomerism / Biaryls / Diels–Alder reaction / Cycloaddition / Alkynes
The Diels–Alder cycloaddition reaction of tetracyclone and
functionalized, internal aryl acetylenes gave access to a
number of bulky atropisomeric biaryls in good to excellent
yield. The synthesis is convenient and yields the pure biaryls
without tedious work-up and purification procedures. Exem-
plarily the atropisomers have been resolved via the dia-
stereomers in an easy and efficient manner to yield the
enantiomers.
dium-catalyzed reactions, namely the transformation of un-
activated aryl chlorides in cross-coupling reactions.[9] The
Diels–Alder approach for the reaction of functionalized
acetylenes and dienes has also been utilized to prepare less
substituted phosphoryl group-containing biaryls, that can
act as ligands in other palladium-catalyzed cross-coupling
reactions.[10] Herein we present an approach to apply the
Diels–Alder cycloaddition strategy to the synthesis of func-
tionalized, sterically hindered atropisomeric hexaarylbenz-
enes, potential ligands for general as well as for asymmetric
catalytic purposes.
Introduction
The Diels–Alder cycloaddition of tetraphenylcyclopen-
tadienone (tetracyclone, 1) or its aryl-substituted derivatives
with acetylenes has been developed in recent years into a
powerful tool for the preparation of a number of interesting
molecular architectures, like e.g. hexaarylbenzenes,[1] den-
drimers,[2] molecular propellers,[3] polycyclic aromatic com-
pounds,[4] or discotic liquid crystals.[5] The [4+2] cycload-
dition reaction with heterocyclic alkynes or nitriles also
proved to be a suitable approach for the synthesis of ligand
systems in the preparation of coordination compounds with
transition metal ions, which exhibit interesting properties.[6]
The reaction of 1 with acetylenes in general proceeds at
high temperatures with the extrusion of carbon monoxide
from the primary cycloaddition intermediate, yielding the
aromatic products.[7] The circular array of six aromatic
rings around the central benzene ring in hexaarylbenzenes
leads to a propeller-shaped structure, and the property can
give rise to chiral conformations if unequally substituted
aryls are used, resulting from the introduction of axial chi-
rality into the molecule and therefore the formation of
atropisomers.[8] Substituted polyphenylated arenes have re-
cently also found interest for the preparation of very bulky
phosphane ligands, that can be used in a number of palla-
Results and Discussion
Earlier we reported that a number of activated internal 1-
naphthylacetylenes can be successfully utilized in cobalt(I)-
catalyzed enantioselective [2+2+2] cross-cyclotrimerization
reactions with other acetylenes to give axially chiral biphen-
yls with good yields and enantioselectivities.[11] In this work
we have applied the same substrate acetylenes 2a–l as dieno-
philes for the [4+2] cycloaddition with tetracyclone
(Scheme 1).
The conditions chosen are quite general for such type of
cycloaddition reactions (diphenyl ether, 260 °C, 8 h). The
reaction proceeds smoothly in most cases to give the com-
pounds 3a–i after a very simple work-up procedure with
excellent yields (Table 1). The products are high-melting,
crystalline substances which are easy to purify chromato-
graphically or with a simple crystallization. At first view,
interestingly, (phosphoryl)acetylenes with bulky aliphatic
groups (R2 = tert-butyl, adamantyl, entry 10 and 11) have
not furnished any cycloaddition products under standard
conditions.
[a] Leibniz-Institut für Katalyse e. V. an der Universität Rostock
(LIKAT),
Albert-Einstein-Str. 29a, 18059 Rostock, Germany
Fax: +49-381-128151213
E-mail: marko.hapke@catalysis.de
[b] Universität Bonn, Kekulé-Institut für Organische Chemie und
Biochemie,
Gerhard-Domagk-Str. 1, 53121 Bonn, Germany
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.200901080.
Eur. J. Org. Chem. 2010, 509–514
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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M. Hapke et al.
FULL PAPER
group of the naphthyl fragment (Scheme 2). In the case of
4, we basically obtained a 1:1 ratio of the resulting dia-
stereomers 5. The introduction of chirality in the substrates
obviously has no influence on the preferred formation of
one of the diastereomers. When turning to the chiral deriva-
tive 6, unfortunately the expected diastereomers 7 could not
be isolated and the ratio determined. Instead, the biaryl rac-
8, bearing a free hydroxy group at the naphthyl ring, was
isolated in ca. 41% yield, presumably due to the elimination
of the camphoryl group during the reaction.
Scheme 1. Diels–Alder cycloaddition of tetracyclone (1) with dif-
ferent acetylenes 2a–l, yielding the biaryls 3a–i.
Table 1. Synthesis of the functionalized biaryls.
