The synthesis of new chiral P,N-ligands on the basis of camphor

Article abstract of DOI:10.1016/j.tetasy.2011.11.001

The synthesis of new chiral P,N-ligands has been developed starting from 1,3-dicarbonyls, which are readily available from camphor. Iridium complexes derived from these ligands are also described. Furthermore, some preliminary results related to catalytic

Full text of DOI:10.1016/j.tetasy.2011.11.001

Tetrahedron: Asymmetry 22 (2011) 1936–1941
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
The synthesis of new chiral P,N-ligands on the basis of camphor
Ilyas Ilaldinov a, Daniya Fatkulina a, Sergey Bucharov a, Ralf Jackstell b, Anke Spannenberg b, Matthias Beller b,
Renat Kadyrov c,
⇑
a Kazan State Technological University, Karl-Marx 68, Razan 420015, Russia
b Leibniz-Institut für Katalyse e.V., Albert-Einstein-Str. 29a, 18059 Rostock, Germany
c Evonik Industries AG, Rodenbacher Chaussee 4, 63457 Hanau-Wolfgang, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 25 October 2011
Accepted 1 November 2011
The synthesis of new chiral P,N-ligands has been developed starting from 1,3-dicarbonyls, which are
readily available from camphor. Iridium complexes derived from these ligands are also described. Fur-
thermore, some preliminary results related to catalytic hydrogenation with these iridium complexes
are presented.
Ó 2011 Elsevier Ltd. All rights reserved.
1. Introduction
These encouraging findings prompted us to design a new pyra-
zole containing ligand D with chirality introduced from enantiome-
The mixed-donor bidentate P,N-ligands have proven to be
highly versatile and efficient ligands for a broad range of catalytic
transformations.1–6 Particularly in asymmetric catalysis P,N-li-
gands B (Scheme 1) bearing a chiral oxazoline moiety have at-
tracted the most attention due to their easy preparation from an
amino acid chiral pool.7–10 In addition to its straightforward syn-
thesis in both enantiomeric forms, N,N-dimethyl-1-ferrocenyleth-
ylamine has found huge popularity for the construction of
modular P,N- and P,P-ligands.11,12 Bidentate chiral ligands A
containing phosphine as well as a pyrazole moiety were prepared
from this unique chiral source.13 These ligands were shown to pro-
mote different types of asymmetric transformations with high
enantioselectivities.14–16 Non-chiral N-(2-diphenylphosphino-phe-
nyl)-pyrazoles have been found to be very useful in certain
cross-coupling17–19 and hydroamination20 reactions. Their chiral
versions will extend the scope of these types of ligands enabling
asymmetric induction. The most prominent structure closely asso-
ciated with this respect represents ‘quinap’ (ligand C) with a chiral
environment induced via axial chirality.21 Although significant
progress has been made in the synthesis of this22–24 and related li-
gands3,25,26 in enantiomerically pure form, a chiral resolution still
remains the method of choice.
rically pure camphor. The methoxy group at the 60-position of the
phenyl ring is expected to be sufficiently bulky to prevent rotation
around the C(aryl)–N(pyrazole) bond and fixes one preferred atrop-
isomer upon coordination to the metalic center. This will reduce the
number of possible diastereomeric intermediates in the catalytic
reactions and thus increase the asymmetric induction. Herein we
report a straightforward synthesis of such chiral P,N-ligands. Fur-
thermore, the coordinative behavior of these ligands to iridium,
as well as the preliminary results of application in the asymmetric
hydrogenation of trans-a-methylstilbene are also described.
2. Results and discussion
b-Diketones 1 easily available from camphor36 were employed
as the starting material in the synthesis of ligands. In our prelimin-
ary attempts to build the desired scaffold, we prepared 7,8,8-tri-
methyl-1-phenyl-4,5,6,7-tetrahydro-4,7-methano-1H-indazole by
the condensation of commercially available phenylhydrazine with
3-hydroxymethylenecamphor according to the literature.37 How-
ever, direct deprotonation at the ortho-position of phenyl ring
using n-BuLi and subsequent addition of chlorodiphenylphosphine
gave a complex reaction mixture. 31P NMR analysis of the reaction
mixture showed an absence of resonance in the range of 0 to
ꢀ10 ppm, which is typical for diphenylarylphosphines. Therefore,
the ortho-bromo substituted arylhydrazine was employed as a
building block since metallation via metal-halogen exchange pro-
ceeds under much milder conditions. Condensation of (2-bromo-
6-methoxyphenyl)hydrazine with 3-formyl- 1a or 3-acyl-camphor
1b resulted in the clean formation of hydrazones which furnish
pyrazoles 2a,b after the treatment with catalytic amounts of
hydrobromic acid at 80 °C. Next, lithiation with n-BuLi at low
One strategy for the construction of a chiral scaffold bearing N-
heterocycles is the annulation of naturally occurring monoterpenes
as a source of chirality.27–32 Numerous examples of homochiral
camphor annulated pyrroles and pyrazoles have been reported as
potentially useful mono-, bi- and tridentate ligands.33–35
⇑
Corresponding author. Tel.: +49 (0) 6181 59 8710; fax: +49 (0) 6181 59 78710.
