Iridium catalysts with Chiral bicyclic pyridine-phosphane ligands for the asymmetric hydrogenation of olefins

Article abstract of DOI:10.1002/ejoc.201301141

New bicyclic pyridine-phosphane ligands were prepared, and their iridium complexes were evaluated in asymmetric hydrogenation of trisubstituted olefins with non-coordinating and weakly coordinating substituents. The iridium catalysts showed high reactivity and enantioselectivity for both types of olefins. New pyridine-derived N,P-chelated iridium catalysts were prepared and evaluated in the asymmetric hydrogenation of trisubstituted olefins. High conversions and enantioselectivities were obtained. Copyright

Full text of DOI:10.1002/ejoc.201301141

FULL PAPER
DOI: 10.1002/ejoc.201301141
Iridium Catalysts with Chiral Bicyclic Pyridine–Phosphane Ligands for the
Asymmetric Hydrogenation of Olefins
Xu Quan,[a] Vijay Singh Parihar,[b] Milan Bera,[c] and Pher G. Andersson*[b,c]
Keywords: Iridium / N,P ligands / Homogeneous catalysis / Hydrogenation / Asymmetric catalysis
New bicyclic pyridine–phosphane ligands were prepared,
and their iridium complexes were evaluated in asymmetric
hydrogenation of trisubstituted olefins with non-coordinating
and weakly coordinating substituents. The iridium catalysts
showed high reactivity and enantioselectivity for both types
of olefins.
Introduction
The asymmetric hydrogenation of olefins with chiral irid-
ium N,P complexes is one of the most efficient and simple
methods to create a chiral center.[1] It overcomes the major
problem that P,P-ligated rhodium and ruthenium catalysts
have in asymmetric hydrogenation, i.e., that these catalysts
normally require the substrates to have a good coordinating
group next to the C=C double bond. Since Pfaltz and co-
workers first introduced chiral N,P complexes based on
Crabtree’s catalyst,[2] [(Cy3P)(pyridine)Ir(COD)]PF6 (Cy =
cyclohexyl, COD = cyclooctadiene), to hydrogenate un-
functionalized olefins,[3] a number of N,P-ligands have been
reported for use in the iridium-catalyzed asymmetric hydro-
genation of alkenes with non-coordinating and weakly co-
ordinating substituents.[4,5] Chiral N,P-ligands have also
been successfully used in several other chemical transforma-
tions, such as allylic substitution and C–C coupling reac-
tions.[6]
During the last few years, chiral bicyclic N,P complexes
of iridium based on various heterocyclic scaffolds (Figure 1,
A–C) have been developed by our group,[7,8] and have been
used successfully in reactions including asymmetric hydro-
genation, Heck coupling,[9] and isomerization of allylic
alcohols.[10]
The nitrogen-containing moiety of the N,P-ligands is a
heterocycle such as a thiazole or an imidazole, and it acts
as an N-donor bonded to the iridium metal. Due to the
Figure 1. Examples of chiral N,P-ligands used in our group.
different electronic properties of the N-donors used, the
heterocyclic scaffolds play an important role in tuning the
reactivities of the catalysts. The linker between the back-
bone and phosphorus can also influence the outcome of the
hydrogenation reaction. For example, complex A, a thiazole
iridium complex with an N-linker (Figure 1) hydrogenated
fluorinated olefins with higher reactivity and with less C–
F-bond cleavage.[7e] Pyridine is one of the most common
heterocycles, and its use as an N-donor can be envisioned.
In an early report, Pfaltz and co-workers prepared a series
of iridium catalysts with pyridine-derived ligands and an
oxygen linker.[11] These iridium complexes were very reac-
tive and enantioselective in the hydrogenation of olefins.
However, N,P-ligands that have an oxygen linker (O–P) are
normally less stable, and this limits their use. N,P-ligands
with carbon–phosphorus bonds (C–P) are more stable,
which makes them more widely applicable. We envisioned
pyridine-derived N,P-ligands with a carbon linker, still
maintaining the backbone structure that we had developed
earlier. In this paper, we report the preparation of new pyr-
idine-bicyclic N,P-ligands and the evaluation of their irid-
ium complexes in the asymmetric hydrogenation of trisub-
stituted olefins.