Entry Acetylenes 2
% Yield of 3[a]
1
2
3
4
5
6
7
8
2a: R1 = H, R2 = P(O)Ph2
3a, 92
3b, 83
2b: R1 = OCH3, R2 = P(O)Ph2
2c: R1 = OCH3, R2 = P(O)[(3,5-CF3)2Ph]2 3c, 93
2d: R1 = OCH3, R2 = P(O)[(4-OCH3)Ph]2 3d, 81
2e: R1 = CH3, R2 = P(O)Ph2
2f: R1 = OCH3, R2 = PPh2
3e, 80
3f, 24
3g, 93
3h, 60
3i, 87
3k, –
3l, –
2g: R1 = OCH3, R2 = COOCH3
2h: R1 = OCH3, R2 = COOPh
2i: R1 = OCH3, R2 = COPh
2k: R1 = OCH3, R2 = P(O)Ad2
2l: R1 = OCH3, R2 = P(O)[tBu]2
9
10
11
[a] Isolated yield.
Scheme 2. Attempted introduction of stereogenic information in
the Diels–Alder cycloaddition reaction with chiral acetylene 4 and
6.
Electron-withdrawing phosphoryl and carbonyl groups
in the acetylenes 2 are in general a prerequisite for a suc-
cessful reaction. This is exemplified by entry 6 (Table 1),
In order to resolve the formed biaryls preparatively, we
where in acetylene 2f the POPh2 group was replaced with have investigated and exemplified the appropriate procedure
the more electron-rich PPh2 moiety, which resulted in a sig- using the biaryl product rac-3b (Scheme 3).
nificantly lower yield of the product 3f. The use of electron-
In the first step the methoxy group was demethylated
deficient (entry 3, 2c) or electron-rich (entry 4, 2d) substi- using BBr3 to quantitatively yield the phenolic derivative
tuted phenyl groups at the phosphorus atom did not show rac-8. However, all of our attempts have failed in preparing
significant differences in the reaction outcome. Several ex- corresponding diastereomeric camphorsulfonates as com-
periments with HPLC using a chiral stationary phase have pound rac-8 did not react with (1S)-(+)-10-camphorsul-
revealed that the compounds 3a–i form racemates. Investi- fonyl chloride (1.2 equiv.), neither in the presence of an ex-
gations towards the interconversion temperature for single cess of pyridine at elevated temperatures (100 °C) nor in
enantiomers in the range up to 60 °C showed no intercon- THF with sodium hydride (1.2 equiv.) as a base. Fortu-
version, which is in agreement with observations made for nately, we did succeed in the preparation of corresponding
hexaarylbenzene systems with substituents in the ortho-po- diastereomeric menthyl carbonates from (+)-menthyl chlo-
sition, where interconversions have only been observed at roformate and compound rac-8 in the presence of NaH in
high temperatures.[8] However, the herein reported biaryls refluxing THF. Both the deprotection as well as the protec-
possess large substituents in the ortho-positions of the bi- tion as the (+)-menthyl carbonates proceeded with very
aryl bond, which is a requirement for a high stability high to nearly quantitative yields. After extensive screening
against interconversion and therefore the configurational of solvents, the individual diastereomers 9 and 10 have been
stability barrier can be expected to be much higher than smoothly separated by chromatography on silica gel with
60 °C.[8b]
Et2O/n-hexane mixture (5:1) as the eluent. The menthyloxy-
We investigated the influence of chiral groups attached carbonyl group in the compounds 9 and 10 was easily and
to the naphthylacetylenes like in 4 (menthyl group) and 6 quantitatively removed by refluxing with hydrazine hydrate
(camphoryl group), where these groups are either directly in THF to give the optically pure (–)-(S)- and (+)-(R)-
attached to the alkyne moiety or bound to the hydroxy enantiomers of the corresponding hydroxyphosphane oxide
510
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Synthesis of Functionalized Atropisomeric Biaryls
Figure 1. ORTEP drawing of the molecular structure of dia-
stereomer 10. The thermal ellipsoids correspond to 30% prob-
ability. Hydrogen atoms have been omitted for clarity.[12]
3b with a solution of AlH3 in THF showed some difficult-
ies, because the reaction gave several unidentified side prod-
ucts.[13] We then turned our attention on the use of tri-
chlorosilane for the reduction of phosphane oxides, which
has also been used for the reduction of chiral phosphane
oxides without the loss of chirality (Scheme 4).[14] The reac-
tion of HSiCl3 in toluene/triethylamine finally yielded the
free phosphane rac-3f with 49% yield after chromatography.
We attempted the separation of rac-3f with HPLC using
preparative chiral stationary phases like the chiral Whelk
and Daicel phases, but observed problems in resolving the
enantiomers. The deoxygenation of the chiral phosphanes 3
according to the above mentioned protocol worked
smoothly and yielded the enantiomeric free phosphanes in
66% yield for (S)-3f and 72% yield for (R)-3f.
Scheme 3. Preparation of the single enantiomeric atropisomers of
3b via diastereomeric resolution as the menthyl carbonates.
8. The oxides can be transformed into the methylated com-
pounds (S/R)-3b by methylation with methyl iodide/NaH in
very good yields.
For the determination of the absolute configuration a
single crystal of the diastereomer 10 has been grown from
a benzene/n-heptane mixture and a X-ray crystal structure
analysis has revealed the (R) configuration of the biphenyl
part of the molecule with respect to the (+)-menthyloxycar-
bonyl group. The molecular structure is depicted in Fig-
Scheme 4. Deoxygenation of phosphane oxide 3b.
