The abnormal behavior of an atropisomer: 3,3′-dibromo-1,1′- difluoro-2,2′-binaphthyl reacting with alkyllithium compounds

Article abstract of DOI:10.1002/ejoc.200500514

1-Fluoro-2-(triethylsilyl)naphthalene (1) and other 1-fluoronaphthalenes bearing a metalation-resistant substituent at the 2-position proved to be totally inert toward base attack. 3-Bromo-1-fluoronaphthalene (6), readily prepared from the 2-bromo isomer 5 by deprotonation-triggered heavy halogen migration, was converted into 3,3′-dibromo-1,1′-difluoro-2,2′- binaphthyl (8) by consecutive treatment with lithium diisopropylamide, copper(II) bromide and nitrobenzene. The dilithiated intermediate generated from the atropisomer 8 by treatment with 2 equiv. of butyllithium reacted with a variety of electrophiles to afford products such as the diacid 12 or the bis(phosphanes) 14 and 15 in high yields. The latter compound was also obtained in a straightforward manner from (4-fluoro-2-naphthyl)diphenylphosphane oxide (16). Unexpectedly, neither the 3,3′-dibromobinaphthyl 8 nor its 3,3′-diiodo analogue 18 were amenable to a unilateral but only to a double-sided halogen/metal permutation. Wiley-VCH Verlag GmbH & Co. KGaA, 2005.

Full text of DOI:10.1002/ejoc.200500514

FULL PAPER
DOI: 10.1002/ejoc.200500514
The Abnormal Behavior of an Atropisomer: 3,3Ј-Dibromo-1,1Ј-difluoro-2,2Ј-
binaphthyl Reacting with Alkyllithium Compounds
Frédéric Leroux,[a] Giuseppe Mangano,[b] and Manfred Schlosser*[b]
Keywords: Aryl-aryl coupling / Atropisomers / Bis(phosphanes) / 1-Fluoronaphthalene / Halogen migration /
Halogen/metal permutation / Hydrogen/metal permutation (“Metalation”)
1-Fluoro-2-(triethylsilyl)naphthalene (1) and other 1-fluoro-
naphthalenes bearing a metalation-resistant substituent at
the 2-position proved to be totally inert toward base attack.
3-Bromo-1-fluoronaphthalene (6), readily prepared from the
2-bromo isomer 5 by deprotonation-triggered heavy halogen
migration, was converted into 3,3Ј-dibromo-1,1Ј-difluoro-
2,2Ј-binaphthyl (8) by consecutive treatment with lithium di-
isopropylamide, copper(II) bromide and nitrobenzene. The
dilithiated intermediate generated from the atropisomer 8 by
treatment with 2 equiv. of butyllithium reacted with a variety
of electrophiles to afford products such as the diacid 12 or
the bis(phosphanes) 14 and 15 in high yields. The latter com-
pound was also obtained in a straightforward manner from
(4-fluoro-2-naphthyl)diphenylphosphane oxide (16). Unex-
pectedly, neither the 3,3Ј-dibromobinaphthyl 8 nor its 3,3Ј-
diiodo analogue 18 were amenable to a unilateral but only
to a double-sided halogen/metal permutation.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2005)
Naphthalenes carrying heteroatoms or functional groups
at the 1-position may undergo a permutational hydrogen/
metal interconversion (“metalation”) at either the 2- or the
8-position.[1,2] When treated with phenyllithium in diethyl
ether at ambient temperature[3] or with butyllithium in
tetrahydrofuran at –60 °C,[4] 1-fluorononaphthalene was de-
protonated at the 2-position rapidly and exclusively. Not
even trace amounts of products resulting from attack at the
8-position were detected, whereas such regioisomers were
invariably formed, depending on the reaction conditions, as
minor or major components, when 1-methoxynaphthalene
served as the substrate.[1]
We wondered whether the peri metalation could be
forced by simply blocking the ortho position. To this end,
1-fluoronaphthalene was converted into a series of deriva-
tives, two of which were selected for further studies. Trap-
ping of the intermediate 1-fluoro-2-naphthyllithium with
chlorotriethylsilane afforded the silane 1 (91%), with N,N-
dimethylformamide the aldehyde 2 (66%), with triethyl
phosphite the phosphane 3 (92%), with copper() bromide
in the presence of nitrobenzene[5] the dimer 4 (84%), and
with elemental bromine the dihalo compound 5 (92%).
