Chiral phosphabarrelene ligands: Synthesis and evaluation in rhodium-catalyzed asymmetric hydrogenation

Article abstract of DOI:10.1055/s-2006-942425

The first chiral and enantiomerically pure monodentate and bidentate phosphabarrelene ligands have been prepared and their potential in rhodium-catalyzed asymmetric hydrogenation has been evaluated. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-942425

PAPER
2121
Chiral Phosphabarrelene Ligands: Synthesis and Evaluation in Rhodium-
Catalyzed Asymmetric Hydrogenation
C
hira
l
Phosphaba
e
rrelene Lig
r
a
nds in R
n
hodium-C
a
h
talyzed Asym
a
metric
H
y
r
drogenat
d
ion Breit,* Evelyn Fuchs
Institut für Organische Chemie und Biochemie, Albert-Ludwigs-Universität Freiburg, Albertstr. 21, 79104 Freiburg i. Brsg., Germany
Fax +49(761)2038715; E-mail: bernhard.breit@organik.chemie.uni-freiburg.de
Received 25 April 2006
Ph
Ph
Abstract: The first chiral and enantiomerically pure monodentate
HBF4⋅Et2O
DCE, reflux
and bidentate phosphabarrelene ligands have been prepared and
their potential in rhodium-catalyzed asymmetric hydrogenation has
been evaluated.
Me
+
R1
O
O
R2
R1
O
BF4
2
R2
Key words: asymmetric catalysis, hydrogenation, ligands, phos-
phorus, rhodium
PH3, 30 bar or
(Me3Si)3P, 80 °C
F
Ph
Br
Phosphabarrelenes 1 have been introduced recently by us
as a new class of modifying ligands for homogeneous
metal complex catalysis.1 The strong pyramidalization at
the phosphorus atom forced by incorporation in a [2.2.2]
bicyclic framework increases the s-character of the lone
pair at phosphorus.1–3 Additionally, s* orbitals of the P–C
bonds are lowered in energy, rendering phosphabar-
relenes interesting p-acceptor ligands for homogeneous
catalysis.
Mg
Ph
THF reflux
P
R1
P
R2
R1
R2
3
rac-1
Scheme 1 Synthesis of chiral phosphabarrelenes
Table 1 Preparation of Chiral Phosphabarrelenes
Compound R1
R2
Yield (%)
2
3
rac-1
24
a
b
c
Ph
Ph
Ph
2-Naphthyl
3-MeOC6H4
2-MeOC6H4
57
62
47
70
81
56
Ph
Ph
R2
31
P
P
R1
R1
R2
29
1
ent-1
sted acid mediated condensation of chalcones with ace-
tophenones (Scheme 1, Table 1).4,5 Transformation to the
corresponding phosphabenzenes (alternatively known as
phosphinines or phosphorins) 3a–c was accomplished by
treatment of 2 with either phosphine at elevated pressure
or with tris(trimethylsilyl)phosphine.5
Figure 1 Chiral phosphabarrelenes
In fact, monodentate phosphabarrelenes furnished rhodi-
um catalysts that enabled the hydroformylation of gener-
ally poorly reactive internal alkenes with extremely high
catalytic activity and with surprisingly low alkene isomer-
ization.1
Reaction of benzyne, generated from 1-bromo-2-fluo-
robenzene and magnesium, with the phosphabenzenes
3a–c in a Diels–Alder reaction furnished the desired chiral
phosphabarrelenes 1a–c in racemic form as air-stable, col-
orless solids in moderate yield.1,6 With the goal of prepar-
ing bidentate phosphabarrelene ligands, liberation of the
hydroxy function of 1b,c as a handle for the attachment of
a second binding site was addressed (Scheme 2).
These properties render these catalysts a unique choice for
the position-selective hydroformylation of internal alk-
enes. Interestingly, phosphabarrelenes equipped with two
different substituents R1 and R2, as shown in Figure 1, are
chiral. Considering the unique electronic properties of this
ligand system combined with an unusual and, so far unex-
plored, asymmetric geometry, induced us to synthesize
and investigate the potential of these systems in asymmet- In case of the 3-methoxyphenyl system rac-1b, ether
ric catalysis, which is the subject of this report.
cleavage occurred cleanly upon treatment with boron tri-
iodide to give the 3-hydroxyphenyl-substituted barrelene
rac-1d. The 2-methoxyphenyl derivative rac-1c proved
more sensitive, and required protection of the phosphine
as the phosphine oxide prior to ether cleavage with boron
tribromide. Reduction back to the phosphine stage was
Preparation of chiral phosphabarrelenes 1 commenced
from pyrylium salts 2a–c, which were obtained by Brøn-
SYNTHESIS 2006, No. 13, pp 2121–2128
x
x.
x
x
.
2
0
0
6
Advanced online publication: 12.06.2006
DOI: 10.1055/s-2006-942425; Art ID: C01606SS
© Georg Thieme Verlag Stuttgart · New York

2122
B. Breit, E. Fuchs
PAPER
In order to learn about the coordination properties of these
ligands, the stoichiometric reaction of 6a with bis(h4-cy-
cloocta-1,5-diene)rhodium(I) tetrafluoroborate was stud-
ied. NMR spectroscopy showed the quantitative
formation of the complex (h4-cycloocta-1,5-diene)rhodi-
um(I)–6a tetrafluoroborate. Furthermore, chemical shift
and signal splitting in the 31P NMR proved that both phos-
phorus atoms of 6a are bound to the same metal center.8
Ph
(i) for rac-1b
(ii) for rac-1c
rac-1b
or
rac-1c
P
Ph
HO
rac-1d (3-OH) 81%
rac-1e (2-OH) 68% (overall)
With chiral monodentate and bidentate phosphabarrelene
ligands in hand, we turned to rhodium-catalyzed asym-
metric hydrogenation. As substrates itaconic ester 7, and
the acetamidoacrylates 8 and 9 were chosen (Scheme 4).
Results of asymmetric hydrogenation are depicted in
Table 2. Of the monodentate phosphabarrelenes, deriva-
tive 1a gave the most promising results. Thus, 1a fur-
nished a rhodium catalyst, which operated with high
activity for the hydrogenation of methyl itaconate, albeit
enantioselectivity was moderate (Table 2, entries 1 and 2).
Scheme 2 Preparation of phenol-substituted phosphabarrelene deri-
vatives rac-1d and rac-1e: Reagents and conditions: (i) BI3, CH2Cl2,
–8 °C; (ii) (a) H2O2, CH2Cl2, r.t.; (b) BBr3·SMe2, DCE, 80 °C; (c)
Cl3SiH, toluene, 110 °C.
achieved with trichlorosilane to furnish 2-hydroxyphenyl-
functionalized rac-1e in good overall yield.
The racemic mixtures of rac-1a–e were each resolved by
preparative chiral HPLC. In all cases clean baseline sepa-
ration was achieved employing Chiralpak AD-H as the
stationary phase to give enantiomerically pure barrelenes
(+)-1a–e and (–)-1a–e. The absolute configuration of the
enantiomerically pure phosphabarrelenes (+)-1a–e and
(–)-1a–e is, as yet, unknown. Transformation of the phe-
nolic phosphabarrelenes into bidentate ligands was readi-
ly accomplished upon reaction with (S)-(1,1¢-binaphthyl-
2,2¢-dioxy)chlorophosphine (4)7 to give the diastereomer-
ic 3- and 2-substituted ligands 5a,b and 6a,b, respectively
(Scheme 3). Note as the absolute configurations of (+)-
and (–)-1d and (+)- and (–)-1e are unknown, the structures
given for the diastereomers (+)-5a/(+)-5b and (+)-6a/(+)-
6b in Scheme 3 may be exchanged.
In the case of the bidentate ligands (+)-5a, (+)-5b, and (+)-
6b, again active hydrogenation catalysts were formed, the
[Rh(cod)2]BF4 (1 mol%)
monodentate ligand (2.8 mol%)
or bidentate ligand (1.4 mol%)
H2 (1 bar), CH2Cl2, r.t.