Conclusions
In conclusion, a simple and convenient way for the syn-
ure 1. The central phenyl ring is almost planar (mean devia- thesis of highly sterically hindered atropisomeric function-
tion from the best plane is 0.032 Å). Four phenyl rings and alized biphenyls based on a Diels–Alder cycloaddition has
the substituted naphthyl ring are twisted into a propeller been developed. The functional groups investigated com-
conformation around the central phenyl ring.
prise esters, ketone or highly interesting phosphane oxides,
We also investigated the deoxygenation of phosphane ox- which are versatile precursors for the preparation of phos-
ide 3b yielding phosphane 3f (Scheme 4). From the prepara- phane ligands used in catalytic applications. The separation
tion of biaryls by cobalt-catalyzed cycloaddition reactions procedure for the racemic atropisomers has been developed
we knew, that the use of AlH3 was advantageous for ob- and successfully applied to furnish the pure enantiomeric
taining the phosphanes without loss of chirality and in high phosphanes. The reduction of the phosphane oxides has
yields in the case of enantiomerically pure biaryl phos- been
exemplarily
investigated
and
HSiCl3/Et3N/
phanes.[11b] The use of this method for the reduction of rac- toluene found as the suitable reduction system.
Eur. J. Org. Chem. 2010, 509–514
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1-(2-{Bis[3,5-bis(trifluoromethyl)phenyl]phosphoryl}-3,4,5,6-tetra-
phenylphenyl)-2-methoxynaphthalene (3c): Reacting tetracyclone (1,
0.5 mmol) and the alkyne 2c (0.5 mmol) in accordance to the General
Procedure furnished the desired compound 3c; yield 470 mg, 93%;
m.p. 306–307 °C. 1H NMR (300 MHz, CDCl3): δ = 7.70 (d, J =
11.0 Hz, 2 H, Ar-H), 7.61–7.49 (m, 4 H, Ar-H), 7.44 (s, 1 H, Ar-H),
7.38–7.27 (m, 2 H, Ar-H), 7.20–7.06 (m, 3 H, Ar-H), 6.83 (q, J =
8.4 Hz, 3 H, Ar-H), 6.75–6.54 (m, 12 H, Ar-H), 6.48–6.27 (m, 4 H,
Ar-H), 6.19 (dd, J = 7.4, 1.0 Hz, 1 H, Ar-H), 3.63 (s, 3 H, OCH3)
ppm. 13C NMR (75 MHz, CDCl3): δ = 154.1, 146.7, 146.6, 146.2,
146.1, 143.3, 143.2, 143.1, 142.9, 140.0, 139.8, 139.4, 139.2, 138.7,
138.4, 138.0, 137.8, 137.7, 133.2, 133.0, 132.5, 131.3, 130.9, 130.8,
130.5, 130.2, 129.9, 129.4, 128.9, 127.3, 126.7, 126.0, 125.9, 125.8,
125.7, 125.6, 125.2, 125.1, 124.4, 123.3, 123.0, 121.4, 120.8, 110.7,
54.9 ppm. 31P NMR (125 MHz, CDCl3): δ = 16.6 ppm. MS (70 eV):
m/z (%) = 1009 (100) [M+], 488 (15). C57H35F12O2P (1010.84): calcd.
C 67.73, H 3.49; found C 67.59, H 3.52.
Experimental Section
General: The NMR spectra were recorded on a Bruker ARX 300
spectrometer at 298 K. Chemical shifts are reported in ppm relative
1
to the H and 13C residue of the deuterated solvent. Mass spectra
were obtained with a Varian AMD-402 instrument at an ionizing
voltage of 70 eV. Relative intensities in percentages are given in pa-
rentheses. Melting points were measured with a Büchi 540 melting
point determination apparatus. Optical rotations were determined
on a Gyromat-HP polarimeter. In all cases the enantiomeric ex-
cesses were analyzed by HPLC with a Liquid Chromatograph 1090
equipped with DAD (Hewlett–Packard) and Chiralyser (IBZ Mess-
technik GmbH, Hannover). The alkyne starting materials 2a–e and
2i–l have been prepared after published procedures from 1-ethynyl-
2-methoxynaphthalene.[11b] The phosphane 2f was prepared follow-
ing the literature procedure.[15] The synthesis and characterization
of compounds 2g, 2h, 4, 6 and the product 5 as well as the details
for the reaction of 4 and 6 with 1 are given in the Supporting
Information.