E-mail address: renat.kadyrov@evonik.com (R. Kadyrov).
0957-4166/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2011.11.001

I. Ilaldinov et al. / Tetrahedron: Asymmetry 22 (2011) 1936–1941
1937
R'
R2
R'
R3
N
N
N
R1
PR2
N
PR2
O
N
N
PR2
PR2
Me
Fe
O
Me
D
A (Togni)
B (phox)
C (quinap)
Scheme 1. Design of new ligand D.
temperature, followed by the slow addition of chlorophosphines
ClPR2 gave the desired ligands 3a,b–6a,b in satisfactory yields
(Scheme 2).
Scheme 1 (D). Therefore, we can assume that this is the preferred
conformation of these ligands upon coordination to the metal cen-
ter. The conformation with an alternative orientation of the phenyl
group (with the methoxy group disposed above the bornene moi-
ety) should be significantly disfavored due to the steric interaction
of the methoxy group with both methyl groups of bornene frag-
ment. This gives rise to the hope that high asymmetric induction
in catalytic transformations with metal complexes bearing these
new ligands should be observed.
The iridium complexes were evaluated in the enantioselective
hydrogenation of trans-a-methylstilbene 7. The highest enantio-
meric excess of 85% was obtained using [Ir(4a)(COD)]BF4 as a
catalyst.
The cationic iridium complexes [Ir(L)(COD)]BF4 can be easily
prepared by the reaction of 2 equiv of ligand (L) with 1 equiv of
[Ir(COD)Cl]2 in CH2Cl2 at 50 °C followed by the exchange of the
chloride in the presence of AgBF4. After filtration from the precip-
itated AgCl, the expected complexes were isolated in appropriate
yields. However, the NMR spectra of all of the prepared Ir-com-
plexes showed very broad NMR signals. The structural character-
ization of the [Ir(4a)(COD)]BF4 complex was performed by X-ray
diffraction. The complex shows a square-planar coordination
geometry around the iridium atom (Fig. 1). The chelating 6-ring
[Ir(COD)(4a)l]BF4/NaBArF
24h, 85bar H2
CH2Cl2/H2O
8, 99%, 85% ee
7
adopts a distorted boat conformation with a typical axial–equatorial
disposition of the two substituents at the P atom. The torsion angle
between the phenyl ring and the five-membered pyrazole-ring
(C(3)–N(2)–C(12)–C(17) = 55.1°) is significantly larger than in the
analogous Ir–phox complexes (24° and 31°).38,39 A key feature in
this structure is the orientation of the phenyl ring with a meth-
oxy-group disposed under the bornene moiety, as shown in
3. Conclusion
In conclusion, novel chiral bidentate P,N-ligands have been pre-
pared from camphor. The coordination behavior of the ligands has
been illustrated through the synthesis of cationic Ir complexes.
Preliminary catalytic results performed with these Ir complexes
showed good results in the hydrogenation of C@C bonds.
R'
N
R'
Br
H2NHN
MeO
a) RT; CH3OH
O
N
Br
b) HBr
O
R'
MeO
1a
H
1b CH3
2a,b
1. n-BuLi
2. ClPR2
R'
R'
Ir
[Ir(COD)Cl]2
AgBF4
R
N
N
N
3a/3b C6H5;
4a/4b C6H11
-
;
BF4
N
PR2
PR2
5a/5b o-CH3C6H4;
6a/6b 3,5-(CF3)2C6H3
MeO
MeO
Scheme 2. Synthesis of ligands and Ir-complexes [Ir(L)(COD)]BF4.

1938
I. Ilaldinov et al. / Tetrahedron: Asymmetry 22 (2011) 1936–1941
was allowed to warm to room temperature and stirred for 3 h, after
which the product was filtered off, and washed with saturated
brine once. The solid was dissolved by the careful addition to a
chilled aqueous solution of 25% sodium hydroxide (200 ml) con-
taining ca. 40 g of potassium tartrate. The product was extracted
with dichloromethane (4 ꢁ 50 ml). The combined organic layers
were washed with 2 M NaOH and water, dried over MgSO4 and
evaporated to give 59.4 g (87%) of desired product as a tan solid.
Mass spectrum, m/z (I rel., %): 219 (9), 218 (95), 217(10), 216
(100), 203 (64), 201(74), 200 (83), 198 (80), 186 (39).