O
O
R1
R2
R1
R2
*
MeO
MeO
7 R1 = CH2CO2Me, R2 = H
8 R1 = NHAc, R2 = H
9 R1 = NHAc, R2 = Ph
Scheme 4
Ph
Ph
P
P
Ph
Ph
O
(+)-1d
(i)
(+)-1e
(i)
O
O
P
P
O
87%
93%
O
O
(+)-5a
(+)-6a
O
O
(S)-4
PCl
Ph
P
Ph
(–)-1d
(–)-1e
Ph
O
P
(i)
(i)
O
O
Ph
96%
98%
P
O
P
O
O
(+)-5b
(+)-6b
Scheme 3 Preparation of chiral bidentate phosphabarrelene/phosphite ligands 5a,b and 6a,b: Reagents and conditions: (i) Et3N, toluene,
–40 °C to r.t.
Synthesis 2006, No. 13, 2121–2128 © Thieme Stuttgart · New York

PAPER
Chiral Phosphabarrelene Ligands in Rhodium-Catalyzed Asymmetric Hydrogenation
2123
MHz, and 125 MHz for 1H, 31P, and 13C respectively). 1H and 13
C
asymmetric induction however, was low (Table 2, entries
7–9). Conversely, when the diastereomer (+)-6a was em-
ployed as a ligand, a dramatic boost in the enantioselectiv-
ity was observed and in the case of the acetamidoacrylates
8 and 9 (Table 2, entries 10, 11, and 13) the rhodium-cat-
alyzed hydrogenation occurred with up to 90% ee.
NMR spectra are referenced according to residual solvent signals.
31P NMR spectra are referenced with 85% H3PO4 as external stan-
dart. HRMS were obtained on a Finnigan MAT 8200 instrument.
Elementary analysis was performed on an elementar vario (Fa. Ele-
mentar Analysensysteme GmbH). Optical rotations were measured
on a Perkin Elmer 241 polarimeter. Separation of the enantiomers
was achieved on a Chiralpak AD-H column using a Knaur K-2501
UV detector. The enantiomeric excess of the phosphabarrelene
ligands was determined by analytical HPLC using a Chiralpak AD-
H column. The absolute configuration of the enantiomerically pure
phosphabarrelenes 1a–e is, as yet, unknown. Hydrogenation exper-
iments were performed following the general procedure using hy-
drogen gas 5.0 (Südwest-Gas). Pyrylium salts 2a–c were obtained
by Brønsted acid mediated condensation of chalcones with ace-
tophenones.4,5 Phosphabenzenes 3a–c5 and (S)-(1,1¢-binaphthyl-
2,2¢-dioxy)chlorophosphine (4)7 were prepared by literature proce-
dures.
Table 2 Results of Asymmetric Hydrogenation
Entry Ligand
Substrate Time
(h)
Conversion ee
(%)a
100
100
100
100
100
44
(%)b
1
2
(+)-1a
(–)-1a
(–)-1a
(–)-1b
(+)-1c
(–)-1e
(+)-5a
(+)-5b
(+)-6b
(+)-6a
(+)-6a
(+)-6a
(+)-6a
7
7
8
7
8
8
8
8
8
8
8
7
9
6
4
31 (R)
31 (S)
14 (S)
<1 (S)
18 (R)
15 (R)
22 (S)
35 (S)
9 (R)
3
19
16
19
70
21
26
20
20
22
20
21
4
8,10-Diphenyl-11-(2-naphthyl)-1-phosphatricyclo[6.2.2.02,7]-
dodeca-2(7),3,5,9,11-pentaene (1a)
5
Mg turnings (1.05 g, 43.21 mmol, 2.7 equiv) were suspended in a
soln of phosphabenzene 3a (5.95 g, 15.90 mmol, 1.0 equiv) in THF
(60 mL) and a small amount of 1-bromo-2-fluorobenzene (0.50 mL
of a total of 4.34 mL, 6.94 g, 39.68 mmol, 2.5 equiv) was added to
start the reaction. Subsequently the remaining 1-bromo-2-fluo-
robenzene was slowly added, keeping the mixture under gentle re-
flux. When the addition was complete, the soln was heated to reflux
for 4 h, then cooled to r.t. and hydrolyzed by addition of H2O (5.0
mL). The THF was removed in vacuo and the residue extracted with
toluene (400 mL). After washing with H2O (3 × 200 mL) and reex-
traction of the aqueous phase with toluene (3 × 100 mL), the com-
bined organic phases were dried (Na2SO4). The solvent was
removed in vacuo, the residue dissolved in CH2Cl2 (250 mL) and
filtered through a small pad of silica gel (6 × 7 cm). The silica gel
was flushed with additional CH2Cl2 (200 mL) and the combined fil-
trates were evaporated to dryness in vacuo. The residue was dis-
solved in cyclohexane (1 L) and irradiated (150 W, visible light)
with cooling (approx. 10 °C) for 48 h to remove an unknown red-
colored byproduct. The suspension was concentrated to 100 mL and
filtered through a small pad of alumina (4 × 5 cm, activity grade
IV). The alumina was flushed with additional cyclohexane (700
mL) and the combined filtrates were evaporated to dryness in vacuo
to give analytically pure phosphabarrelene rac-1a as a pale yellow
foam; yield: 1.73 g (24%); mp 144 °C.
6
7
100
100
100
100
100
100
100
8
9
10
11c
12
13
87 (S)
90 (S)
19 (S)
88 (S)
a Determined by 1H NMR.
b 7: GC (trifluoroacetyl-g-cyclodextrin), 8: GC (hydroxydex-b-
TBDAc), 9: HPLC (Chiralpak-AD).
c Reaction run at –3 °C.
In conclusion, the first chiral monodentate and bidentate
phosphabarrelene ligands have been prepared in enantio-
merically pure form. Both monodentate and bidentate
ligands furnished active rhodium catalysts for rhodium-
catalyzed asymmetric hydrogenation. Best enantioselec-
tivities were found for the chelating phosphabarrelene/
phosphite system (+)-6a with up to 90% ee, thus chiral
phosphabarrelenes are a promising new ligand class for
further studies in asymmetric catalysis including combi-
natorial approaches employing chiral monodentate ligand
libraries.9
Resolution via preparative HPLC (Chiralpak AD-H, n-heptane–
i-PrOH, 95:5):
(–)-1a: [a]D20 –18.7 (c 1.01, CHCl3).
(+)-1a: [a]D20 +18.3 (c 0.99, CHCl3).
1H NMR (499.870 MHz, CDCl3): d = 6.67–6.69 (m, 1 H, H6), 7.06–
7.12 (m, 2 H, H4, H5), 7.31 (t, 3JH,H = 7.4 Hz, 1 H, H4¢¢), 7.40–7.43
(m, 2 H, H3¢¢), 7.45–7.47 (m, 1 H, H6¢¢¢a), 7.48–7.52 (m, 1 H,
H7¢¢¢a), 7.57 (t, 3JH,H = 7.4 Hz, 1 H, H4¢), 7.68–7.71 (m, 2 H, H3¢),
7.79–7.83 (m, 5 H, H2¢¢, H2¢¢¢, H3¢¢¢, H5¢¢¢b), 7.91 (d, 3JH,H = 7.4 Hz,
2 H, H2¢), 7.94 (d, 3JH,H = 8.5 Hz, 1 H, H8¢¢¢b), 7.95–7.97 (m, 1 H,
H3), 8.19 (d, 3JH,P = 6.2 Hz, 1 H, H9), 8.28 (d, 3JH,P = 6.0 Hz, 1 H,
H12), 8.36 (br s, 1 H, H10¢¢¢) (a and b interchangeable assignments).