1-{2-[Bis(4-methoxyphenyl)phosphoryl]-3,4,5,6-tetraphenylphenyl}-
2-methoxynaphthalene (3d): Reaction of tetracyclone (1) and the
alkyne 2d according to the General Procedure gave the desired
compound 3d; yield 647 mg, 81 %; m.p. 278–279 °C. 1H NMR
(300 MHz, CDCl3): δ = 7.61 (d, J = 8.2 Hz, 1 H, Ar-H), 7.42 (d,
J = 7.6 Hz, 1 H, Ar-H), 7.35–7.26 (m, 2 H, Ar-H), 7.21–7.11 (m,
3 H, Ar-H), 7.06 (d, J = 9.0 Hz, 1 H, Ar-H), 6.89–6.54 (m, 16 H,
Ar-H), 6.48–6.37 (m, 5 H, Ar-H), 6.33 (d, J = 9.1 Hz, 1 H, Ar-H),
6.22–6.03 (m, 4 H, Ar-H), 3.68 (s, 3 H, OCH3), 3.61 (s, 3 H, Ar-
OCH3), 3.51 (s, 3 H, ArOCH3) ppm. 13C NMR (75 MHz, CDCl3):
δ = 160.9, 160.3, 153.1, 147.0, 145.0, 143.0, 142.5, 140.2, 139.6,
138.8, 134.8, 133.9, 132.6, 132.0, 131.4, 130.9, 129.7, 128.2, 127.2,
126.3, 125.4, 123.0, 122.4, 113.0, 112.2, 111.0, 60.4, 55.2, 55.1,
54.7 ppm. 31P NMR (125 MHz, CDCl3): δ = 25.7 ppm. MS
(70 eV): m/z (%) = 799 (92) [M+], 784 (37), 768 (29), 536 (100),
383 (29), 261 (68). C55H43O4P·(C4H8O2, EtOAc) (887.01): calcd. C
79.89, H 5.80; found C 79.94, H 5.95.
General Procedure for the Cycloaddition Reaction of Tetracyclone
(1) with Internal Alkynes 2a–l Yielding the Functionalized Biaryls
3: Acetylenes 2a–i (1 mmol), tetracyclone (384 mg, 1 mmol), and
diphenyl ether (2 g) were mixed in a Schlenk tube under argon, and
the flask was placed in a silicon oil bath at 260 °C for 8 h. After
cooling, the mixture was poured into n-hexane (30 mL), and pre-
cipitated products 3a–i were filtered off and washed with n-hexane.
They can be additionally purified by chromatography or recrystalli-
zation from ethyl acetate/n-hexane for extra purity.
1-[2-(Diphenylphosphoryl)-3,4,5,6-tetraphenylphenyl]naphthalene (3a):
Reaction of tetracyclone (1) and the alkyne 2a according to the
General Procedure gave the desired compound 3a; yield 652 mg,
1
92%; m.p. 286–287 °C. H NMR (300 MHz, CDCl3): δ = 7.96 (d,
J = 8.7 Hz, 1 H, Ar-H), 7.91 (d, J = 7.2 Hz, 1 H, Ar-H), 7.67 (d,
J = 7.8 Hz, 1 H, Ar-H), 7.54–7.29 (m, 11 H, Ar-H), 7.23–7.09 (m,
6 H, Ar-H), 7.02–6.89 (m, 6 H, Ar-H), 6.83–6.56 (m, 11 H, Ar-H)
ppm. 13C NMR (75 MHz, CDCl3): δ = 147.6, 147.5, 145.4, 144.1,
144.0, 143.6, 143.5, 142.8, 142.7, 140.3, 140.0, 139.3, 138.9, 137.6,
137.5, 136.6, 135.0, 134.3, 134.0, 133.8, 133.2, 133.0, 132.2, 132.0,
131.9, 131.4, 131.3, 131.2, 130.6, 130.4, 130.3, 130.2, 130.1, 130.0,
129.0, 128.6, 128.5, 127.8, 127.7, 127.6, 127.1, 127.0, 126.7, 126.6,
126.3, 126.1, 126.0, 125.8, 125.6, 125.3, 125.0, 124.5 ppm. 31P
NMR (125 MHz, CDCl3): δ = 23.7 ppm. MS (70 eV): m/z (%) =
708 (100) [M+], 631 (18), 506 (27), 354 (11), 315 (15). C52H37OP
(708.82): calcd. C 88.11, H 5.26; found C 88.05, H 5.22.
1-[2-(Diphenylphosphoryl)-3,4,5,6-tetraphenylphenyl]-2-methylnaph-
thalene (3e): The reaction of tetracyclone (1, 0.5 mmol) and the
alkyne 2e (0.5 mmol) under the conditions described in the General
Procedure gave the desired compound 3e; yield 289 mg, 80%; m.p.
271–274 °C. 1H NMR (300 MHz, CDCl3): δ = 7.80 (d, J = 8.4 Hz,
1 H, Ar-H), 7.54–7.41 (m, 2 H, Ar-H), 7.35–7.18 (m, 4 H, Ar-H),
7.10–6.90 (m, 9 H, Ar-H), 6.89–6.46 (m, 17 H, Ar-H), 6.41–6.31
(m, 3 H, Ar-H), 2.53 (s, 3 H, CH3) ppm. 13C NMR (75 MHz,
CDCl3): δ = 147.4, 147.2, 145.8, 145.7, 143.5, 143.2, 142.0, 141.9,
141.8, 139.9, 139.7, 138.8, 138.1, 138.0, 135.6, 135.5, 135.3, 135.2,
134.5, 134.0, 133.6, 133.5, 133.1, 132.9, 132.3, 131.2, 131.1, 130.8,
130.5, 130.1, 130.0, 129.9, 129.7, 129.6, 129.0, 128.8, 128.7, 128.4,
127.9, 127.5, 127.4, 127.3, 127.2, 126.6, 126.4, 126.3, 126.2, 126.1,
125.9, 125.7, 125.5, 125.4, 125.3, 125.2, 124.2, 31.7, 22.7, 22.2 ppm.