Whereas protons may be abstracted from trimethylsilyl
groups,[6,7] triethylsilyl entities were so far always found to
be inert towards even the strongest organometallic reagents.
Therefore, the silane 1 and the binaphthyl 4 were exposed
to the action of both sec-butyllithium in tetrahydrofuran
at –75 °C and potassium tert-butoxide activated butyllith-
ium[8,9] in hexanes at +25 °C over prolonged periods of
time. In either case the starting materials were recovered
quantitatively.
1-Fluoronaphthalene being an inexpensive substance (re-
tail price about 100 j/mol), we decided to explore its chem-
istry further. As previously accomplished with 1-fluoro-2-
iodonaphthalene,[10] the bromo compound 5 was subjected
to a deprotonation-triggered heavy halogen migration. The
2-bromo-1-fluoro-3-naphthyllithium initially generated
[a] Laboratoire de Stéréochimie (CNRS UMR 7509), Université
Louis Pasteur (ECPM),
25 rue Becquerel, 67087 Strasbourg, France
[b] Institute of Chemical Sciences and Engineering, Ecole Polytech-
nique Fédérale, BCh
1015 Lausanne, Switzerland
E-mail: manfred.schlosser@epfl.ch
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F. Leroux, G. Mangano, M. Schlosser
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with lithium diisopropylamide instantaneously isomerized
to the 3-bromo-1-fluoro-2-naphthyllithium which gave 3-
bromo-1-fluoronaphthalene (6; 89%) upon neutralization,
3-bromo-1-fluoro-2-iodonaphthalene (7; 80%) upon trap-
ping with elemental iodine, and 3,3Ј-dibromo-1,1Ј-difluoro-
2,2Ј-binaphthyl (8; 66%) upon oxidative dimerization using
copper() bromide in the presence of nitrobenzene.
A twofold halogen/metal permutation performed with
butyllithium (2.0 equiv.) or tert-butyllithium (4.0 equiv.)
transformed the dibromo compound 8 into a dilithio spe-
cies which reacted with N,N-dimethylformamide to afford
the dialdehyde 9 (61%). This was reduced to the dialcohol
10 (85%). The same compound was obtained directly, al-
though in only poor yield (Ͻ30%), when the dilithio species
was treated with paraformaldehyde. The organometallic in-
termediate was furthermore converted into the dibenzofluo-
rinone 11 (with methyl chloroformate; 91%), the dicarb-
oxylic acid 12 (with dry ice; 58%), the benzonaphthophos-
phindene 13 [with dichloro(phenyl)phosphane; 70%], the
bis(dicyclohexylphosphane) 14 (with chlorodicyclohexyl-
phosphane; 67%) and the bis(diphenylphosphane) 15 (with
chlorodiphenylphosphane; 15%).
The same bis(phosphane) was accessed also by a dif-
ferent route. Consecutive treatment of 3-bromo-1-fluoro-
naphthalene (6) with tert-butyllithium and diphenylphos-
phinic chloride gave the phosphane oxide 16 (60%) which,
after ortho-lithiation,[11] was oxidatively coupled to the bis-
(phosphane oxide) 17 (71%). This compound was eventu- permutational halogen/metal interconversion at an interme-
ally reduced with trichlorosilane to the bis(phosphane) 15 diate stage failed. No matter what reagent and what reac-
(63%).
tion conditions were employed, roughly 50% of the 3,3Ј-
To prepare bis(phosphanes) having two different sets of disubstituted product (e.g., diacid 12) was formed and half
P-substituents, for example phenyl on one and cyclohexyl of the starting material was recovered whenever only 1 mol-
on the other side, a 3Ј-bromo-2,2Ј-binaphthyl-3-yllithium equiv. of the alkyllithium was added. The same situation
would be required. Unfortunately, all attempts to stop the was encountered when the diiodo compound 18, prepared
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The Abnormal Behavior of an Atropisomer
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from the dibromo-2,2Ј-binaphthyl 8 by consecutive reaction
with butyllithium and iodine (2 equiv. each) in 80% yield,
was treated with isopropylmagnesium chloride.