All reactions were carried out in dried glassware under an argon at-
mosphere 5.0 (Südwest-Gas). Air and moisture sensitive liquids and
solutions were transferred via syringe. All reagents were obtained
commercially unless otherwise noted. All solvents were dried and
distilled by standard procedures. Organic solutions were concen-
trated under reduced pressure by rotary evaporation. Chromato-
graphic purification of products was accomplished using flash
chromatography10 on Merck silica gel Si 60 (200–400 mesh). NMR
spectra were acquired on a Varian Mercury spectrometer (300
MHz, 121 MHz, and 75 MHz for 1H, 31P, and 13C respectively), on
a Bruker AMX 400 (400 MHz, 162 MHz, and 100 MHz for 1H, 31P,
and 13C respectively) and on a Bruker DRX 500 (500 MHz, 202
13C NMR (125.692 MHz, CDCl3): d = 63.8 (C8), 123.8 (d,
3
3JC,P = 9.1 Hz, C2¢¢¢), 124.2 (d, JC,P = 13.3 Hz, C4), 124.3 (d,
3JC,P = 0.9 Hz, C6), 125.2 (d, 3JC,P = 18.5 Hz, C10¢¢¢), 125.9 (C6¢¢¢a),
3
126.0 (d, JC,P = 13.0 Hz, 2 C, C2¢¢), 126.2 (C7¢¢¢a), 127.2 (d,
4JC,P = 1.5 Hz, C5), 127.5 (C3¢¢¢), 127.6 (C4¢), 127.6 (d, 5JC,P = 1.5
6
Hz, C4¢¢), 128.1 (d, JC,P = 1.2 Hz, C5¢¢¢), 128.2 (C8¢¢¢), 128.5 (d,
4JC,P = 0.9 Hz, 2 C, C3¢¢), 128.9 (2 C, C2¢), 129.1 (2 C, C3¢), 131.6
2
(d, JC,P = 39.1 Hz, C3), 132.8 (d, JC,P = 1.5 Hz, C4¢¢¢b), 133.5 (d,
Synthesis 2006, No. 13, 2121–2128 © Thieme Stuttgart · New York

2124
B. Breit, E. Fuchs
PAPER
5
5
5
5
4
6
4
4
4
6
6
6
3
7
3
3
3
4´
3´
4´
3´
4´
3´
7
4´
3´
7
7
2
8
2
2
8
2
8
8
1´
2´
1´
9
10
1´
9
10
1´
9
10
2´
2´
2´
12
12
12
12
11
9
6´´´
6´´´
8´´´
5´´´
10´´´
6´´´
3´´´
P
P
1
P
1
11
11
11
P
9´´´
10
1
1
5´´´
4´´´
5´´´
4´´´
5´´´
4´´´
7´´´
6´´´
2´´
2´´
2´´
2´´
1´´´
2´´´
1´´´
2´´´
1´´´
2´´´
1´´´
2´´´
1´´
1´´
1´´
1´´
3´´
4´´
3´´
4´´
3´´
4´´
3´´
4´´
4´´´
OMe
3´´´
OMe
3´´´
3´´´
OH
rac-1b
rac-1c
rac-1d
rac-1a
5
5
5
4
4
4
6
6
6
3
3
3
4´
3´
4´
3´
7
7
4´
3´
7
2
2
8
2
8
8
1´
1´
9
1´
9
2´
2´
2´
12
11
12
11
12
11
9
6´´´
6´´´
3´´´
6´´´
P
P
P
10
1´´
10
10
1
1
1
5´´´
4´´´
5´´´
4´´´
5´´´
4´´´
1´´´
2´´´
2´´
1´´´
2´´´
1´´´
2´´´
2´´
2´´
3´´
O
O
1´´
1´´
3´´
3´´
4´´
OH
OMe
OH
3´´´
3´´´
4´´
4´´
rac-ox-1c
rac-ox-1e
rac-1e
5
6
5
5
4
4
3
5
4
3
4
3
6
7
6
7
6
3
2
4´
3´
4´
3´
7
4´
7
4´
3´
8
2
9
8
1´
9
1´
2´
3´
2´
2
8
2
8
12
1´
9
2´
1´
2´
12
11
6´´´
2´´
12
9
10
11
P
1
P
2´´
6´´´
3´´´
12
11
1´´
10
1´´´
2´´´
P
1
11
10
P
1
3´´
4´´
5´´´
4´´´
10
6´´´
2´´
3´´
4´´
1´´
1
1´´´
2´´´
5´´´
6´´´
5´´´
4´´´
1´´
1´´´
2´´´
2´´
1´´
1´´´
3´´
4´´
5´´´
4´´´
O
3´´´
3´´
O
13
P
2´´´
3´´´
O
3´´´
13
O
O
O
4´´
O
P
P
13
P
O
13
O
O
O
O
(+)-5a
(+)-5b
(+)-6a
(+)-6b
Figure 2
2
JC,P = 1.2 Hz, C9¢¢¢b), 135.9 (d, JC,P = 24.8 Hz, C1¢¢¢), 138.6 (d,
bined organic phases were dried (Na2SO4) and irradiated (150 W,
visible light) with cooling (approx. 10 °C) for 48 h to remove an un-
known red-colored byproduct. The suspension was concentrated to
100 mL and filtered through a small pad of silica gel (7 × 7 cm). The
silica gel was flushed with additional cyclohexane–EtOAc (5:1, 300
mL) and the combined filtrates were evaporated to dryness in vac-
uo. The residue was recrystallized (MeOH, 50 mL) to give rac-1b
in analytically pure form (0.80 g, 1.85 mmol). The mother liquor
was evaporated to dryness in vacuo, the residue dissolved in CH2Cl2
(20 mL) and filtered through a small pad of silica gel (3 × 3 cm).
The silica gel was flushed with additional CH2Cl2 (100 mL) and the
combined filtrates again were irradiated (150 W, visible light) with
cooling (approx. 10 °C) for 2 h to remove an unknown red-colored
byproduct. The suspension was filtered through a small pad of silica
gel (3 × 3 cm) to give, after evaporation, a further 1.01 g (2.35
mmol) rac-1b in analytically pure form as a colorless solid; total
yield: 1.81 g (31%); mp 98–100 °C.
1
2JC,P = 24.8 Hz, C1¢¢), 141.0 (d, JC,P = 11.2 Hz, C2), 141.2 (C1¢),
147.3 (d, 2JC,P = 5.1 Hz, C9 or C12), 147.4 (d, 2JC,P = 5.2 Hz, C9 or
C12), 152.3 (d, JC,P = 16.0 Hz, C10c), 152.4 (d, JC,P = 15.7 Hz,
1
1
C11c), 155.3 (d, JC,P = 3.3 Hz, C7) (a,b,c interchangeable assign-
2
ments).
31P NMR (121.474 MHz, CDCl3): d = –69.4 (s).
Anal. Calcd for C33H23P (450.51): C, 87.98; H, 5.15. Found: C,
87.68; H 5.29.
11-(3-Methoxyphenyl)-8,10-diphenyl-1-phosphatricyc-
lo[6.2.2.02,7]dodeca-2(7),3,5,9,11-pentaene (1b)
Mg turnings (0.72 g, 29.75 mmol, 2.2 equiv) were suspended in a
soln of phosphabenzene 3b (4.82 g, 13.60 mmol, 1.0 equiv) in THF
(70 mL) and a small amount of 1-bromo-2-fluorobenzene (0.50 mL
of a total of 3.10 mL, 4.96 g, 28.34 mmol, 2.1 equiv) was added to
start the reaction. Subsequently the remaining 1-bromo-2-fluo-
robenzene was slowly added, keeping the mixture under gentle re-
flux. When the addition was complete, the soln was heated to reflux
for 3.5 h, then cooled to r.t. and hydrolyzed by addition of H2O (5.0
mL). The THF was removed in vacuo and the residue extracted with
Et2O (600 mL). After washing with 3% aq HCl (4 × 200 mL) and
reextraction of the aqueous phase with Et2O (3 × 100 mL), the com-
Resolution via preparative HPLC (Chiralpak AD-H, n-heptane–
i-PrOH, 90:10):
(–)-1b: [a]D20 –3.3 (c 0.98, CHCl3).
(+)-1b: [a]D20 +3.1 (c 1.00, CHCl3).