31P NMR (125 MHz, CDCl3): δ = 24.1 ppm. MS (70 eV): m/z (%)
= 722 (32) [M+], 631 (100), 520 (45), 443 (16), 361 (12). C53H39OP
(722.85): calcd. C 88.06, H 5.44; found C 88.11, H 5.65.
1-[2-(Diphenylphosphoryl)-3,4,5,6-tetraphenylphenyl]-2-methoxy-
naphthalene (3b): After reaction of tetracyclone (1) and the alkyne
2b according to the General Procedure the desired compound 3b
was obtained; yield 613 mg, 83 %; m.p. 285–286 °C. 1H NMR
(300 MHz, CDCl3): δ = 8.03 (d, J = 8.4 Hz, 1 H, Ar-H), 7.84 (d,
J = 7.6 Hz, 1 H, Ar-H), 7.70 (d, J = 7.7 Hz, 2 H, Ar-H), 7.63–7.51
(m, 3 H, Ar-H), 7.40 (d, J = 9.7 Hz, 1 H, Ar-H), 7.36–7.05 (m, 12
1-[2-(Diphenylphosphanyl)-3,4,5,6-tetraphenylphenyl]-2-methoxy-
H, Ar-H), 7.01–6.95 (m, 10 H, Ar-H), 6.82 (d, J = 7.3, 1.3 Hz, 1 naphthalene (3f): According to the General Procedure tetracyclone
H, Ar-H), 6.76–6.65 (m, 2 H, Ar-H), 6.61–6.49 (m, 3 H, Ar-H), (1) and the alkyne 2f were reacted to give compound 3f; yield
3.99 (s, 3 H, OCH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 171.6,
153.5, 147.4, 147.3, 145.6, 143.4, 143.3, 143.0, 142.9, 140.5, 140.3,
139.9, 139.7, 139.6, 138.7, 138.6, 137.3, 136.3, 136.2, 136.1, 135.0,
134.4, 134.3, 133.3, 133.2, 131.8, 131.5, 131.2, 131.0, 130.9, 130.6,
130.5, 130.0, 129.9, 129.7, 128.4, 127.6, 127.5, 127.0, 126.9, 126.8,
126.7, 126.6, 126.4, 126.0, 125.8, 125.7, 125.6, 123.4, 122.4, 117.1,
111.1, 60.9, 54.9 ppm. 31P NMR (125 MHz, CDCl3): δ = 24.1 ppm.
173 mg, 24 %; m.p. 220–221 °C (dec.). 1H NMR (300 MHz,
CDCl3): δ = 7.81 (d, J = 8.4 Hz, 1 H, Ar-H), 7.61–7.46 (m, 3 H,
Ar-H), 7.38–6.25 (m, 32 H, Ar-H), 3.66 (s, 3 H, OCH3) ppm. 13C
NMR (75 MHz, CDCl3): δ = 154.3, 154.2, 147.3, 143.6, 143.2,
143.1, 142.8, 142.2, 142.0, 140.6, 140.5, 140.4, 139.6, 137.5, 137.4,
137.3, 134.4, 134.2, 134.1, 132.7, 132.4, 132.3, 132.1, 131.4, 131.3,
131.0, 129.6, 129.5, 129.0, 128.0, 127.8, 127.4, 127.3, 127.0, 126.9,
MS (70 eV): m/z (%) = 738 (100) [M+], 536 (55), 353 (25), 201 (56). 126.6, 126.5, 126.4, 126.3, 126.2, 126.1, 125.9, 125.8, 125.7, 125.3,
C53H39O2P (738.85): calcd. C 86.16, H 5.32; found C 86.11, H 5.44.
125.2, 125.1, 124.9, 124.5, 124.4, 122.8, 111.4, 54.8 ppm. 31P NMR
512
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Synthesis of Functionalized Atropisomeric Biaryls
(125 MHz, CDCl3): δ = –2.3 ppm. MS (70 eV): m/z (%) = 722 (28) CDCl3): δ = 30.3 ppm. MS (70 eV): m/z (%) = 724 (29) [M+], 522
[M+], 691 (100), 361 (10). HRMS (EI) for C53H38PO [M+] calcd. (100), 362 (18), 201 (9). C52H37O2P (724.82): calcd. C 86.17, H
721.2655; found 721.2661.
5.15; found C 85.94, H 5.11.