[a] Department of Chemistry – BMC, Uppsala University,
Husargatan 3, Box 576, 75123 Uppsala, Sweden
[b] Department of Organic Chemistry, Stockholm University, The
Arrhenius Laboratory,
10691 Stockholm, Sweden
E-mail: phera@organ.su.se
http://www.organ.su.se/pga/index.html
[c] School of Chemistry and Physics, University of KwaZulu-
Natal,
Results and Discussion
As shown in Scheme 1, iridium complexes 7a–7d were
prepared from the corresponding bicyclic pyridine deriva-
tives, 1a and 1b. Compounds 1a and 1b were lithiated and
Durban, South Africa
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201301141.
140
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Iridium Catalysts with Chiral Bicyclic Ligands
treated with dimethyl carbonate to give racemic esters 2a
trans-α-Methylstilbene (Table 1, entry 1) gave full conver-
and 2b, which were resolved by preparative HPLC sion to the product with 99% ee using 7b. With 7a, sub-
(Chiralcel OD-column, 20ϫ250 mm). Optically pure pyr- strates 9 and 10 (Table 1, entries 2 and 3) were fully con-
idine esters were further reduced to alcohols 3a and 3b by verted into the corresponding products with 93 and 91%
DIBAL-H (diisobutylaluminium hydride), and the phenyl ee, respectively. With functionalized olefins, 7a and 7b per-
groups were introduced by Suzuki coupling reactions. formed better than 7c and 7d. Complex 7a gave the best
Alcohols 4a and 4b were converted into the corresponding results for substituted functionalized olefins 11 and 13 as
iodinated compounds (i.e., 5a and 5b) by treatment with well (Table 1, entries 4 and 6). β-Substituted allylic alcohol
iodine, triphenylphosphane, and a catalytic amount of imid- 12 (Table 1, entry 5) was the only exception, and this sub-
azole. Borane-protected N,P-ligands 6a–6d were obtained strate was hydrogenated by 7c with full conversion to the
by substitution with in-situ-prepared Ar2P(BH3)Li (Ar = product with 99% ee. The difference in reactivity between
Ph or o-Tol). Chiral HPLC confirmed that no racemization the five- and six-membered-ring catalysts was obvious when
occurred during any of the manipulations with the chiral α-methylcinnamic ester 14 was used as a substrate: 7c and
compounds. The protecting group was removed by treat- 7d gave less than 5% conversion, whereas 99% conversion
ment with diethylamine. The free N,P-ligands were sub- was achieved using 7b. For the other two α-functionalized
sequently treated with [Ir(COD)Cl]2 to form the iridium olefins (Table 1, entries 8 and 9), full conversions were
complexes, and anion exchange was achieved by addition achieved using 7b to give the products with 75 and 76% ee.
of NaBArF·3H2O to give iridium N,P complexes 7a–7d.
We have previously developed a selectivity model to ra-
tionalize and predict the absolute configuration of the prod-
uct of hydrogenation.[12] The olefin coordinates trans to
phosphorus, which is in agreement with other proposed
mechanisms.[13] As shown in Figure 2a, the phenyl group
on the pyridine ring occupies quadrant 3, which is the most
hindered quadrant. Quadrants 1 and 4 are the least hin-
dered sites, and are trans to each other. The ligand partly
occupies quadrant 2, and its steric bulk makes this quad-
rant semi-hindered. In Figure 2b, a simplified model, using
trans-α-methylstilbene as an example, the smallest substitu-
ent, hydrogen, should be positioned in the most hindered
quadrant 3, and the most sterically demanding substituents,
the two phenyl rings, will be located in quadrants 1 and 4.
This selectivity model predicts the stereochemical outcome
of the hydrogenation reaction (Figure 2, c), which is in
agreement with the experimental results. In the case of con-
jugated α,β-unsaturated esters, electronic effects should be
taken into consideration. The hydrogenation product of
trans-α-methyl cinnamate (Table 1, entry 7) gave the (R)-
mismatched configuration with the selectivity model, which
is opposite to what was observed experimentally. This is a
Scheme 1. Preparation of iridium complexes 7a–7d. Reaction con-
ditions: a) diisopropylamine, BuLi, (MeO)2CO, Et2O, –30 °C then
room temp.; b) preparative HPLC (Chiralcel OD-column,
20ϫ250 mm; hexane/2-propanol, 99:1; 3 mLmin–1); c) DIBAL-H,
Et2O, –78 °C; d) PhB(OH)2, DPPF (1,1Ј-bis(diphenylphosphanyl)-
ferrocene), PdCl2, K2CO3, toluene, H2O, reflux; e) I2, PPh3, imid-
azole, CH2Cl2, room temp.; f) Ar2P(BH3)H, BuLi, THF, –78 °C;
g) diethylamine, room temp.; h) [Ir(COD)Cl]2, CH2Cl2, room
temp.; i) NaBArF·3H2O, H2O.