Synthesis 2006, No. 13, 2121–2128 © Thieme Stuttgart · New York

PAPER
Chiral Phosphabarrelene Ligands in Rhodium-Catalyzed Asymmetric Hydrogenation
2125
1H NMR (499.873 MHz, CDCl3): d = 2.18 (s, 3 H, OCH3), 6.57–
6.59 (m, 1 H, H6), 6.82 (ddd, 3JH,H = 8.0 Hz, J = 2.5 Hz, J = 1.1 Hz,
1 H, H4¢¢¢), 6.99–7.05 (m, 2 H, H4, H5), 7.25–7.32 (m, 4 H, H4¢¢,
H2¢¢¢, H5¢¢¢, H6¢¢¢), 7.34–7.37 (m, 2 H, H3¢¢), 7.51–7.54 (m, 1 H,
H4¢), 7.62–7.65 (m, 2 H, H3¢), 7.69–7.70 (m, 2 H, H2¢¢), 7.82 (d,
3JH,H = 7.4 Hz, 2 H, H2¢), 7.83–7.85 (m, 1 H, H3), 8.09 (d,
3JH,P = 6.1 Hz, 1 H, H9a), 8.10 (d, 3JH,P = 6.0 Hz, 1 H, H12a) (a inter-
changeable assignments).
(C5), 127.4 (2 C, C4¢, C4¢¢), 128.4 (2 C, C3¢¢), 128.5 (d, 3JC,P = 8.7
Hz, C6¢¢¢), 128.8 (C4¢¢¢), 128.9 (2 signals, 4 C, C2¢, C3¢), 131.5 (d,
2
2JC,P = 39.2 Hz, C3), 139.0 (d, JC,P = 24.7 Hz, C1¢¢), 141.5 (C1¢),
2
142.1 (d, 1JC,P = 13.1 Hz, C2), 147.0 (d, JC,P = 4.4 Hz, C9), 148.9
(d, 2JC,P = 4.4 Hz, C12), 152.0 (d, 1JC,P = 17.4 Hz, C10a), 153.0 (d,
1JC,P = 17.4 Hz, C11a), 155.7 (d, 2JC,P = 2.9 Hz, C7), 156.9 (C2¢¢¢) (a
interchangeable assignments; signal for C1¢¢¢ not detectable).
31P NMR (121.474 MHz, CDCl3): d = –61.9 (s).
13C NMR (125.692 MHz, CDCl3): d = 55.3 (CH3), 63.8 (d,
HRMS: m/z calcd for C30H23OP: 430.1487; found: 430.1483.
3
3JC,P = 2.4 Hz, C8), 111.7 (d, JC,P = 13.6 Hz, C2¢¢¢a), 113.0 (d,
3
5JC,P = 1.2 Hz, C4¢¢¢), 118.6 (d, JC,P = 13.3 Hz, C6¢¢¢a), 124.1 (d,
3-{8,10-Diphenyl-1-phosphatricyclo[6.2.2.02,7]dodeca-
2(7),3,5,9,11-pentaen-11-yl}phenol (1d)
3
3JC,P = 13.3 Hz, C4), 124.3 (d, JC,P = 1.2 Hz, C6), 125.9 (d,
3JC,P = 13.0 Hz, 2 C, C2¢¢), 127.2 (d, 4JC,P = 1.5 Hz, C5), 127.6 (C4¢),
To a soln of 1b (205 mg, 0.477 mmol, 1.0 equiv) in CH2Cl2 (9 mL)
was added dropwise a soln of BI3 (224 mg, 0.572 mmol, 1.2 equiv)
in CH2Cl2 (3 mL) at –8 °C. The reaction was warmed to 0 °C over
1 h and hydrolyzed by the addition of a small amount of ice. The or-
ganic phase was washed consecutively with H2O (3 × 15 mL) and
sat. Na2S2O3 soln (2 × 10 mL). The aqueous phases were reextract-
ed with CH2Cl2 (2 × 15 mL) and the combined organic phases were
dried (MgSO4) and evaporated to dryness in vacuo. The residue was
purified by flash chromatography (silica gel, cyclohexane–EtOAc,
10:1) to give rac-1d as a colorless solid in analytically pure form;
yield: 161 mg (81%); mp 208 °C.
4
127.7 (d, 5JC,P = 1.5 Hz, C4¢¢), 128.5 (d, JC,P = 1.2 Hz, 2 C, C3¢¢),
128.9 (2 C, C2¢), 129.1 (2 C, C3¢), 129.5 (d, 4JC,P = 0.9 Hz, C5¢¢¢),
131.7 (d, 2JC,P = 39.1 Hz, C3), 138.6 (d, 2JC,P = 24.8 Hz, C1¢¢), 140.2
2
1
(d, JC,P = 24.8 Hz, C1¢¢¢), 141.1 (d, JC,P = 11.5 Hz, C2), 142.2
(C1¢), 147.2 (d, 2JC,P = 4.5 Hz, C9), 147.6 (d, 2JC,P = 4.9 Hz, C12),
152.4 (d, JC,P = 16.1 Hz, C10b), 152.6 (d, JC,P = 16.1 Hz, C11b),
155.2 (d, 2JC,P = 3.6 Hz, C7), 159.8 (d, 4JC,P = 1.2 Hz, C3¢¢¢) (a and b
interchangeable assignments).
1
1
31P NMR (121.474 MHz, CDCl3): d = –68.6 (s).
HRMS: m/z calcd for C30H23OP: 430.1487; found: 430.1479.
Resolution via preparative HPLC (Chiralpak AD-H, n-heptane–
11-(2-Methoxyphenyl)-8,10-diphenyl-1-phosphatricyc-
lo[6.2.2.02,7]dodeca-2(7),3,5,9,11-pentaene (1c)
EtOH, 50:50):
(–)-1d: [a]D20 –3.3 (c 1.01, CHCl3).
(+)-1d: [a]D20 +3.1 (c 1.00, CHCl3).
Mg turnings (0.45 g, 18.52 mmol, 2.2 equiv) were suspended in a
soln of phosphabenzene 3c (3.00 g, 8.47 mmol, 1.0 equiv) in THF
(50 mL) and a small amount of 1-bromo-2-fluorobenzene (0.20 mL
of a total of 1.93 mL, 3.09 g, 17.66 mmol, 2.1 equiv) was added to
start the reaction. Subsequently the remaining 1-bromo-1-fluo-
robenzene was slowly added, keeping the mixture under gentle re-
flux. When the addition was complete, the soln was heated to reflux
for 4 h, then cooled to r.t. and hydrolyzed by addition of H2O (3.0
mL). The THF was removed in vacuo and the residue extracted with
Et2O (5 × 100 mL). After washing with 3% aq HCl (5 × 100 mL)
and reextraction of the aqueous phase with Et2O (2 × 100 mL), the
combined organic phases were dried (Na2SO4). The solvent was re-
moved in vacuo, the residue dissolved in cyclohexane (20 mL) and
filtered through a small pad of basic alumina (3 × 3 cm, activity
grade IV). The alumina was flushed with additional cyclohexane
(400 mL) and the combined filtrates were irradiated (150 W, visible
light) with cooling (approx. 10 °C) for 20 h to remove an unknown
red-colored byproduct. The suspension was concentrated to 100 mL
and filtered through a small pad of alumina (4 × 4 cm). The alumina
was flushed with additional cyclohexane (400 mL) and the com-
bined filtrates were evaporated to dryness in vacuo. The residue was
recrystallized (MeOH, 30 mL) to give analytically pure phospha-
barrelene rac-1c as a colorless solid; yield: 1.04 g (29%); mp 183–
185 °C.
1H NMR (499.870 MHz, CDCl3): d = 5.03 (br, 1 H, OH), 6.54–6.56
(m, 1 H, H6), 6.72 (ddd, 3JH,H = 8.0 Hz, J = 2.5 Hz, J = 0.8 Hz, 1 H,
H4¢¢¢), 6.97–7.03 (m, 2 H, H4, H5), 7.17–7.20 (m, 2 H, H2¢¢¢a, H5¢¢¢),
7.22–7.26 (m, 2 H, H4¢¢, H6¢¢¢a), 7.31–7.34 (m, 2 H, H3¢¢), 7.49 (t,
3JH,H = 7.4 Hz, 1 H, H4¢), 7.59–7.62 (m, 2 H, H3¢), 7.66-7.68 (m, 2
H, H2¢¢), 7.79 (d, 3JH,H = 7.4 Hz, 2 H, H2¢), 7.79–7.81 (m, 1 H, H3),
3
3
8.05 (d, JH,P = 6.2 Hz, 1 H, H9b), 8.06 (d, JH,P = 6.0 Hz, 1 H,
H12¢¢¢b) (a and b interchangeable assignments).