2-Methoxy-1-[(2-methoxycarbonyl)-3,4,5,6-tetraphenylphenyl]naph- Resolution of rac-1-[2-(Diphenylphosphoryl)-3,4,5,6-tetraphenyl-
thalene (3 g): After reaction of tetracyclone (1) and the alkyne 2g
according to the General Procedure the desired compound 3g was
phenyl]naphthalene-2-ol (rac-8): Racemate 8 (724 mg, 1 mmol) was
added to the suspension of NaH (40 mg, 1.2 mmol, 60% suspen-
obtained; yield 556 mg, 93 %; m.p. 243–244 °C. 1H NMR sion in paraffin oil) in THF (10 mL). The mixture was stirred for
(300 MHz, CDCl3): δ = 8.06 (d, J = 8.5 Hz, 1 H, Ar-H), 7.52–7.33
(m, 5 H, Ar-H), 7.26 (d, J = 7.7 Hz, 1 H, Ar-H), 7.13–6.62 (m, 17
H, Ar-H), 6.52–6.45 (m, 2 H, Ar-H), 3.36 (s, 3 H, OCH3), 2.71 (s,
30 min, and (+)-menthyl chloroformate (212 µL, 1 mmol) was
added. The reaction was heated under reflux for 10 h, then cooled
and filtered through a thin pad of silica. The solvent was removed,
3 H, COOCH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 169.2, and the residue containing the two diastereomers was plugged to
154.1, 142.3, 142.1, 140.4, 140.0, 139.7, 139.6, 138.2, 135.7, 133.7,
133.1, 131.5, 131.3, 131.2, 130.4, 130.2, 130.0, 129.6, 129.5, 129.3,
128.3, 127.5, 127.2, 126.7, 126.6, 126.5, 126.0, 125.9, 125.8, 125.6,
125.5, 123.1, 122.0, 112.6, 56.3, 51.1 ppm. MS (70 eV): m/z (%) =
597 (100) [M+], 421 (15), 282 (27). C43H32O3 (596.71): calcd. C
86.55, H 5.41; found C 86.43, H 5.38.
silica. Repeated chromatographic separation with an Et2O/n-hex-
ane mixture (5:1) as the eluent furnished first the diastereoisomer
9 (435 mg, 96% yield), and then the diastereomer 10 as the second
fraction (384 mg, 85% yield).
1
Diastereomer 9: M.p. 307–308 °C. H NMR (300 MHz, CDCl3): δ
= 7.76 (d, J = 8.3 Hz, 1 H, Ar-H), 7.55–7.44 (m, 2 H, Ar-H), 7.43–
2-Methoxy-1-[(2-phenoxycarbonyl)-3,4,5,6-tetraphenylphenyl]naph- 7.35 (m, 1 H, Ar-H), 7.34–7.11 (m, 7 H, Ar-H), 7.05–6.46 (m, 24
thalene (3h): Reacting tetracyclone (1, 0.5 mmol) and the alkyne 2h
(0.5 mmol) in accordance to the General Procedure furnished the
desired compound 3h; yield 196 mg, 60 %; m.p. 174–175 °C. 1H
H, Ar-H), 6.37–6.30 (m, 1 H, Ar-H), 4.92 (dd, J = 10.8, 4.4 Hz,
menthyl-H), 2.58 (d, J = 11.7 Hz, 1 H, menthyl-H), 2.28–2.16 [m,
1 H, CH(CH3)2], 1.92–1.62 (m, 4 H, menthyl-H), 1.48–1.19 (m, 3
NMR (300 MHz, CDCl3): δ = 8.19 (d, J = 8.5 Hz, 1 H, Ar-H), H, menthyl-H), 1.12 [dd, J = 6.8, 2.0 Hz, 6 H, CH(CH3)2], 1.05 (J
7.57 (d, J = 8.1 Hz, 1 H, Ar-H), 7.52–7.45 (m, 3 H, Ar-H), 7.38 = 7.0 Hz, 3 H, CH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 152.5,
(d, J = 7.9 Hz, 1 H, Ar-H), 7.26 (d, J = 7.7 Hz, 1 H, Ar-H), 7.19
147.2, 147.0, 145.1, 143.6, 143.5, 142.4, 142.2, 139.9, 139.7, 138.5,
(s, 1 H, Ar-H), 7.12–7.04 (m, 3 H, Ar-H), 6.99–6.43 (m, 18 H, Ar- 138.1, 138.0, 137.1, 137.0, 135.8, 135.6, 134.6, 134.4, 134.2, 133.7,
H), 5.98 (d, J = 1.5 Hz, 1 H, Ar-H), 5.95 (d, J = 1.0 Hz, 1 H, Ar-
H), 3.32 (s, 3 H, OCH3) ppm. 13C NMR (75 MHz, CDCl3): δ =
167.1, 154.4, 150.2, 142.7, 142.3, 140.6, 140.0, 139.9, 139.4, 138.2,
135.0, 133.8, 133.1, 131.5, 131.4, 131.3, 130.8, 130.4, 130.2, 129.8,
129.5, 128.9, 128.4, 127.7, 127.5, 127.4, 126.9, 126.8, 126.7, 126.3,
126.2, 125.9, 125.7, 125.6, 125.3, 123.2, 121.7, 121.0, 118.9, 112.9,
56.3 ppm. MS (70 eV): m/z (%) = 658 (5) [M+], 565 (100), 282 (10).
C48H34O3 (658.78): calcd. C 87.51, H 5.20; found C 87.51, H 5.17.