Experimental Section
General: Details concerning standard operations and abbreviations
can be found in previous publications from this laboratory.[28–30]
1H and (1H-decoupled) 13C NMR spectra were recorded at 400 and
101 MHz, respectively, of samples dissolved in deuterochloroform.
Triethyl(1-fluoro-2-naphthyl)silane
(1):
1-Fluoronaphthalene
(5.5 mL, 7.3 g, 50 mmol) was added to a solution of sec-butyllith-
ium (50 mmol) in tetrahydrofuran (0.10 L) and hexanes (40 mL),
cooled in a methanol/dry ice bath. After 2 h at –75 °C, the mixture
was treated with chlorotriethylsilane (8.4 mL, 7.5 g, 50 mmol) and
distilled without any further workup; colorless liquid; b.p. 188–
20
1
190 °C/15 Torr; nD = 1.5553; yield: 11.8 g (91%). H NMR: δ =
8.09 (dd, J = 5.8, 3.4 Hz, 1 H), 7.81 (symm. m, 1 H), 7.59, (d, J =
8.0 Hz, 1 H), 7.49 (dt, J = 9.5, 3.2 Hz, 2 H), 7.41 (dd, J = 8.2,
5.2 Hz, 1 H), 1.00 (q, J = 6.9 Hz, 9 H), 0.93 (t, J = 6.9 Hz, 6 H).
13C NMR: δ = 165.3, 162.8, 136.0, 131.0, 127.5, 127.2, 126.5, 123.2,
121.0, 116, 10.3, 4.1 ppm. C16H21FSi (260.43): calcd. C 73.79, H
8.13; found C 73.74, H 8.23.
1-Fluoronaphthalene-2-carbaldehyde (2): The reaction was started
as described above, but chlorotriethylsilane was replaced by N,N-
dimethylformamide (3.9 mL, 3.7 g, 50 mmol). The mixture was
poured into water (0.15 L) and extracted with diethyl ether
(3×20 mL). After evaporation of the volatiles, the residue was crys-
tallized from ethanol; yellow prisms; m.p. 35–36 °C; 2,4-dinitro-
phenylhydrazone: m.p. 262–265 °C (decomp.) (ref.[31] 265 °C); yield:
This behavior contrasts strikingly with that of numerous
other o,oЈ-dibromo-1,1Ј-biaryls and even of 2,2Ј,6,6Ј-tetra-
bromobiphenyl which enable a stepwise replacement of the
two halogens without any problem.[12] At the moment, we
can only offer a tentative explanation of the divergent reac-
tion mode observed with the binaphthyl 8. Although the
planes of the two aromatic rings of biphenyl occupy a dihe-
dral angle of approximately 45 °C[13] and are more strongly
twisted in 2,2Ј-difluorobiphenyl[14] or in 2,2Ј,6,6Ј-tetrafluo-
robiphenyl derivatives[5,15–18] (dihedral angles Ն 55°), 6,6Ј-
difluoro-2,2Ј-biphenyldiyldilithium and 1,1Ј-difluoro-2,2Ј-
binaphthyldiyldilithium (and analogous magnesium deriva-
tives as well) may adopt a flattened array. Strong interac-
tions are known to exist between fluorine and metals, both
covalently bound to carbon.[19–27] The resulting gain in en-
ergy may suffice to planarize the biaryl structure already
after the introduction of the first metal atom (intermediate
19) and, all the more, after the introduction of the second
metal (intermediate 20).
1
5.7 g (66%). H NMR: δ = 10.59 (d, J = 0.6 Hz, 1 H), 8.23 (d, J
= 5.5 Hz, 1 H), 7.88 (d, J = 5.5 Hz, 1 H), 7.84 (dd, J = 5.9, 4.5 Hz,
1 H), 7.65 (symm. m, 3 H) ppm. 13C NMR: δ = 164.9, 162.0, 138.2,
130.0, 128.0, 127.5, 124.5, 123.5, 123.0, 122.0, 119.0 ppm.