13C NMR (125.692 MHz, CDCl3): d = 63.8 (d, 3JC,P = 2.1 Hz, C8),
3
5
112.8 (d, JC,P = 13.3 Hz, C2¢¢¢a), 114.6 (d, JC,P = 1.2 Hz, C4¢¢¢),
3
3
118.5 (d, JC,P = 13.3 Hz, C6¢¢¢a), 124.2 (d, JC,P = 13.3 Hz, C4),
124.3 (d, 3JC,P = 0.9 Hz, C6), 125.9 (d, 3JC,P = 13.0 Hz, 2 C, C2¢¢),
127.2 (d, 4JC,P = 1.5 Hz, C5), 127.6 (C4¢), 127.7 (d, 5JC,P = 1.5 Hz,
C4¢¢), 128.5 (d, 4JC,P = 1.2 Hz, 2 C, C3¢¢), 128.9 (2 C, C2¢), 129.1 (2
4
2
C, C3¢), 129.7 (d, JC,P = 1.2 Hz, C5¢¢¢), 131.7 (d, JC,P = 39.1 Hz,
2
2
C3), 138.6 (d, JC,P = 24.8 Hz, C1¢¢), 140.3 (d, JC,P = 25.1 Hz,
1
C1¢¢¢), 141.0 (d, JC,P = 11.2 Hz, C2), 141.1 (C1¢), 147.2 (d,
2JC,P = 4.8 Hz, C9), 147.7 (d, JC,P = 4.8 Hz, C12), 152.1 (d,
2
1JC,P = 16.1 Hz, C10b), 152.5 (d, JC,P = 16.1 Hz, C11b), 155.1 (d,
1
2JC,P = 3.3 Hz, C7), 155.7 (d, JC,P = 1.2 Hz, C3¢¢¢) (a and inter-
4
b
changeable assignments).
31P NMR (121.474 MHz, CDCl3): d = –68.9 (s).
Resolution via preparative HPLC (Chiralpak AD-H, i-PrOH–
HRMS: m/z calcd for C29H21OP: 416.1330; found: 416.1326.
MeCN, 60:40):
(–)-1c: [a]D20 –31.6 (c 0.83, CHCl3).
(+)-1c: [a]D20 +31.2 (c 1.00, CHCl3).
2-{8,10-Diphenyl-1-phosphatricyclo[6.2.2.02,7]dodeca-
2(7),3,5,9,11-pentaen-11-yl}phenol (1e)
1H NMR (400.130 MHz, CDCl3): d = 3.74 (s, 3 H, OCH3), 6.52–
6.53 (m, 1 H, H6), 6.86–6.90 (m, 2 H, H3¢¢¢, H5¢¢¢), 6.96–7.03 (m, 2
H, H4, H5), 7.15–7.17 (m, 1 H, H6¢¢¢), 7.20–7.25 (m, 2 H, H4¢¢,
H4¢¢¢), 7.31–7.35 (m, 2 H, H3¢¢), 7.47 (t, 3JH,H = 7.3 Hz, 1 H, H4¢),
7.56–7.60 (m, 2 H, H3¢), 7.72–7.74 (m, 2 H, H2¢¢), 7.76–7.79 (m, 3
H, H3, H2¢), 7.86 (d, 3JH,P = 6.0 Hz, 1 H, H12), 8.06 (d, 3JH,P = 5.6
Hz, 1 H, H9).
13C NMR (100.620 MHz, CDCl3): d = 55.4 (CH3), 63.4 (d,
3JC,P = 2.9 Hz, C8), 110.9 (C3¢¢¢), 120.7 (C5¢¢¢), 124.0 (C6), 124.1
(d, 3JC,P = 13.1 Hz, C4), 126.0 (d, 3JC,P = 13.1 Hz, 2 C, C2¢¢), 126.9
Oxidation: To a soln of 1c (475 mg, 1.10 mmol, 1.0 equiv) in
CH2Cl2 (20 mL) was added dropwise 35% H2O2 in H2O (170 mL,
1.99 mmol, 1.8 equiv). After stirring overnight at r.t. the organic
phase was washed with H2O (3 × 7 mL), treated with a small
amount MnO2 to destroy peroxides, dried (MgSO4) and evaporated
to dryness in vacuo. The residue was purified by flash chromatog-
raphy (silica gel, cyclohexane–EtOAc, 1:1) to give 11-(2-meth-
oxyphenyl)-8,10-diphenyl-1-phosphatricyclo[6.2.2.02,7]dodeca-
2(7),3,5,9,11-pentaene 1-oxide (rac-ox-1c) in analytically pure
form; yield: 411 mg (84%).
Synthesis 2006, No. 13, 2121–2128 © Thieme Stuttgart · New York

2126
B. Breit, E. Fuchs
PAPER
1H NMR (400.130 MHz, CDCl3): d = 3.74 (s, 3 H, OCH3), 6.48–
6.51 (dd, J = 7.7 Hz, J = 5.2 Hz, 1 H, H6), 6.90–6.93 (m, 2 H), 7.07
(t, J = 7.5 Hz, 1 H), 7.17–7.30 (m, 4 H), 7.35–7.39 (m, 2 H, H3¢¢),
Bidentate Ligands 5 and 6; General Procedure
To a soln of (S)-(1,1¢-binaphthyl-2,2¢-dioxy)chlorophosphine (4,
1.3–1.5 equiv) in toluene was added slowly a soln of enantiomeri-
cally pure phosphabarrelene (+)- or (–)-1d or (+)- or (–)-1e in tolu-
ene at –40 °C. Subsequently Et3N (1.3–1.5 equiv) was added and
the soln was warmed to r.t. over 5 h and stirred overnight. The or-
ganic phase was washed with H2O (3 × 15 mL), the aqueous phases
were reextracted with toluene (3 × 10 mL), and the combined or-
ganic phases were dried (MgSO4). After evaporation of the solvent
in vacuo, the residue was dissolved in CH2Cl2 (10 mL) and filtered
through a small pad of neutral alumina (2 × 3 cm, activity grade IV).
The alumina was flushed with additional CH2Cl2 (60 mL) and the
combined filtrates were evaporated to dryness in vacuo to give the
bidentate phosphabarrelenes in analytically pure form.
3
7.49 (t, JH,H = 7.3 Hz, 1 H, H4¢), 7.57–7.61 (m, 2 H, H3¢), 7.69–
7.74 (m, 2 H, H2¢¢), 7.81–7.84 (m, 2 H, H2¢), 7.83 (d, 3JH,P = 32.7
Hz, 1 H, H12a), 8.00 (d, 3JH,P = 31.8 Hz, 1 H, H9a), 8.03–8.07 (m, 1
H, H3) (a interchangeable assignments).
31P NMR (121.468 MHz, CDCl3): d = 11.1 (s).
Deprotection: Oxide rac-ox-1c (560 mg, 1.25 mmol, 1.0 equiv) was
dissolved in DCE (15 mL) in a pressure vessel at r.t. A suspension
of BBr3·SMe2 (1.375 g, 4.40 mmol, 3.5 equiv) in DCE (6 mL) was
added to the mixture which was then heated to 80 °C overnight. The
reaction was cooled to 0 °C and hydrolyzed by cautious addition of
ice. The organic phase was washed with H2O (3 × 10 mL) and the
aqueous phases were reextracted with CH2Cl2 (2 × 10 mL). The
combined organic phases were dried (MgSO4) and evaporated to
dryness in vacuo. The residue was purified by flash chromatogra-
phy (silica gel, cyclohexane–EtOAc, 3:1) to give 11-(2-hy-
droxyphenyl)-8,10-diphenyl-1-phosphatricyclo[6.2.2.02,7]dodeca-
2(7),3,5,9,11-pentaene 1-oxide (rac-ox-1e) in analytically pure
form; yield: 508 mg (94%).