4.3. (4S,7R)-7,8,8-Trimethyl-1-(2-bromo-6-methoxyphenyl)-
4,5,6,7-tetrahydro-4,7-methano-1H-indazole 2a
(a)
A solution of (2-bromo-6-methoxyphenyl)hydrazine in
100 ml of methanol was added to a solution of (1R)-2-hydroxym-
ethylenecamphor in MeOH (50 ml), the product precipitated
immediately with an exothermic reaction. The reaction mixture
was allowed to cool to room temperature within 2 h and addition-
ally cooled in an ice bath to complete the precipitation, filtered off,
washed with 95% ethanol and air dried to give 32.7 g of hydrazone
as a colorless solid. (3-[2-(2-bromo-6-methoxyphenyl)-hydrazo]
methylenecamphor decomposes slowly at room temperature).
(b) To the suspension of 3-[2-(2-bromo-6-methoxy-
phenyl)hydrazo]methylenecamphor (21.69 g, 57.2 mmol) in acetic
acid(150 ml), 0.5 ml of 47% HBr was added and the mixture was
heated at 80 °C for 2 h. The resulting clear red solution was allowed
to cool to ambient temperature, after which the reaction mixture
was evaporated in vacuum and treated with chilled aq 2 M NaOH
(50 ml). The product was extracted with ether (3 ꢁ 50 ml), and
the combined organic layers were washed with aqueous sodium
bicarbonate then with brine, dried over MgSO4, filtered, diluted
with heptane and the ether slowly removed on a rotary evaporator
to give 16.21 g (78%) of pure product. 1H NMR (400 MHz, CDCl3) d
7.32 (s, 1H), 7.26 (d, J = 8.2, 1H), 7.16 (dd, J = 2.0, J = 8.4, 1H), 7.11
(d, J = 1.9, 1H), 3.77 (s, 3H), 2.80 (d, J = 3.8, 1H), 2.07 (tdd, J =
3.8, J = 9.4, J = 11.8, 1H), 1.75 (ddd, J = 3.8, J = 9.5, J = 12.0, 1H),
1.38 (m, 1H), 1.19 (ddd, J = 3.6, J = 9.0, J = 12.0, 1H), 0.91 (s, 3H),
0.88 (s, 3H), 0.75 (s, 3H). 13C NMR (CDCl3) d: 155.69, 154.68,
132.87, 129.52, 128.70, 128.68, 123.70, 122.66, 115.11, 63.40,
55.73, 52.86, 47.48, 32.97, 27.61, 20.25, 19.67, 10.19. Mass spec-
trum, m/z (I rel., %): 362, 360 (95), 347 (60), 345 (60), 319 (100),
317 (100).
Figure 1. ORTEP view of the complex [Ir(4a)(COD)]BF4, Hydrogen atoms and the
BF4 anion are omitted for the sake of clarity. Selected bonds lengths (Å) and angles
(°): Ir(1)–P(1) 2.319(1), Ir(1)–N(1) 2.078(3), Ir(1)–C(31) 2.204(4), Ir(1)–C(32)
2.177(3), Ir(1)–C(35) 2.148(4), Ir(1)–C(36) 2.109(4), P(1)–C(13) 1.838(4), C(12)–
C(13) 1.410(5), C(12)–N(2) 1.430(4), N(1)–N(2) 1.377(2), C(1)–N(1) 1.350(4), C(1)–
C(2) 1.383(4), C(2)–C(3) 1.374(4), C(3)–N(2) 1.352(4), C(31)–C(32) 1.364(8), C(35)–
C(36) 1.391(7), N(1)–Ir(1)–P(1) 85.58(9), Ir(1)–N(1)–N(2) 126.8(2), Ir(1)–P(1)–C(13)
106.62(12), P(1)–C(13)–C(12) 119.4(3), C(13)–C(12)–N(2) 121.4(3), C(12)–N(2)–
N(1) 123.9(3), C(1)–N(1)–N(2) 106.1(2), C(3)–N(2)–N(1) 109.4(3), C(2)–C(3)–N(2)
108.3(3), C(1)–C(2)–C(3) 106.0(3), N(1)–C(1)–C(2) 110.2(3).
4. Experimental
4.1. General
NMR spectra were recorded on Brucker ARX 300 MHz and Bruc-
ker ARX 400 MHz spectrometer at rt. 1H NMR and 13C NMR spectra
are reported in parts per million with TMS (d = 0.00 ppm) as the
internal standard. 31P NMR spectra are reported in parts per mil-
lion with 85% H3PO4 as an external reference. Proton chemical
shifts (d) and coupling constants (J) are given in ppm and in Hertz,
respectively. Spin multiplicities are given as s (singlet), d (doublet),
t (triplet), q (quartet), p (pentet), and m (multiplet) as well as br
(broad). High resolution mass spectra (HRMS) were performed on
ESI-TOF/MS mass instrument. Optical rotations were measured
on a Fluke GYROMAT-HP polarimeter at 21–3 °C. Reactions were
monitored by thin layer chromatography (TLC, silica gel G254
plates). Column chromatography purifications were carried out
using silica gel (200–300 mesh). Toluene, ether, and THF were dis-
tilled from sodium and benzophenone. CH2Cl2 was distilled over
CaH2 under argon. 6-Bromo-2-anisidine,40 (1R)-3-hydroxymethyl-
enecamphor,33 and (1R)-3-acethylcamphor41 were synthesised
according to literature procedures. All other chemicals were ob-
tained commercially and used as received without further
purification.