Tris(1-fluoronaphth-2-yl)phosphane (3): Analogously, using 1-fluo-
ronaphthalene (11 mL, 15 g, 0.10 mol), sec-butyllithium (0.10 mol)
and phosphorus trichloride (2.4 mL, 4.5 g, 33 mmol). After 2 h at
–75 °C, the mixture was poured into water. The organic layer was
separated and the aqueous one was extracted with ethyl acetate
(3×20 mL). The combined organic phases were dried and concen-
trated under reduced pressure. The residue was crystallized from a
1:1 (v/v) ethyl acetate/pentane mixture to obtain fine colorless
needles; m.p. 173–174 °C; yield: 14.2 g (92%). 1H NMR: δ = 8.1
(m, 3 H), 7.8 (m, 3 H), 7.5 (m, 9 H), 7.1 (m, 3 H) ppm. 13C NMR:
δ = 162.3 (d, J = 17.5 Hz), 159.7 (d, J = 17.5 Hz), 136, 129.3,
127.8 (d, J = 22.5 Hz), 126.8, 124.0, 123.4 (d, J = 17.5 Hz), 121.0,
115.5 ppm. C30H18F3P (466.43): calcd. C 77.25, H 3.89; found C
77.14, H 3.89.
1,1Ј-Difluoro-2,2Ј-binaphthyl (4): After treating 1-fluoronaphtha-
lene (0.10 mol) with sec-butyllithium (0.10 mol) at –75 °C for 2 h,
cupric bromide (22 g, 0.10 mol) was added under vigorous stirring
and 45 min later, still at –75 °C, nitrobenzene (10 mL, 12 g,
0.10 mol). At +25 °C, the mixture was filtered through basic alu-
mina (0.30 kg) and the filter cake was washed with hexane
(3×0.20 L). After evaporation of the volatiles, the residue was crys-
tallized from ethanol; colorless platelets; m.p. 152–153 °C; yield:
1
12.0 g (84%). H NMR: δ = 8.21 (d, J = 7.5 Hz, 2 H), 7.90 (d, J
= 7.5 Hz, 2 H), 7.73 (d, J = 8.4 Hz, 2 H), 7.58 (symm. m, 6 H)
ppm. 13C NMR: δ = 155.6, 134.6, 128.4, 127.5, 127.4, 124.1, 123.7,
121.4, 118.0, 113.1 ppm. C20H12F2 (290.31): calcd. C 82.75, H 4.17;
found C 82.76, H 4.16.
2-Bromo-1-fluoronaphthalene (5): Analogously, using 1-fluoronaph-
thalene (50 mmol), sec-butyllithium (50 mmol) and, after 2 h at
–75 °C, bromine (2.6 mL, 8.0 g, 50 mmol) in precooled hexanes
(0.10 L). The mixture was washed with a 10% aqueous solution
(0.20 L) of sodium sulfite. Distillation under reduced pressure af-
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F. Leroux, G. Mangano, M. Schlosser
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forded a colorless liquid; b.p. 120–121 °C/15 Torr (ref.[4] 93 °C/
phenyllithium (1.0 equiv.) as the exchange reagent, diethyl ether in-
stead of tetrahydrofuran as the solvent, and –125 or –100 °C rather
0.1 Torr; m.p.[4] –4 to –2 °C); nD = 1.6328 (ref.[4] 1.6322); yield:
20
1
10.3 g (92%). H NMR: δ = 8.0 (m, 1 H), 7.8 (m, 1 H), 7.5 (m, 4 than –75 °C as the reaction temperature (standard exposure time
H) ppm. 13C NMR: δ = 158.1, 151.3, 134.0, 129.6, 127.9, 127 (m),
125.0, 124.5 (d, J = 25.0 Hz), 120.0, 103.9 (d, J = 25.0 Hz) ppm.
15 min). According to the H and 19F NMR spectra, a mixture of
unconsumed starting material 8 and dialdehyde 9 was obtained in
all these cases.
1
3-Bromo-1-fluoronaphthalene (6): 2,2,6,6-Tetramethylpiperidine
(8.5 mL, 7.1 g, 50 mmol) and 2-bromo-1-fluoronaphthalene (5;
11 g 50 mmol) were added consecutively to a solution of butyllith-
ium (50 mmol) in tetrahydrofuran (0.10 L) and hexanes (25 mL),
cooled in a methanol/dry ice bath. After 6 h at –75 °C, the mixture
was poured into brine (0.10 L). The organic layer was concentrated.