3-{8,11-Diphenyl-1-phosphatricyclo[6.2.2.02,7]dodeca-
2(7),3,5,9,11-pentaen-10-yl}phenyl(S)-1,1¢-Binaphthyl-2,2¢-diyl
Phosphite [(+)-5a] from (+)-1d
Starting from 4 (88.7 mg, 0.253 mmol) in toluene (4.0 mL) and (+)-
1d (81.0 mg, 0.195 mmol) in toluene (8.0 mL) and using Et3N (27.0
mg, 0.264 mmol), 5a was obtained as a colorless solid; yield: 124
mg (87%); mp 132–138 °C.
1H NMR (300.066 MHz, CDCl3): d = 6.51–6.56 (dd, J = 7.5 Hz,
J = 5.3 Hz, 1 H, H6), 6.82–6.87 (m, 1 H), 7.00 (d, J = 7.5 Hz, 1 H),
7.08–7.38 (m, 7 H), 7.50–7.55 (m, 1 H, H4¢), 7.60–7.65 (m, 2 H,
[a]D20 +77.9 (c 1.09, CHCl3).
1H NMR (499.870 MHz, CDCl3): d = 6.60 (d, 3JH,H = 6.9 Hz, 1 H,
H6), 7.01–7.07 (m, 2 H, H4, H5), 7.13–7.15 (m, 1 H, H4¢¢¢), 7.26–
7.35 (m, 7 H), 7.37–7.49 (m, 4 H), 7.51–7.57 (m, 3 H, H4¢, H2¢¢¢,
H6¢¢¢), 7.60 (d, J = 8.8 Hz, 1 H), 7.64 (pt, 3JH,H = 7.6 Hz, 2 H, H3¢),
7.74 (d, 3JH,H = 7.7 Hz, 2 H, H2¢¢), 7.83 (d, 3JH,H = 7.5 Hz, 2 H, H2¢),
7.86–7.88 (m, 1 H, H3), 7.90–7.93 (m, 2 H), 7.95 (d, J = 8.2 Hz, 1
H), 8.01 (d, J = 8.8 Hz, 1 H), 8.11 (d, 3JH,P = 5.8 Hz, 1 H, H9a), 8.12
(d, 3JH,P = 5.7 Hz, 1 H, H12a) (a interchangeable assignments).
3
H3¢), 7.70–7.73 (m, 4 H, H2¢¢, H2¢), 7.96 (d, JH,P = 29.7 Hz, 1 H,
H9a), 8.03–8.08 (m, 1 H, H3), 8.07 (d, 3JH,P = 32.4 Hz, 1 H, H12a),
9.62 (s, 1 H, OH) (a interchangeable assignments).
31P NMR (121.468 MHz, CDCl3): d = 18.3 (s).
Reduction: To a soln of rac-ox-1e (128 mg, 0.296 mmol, 1.0 equiv)
in toluene (8 mL) in a pressure vessel was added trichlorosilane
(140 mL, 188 mg, 1.385 mmol, 4.7 equiv) at 0 °C. The mixture was
stirred for 10 min at r.t. and then it was heated to 110 °C overnight.
The mixture was cooled to r.t., cautiously poured into aq 2 M NaOH
(15 mL), and the H2O phase was extracted with toluene (2 × 10
mL). The combined organic phases were washed with H2O (3 × 8
mL), dried (MgSO4) and evaporated to dryness in vacuo. The resi-
due was purified by flash chromatography (silica gel, cyclohexane–
EtOAc, 5:1) to give rac-1e in analytically pure form as a colorless
solid; yield: 106 mg (86%); mp 205–210 °C.
13C NMR (125.692 MHz, CDCl3): d = 63.8 (d, 3JC,P = 2.1 Hz, C8),
117.9 (dd, 3JC,P = 13.3 Hz, 3JC,P = 7.0 Hz, C2¢¢¢), 119.3 (d, 3JC,P = 8.8
3
Hz, C4¢¢¢), 121.68, 121.71, 122.0 (d, JC,P = 13.6 Hz, C6¢¢¢), 122.9
(d, J = 2.4 Hz, 2 C, quart. C), 124.1 (d, 3JC,P = 13.3 Hz, C4), 124.3
3
(C6), 125.0, 125.2, 125.9 (d, JC,P = 13.0 Hz, 2 C, C2¢¢), 126.2,
126.4, 126.9, 127.0, 127.2 (d, 4JC,P = 1.5 Hz, C5), 127.6 (C4¢), 127.7
(d, 5JC,P = 1.2 Hz, C4¢¢), 128.3, 128.4, 128.6 (d, 4JC,P = 0.9 Hz, 2 C,
C3¢¢), 128.9 (2 C, C2¢), 129.1 (2 C, C3¢), 129.8, 129.9, 130.5, 131.3
(quart. C), 131.6 (quart. C), 131.8 (d, 2JC,P = 39.1 Hz, C3), 132.6 (d,
J = 1.2 Hz, quart. C), 132.8 (d, J = 1.2 Hz, quart. C), 138.5 (d,
Resolution via preparative HPLC (Chiralpak AD-H, n-heptane–
EtOH, 50:50):
(–)-1e: [a]D20 –13.9 (c 0.77, CHCl3).
(+)-1e: [a]D20 +13.4 (c 0.76, CHCl3).
1H NMR (300.064 MHz, CDCl3): d = 5.11 (s, 1 H, OH), 6.55–6.58
(m, 1 H, H6), 6.83 (d, 3JH,H = 8.1 Hz, 1 H, H3¢¢¢), 6.88–6.93 (m, 1 H,
H5¢¢¢), 7.00–7.03 (m, 2 H, H4, H5), 7.10–7.16 (m, 1 H, H4¢¢¢), 7.23–
7.35 (m, 4 H, H3¢¢, H4¢¢, H6¢¢¢), 7.46–7.51 (m, 1 H, H4¢), 7.57–7.62
(m, 2 H, H3¢), 7.67–7.70 (m, 2 H, H2¢¢), 7.75–7.78 (m, 2 H, H2¢),
7.78–7.84 (m, 1 H, H3), 8.06 (d, 3JH,P = 6.2 Hz, 1 H, H9a), 8.07 (d,
3JH,P = 6.0 Hz, 1 H, H12a) (a interchangeable assignments).
2JC,P = 24.8 Hz, C1¢¢), 140.6 (d, JC,P = 25.1 Hz, C1¢¢¢), 140.8 (d,
2
1JC,P = 11.2 Hz, C2), 141.0 (C1¢), 146.9 (d, J = 2.4 Hz, quart. C),
147.2 (d, 2JC,P = 4.5 Hz, C9a), 147.5 (d, J = 4.5 Hz, quart. C), 148.4
(d, 2JC,P = 4.8 Hz, C12a), 151.8 (d, 1JC,P = 16.1 Hz, C10b), 151.9 (dd,
4
1
2JC,P = 7.9 Hz, JC,P = 1.2 Hz, C3¢¢¢), 152.4 (d, JC,P = 16.0 Hz,
C11b), 155.0 (d, 2JC,P = 3.3 Hz, C7) (a and b interchangeable assign-
ments).
31P NMR (121.474 MHz, CDCl3): d = 144.8 (s, P13), –68.9 (s, P1).
HRMS: m/z calcd for C49H32O3P2: 730.1827; found: 730.1812.
3-{8,11-Diphenyl-1-phosphatricyclo[6.2.2.02,7]dodeca-
2(7),3,5,9,11-pentaen-10-yl}phenyl(S)-1,1¢-Binaphthyl-2,2¢-diyl
Phosphite [(+)-5b] from (–)-1d
Starting from 4 (38.3 mg, 0.109 mmol) in toluene (3.0 mL) and (–)-
1d (35.0 mg, 0.084 mmol) in toluene (5.0 mL) using Et3N (11.6 mg
(0.114 mmol), 5b was obtained as a colorless solid; yield: 59 mg
(96%); mp 132–138 °C.