4.4. (4S,7R)-3,7,8,8-Tetramethyl-1-(2-bromo-6-
methoxyphenyl)-4,5,6,7-tetrahydro-4,7-methano-1H-indazole
2b
(1R)-3-Acetylcamphor (7.93 g, 36.5 mmol) was added to a solu-
tion of (2-bromo-6-methoxyphenyl)hydrazine (7.1 g, 36.5 mmol)
in methanol (50 ml). After 30 min of stirring, 10 drops of 47%
HBr were added and refluxed for 5 h. Methanol was evaporated
and the residue dissolved in a 100 ml mixture of ethyl acetate
and hexane (1:1) and filtered through a short pad silica gel, and
washed with 200 ml of ethyl acetate–hexane (1:1). The combined
filtrates were evaporated, the residue dissolved in hot hexane
(100 ml) cooled in an ice-bath, the precipitated product filtered
off and washed twice with cold pentane to give 7.25 g (53%) of
the desired product. 1H NMR (400 MHz, CDCl3) d 7.26 (d, J = 8.2,
1H), 7.14 (dd, J = 2.0, J = 8.4, 1H), 7.08 (d, J = 2.0, 1H), 3,76 (s, 3H),
2.74 (d, J = 3.8, 1H), 2.24 (s, 3H), 2.05 (tdd, J = 3.8, J = 9.4, J = 11.7,
1H), 1.72 (ddd, J = 3.8, J = 9.3, J = 12.0, 1H), 1.38 (m, 1H), 1.17
(ddd, J = 3.4, J = 8.9, J = 12.0, 1H), 0.89 (s, 3H), 0.87 (s, 3H), 0.77 (s,
3H). 13C NMR (CDCl3) d: 156.27, 154.62, 141.96, 129.60, 128.76,
127.48, 123.69, 122.29, 114.96, 63.29, 55.65, 53.29, 46.94, 32.92,
4.2. 6-Bromo-2-methoxyphenylhydrazine
To a cooled (in an ice bath) suspension of 6-bromo-2-anisidine
(63.52 g, 0.314 mol) in concentrated hydrochloric acid (130 ml)
was added dropwise a solution of sodium nitrite (22 g, 0.32 mol)
in water (100 ml) while the temperature was kept below 5 °C. After
stirring for a further 30 min at 4 °C the red solution of the diazo
compound was filtered and to the filtrate the chilled solution of ti-
n(II) chloride dihydrate (175 g, 0.78 mol) in concentrated hydro-
chloric acid (200 ml) was added dropwise while occasionally
adding water (all together ca. 500 ml water were added), while
hydrazine hexachlorostannane precipitated. The reaction mixture

I. Ilaldinov et al. / Tetrahedron: Asymmetry 22 (2011) 1936–1941
1939
27.40, 20.30, 19.74, 12.63, 10.18. Mass spectrum, m/z (I rel., %): 376
4.9. (4S,7R)-3,7,8,8-Tetramethyl-1-(2-dicyclohexylphosphino-6-
(18), 374 (18), 361 (24), 359 (24), 333 (100) 331 (100).
methoxyphenyl)-4,5,6,7-tetrahydro-4,7-methano-1H-indazole
4b
4.5. General procedure for the synthesis of the ligands 3–6
Prepared from 2b (751 mg, 2 mmol) and chloro-dicyclohexyl-
A solution of 1.6 M n-BuLi in hexane (2.6 mmol) was added to a
stirred solution of 2a or 2b (2 mmol) in dry THF (30 ml) at ꢀ70 °C.
After 15 min of stirring, the appropriate chlorophosphine (2 mmol)
in 3 ml of THF was added dropwise keeping the temperature below
ꢀ70 °C and allowed to warm to room temperature with stirring
over night, then quenched by the careful addition of aq NH4Cl
(50 ml) solution. The product was extracted with 10 ml ether, the
organic layer was dried over MgSO4, and concentrated in vacuum.
The crude product was purified by column chromatography using
25% ethyl acetate in hexane as eluent.
phosphine (465 mg, 2 mmol). Yield 671 mg (67%). ½a D22
¼ ꢀ12:9
ꢂ
(c 1, ethyl acetate). 1H NMR (400 MHz, CD2Cl2) d: 7.21 (dd,
J = 7.7, J = 0.8, 1H), 7.02 (ddd, J = 7.7, J = 5.2, J = 1.5, 1H), 6.98
(dd, J = 7.7, J = 1.6, 1H), 3.71 (s, 3H), 2.65 (d, J = 3.8, 1H), 2.11 (s,
3H), 1.98 (ddt, J = 11.6, J = 9.3, J = 3.9, 1H), 1.66 (ddd, J = 11.9,
J = 9.4, J = 3.8, 1H), 0.79 (s, 6H), 0.86–1.87 (m, 24H), 0.67 (s, 3H).