Upon distillation of the residue, a colorless liquid was collected;
1,1Ј-Difluoro-3,3Ј-hydroxymethyl-2,2Ј-binaphthyl (10): 1,1Ј-Di-
fluoro-2,2Ј-binaphthyl-3,3Ј-dicarbaldehyde (9; 6.9 g, 20 mmol) and
lithium aluminum hydride (1.5 g, 40 mmol) were dissolved in tetra-
hydrofuran (0.20 L). The reaction mixture was heated at 65 °C for
2 h under vigorous stirring. Methanol (20 mL) was added dropwise
and the resulting suspension was filtered through a Celite filter pad
(30 g). The yellow orange solid residue obtained after evaporation
of the volatiles was crystallized from a 1:1 (v/v) ethyl acetate/pen-
tane mixture; colorless platelets; m.p. 130–132 °C; yield: 5.96 g
b.p. 85–86 °C/10 Torr (ref.[32] 74–78 °C/0.3 Torr), nD = 1.6318
20
(ref.[32] 1.6314); yield: 10.0 g (89%). 1H NMR: δ = 8.01 (dd, J =
6.4, 3.3 Hz, 1 H), 7.76 (s, 1 H), 7.71 (symm. m, 1 H), 7.51 (dd, J
= 9.7, 3.3 Hz, 2 H), 7.25 (dd, J = 9.8, 1.7 Hz, 1 H) ppm. 13C NMR:
δ = 160.3, 154.1, 135.9, 129.2, 127.6, 126.2, 121.9, 119.8, 115.0 (dd,
J = 23.4, 7.8 Hz), 113.2 (dd, J = 23.4, 7.8 Hz) ppm.
1
(85%). H NMR: δ = 8.0 (m, 2 H), 7.8 (m, 2 H), 7.69 (s, 2 H), 7.5
(m, 4 H), 4.38 (s, 4 H) ppm. 13C NMR: δ = 156.8, 154.3, 138.0,
134.7, 127.9, 127.5, 126.7, 123.7, 123.0, 120.8, 63.3 ppm.
C22H16F2O2 (350.36): calcd. C 75.42, H 4.60; found C 75.06, H
4.70.
3-Bromo-1-fluoro-2-iodonaphthalene
(7):
Diisopropylamine
(7.0 mL, 5.0 g, 50 mmol) and 3-bromo-1-fluoronaphthalene (6;
11 g, 50 mmol) were added consecutively to a solution of butyllith-
ium (50 mmol) in tetrahydrofuran (0.10 L) and hexanes (25 mL),
kept in a methanol/dry ice bath. After 2 h at –75 °C, the mixture
was treated with iodine (13 g, 50 mmol) in tetrahydrofuran (50 mL)
before being washed with a 10% aqueous solution (50 mL) of so-
dium sulfite. The aqueous layer was extracted with diethyl ether
(3×20 mL). The combined organic layers were dried and the sol-
vents evaporated. Crystallization of the residue from ethanol gave
colorless fine needles; m.p. 109–110 °C; yield: 14.0 g (80%). 1H
NMR: δ = 8.0 (m, 2 H), 7.8 (m, 1 H), 7.6 (m, 2 H) ppm. 13C NMR:
δ = 161.0, 155.1, 135.5, 128.9, 127.5, 127.0, 122.0, 120.9, 112.2,
85.2 (d, J = 30.0 Hz) ppm. C10H5BrFI (350.95): calcd. C 34.22, H
1.44; found C 34.41, H 1.04.
5,6-Difluoro-12H-dibenzo[b,h]fluoren-12-one (11): At –75 °C, 3,3Ј-
dibromo-1,1Ј-difluoro-2,2Ј-binaphthyl (8.9 g, 20 mmol) was added
to a solution of butyllithium (40 mmol) in tetrahydrofuran (80 mL)
and hexanes (26 mL). After 5 min, the mixture was treated with
methyl chloroformate (1.5 mL, 1.9 g, 20 mmol), before being
poured into water (0.10 L). The aqueous phase was extracted with
diethyl ether (3×20 mL). The combined organic layers were dried
and the solvents evaporated. The residue was recrystallized from a
1:1 (v/v) ethyl acetate/pentanes mixture; yellow prisms; m.p. 290–
1
291 °C (decomp.); yield: 5.70 g (91%). H NMR: δ = 7.6 (m, 2 H),
7.5 (m, 4 H), 7.4 (m, 4 H) ppm. 13C NMR: δ = 164.2, 142.5, 136.0,
133.7, 128.7, 128.2, 128 (m), 127.4, 124.5, 121.6, 120.7 ppm.
C21H10F2O (316.30): calcd. C 79.74, H 3.19; found C 77.40, H 3.96.