3
13C NMR (75.451 MHz, CDCl3): d = 63.8 (d, JC,P = 2.6 Hz, C8),
115.9 (C3¢¢¢), 120.9 (C5¢¢¢), 124.2 (d, 3JC,P = 13.2 Hz, C4), 124.4 (d,
3JC,P = 1.2 Hz, C6), 125.9 (d, 3JC,P = 12.7 Hz, 2 C, C2¢¢), 126.6 (d,
4
2JC,P = 23.0 Hz, C1¢¢¢), 127.3 (d, JC,P = 1.7 Hz, C5), 127.6 (C4¢),
4
127.7 (d, 5JC,P = 1.7 Hz, C4¢¢), 128.6 (d, JC,P = 1.2 Hz, 2 C, C3¢¢),
3
128.8 (2 C, C2¢), 128.9 (d, JC,P = 10.7 Hz, C6¢¢¢), 128.9 (C4¢¢¢),
2
129.1 (2 C, C3¢), 131.8 (d, JC,P = 38.6 Hz, C3), 138.5 (d,
[a]D20 +73.2 (c 1.05, CHCl3).
1
2JC,P = 24.5 Hz, C1¢¢), 140.9 (C1¢), 141.1 (d, JC,P = 12.4 Hz, C2),
1H NMR (499.870 MHz, CDCl3): d = 6.58 (d, 3JH,H = 6.9 Hz, 1 H,
H6), 7.00–7.06 (m, 2 H, H4, H5), 7.11–7.13 (m, 1 H, H4¢¢¢), 7.25–
7.37 (m, 7 H), 7.40–7.47 (m, 4 H), 7.50–7.53 (m, 3 H, H4¢, H2¢¢¢,
H6¢¢¢), 7.58 (d, J = 8.8 Hz, 1 H), 7.63 (pt, 3JH,H = 7.7 Hz, 2 H, H3¢),
7.70 (d, 3JH,H = 7.7 Hz, 2 H, H2¢¢), 7.81 (d, 3JH,H = 7.5 Hz, 2 H, H2¢),
7.83–7.84 (m, 1 H, H3), 7.87 (d, J = 8.6 Hz, 2 H), 7.94 (d, J = 8.3
147.1 (d, 2JC,P = 4.6 Hz, C9), 150.2 (d, 1JC,P = 18.4 Hz, C11), 150.6
2
3
(d, JC,P = 4.0 Hz, C12), 152.2 (d, JC,P = 2.6 Hz, C2¢¢¢), 152.8 (d,
1JC,P = 17.6 Hz, C10), 154.9 (d, 2JC,P = 3.3 Hz, C7).
31P NMR (121.468 MHz, CDCl3): d = –63.0 (s).
HRMS: m/z calcd for C29H21OP: 416.1330; found: 416.1320.
Synthesis 2006, No. 13, 2121–2128 © Thieme Stuttgart · New York

PAPER
Chiral Phosphabarrelene Ligands in Rhodium-Catalyzed Asymmetric Hydrogenation
2127
Hz, 1 H), 8.00 (d, J = 8.8 Hz, 1 H), 8.08 (d, 3JH,P = 6.2 Hz, 1 H, H9a),
8.11 (d, 3JH,P = 5.8 Hz, 1 H, H12a) (a interchangeable assignments).
13C NMR (125.692 MHz, CDCl3): d = 63.9 (d, 3JC,P = 1.81 Hz, C8),
[a]D20 +132.0 (c 1.00, CHCl3).
1H NMR (499.870 MHz, C6D6): d = 6.67–6.69 (m, 2 H, H4, H6),
6.73–6.76 (m, 1 H, H5), 6.85–6.93 (m, 4 H), 7.01 (t, 3JH,H = 7.2 Hz,
1 H), 7.07–7.12 (m, 4 H), 7.15–7.21 (m, 5 H), 7.30 (d, J = 7.1 Hz, 1
H), 7.34 (d, J = 8.8 Hz, 1 H), 7.42 (d, J = 8.5 Hz, 2 H), 7.51–7.59
(m, 6 H), 7.68 (d, 2JH,H = 7.7 Hz, 2 H, H2¢¢), 7.84–7.88 (m, 1 H, H3),
7.91 (d, 2JH,P = 5.9 Hz, 1 H, H9a), 8.27 (d, 2JH,P = 6.0 Hz, 1 H, H12a)
(a interchangeable assignments).
3
3
117.9 (dd, JC,P = 13.2 Hz, JC,P = 7.5 Hz, C2¢¢¢), 119.3 (dd,
3JC,P13 = 8.8 Hz, JC,P = 0.9 Hz, C4¢¢¢), 121.7 (br s, 2 C), 122.0 (d,
5
3JC,P = 13.3 Hz, C6¢¢¢), 122.8 (d, J = 2.4, 2 C, quart. C), 124.2 (d,
3JC,P = 13.3 Hz, C4), 124.4 (d, JC,P = 0.9 Hz, C6), 125.0, 125.2,
3
3
125.9 (d, JC,P = 13.0 Hz, 2 C, C2¢¢), 126.2, 126.4, 126.9, 127.0,
127.3 (d, 4JC,P = 1.5 Hz, C5), 127.6 (C4¢), 127.7 (d, 5JC,P = 1.5 Hz,
C4¢¢), 128.3, 128.4, 128.6 (d, 4JC,P = 0.9 Hz, 2 C, C3¢¢), 128.9 (2 C,
C2¢), 129.1 (2 C, C3¢), 129.8, 129.9, 130.5, 131.3 (quart. C), 131.7
(quart. C), 131.8 (d, 2JC,P = 39.1 Hz, C3), 132.6 (d, J = 1.2 Hz, quart.
C), 132.8 (d, J = 1.5 Hz, quart. C), 138.5 (d, 2JC,P = 24.5 Hz, C1¢¢),
13C NMR (125.692 MHz, C6D6): d = 64.5 (d, JC,P = 2.4 Hz, C8),
3
121.3 (d, J = 10.6 Hz), 122.0, 122.1 (d, J = 1.2 Hz), 123.3 (d,
J = 2.4 Hz, 2 C, quart. C), 124.4 (d, 3JC,P = 13.0 Hz, C4), 124.8 (2
C), 125.0, 125.3, 126.4, 126.5 (d, 3JC,P = 13.0 Hz, 2 C, C2¢¢), 126.6,
127.2, 127.3, 127.4, 127.5, 127.7, 128.6 (2 C, C3¢¢), 128.7, 128.72,
129.1 (2 C, C2¢), 129.4 (2 C, C3¢), 130.2, 130.5, 130.6, 130.7, 131.6
(quart. C), 132.1 (quart. C), 132.2 (d, 2JC,P = 38.8 Hz, C3), 134.0 (d,
J = 1.2 Hz, quart. C), 133.3 (d, J = 1.5 Hz, quart. C), 139.3 (d,
2
1
140.7 (d, JC,P = 25.1 Hz, C1¢¢¢), 140.8 (d, JC,P = 11.2 Hz, C2),
141.0 (C1¢), 147.0 (d, J = 2.4 Hz), 147.2 (d, JC,P = 4.5 Hz, C9a),
2
147.5 (d, J = 4.5 Hz), 148.4 (d, JC,P = 4.9 Hz, C12a), 151.8 (d,
2
1JC,P = 16.4 Hz, C10b), 151.9 (dd, JC,P = 7.9 Hz, JC,P = 1.2 Hz,
C3¢¢¢), 152.5 (d, 1JC,P = 16.1 Hz, C11b), 155.1 (d, 2JC,P = 3.6 Hz, C7)
(a and b interchangeable assignments).
2
4
2JC,P = 24.8 Hz, C1¢¢), 141.6 (C1¢), 141.9 (d, JC,P = 13.0 Hz, C2),
1
147.5 (d, J = 2.1 Hz, quart. C), 147.9 (d, 2JC,P = 4.2 Hz, C9a), 148.5
(d, J = 4.2 Hz, quart. C), 149.0 (dd, J = 5.9 Hz, J = 3.2 Hz, quart. C),
31P NMR (121.474 MHz, CDCl3): d = 144.6 (s, P13), –69.0 (s, P1).