13C NMR (CD2Cl2) d 156.45, 153.49 (d, J = 5.1), 141.58, 137.04
(d, J = 21.2), 130.22, 127.87 (d, J = 5.8), 127.58, 126.33 (d,
J = 13.5), 118.35 (d, J = 27.7), 63.60, 55.70, 53.61, 47.37, 33.26,
33.07 (d, J = 12.2), 33.02 (d, J = 12.9), 30.41 (d, J = 16.7), 29.26 (d,
J = 7.7), 29.23 (d, J = 7.7), 27.76 (d, v = 6.4), 27.49 (d, J = 8.4),
27.34, 26.84, 20.47, 19.89, 12.69, 10.1. 31P NMR (CD2Cl2) d: 4.78.
4.6. (4S,7R)-7,8,8-Trimethyl-1-(2-diphenylphosphino-6-
methoxyphenyl)-4,5,6,7-tetrahydro-4,7-methano-1H-indazole
3a
HMRS (ESI) calcd for:
493.3349.
C
31H46N2OP (M+H)+ 493.3342, found:
Prepared from 2a (722 mg, 2 mmol) and chloro-diphenylphos-
4.10. (4S,7R)-7,8,8-Trimethyl-1-[2-(di-o-tolylphosphino)-6-
methoxyphenyl]-4,5,6,7-tetrahydro-4,7-methano-1H-indazole
5a
phine (441 mg, 2 mmol). Yield 548 mg, (54%). ½a D21
ꢂ
¼ ꢀ3:7 (c 0.5,
CH2Cl2). 1H NMR (300 MHz, CDCl3) d 7.29–7.25 (m, 12H), 6.85
(dd, J = 1.5, J = 8.3, 1H), 6.81 (ddd, J = 1.5, J = 6.4, J = 7.9, 1H), 3.55
(s, 3H), 2.72 (d, J = 3.8, 1H), 1.99 (tdd, J = 3.9, J = 9.4, J = 11.8, 1H),
1.66 (ddd, J = 3.7, J = 9.4, J = 12.0, 1H), 1.32 (br m, 1H), 1.12 (ddd,
J = 3.5, J = 9.0, J = 12.1, 1H), 0.85 (s, 3H), 0.81 (s, 3H), 0.68 (s, 3H).
31P NMR (CDCl3) d -3.00. HMRS (ESI) calcd for: C30H32N2OP
(M+H)+ 467.2247, found: 467.2251.
Prepared from 2a (722 mg, 2 mmol) and chloro-di-o-tolylphos-
phine (497 mg, 2 mmol). Yield 524 mg (52%). ½a D22
¼ ꢀ13:2 13.2 (c
ꢂ
0.5, CD2Cl2). 1H NMR (400 MHz, CD2Cl2) d: 7.23 (dd, J = 7.8, J = 1.4,
1H), 6.99–7.21 (m, 7H), 6.86 (dd, J = 8.3, J = 1.5, 1H), 6.74 (ddd,
J = 7.9, J = 6.4, J = 1.6, 1H), 6.67–72 (m, 2H), 3.55 (s, 3H), 2.71 (d,
J = 3.8), 2.33 (d, J = 0.9, 6H), 1.99 (ddt, J = 11.7, J = 9.4, J = 3.9,
1H), 1.67 (ddd, J = 12.0, J = 9.4, J = 3.7, 1H), 1.03–1.35 (m, 2H),
0.83 (s, 3H), 0.80 (s, 3H), 0.65 (s, 3H). 13C NMR (CD2Cl2) d:
156.02, 143.06, 142.72, 138.16 (d, J = 11.6), 135.29 (d, J = 11.6),
135.26 (d, J = 10.9), 133.19, 132.69, 130.51 (d, J = 5.2), 130.37,
129.30, 128.99, 128.83 (d, J = 7.1), 126.58 (d, J = 16.1), 126.58,
117.40 (d, J = 26.4), 63.81, 55.64, 53.23, 47.94, 32.28, 28.05,
21.42, 21.13, 20.42, 19.84, 10.16. 31P NMR (CD2Cl2) d ꢀ19.66.