1,1Ј-Difluoro-2,2Ј-binaphthyl-3,3Ј-dicarboxylic Acid (12): An analo-
gous reaction was carried out but the mixture was poured onto
freshly crushed dry ice, covered by a tetrahydrofuran layer (rather
than treated with methyl chloroformate). The semisolid product
was dissolved in a 10% aqueous solution of potassium hydroxide
(20 mL). Washing with diethyl ether (3×20 mL) and acidification
of the aqueous phase to pH = 5 gave a white precipitate that was
crystallized from a 1:1 (v/v) mixture of toluene and heptanes; color-
less platelets; m.p. Ͼ350 °C; yield: 4.40 g (58%). 1H NMR: δ = 8.68
(s, 2 H), 8.36 (d, J = 8.0 Hz, 2 H), 8.20 (d, J = 8.0 Hz, 2 H), 7.87
(symm. m, 4 H) ppm. 13C NMR: δ = 167.9, 156.9, 154.5, 133.8,
130.8, 130.4, 129.3, 128.1, 125.4, 121.5, 118.1 ppm. C22H12F2O4
(378.33): calcd. C 69.84, H 3.20; found C 69.78, H 3.34.
3,3Ј-Dibromo-1,1Ј-difluoro-2,2Ј-binaphthyl (8): 3-Bromo-1-fluoro-2-
iodonaphthalene (7; 18 g, 50 mmol) was consecutively treated with
butyllithium (50 mmol), cupric bromide (50 mmol) and nitroben-
zene (50 mmol) as described above for the preparation of the di-
fluorobinaphthyl 4. The same workup procedure gave colorless
prisms (from methanol); m.p. 201–202 °C (reprod.); yield: 7.39 g
1
(66%). H NMR: δ = 8.1 (m, 2 H), 8.05 (s, 2 H), 7.8 (m, 2 H), 7.6
(m, 4 H) ppm. 13C NMR: δ = 160, 157.7, 134.7, 128.5, 127.2, 126.6,
125.5, 122.1, 121.8, 120.5 ppm. C20H10F2Br2 (448.10): calcd. C
53.61, H 2.25; found C 53.52, H 2.63.
1,1Ј-Difluoro-2,2Ј-binaphthyl-3,3Ј-dicarbaldehyde (9): 3,3Ј-Bromo-
1,1Ј-difluoro-2,2Ј-binaphthyl (8; 8.9 g, 20 mmol) was added to a
solution of butyllithium (40 mmol) in tetrahydrofuran (80 mL) and
hexanes (25 mL), cooled in a methanol/dry ice bath. The mixture
was transferred through a stainless steel capillary into a solution
of N,N-dimethylformamide (2.0 mL, 2.9 g, 40 mmol) in tetra-
hydrofuran (25 mL), kept at –75 °C, before being poured into water
(0.10 L). Extraction of the aqueous phase with diethyl ether
(3×20 mL), concentration of the combined organic layers after
drying and crystallization of the residue from a 1:1 (v/v) mixture
of ethyl acetate and pentanes afforded colorless platelets; m.p. 352–
353 °C (decomp.); yield: 4.23 g (61%). 1H NMR: δ = 8.37 (s, 2 H),
8.18 (d, J = 8.0 Hz, 3 H), 8.10 (d, J = 8.0 Hz, 3 H) ppm. 13C NMR:
δ = 165.5, 134.5, 134.0, 132.8, 131.5, 130.7, 129.9, 127.3, 121.5,
113.7, 109.2 ppm. C22H12F2O2 (346.33): calcd. C 76.30, H 3.49;
found C 75.96, H 3.62. All attempts failed to accomplish unilateral
substitution by employing butyllithium in equimolar amounts
(1.0 equiv.), in the presence or absence of N,N,NЈ,NЈЈ,NЈЈ-penta-
methyldiethylenetriamine, tert-butyllithium (1.0 and 2.0 equiv.) or
1,13-Difluoro-7-phenyl-7H-benzo[f]naphtho[2,3-b]phosphindole (13):
An analogously prepared reaction mixture was treated dropwise,
at –75 °C, with dichloro(phenyl)phosphane (2.7 mL, 3.6 g,
20 mmol) in tetrahydrofuran (40 mL). The solvents were evapo-
rated and the orange-yellow residue repetitively extracted with a
hot 1:1 (v/v) mixture of ethyl acetate and methanol. Upon concen-
tration and cooling, colorless platelets were obtained; m.p. 214–
215 °C (reprod.); yield: 5.55 g (70%). 1H NMR: δ = 8.29 (d, J =
8.2 Hz, 2 H), 7.93 (d, J = 7.5 Hz, 2 H), 7.79 (d, J = 8.2 Hz, 2 H),
7.5 (m, 4 H), 7.3 (m, 1 H), 7.2 (m, 4 H) ppm. 13C NMR: δ = 134.5,
133.0, 132.5, 131.4, 131.1, 129.7, 129.0, 128.6, 127.6, 127.1, 126.9,
126.6, 122.0, 121.6 ppm. C26H15F2P (396.37): calcd. C 78.78, H
3.81; found C 78.46, H 4.10.