133.2, 133.0, 131.4, 130.9, 130.7, 130.6, 130.5, 130.1, 129.7, 129.5,
129.3, 127.9, 127.2, 127.0, 126.9, 126.6, 126.5, 126.4, 126.3, 125.9,
125.8, 125.7, 125.6, 125.5, 125.4, 125.3, 125.2, 125.1, 124.9, 119.3,
78.8, 47.7, 41.1, 34.2, 31.4, 27.3, 24.3, 22.3, 20.7, 17.4 ppm (due to
the large number of signals with similar shifts and splitting of sig-
nals due to C–P coupling all observed peaks are given). 31P NMR
(125 MHz, CDCl3): δ = 26.74 ppm. MS (70 eV): m/z (%) = 907 (23)
[M+], 724 (33), 522 (100), 200 (13). [α]2D0 = –103.4 (c = 1.0, CHCl3).
C63H55O4P (907.08): calcd. C 83.42, H 6.11; found C 83.81, H 6.34.
2-Methoxy-1-[2-(phenylcarbonyl)-3,4,5,6-tetraphenylphenyl]naph-
thalene (3i): Reaction of tetracyclone (1) and the alkyne 2i according
to the General Procedure gave the desired compound 3i; yield
1
Diastereomer 10: M.p. 282–283 °C. H NMR (300 MHz, CDCl3):
δ = 7.78 (d, J = 8.2 Hz, 1 H, Ar-H), 7.54–7.36 (m, 5 H, Ar-H),
7.34–7.26 (m, 1 H, Ar-H), 7.22 (d, J = 8.9 Hz, 1 H, Ar-H), 7.15–
1
559 mg, 87%; m.p. 269–270 °C. H NMR (300 MHz, CDCl3): δ =
7.69 (d, J = 8.5 Hz, 1 H, Ar-H), 7.58–7.41 (m, 4 H, Ar-H), 7.32– 7.02 (m, 3 H, Ar-H), 7.0–6.61 (m, 20 H, Ar-H), 6.59–6.32 (m, 5 H,
6.45 (m, 26 H, Ar-H), 3.52 (br. s, 3 H, OCH3) ppm. 13C NMR
Ar-H), 4.77 (td, J = 10.7, 4.5 Hz, 1 H, menthyl-H), 2.40–2.15 [m,
(75 MHz, CDCl3): δ = 197.6, 142.4, 141.9, 140.8, 140.6, 140.2, 139.8, 2 H, menthyl-H, CH(CH3)2], 1.92–1.57 (m, 4 H, menthyl-H), 1.39–
139.6, 139.1, 138.6, 137.8, 133.1, 131.8, 131.6, 131.4, 131.0, 129.8,
129.6, 129.2, 129.0, 127.3, 127.1, 127.0, 126.8, 126.7, 126.6, 126.2,
126.1, 126.0, 125.9, 125.6, 125.4, 123.0, 121.3, 111.2, 55.0 ppm. MS
(70 eV): m/z (%) = 642 (100) [M+], 282 (19), 105 (94). C48H34O2
(642.78): calcd. C 89.41, H 5.63; found C 89.49, H 5.58.
1.16 (m, 4 H, menthyl-H), 1.13 (d, J = 7.1 Hz, 3 H, CH3), 1.05 [d,
J = 6.7 Hz, 6 H, CH(CH3)2] ppm. 13C NMR (75 MHz, CDCl3): δ
= 152.3, 147.1, 147.0, 146.4, 145.2, 145.1, 143.7, 143.6, 142.4, 142.2,
139.9, 139.7, 138.7, 137.9, 137.8, 137.0, 136.9, 136.3, 135.5, 134.9,
134.4, 134.1, 134.0, 133.7, 133.0, 132.9, 131.2, 131.1, 130.9, 130.8,
130.7, 130.6, 130.4, 130.3, 130.1, 129.9, 129.8, 129.6, 129.5, 129.4,
127.6, 127.2, 127.1, 127.0, 126.7, 126.6, 126.5, 126.3, 126.2, 126.0,
125.8, 125.7, 125.5, 125.3, 125.2, 125.0, 119.1, 79.2, 77.3, 47.3, 40.9,
35.4, 34.2, 31.5, 26.8, 26.5, 23.8, 22.2, 20.9, 16.9 ppm (due to the
large number of signals with similar shifts and splitting of signals
due to C–P coupling all observed peaks are reported). 31P NMR
(125 MHz, CDCl3): δ = 26.72 ppm. MS (70 eV): m/z (%) = 907
(0.5) [M+], 522 (2), 215 (33). [α]2D0 = +94.1 (c = 0.77, CHCl3).
rac-1-[2-(Diphenylphosphoryl)-3,4,5,6-tetraphenylphenyl]naphthal-
ene-2-ol (rac-8) by Demethylation of 3b: rac-Phosphane oxide 3b
(0.739 g, 1 mmol) was dissolved in dry CH2Cl2 (40 mL), and BBr3
(20 mL, 2 mmol, 1  solution on n-hexane) was added dropwise to
the cooled solution (0 °C). After the addition is completed, the
mixture was warmed up to room temp. and stirred for 8 h. The
resulted solution was poured into water, the organic layer was
washed with sat. NaHCO3 solution, then separated and dried with
Na2SO4. The solvent was evaporated to give the title compound
Hydrolysis of Diastereomers 9 and 10 in the Preparation of the
Enantiomers (S)-8 and (R)-8: General procedure for the hydrolysis:
a solution of diastereomer 9 (400 mg, 0.44 mmol) in THF (5 mL)
was treated with hydrazine hydrate (200 µL, 6.42 mmol) and stirred
under reflux for 4 h. To the cooled mixture CH2Cl2 (20 mL) was
added and the mixture washed with water. The organic layer was
separated and the aqueous phase was again extracted with CH2Cl2.