4.7. (4S,7R)-3,7,8,8-Tetramethyl-1-(2-diphenylphosphino-6-
methoxyphenyl)-4,5,6,7-tetrahydro-4,7-methano-1H-indazole
3b
Prepared from 2b (751 mg, 2 mmol) and chloro-diphenylphos-
phine (441 mg, 2 mmol). Yield 532 mg (53%). ½a D22
¼ þ7:5 (c 0.5,
ꢂ
CH2Cl2). 1H NMR (400 MHz, CDCl3) d 7.29–7.25 (m 11H), 6.84 (dd,
J = 1.5, J = 8.3, 1H), 6.79 (ddd, J = 1.5, J = 6.4, J = 7.9, 1H), 3.55 (s,
3H), 2.65 (d, J = 3.8, 1H), 2.18 (s, 3H), 1.98–1.92 (m, 1H), 1.63 (ddd,
J = 3.7, J = 9.4, J = 12.0, 1H), 1.30–1.35 (m, 1H), 1.09 (ddd, J = 3.5,
J = 9.0, J = 12.1, 1H), 0.83 (s, 3H), 0.80 (s, 3H), 0.69 (s, 3H). 13C NMR
(CD2Cl2) d 153.21, 152.85 (d, J = 9.1), 140.59, 138.04 (d, J = 12.8),
136.21 (d, J = 11.9), 136.19 (d, J = 11.9), 132.98 (d, J = 20.1), 128.76,
128.16, 127.80 (d, J = 7.3), 127.48 (d, J = 6.4), 126.36, 124.75 (d,
J = 15.5), 115.65 (d, J = 25.6), 62.39, 54.41, 52.54, 46.20, 32.07,
26.61, 19.30, 18.73, 11.49, 9.12. 31P NMR (CDCl3) d ꢀ3.05. HMRS
(ESI) calcd for: C31H34N2OP (M+H)+ 481.2403, found: 481.2400.
HMRS (ESI) calcd for:
495.2566.
C
32H36N2OP (M+H)+ 495.2560, found:
4.11. (4S,7R)-3,7,8,8-Tetramethyl-1-[2-(di-o-tolylphosphino)-6-
methoxyphenyl)-4,5,67-tetrahydro-4,7-methano-1H-indazole
5b
Prepared from 2b (751 mg, 2 mmol) and chloro-di-o-tolylphos-
phine (497 mg, 2 mmol). Yield 560 mg (66%). ½a D22
¼ ꢀ0:55 (c 1,
ꢂ
ethyl acetate). 1H NMR (400 MHz, CD2Cl2) d: 7.21 (dd, J = 7.8,
J = 1.4, 1H), 7.13–7.19 (m, 4H), 6.99–7.05 (m, 2H), 6.84 (dd,
J = 8.4, J = 1.6, 1H), 6.74 (ddd, J = 7.8, J = 6.4, J = 1.4, 1H), 6.67–6.72
(m, 2H), 3.55 (s, 3H), 2.65 (d, J = 3.8), 2.31 (m, 6H), 2.11 (s, 3H),
1.98 (ddt, J = 11.6, J = 9.4, J = 3.8, 1H), 1.65 (ddd, J = 12.0, J = 9.4,
J = 3.6, 1H), 1.02–1.35 (m, 2H), 0.80 (s, 3H), 0.79 (s, 3H), 0.67 (s,
3H). 13C NMR (CD2Cl2) d: 156.47, 142.83 (d, J = 25.8), 141.70,
137.72 (d, J = 11.6) 135.31 (d, J = 11.6), 135.29 (d, J = 11.6),
133.14, 130.45 (d, J = 4.5), 130.42, 129.22, 128.82, 128.73, 127.70,
126.55 (d, J = 16.1), 126.52, 117.30 (d, J = 27.7), 62.36, 55.54,
53.62, 47.33, 32.24, 27.74, 21.37, 21.09, 20.42, 19.85, 12.65,
4.8. (4S,7R)-7,8,8-Trimethyl-1-(2-dicyclohexylphosphino-6-
methoxyphenyl)-4,5,6,7-tetrahydro-4,7-methano-1H-indazole
4a
Prepared from 2a (722 mg, 2 mmol) and chloro-dicyclohexyl-
phosphine (465 mg, 2 mmol). Yield 560 mg (56%). ½a D23
¼ þ4:2 (c
ꢂ
0.5, CH2Cl2). 1H NMR (400 MHz, CD2Cl2) d 7.23 (dd, J = 7.7, J = 0.8,
1H), 7.12 (s, 1H), 7.04 (ddd, J = 7.7, J = 5.3, J = 1.5, 1H), 7.01 (dd,
J = 7.7, J = 1.3, 1H), 3.71 (s, 3H), 2.71 (d, J = 3.8, 1H), 2.00 (ddt,
J = 11.7, J = 9.4, J = 3.9, 1H), 1.68, (ddd, J = 11.9, J = 9.4, J = 3.8, 1H),
1.26 (qt, J = 12.6, J = 3.2, 1H), 0.85–1.92 (m, 23H), 0.80 (s, 6H), 0.66
(s, 3H). 13C NMR (CD2Cl2) d: 155.98, 153.58 (d, J = 10.3), 137.56 (d,
J = 20.6), 132.56, 130.15, 128.86, 127.91 (d, J = 5.8), 126.39 (d,
J = 13.5), 118.43 (d, J = 27.7), 63.76, 55.79, 53.20, 47.95, 33.30,
33.08 (d, J = 12.2), 33.04, (d, J = 12.2), 30.41 (d, J = 16.7), 29.28 (d,
J = 7.1), 29.27 (d, J = 7.1), 28.08, 27.64 (d, J = 12.9), 27.40 (d, J = 7.7),
26.85, 20.46, 19.85, 10.15. 31P NMR (CD2Cl2) d 5.08. HMRS (ESI) calcd
for: C30H44N2OP (M+H)+ 479.3186, found: 479.3190.