3,3Ј-Bis(dicyclohexylphosphanyl)-1,1Ј-difluoro-2,2Ј-binaphthyl (14):
Prepared
analogously, using
chlorodicyclohexylphosphane
(8.8 mL, 9.3 g, 40 mmol) in tetrahydrofuran (40 mL). The orange-
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yellow solid left behind upon evaporation of the volatiles was crys-
tallized from a 1:1 (v/v) mixture of ethyl acetate and methanol;
colorless platelets; m.p. 240–242 °C (reprod.); yield: 9.15 g (67%).
1H NMR: δ = 8.0 (m, 2 H), 7.91 (s, 2 H), 7.76 (s, 2 H), 7.5 (m, 4
H), 1.9 (m, 4 H), 1.8 (m, 8 H), 1.5 (m, 8 H), 1.4 (m, 8 H), 1.3 (m,
8 H), 1.0 (m, 8 H) ppm. 13C NMR: δ = 134.0, 127.9, 127.0, 126.6,
123.5, 121.0, 36.0, 32.7, 30.8, 30.0, 29.1, 28.3, 27.0, 26.2 ppm.
1,1Ј-Difluoro-3,3Ј-diiodo-2,2Ј-binaphthyl (18): Obtained analo-
gously as described for the preparation of compound 9 by the treat-
ment with a solution of iodine (10 g, 40 mmol) in tetrahydrofuran
(40 mL). The mixture was washed with a 10% solution of sodium
sulfite (50 mL) which was then reextracted with diethyl ether
(3×20 mL). The combined organic layers were dried and the sol-
vents evaporated. The white residue was crystallized from toluene;
C44H54F2P2 (682.84): calcd. C 77.39, H 7.97; found C 77.78, H colorless prisms; m.p. 243–244 °C (reprod.); yield: 17.3 g (80%). 1H
8.04.
NMR: δ = 8.37 (s, 2 H), 8.1 (m, 2 H), 7.9 (m, 2 H), 7.6 (m, 4 H)
ppm. 13C NMR: δ = 156.7, 136.4, 134.2, 128.6, 127.5, 126.9, 123.7,
123.5, 121.6, 97.0 ppm. C20H10F2I2 (542.10): calcd. C 44.31, H
1.86; found C 44.46, H 1.98.
1,1Ј-Difluoro-3,3Ј-bis(diphenylphosphanyl)-2,2Ј-binaphthyl (15): Pre-
pared essentially as described in the preceding paragraph by treat-
ment of the reaction mixture with chlorodiphenylphosphane
(7.2 mL, 8.8 g, 40 mmol) in tetrahydrofuran (40 mL) at +25 °C.
Water (0.10 L) was added, the organic layer was separated and the
aqueous phase was extracted with diethyl ether (3×20 mL). The
combined organic phases were dried and the solvents evaporated.
The yellow solid was recrystallized from a 1:1 (v/v) ethyl acetate/
hexanes mixture to afford colorless prisms; m.p. 68–70 °C; yield:
Acknowledgments
This work was financially supported by the Schweizerische Natio-
nalfonds zur Förderung der wissenschaftlichen Forschung, Bern
(grant 20-55Ј303-98), the Bundesamt für Bildung und Wissen-
schaft, Bern (grant 97.0083 linked to the TMR project FMRXCT-
970129) and the Bundesamt für Berufsbildung und Technologie,
Bern, in the framework of a KTI project (contract 5474.1 KTS).