The newly prepared iridium complexes (i.e., 7a–7d) were
evaluated in the asymmetric hydrogenation of trisubstituted
olefins. As shown in Table 1, complexes 7a and 7b, contain-
ing a five-membered ring, generally showed better reactivity
and selectivity. For the unfunctionalized substrates (Table 1,
entries 1–3), complexes 7a and 7b gave higher conversions
and better enantioselectivities. Complexes 7c and 7d, with
similar ligand structures but based on six-membered rings,
gave significantly lower reactivity or selectivity.
Figure 2. Selectivity model used to predict the absolute configura-
tion.
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141

X. Quan, V. S. Parihar, M. Bera, P. G. Andersson
FULL PAPER
Table 1. Asymmetric hydrogenation of trisubstituted olefins with 7a–7d.
common phenomenon with some α-methyl cinnamate sub-
strates, and is probably due to a strong electronic effect that
prevents hydride insertion at the electron-rich terminus on
Experimental Section
General Methods: All reagents used were commercially available.
CH2C2 was freshly distilled from CaH2 under nitrogen. THF was
the C=C double bond, and leads to the formation of a steri- freshly distilled from sodium benzophenone under nitrogen. Chro-
matographic separations were performed on Kieselgel 60H silica
gel (particle size: 0.063–0.100 mm). Thin layer chromatography
(TLC) was performed on aluminum plates coated with Kieselgel 60
(0.20 mm, UV254), and plates were visualized under ultraviolet
light (ν = 254 nm), or by staining with ethanolic phosphomolybdic
acid and heating. 1H NMR spectra were recorded at 500 or
300 MHz in CDCl3, and were referenced internally to the residual
cally disfavored but electronically favored product.
Conclusions
In this study, bicyclic pyridine–phosphane ligands were
prepared, and their iridium complexes were evaluated as CHCl3 peak (δ = 7.26 ppm). 13C NMR spectra were recorded at
100 or 75 MHz in CDCl3, and were referenced to the central peak
of CDCl3 (δ = 77.0 ppm). 31P NMR spectra were recorded at
121.47 MHz in CDCl3. Chemical shifts are reported in ppm (δ
scale). Enantiomeric excesses were determined either using HPLC
with a chiral column and a diode array detector at 220 and 254 nm,
or by GC with a chiral column and an MS detector. Optical rota-
tions were recorded with a thermostatted polarimeter using a so-
dium lamp (589 nm) and a 1.0 dm cell. HRMS (ESI) data were
obtained using a Bruker microTOF-Q II instrument operating at
ambient temperature. IR spectra were measured using a Perkin–
Elmer FTIR instrument.
catalysts for the asymmetric hydrogenation of various ole-
fins. Good conversions and enantioselectivities were ob-
tained. In most cases, five-membered-ring-containing irid-
ium complexes 7a and 7b were better catalysts than six-
membered-ring-containing complexes 7c and 7d. We found
that these catalysts gave results competitive with those ob-
tained with other heterocyclic iridium complexes. The car-
bon–phosphorus bond in these ligands makes them rela-
tively stable and allows their isolation and their “in situ”
use for other reactions.
142
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Eur. J. Org. Chem. 2014, 140–146

Iridium Catalysts with Chiral Bicyclic Ligands
Preparation of Carboxylated Pyridine Derivitives 2a and 2b: nBuLi
(2.5 m in hexane; 2.0 equiv.) was added to a solution of 1a or 1b
(1.0 mmol) and diisopropylamine (1.0 mmol) in dry Et2O (20 mL)
at –30 °C under an argon atmosphere. The mixture was stirred at
–30 °C for 1 h, and then dimethyl carbonate (1.1 mmol) was added.
The solution was stirred at –30 °C for 1 h, then it was allowed to
warm slowly to room temperature and stirred overnight. The reac-
tion mixture was quenched by the addition of ammonium chloride
(saturated aqueous solution), and the aqueous phase was extracted
with Et2O. The combined organic extracts were washed further
with brine, dried with MgSO4, and filtered. The solvent was re-
moved under vacuum, and the residue was purified by flash column
chromatography (pentane/ethyl acetate = 10:1) to give pure 2a or
2b. The racemic mixtures were separated by preparative HPLC
(Chiralcel OD-column, 20ϫ250 mm; hexane/2-propanol, 99.5:0.5;
3 mLmin–1).