10.16. 31P NMR (CD2Cl2)
33H38N2OP (M+H)+ 509.2716, found: 509.2721.
d
ꢀ19.70. HMRS (ESI) calcd for:
C
4.12. (4S,7R)-7,8,8-Trimethyl-1-[2-bis(3,5-
ditrifluoromethylphenyl)phosphino-6-methoxyphenyl]-4,5,6,7-
tetrahydro-4,7-methano-1H-indazole 6a
Prepared from 2a and chloro-bis(3,5-ditrifluoromethylphe-
nyl)phosphine (985 mg, 2 mmol). Yield 654 mg (65%).

1940
I. Ilaldinov et al. / Tetrahedron: Asymmetry 22 (2011) 1936–1941
½
a 2D2
ꢂ
¼ ꢀ8:4 (c 0.5, CD2Cl2). 1H NMR (300 MHz, CD2Cl2) d: 7.88 (s,
4.17. [(4S,7R)-3,7,8,8-Tetramethyl-1-(2-di-o-tolylphosphino-6-
methoxyphenyl)-4,5,6,7-tetrahydro-4,7-methano-1H–indazole]
(1,5-cyclooctadiene) iridium(I) tetrafluoroborate
2H), 7.72 (dd, J = 6.6, J = 1.7, 4H), 7.38 (dd, J = 7.8, J = 1.7, 1H), 7.19
(s, 1H), 6.92 (dd, J = 9.3, J = 1.7, 1H), 6.85 (td, J = 7.6, J = 1.7, 1H),
3.62 (s, 3H), 2.72 (d, J = 3.7, 1H), 2.01 (ddt, J = 11.7, J = 9.5,
J = 3.9, 1H), 1.70 (ddd, J = 12.0, J = 9.5, J = 3.7, 1H), 1.27–1.36 (m,
1H), 1.09 (ddd, J = 12.0, J = 8.8, J = 3.4, 1H), 0.83 (s, 3H), 0.81(s,
Prepared from 5b (254 mg, 0.5 mmol) following the general
procedure as an orange solid. Yield 320 mg (71%). HMRS (ESI) calcd
for: C43H49IrN2OP (M⁄+) 831.3179, found: 831.3179.
3H), 0.65 (s, 3H). 13C NMR (CD2Cl2)
d 156.21, 154.82 (d,
J = 11.0), 139.84 (d, J = 18.3), 139.79 (d, J = 18.3), 137.97 (d,
J = 17.4), 134.68 (d, J = 11.9), 133.76 (d, J = 21.0), 133.73 (d,
J = 19.2), 132.55 (q, J = 33.5), 132.49 (q, J = 33.5), 130.84,
129.75(d, J = 8.2), 129.51, 126.50 (d, J = 18.3), 124.01 (sept,
J = 3.8), 123.50 (q, J = 272.9), 117.03 (d, J = 27.4), 64.03, 55.90,
53.39, 47.93, 33.20, 27.99, 20.37, 19.81, 10.04. 31P NMR (CD2Cl2)
d ꢀ2.66. HMRS (ESI) calcd for: C34H28F12N2OP (M+H)+ 739.1742,
found: 739.1755.
4.18. {(4S,7R)-7,8,8-Trimethyl-1-[2-bis(3,5-
ditrifluoromethylphenyl)phosphino-6-methoxyphenyl]-4,5,6,7-
tetrahydro-4,7-methano-1H-indazole} (1,5-cyclooctadiene)
iridium(I) tetrafluoroborate
Prepared from 6a (369 mg, 0.5 mmol) following the general
procedure as an orange solid. Yield (451 mg, 79%). HMRS (ESI)
calcd for: C42H39F12IrN2OP (M⁄+) 1037.2209, found: 1037.2222.
4.13. (4S,7R)-3,7,8,8-Tetramethyl-1-[2-bis(3,5-
ditrifluoromethylphenyl)phosphino-6-methoxyphenyl]-4,5,6,7-
tetrahydro-4,7-methano-1H-indazole 6b
4.19. General hydrogenation procedure
An aliquot (200 ll) of the Ir-complex solution in CH2Cl2 (0.05 M,
0.01 mmol) was added to a solution of 1 mmol substrate and
198 mg of tetradecane in 4 ml of CH2Cl2 under argon. The cata-
lyst–substrate–tetradecane solution was transferred to the iner-
tized autoclave charged with NaBArF (0.015 mmol), then 1 ml of
water was added and the autoclave pressurized with hydrogen to
40 bar and stirred for 24 h. After releasing the hydrogen, the organ-
ic layer was dried over MgSO4, passed through a short pad of silica
gel and used directly for chiral HPLC analysis to measure the enan-
tiomeric excess and for GC analysis to measure the conversion.