The combined organic phases were washed with water and brine
and dried with Na2SO4. The solvent was removed to give the prod-
1
rac-8 as a colorless solid (710 mg, 98%), m.p. Ͼ350 °C. H NMR
(300 MHz, CDCl3): δ = 8.89 (br. s, 1 H, OH), 7.26–6.19 (m, 36 H,
Ar-H) ppm. 13C NMR (75 MHz, CDCl3): δ = 153.9, 145.8, 145.7,
145.5, 144.0, 143.9, 143.0, 142.9, 140.7, 140.6, 139.7, 139.3, 138.7,
138.5, 138.4, 135.2, 133.8, 132.9, 132.5, 132.2, 131.8, 131.2, 131.1,
130.8, 130.4, 130.1, 129.9, 129.6, 129.1, 128.9, 128.6, 127.6, 127.5,
127.1, 126.9, 126.8, 126.7, 126.6, 126.3, 126.2, 126.1, 126.0, 125.9,
125.6, 125.4, 125.3, 124.6, 122.6, 121.7 ppm. 31P NMR (125 MHz,
Eur. J. Org. Chem. 2010, 509–514
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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513

M. Hapke et al.
FULL PAPER
uct (S)-8, [α]2D0 = –155.1 (c = 0.8, THF), as a white solid in near
quantitative yield.
The product (R)-8, [α]2D0 = +162.5 (c = 0.8, THF), was obtained
from diastereomer 10 following the hydrolysis procedure for (S)-8.
Both enantiomers showed optical purity Ͼ99% ee (HPLC).
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Preparation of Enantiomeric (S)-3b and (R)-3b by Methylation of
the Enantiomers (S)-8 and (R)-8: The hydroxyphosphane oxide (R)-
6 (150 mg, 0.207 mmol) was dissolved in 5 mL of THF and NaH
(16.6 mg, 0.414 mmol) added. After stirring at room temp. for 1 h
methyl iodide (32 µL, 74 mg, 0.518 mmol) was added and the reac-
tion mixture stirred at room temp. for another 12 h. The reaction
was quenched with sat. NH4Cl solution and extracted with diethyl
ether. The combined organic phases were washed with water and
brine and dried with Na2SO4. The residue obtained after evapora-
tion can be purified by column chromatography on silica gel with
diethyl ether/n-hexane (5:1 v/v) as the eluent to quantitatively yield
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=
–92.7 (c = 1.0, CHCl3). The corresponding enantiomer (R)-3b was
obtained in a comparable manner in 77% yield with [α]2D8 = +80.4
(c = 0.833, CHCl3). The other characterization data are in agree-
ment with the data reported for 3.
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Preparation of Phosphanes 3f by the Deoxygenation of Phosphane
Oxides 3b: In a 50 mL Schlenk flask compound rac-3b (148 mg,
0.2 mmol) was dissolved in 15 mL of dry toluene under argon and
then dry Et3N (0.28 mL, 2 mmol) and HSiCl3 (0.1 mL, 1 mmol)
added. The mixture was heated to 90 °C and stirred for 72 h. After
cooling the reaction mixture was diluted with diethyl ether and
washed with sat. NaHCO3 solution. The organic phase is dried
with Na2SO4, the solvent evaporated and the residue purified by
flash chromatography with silica gel using n-hexane/ethyl acetate
(1:1, v/v) as the eluent, yielding rac-3f as a white solid (70 mg,
49%). The NMR spectroscopic data are corresponding to the data
reported for rac-3f. Following this procedure (S)-3b (135 mg,
0.183 mmol) was reduced to (S)-3f (87 mg, 66%), [α]2D7 = –2.04 (c
= 0.539, CHCl3) and (R)-3b (101 mg, 0.137 mmol) was reduced to
(R)-3f (71 mg, 72%), [α]2D8 = +6.21 (c = 0.986, CHCl3).
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www.ccdc.cam.ac.uk/data_request/cif.
Supporting Information (see also the footnote on the first page of this
article): Synthetic procedure for the synthesis of starting materials
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6 with 1 as well as 1H and 13C NMR spectra of the biaryl compounds
3, 8, 9, 10 and crystallographic data for diastereomer 10.
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to PPh3 with only insignificant amounts of side products, as
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Acknowledgments
We thank Fabian Fischer and the Analytical Department for excel-
lent technical assistance and Prof. Uwe Rosenthal for helpful dis-
cussions und support.
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Received: September 22, 2009
Published Online: December 2, 2009
514
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© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 509–514