(75 MHz, CDCl3): δ = 160.3, 147.5, 139.9, 131.4, 121.9, 67.0, 42.4,
28.2, 25.8, 21.2 ppm. IR (neat): ν = 2940, 1568, 1418, 1237, 1167,
˜
1033, 875, 8181 cm–1. HRMS (ESI): calcd. for C9H11ClNO [M +
H]+ 184.0529; found 184.0524.
Preparation of 4a and 4b: Alcohol 3a or 3b (1.0 mmol), PhB-
(OH)2 (1.5 mmol), and DPPF·PdCl2·CH2Cl2 (0.1 mmol) were
added to toluene (20 mL), and then K2CO3 (2.0 mmol) and H2O
(1 mL) were added. The mixture was heated to reflux under an
argon atmosphere overnight. After the reaction was complete, the
reaction mixture was cooled to room temperature and extracted
with diethyl ether. The combined organic extracts were washed with
brine, dried with MgSO4, and filtered. The solvent was removed
under vacuum, and the residue was purified by flash column
chromatography (pentane/ethyl acetate = 5:1) to give the pure prod-
uct.
(S)-(2-Phenyl-6,7-dihydro-5H-cyclopenta[b]pyridin-7-yl)methanol
(4a): Obtained in 78% yield. [α]2D5 = 29.3 (c = 1.00, CHCl3). 1H
NMR (500 MHz, CDCl3): δ = 7.94 (d, J = 8.0 Hz, 2 H), 7.54 (m,
2 H), 7.45 (m, 2 H), 7.38 (m, 1 H), 4.98 (br. s, 1 H), 3.99 (m, 1 H),
3.86 (t, J = 10 Hz, 1 H), 3.48 (m, 1 H), 2.93 (dd, J = 5.5, 9.5 Hz,
2 H), 2.28 (m, 1 H), 1.71 (m, 1 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 167.5, 155.2, 139.1, 135.7, 133.2, 128.7, 126.7, 118.9,
Methyl (S)-2-Chloro-6,7-Dihydro-5H-cyclopenta[b]pyridine-7-carb-
oxylate [(S)-2a]: Obtained in 86% yield. [α]2D5 = 21.1 (c = 1, CHCl3).
1H NMR (500 MHz, CDCl3): δ = 7.50 (d, J = 8.0 Hz, 1 H), 7.15
(d, J = 8.0 Hz, 1 H), 4.09 (dd, J = 6.0, 8.5 Hz, 1 H), 3.75 (s, 3 H),
3.11 (m,1 H), 2.90 (m, 1 H), 2.45 (m, 2 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 173.3, 162.3, 150.0, 136.5, 135.3, 122.9, 52.5,
51.0, 29.2, 28.2 ppm. IR (neat): ν = 1731, 1568, 1421, 1164,
˜
823 cm–1. HRMS (ESI): calcd. for C10H11ClNO2 [M + H]+
212.0478; found 212.0473.
66.6, 46.1, 29.3, 26.1 ppm. IR (neat): ν = 2941, 1586, 1572, 1431,
˜
1226, 1025, 833, 747, 692 cm–1. HRMS (ESI): calcd. for C15H16NO
[M + H]+ 226.1232; found 226.1226.
Methyl (S)-2-Chloro-5,6,7,8-tetrahydroquinoline-8-carboxylate (2b):
Obtained in 90% yield. [α]2D5 = 26.34 (c = 0.2, CHCl3). H NMR
1
(S)-(2-Phenyl-5,6,7,8-tetrahydroquinolin-8-yl)methanol (4b): Ob-
tained in 80% yield. [α]2D5 = 27.7 (c = 1.00, CHCl3). 1H NMR
(500 MHz, CDCl3): δ = 7.86 (d, J = 7 Hz, 2 H), 7.58–7.50 (m, 4
H), 7.38 (m, 1 H), 3.82–3.87 (m, 2 H), 3.14 (m, 1 H), 2.82–2.78 (m,
2 H), 2.03–1.96 (m, 2 H), 1.77 (m, 1 H), 1.45 (m, 1 H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 160.1, 154.1, 139.1, 138.3, 131.1,
129.0, 126.8, 118.7, 100.3, 67.9, 42.1, 28.7, 26.4, 21.9 ppm. IR
(500 MHz, CDCl3): δ = 7.41 (t, J = 8 Hz, 1 H), 7.16 (d, J = 8 Hz,
1 H), 3.98 (m, 3 H), 3.76 (s, 3 H), 2.85 (m, 1 H), 2.76 (m, 1 H),
2.25 (m, 1 H), 2.12 (m, 1 H), 1.95 (m, 1 H), 1.83 (m, 1 H) ppm.