Prepared from 2b (751 mg, 2 mmol) and chloro-bis(3,5-ditri-
fluoromethylphenyl)phosphine (985 mg, 2 mmol). Yield 733 mg
(73%). ½a 2D3
ꢂ
¼ ꢀ13 (c 0.5, CD2Cl2); 1H NMR (400 MHz, CD2Cl2) d:
7.86 (sept, J = 0.7, 2H), 7.71 (dd, J = 6.6, J = 1.7, 4H), 7.36 (dd,
J = 7.9, J = 1.6, 1H), 6.90 (dd, J = 9.2, J = 1.6, 1H), 6.83 (td, J = 7.6,
J = 1.7, 1H), 3.61 (s, 3H), 2.65 (d, J = 3.7, 1H), 2.10 (s, 3H), 1.98
(ddt, J = 11.7, J = 9.4, J = 3.9, 1H), 1.67 (ddd, J = 12.0, J = 9.4,
J = 3.7, 1H), 1.27–1.35 (m, 1H), 1.03–1.11 (m, 1H), 1.06 (s, 3H),
0.81 (s, 3H), 0.79 (s, 3H), 0.66 (s, 3H). 13C NMR (CD2Cl2) d:
156.71, 154.70 (d, J = 11.0), 142.38, 139.96 (d, J = 19.2),
139.94(d, J = 18.3), 138.01 (d, J = 18.3), 133.76 (d, J = 21.0),
133.74 (d, J = 20.1), 132.56 (q, J = 33.5), 132.50(q, J = 33.5),
132.26, 129.72 (d, J = 7.3), 128.37, 126.55 (d, J = 18.3), 123.98 (p,
J = 3.7), 123.53(q, J = 272.9), 116.98 (d, J = 27.4), 63.95, 55.84,
53.87, 47.39, 33.20, 27.74, 20.43, 19.89, 12.63, 10.09. 31P NMR
(CD2Cl2) d ꢀ2.62. HMRS (ESI) calcd for: C35H28F12N2OP (M+H)+
753.1899, found: 753.1911.
4.20. X-ray crystal structure analysis
Single crystals of complex [Ir(4a)(COD)]BF4 were grown by slow
diffusion of diethyl ether into a saturated solution in CH2Cl2.
Data were collected on a STOE IPDS II diffractometer using
graphite-monochromated Mo K
a radiation. The structure was
solved by direct methods (SIR2004)42 and refined by full-matrix
least-squares procedures on F2 (SHELXL-97).43 XP (Bruker AXS)
was used for graphical representation.
Crystal data for [Ir(4a)(COD)]BF4ꢃ0.5CH2Cl2: C38.5H56BClF4Ir-
4.14. General procedure for the preparation of iridium
complexes
N2OP, M = 908.28, crystal size: 0.50 ꢁ 0.22 ꢁ 0.15 mm, orange
crystal,
monoclinic,
space
group
C2,
a = 16.8787(4),
b = 11.8658(3), c = 20.4194(5) Å, b = 111.142(2)°, V = 3814.3(2) Å3,
In a sealed Schlenk tube, the [Ir(COD)Cl]2 (168 mg, 0.25 mmol)
and the ligand (0.5 mmol) in 10 ml of CH2Cl2 was heated at 50 °C
for 3 h. The resulting deep red solution was allowed to cool to
ambient temperature and a solution of AgBF4 (97 mg, 0.5 mmol)
in 2 ml of CH2Cl2 was then added at once. The precipitated AgCl
was filtered off and the solvent evaporated. The product was crys-
tallized from CH2Cl2/diethyl ether.
T = 150 K, Z = 4,
q
calcd = 1.582 g cmꢀ3 = 3.665 mmꢀ1, absorption
, l
correction: numerical (max. and min. transmission: 0.6146 and
0.3355), 32071 reflections measured, 9110 independent reflections
(Rint = 0.0263), final R values (I > 2r(I)): R1 = 0.0219, wR2 = 0.0499,
final
R values (all data): R1 = 0.0252, wR2 = 0.0504, GOF on
F2 = 0.961, 438 parameters.
CCDC 840596 contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.
4.15. [(4S,7R)-7,8,8-Trimethyl-1-(2-diphenylphosphino-6-
methoxyphenyl)-4,5,6,7-tetrahydro-4,7-methano-1H-indazole]
(1,5-cyclooctadiene) iridium(I) tetrafluoroborate
Acknowledgment
Prepared from 3a (233 mg, 0.5 mmol) following the general
procedure as an orange solid. Yield 295 mg (68%). HMRS (ESI) calcd
for: C38H43IrN2OP (M⁄+) 765.2713, found: 765.2718.
Financial support from the Government of Tatarstan (fond ‘Alg-
arysh’) is gratefully acknowledged.
4.16. [(4S,7R)-7,8,8-Trimethyl-1-(2-dicyclohexylphosphino-6-
methoxyphenyl)-4,5,6,7-tetrahydro-4,7-methano-1H-indazole
(1,5-cyclooctadiene) iridium(I) tetrafluoroborate
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