1
1.97 g (15%). H NMR: δ = 8.1 (m, 2 H), 7.7 (m, 2 H), 7.60 (d, J
= 9.0 Hz, 2 H), 7.51 (dquint, J = 6.0, 2.0 Hz, 4 H), 7.35 (d, J =
5.0 Hz, 18 H), 7.03 (dq, J = 6.0, 1.0 Hz, 2 H) ppm. 13C NMR: δ =
160.0 (d, J = 7 Hz), 157.8 (d, J = 7.0 Hz), 137.0 (d, J = 10 Hz),
136.0 (d, J = 20 Hz), 135 (m), 134.0 (dd, J = 25, 5 Hz), 130.0 (d, J
= 7.0 Hz), 129.4, 129 (m), 128.0, 127.4 (d, J = 30 Hz), 124 (m),
120.9, 113 (m) ppm. C44H30F2P2 (658.67): calcd. C 80.24, H 4.59;
found C 79.99, H 4.84.
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158.
(1-Fluoronaphth-3-yl)diphenylphosphane Oxide (16): 3-Bromo-1-
fluoronaphthalene (6; 2.2 g, 10 mmol) and diphenylphosphinic
chloride (1.9 mL, 2.3 g, 10 mmol) were added consecutively to a
solution of tert-butyllithium (20 mmol) in tetrahydrofuran (40 mL)
and hexanes (15 mL) cooled to –75 °C. When having reached
+25 °C, the reaction mixture was absorbed on silica gel (50 mL)
and was eluted with ethyl acetate from a column filled with more
silica (0.45 L). The material collected after evaporation of the sol-
vent was triturated with diethyl ether and crystallized from toluene;
colorless platelets; m.p. 134–135 °C; yield: 2.08 g (60%). 1H NMR:
δ = 8.1 (m, 2 H), 7.9 (m, 1 H), 7.7 (m, 4 H), 7.6 (m, 1 H), 7.5 (m,
3 H), 7.4 (m, 4 H), 7.3 (m, 1 H) ppm. 13C NMR: δ = 160.1 (d, J
= 17.5 Hz), 157.6 (d, J = 17.5 Hz), 135 (m), 134 (m), 133 (m), 132
(m), 131.9, 131 (m), 130 (m), 129 (m), 128.1, 125.5 (d, J = 12.5 Hz),
120.9, 111.0 ppm. C22H16FOP (346.34): calcd. C 76.29, H 4.66;
found C 76.09, H 4.56.
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isopropylamine (1.4 mL, 1.0 g, 10 mmol) and (1-fluoronaphth-3-yl)-
diphenylphosphane oxide (16; 3.5 g, 10 mmol) were added consecu-
tively to butyllithium (10 mmol) in tetrahydrofuran (50 mL) and
hexanes (6.0 mL), kept in a methanol/dry ice bath. After 15 min
at –75 °C, the mixture was treated with copper() bromide (4.5 g,
20 mmol) and after stirring for 1 h at –75 °C, with nitrobenzene
(2.5 g, 2.0 mL). The reaction mixture was filtered through an alu-
mina pad (0.10 L) and the filter cake was washed with chloroform
(3×50 mL). The combined organic phases were concentrated and
the residue was crystallized from a 1:5 (v/v) mixture of diethyl ether
and isopropyl alcohol; colorless cubes; m.p. 189–190 °C; yield:
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1
2.45 g (71%). H NMR: δ = 7.5 (m, 8 H), 7.6 (m, 6 H), 7.68 (t, J
[23] J. Karl, G. Erker, R. Fröhlich, J. Am. Chem. Soc. 1997, 119,
11165–11173.
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= 7.5 Hz, 2 H), 7.7 (m, 10 H), 7.85 (d, J = 15.0 Hz, 2 H), 8.10 (d,
J = 8.0 Hz, 2 H) ppm. 13C NMR: δ = 157.5 (d, J = 2.5 Hz), 155
(d, J = 2.5 Hz), 133 (m), 132 (m), 131 (m), 130 (m), 129.6, 129 (m),
128.4, 128 (m), 127 (m), 126 (m), 120.6, 105 (m) ppm.
C44H30F2O2P2 (690.65): calcd. C 76.52, H 4.38; found C 76.34, H
4.60.
Eur. J. Org. Chem. 2005, 5049–5054
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5053

F. Leroux, G. Mangano, M. Schlosser
FULL PAPER
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Received: July 11, 2005
Published Online: October 19, 2005
5054
www.eurjoc.org
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2005, 5049–5054