149.1 (d, JC,P = 17.6 Hz, C10b), 152.8 (d, JC,P = 3.9 Hz, C12a),
153.2 (d, 1JC,P = 17.6 Hz, C11b), 155.6 (d, 2JC,P = 3.3 Hz, C7) (a and
b interchangeable assignments; signal for C1¢¢¢ not detectable).
1
2
HRMS: m/z calcd for C49H32O3P2: 730.1827; found: 730.1819.
2-{8,11-Diphenyl-1-phosphatricyclo[6.2.2.02,7]dodeca-
2(7),3,5,9,11-pentaen-10-yl}phenyl(S)-1,1¢-Binaphthyl-2,2¢-diyl
Phosphite [(+)-6a] from (+)-1e
Starting from 4 (95.3 mg, 0.272 mmol) in toluene (4.0 mL) and (+)-
1e (87.0 mg, 0.209 mmol) in toluene (8.0 mL) using Et3N (29.1 mg,
0.286 mmol), 6a was obtained as a colorless solid; yield: 142 mg
(93%); mp 140 °C.
31P NMR (121.474 MHz, C6D6): d = 145.3 (d, 5JP,P = 6.1 Hz, P13),
–63.6 (d, 5JP,P = 6.1 Hz, P1).
HRMS: m/z calcd for C49H32O3P2: 730.1827; found: 730.1820.
Hydrogenation Experiments; General Procedure
Monodentate ligands: [Rh(cod)2]BF4 (2.0 mg, 4.9 mmol, 1.0 mol%)
and the particular monodentate phosphabarrelene ligand (13.8
mmol, 2.7 mol%) were dissolved in CH2Cl2 (6 mL) and stirred at r.t.
for 20 min.
[a]D20 +158.0 (c 1.10, CHCl3).
1H NMR (499.870 MHz, CDCl3): d = 6.51 (d, 3JH,H = 6.9 Hz, 1 H,
H6), 6.92–6.97 (m, 2 H, H4, H5), 7.11–7.14 (m, 2 H), 7.16–7.20 (m,
2 H), 7.24–7.26 (m, 4 H), 7.30–7.36 (m, 4 H), 7.38–7.45 (m, 3 H),
Bidentate ligands: [Rh(cod)2]BF4 (2.0 mg, 4.9 mmol, 1.0 mol%) and
the particular bidentate phosphabarrelene ligand (6.8 mmol, 1.3
mol%) were dissolved in CH2Cl2 (6 mL) and stirred at r.t. for 90
min.
3
7.48–7.50 (m, 3 H), 7.55 (d, JH,H = 7.4 Hz, 2 H, H2¢¢), 7.68–7.69
(m, 2 H), 7.71 (d, 3JH,H = 7.7 Hz, 2 H, H2¢), 7.79 (d, 3JH,H = 8.2 Hz,
1 H), 7.88 (d, 2JH,P = 5.8 Hz, 1 H, H9a), 7.90–7.92 (m, 2 H), 8.18 (d,
2JH,P = 5.9 Hz, 1 H, H12a) (a interchangeable assignments).
Subsequently the appropriate substrate 7–9 (0.51 mmol, 1.0 equiv)
was added in one portion. The reaction vessel was evacuated and re-
filled with H2 gas five times. The mixture was vigorously stirred un-
der a H2 atmosphere (hydrogen balloon) at r.t. Conversion was
determined by 1H NMR after the noted time (Table 2). Enantiomer-
ic excess was determined by chiral GC or HPLC analysis.
13C NMR (125.602 MHz, CDCl3): d = 63.8 (d, 3JC,P = 1.5 Hz, C8),
120.4 (d, J = 12.7 Hz), 121.7, 121.73 (d, J = 0.9 Hz), 122.7 (d,
3
J = 2.4 Hz, 2 C, quart. C), 123.9 (d, JC,P = 13.0 Hz, C4), 124.2,
3
124.3, 124.8, 125.1, 126.0 (d, JC,P = 13.0 Hz, 2 C, C2¢¢), 126.1,
126.2, 126.9, 126.94, 127.1, 127.4 (2 C), 128.3 (2 C, C3¢¢), 128.34,
128.4, 128.9 (2 C, C2¢ or C3¢), 129.0 (2 C, C2¢ or C3¢), 129.9, 130.0,
130.1, 130.2, 131.1 (quart. C), 131.6 (quart. C), 131.9 (d,
2JC,P = 38.5 Hz, C3), 132.5 (quart. C), 132.8 (quart. C), 138.7 (d,
Dimethyl Itaconate (Dimethyl 2-Methylenebutanedioate, 7)
GC: G-TA, trifluoroacetyl-g-cyclodextrin column, 30 m × 0.5 mm,
75 °C, tR [(S)-enantiomer] = 32.2 min, tR [(R)-enantiomer] = 35.2
min.
1
2JC,P = 24.5 Hz, C1¢¢), 141.1 (C1¢), 141.3 (d, JC,P = 12.7 Hz, C2),
146.9 (d, J = 2.1 Hz, quart. C), 147.2 (d, 2JC,P = 4.2 Hz, C12a), 147.8
(d, J = 4.8 Hz, quart. C), 148.6 (dd, J = 2.4 Hz, J = 1.5 Hz, quart. C),
Methyl 2-Acetamidoacrylate (8)
GC: Hydrodex-b-TBDAc column, 25 m × 0.25 mm, 120 °C, tR
[(R)-enantiomer] = 14.0 min, tR [(S)-enantiomer] = 20.3 min.
1
2
149.2 (d, JC,P = 17.6 Hz, C10b), 151.1 (d, JC,P = 3.9 Hz, C9a),
152.8 (d, 1JC,P = 17.9 Hz, C11b), 155.0 (d, 2JC,P = 3.3 Hz, C7) (a and
b interchangeable assignments; signal for C1¢¢¢ not detectable).
Methyl a-Acetamidocinnamate (9)
31P NMR (121.474 MHz, CDCl3): d = 144.3 (d, 5JP,P = 7.8 Hz, P13),
HPLC: Chiralpak-AD column, 25 cm × 4.6 mm, n-heptane–
i-PrOH, 90:10), 254 nm, tR [(R)-enantiomer] = 15.0 min, tR [(S)-
enantiomer] = 19.5 min.
–63.2 (d, 5JP,P = 7.8 Hz, P1).
HRMS: m/z calcd for C49H32O3P2: 730.1827; found: 730.1816.
2-{8,11-Diphenyl-1-phosphatricyclo[6.2.2.02,7]dodeca-
2(7),3,5,9,11-pentaen-10-yl}phenyl(S)-1,1¢-Binaphthyl-2,2¢-diyl
Phosphite [(+)-6b] from (–)-1e
Starting from 4 (35.0 mg, 0.100 mmol) in toluene (1.5 mL) and (–)-
1e (28.0 mg, 0.067 mmol) in toluene (2.5 mL) using Et3N (10.4 mg,
0.103 mmol), 6b was obtained as a colorless solid; yield: 48 mg
(98%); mp 189–193 °C.
Acknowledgment
The authors thank the DFG (GRK 1038), the Fonds der Chemischen
Industrie, the Alfried-Krupp Award for young university teachers
(to B.B.) as well as BASF AG for financial support. We also thank
S. Berger for technical and Dr. R. Krieger and G. Fehrenbach for
analytical assistance.
Synthesis 2006, No. 13, 2121–2128 © Thieme Stuttgart · New York

2128
B. Breit, E. Fuchs
PAPER
(7) Scherer, J.; Huttner, G.; Büchner, M.; Bakos, J. J.
Organomet. Chem. 1996, 520, 45.
References
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Pphosphite: d = 125.2 (dd, 1JP,Rh = 254.8 Hz, 2JP,P = 52.4 Hz;
(1) Breit, B.; Fuchs, E. Chem. Commun. 2004, 694.
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P
barrelene: d = –14.2 (dd, 1JP,Rh = 154.8 Hz, 2JP,P = 52.4 Hz).
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Angew. Chem. Int. Ed. 2003, 42, 790; Angew. Chem. 2003,
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Synthesis 2006, No. 13, 2121–2128 © Thieme Stuttgart · New York