13C NMR (75 MHz, CDCl3): δ = 174.1, 154.2, 148.2, 140.0, 131.5,
122.8, 52.3, 47.8, 27.7, 26.7, 19.9 ppm. IR (neat): ν = 2948, 1732,
˜
1566, 1442, 1430, 1161, 1135, 1003, 814 cm–1. HRMS (ESI): calcd.
for C11H12ClNO2Na [M + Na]+ 248.0454; found 248.0449.
(neat): ν = 3352, 2935, 1563, 1442, 1428, 1137, 1032, 992, 870,
˜
8 3 7 c m – 1 . H R M S ( E S I ) : c a l c d . fo r C 1 6 H 1 8 N O [ M +
H]+ 240.1388; found 240.1383.
Preparation of Pyridine Alcohols 3a and 3b: DIBAL-H (1.0 m in
THF; 2.5 equiv.) was added dropwise to a solution of ester 2a or
2b (1.0 mmol) in THF (10 mL), at –78 °C under an argon atmo-
sphere. After the addition was complete, the reaction mixture was
stirred at –78 °C for a further 2 h, and then it was allowed to warm
up to room temperature over 1 h. After the reaction was complete,
ammonium chloride (saturated aqueous solution) was added, and
the aqueous phase was extracted with dichloromethane. The com-
bined organic extracts were washed with brine, dried with MgSO4,
and filtered. The crude product was purified by flash column
chromatography (dichloromethane/methanol = 20:1) to give the
pure product.
Iodination of 4a and 4b: Iodine (3.0 mmol), triphenylphosphane
(3.0 mmol), and imidazole (3.0 mmol) were added to a solution of
compound 4a or 4b (1.0 mmol) in dry dichloromethane (15 mL).
The mixture was stirred at room temperature overnight. After the
reaction was complete, the mixture was diluted with dichlorometh-
ane and washed with sodium thiosulfate (saturated aqueous). The
separated organic phase was washed with brine, dried with MgSO4,
and filtered. The solvent was removed under vacuum, and the resi-
due was purified by flash column chromatography (pentane/diethyl
ether = 5:1) to give the pure product.
(S)-7-(Iodomethyl)-2-phenyl-6,7-dihydro-5H-cyclopenta[b]pyridine
(5a): Obtained in 87% yield. [α]2D5 = 18.4 (c = 1.00, CHCl3). 1H
NMR (500 MHz, CDCl3): δ = 8.01 (m, 2 H), 7.55 (m, 2 H), 7.47
(m, 2 H), 7.40 (m, 1 H), 3.89 (m, 1 H), 3.51 (m, 2 H), 2.95 (m, 2
H), 2.5 (m, 1 H), 1.96 (m, 1 H) ppm. 13C NMR (75 MHz, CDCl3):
δ = 164.9, 156.4, 139.9, 135.8, 133.6, 129.0, 128.9, 127.1, 119.2,
(S)-(2-Chloro-6,7-dihydro-5H-cyclopenta[b]pyridin-7-yl)methanol
1
(3a): Obtained in 87% yield. [α]2D5 = 8.2 (c = 1, CHCl3). H NMR
(500 MHz, CDCl3): δ = 7.45 (d, J = 8.0 Hz, 1 H), 7.10 (d, J =
8.0 Hz, 1 H), 3.90 (m, 1 H), 3.81 (dd, J = 7.5, 10.5 Hz, 1 H), 3.47
(br. s, 1 H), 3.35 (m, 1 H), 2.92 (m, 2 H), 2.28 (m, 1 H), 1.84 (m,
1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 167.3, 149.3, 136.3,
47.8, 31.5, 28.4, 12.3 ppm. IR (neat): ν = 1586, 1571, 1442, 1431,
135.1, 122.1, 65.5, 46.9, 28.9, 26.5 ppm. IR (neat): ν = 2940, 1568,
˜
˜
1163, 832, 765, 691 cm–1. HRMS (ESI): calcd. for C15H15IN [M +
H]+ 336.0249; found 336.0244.
1418, 1237, 1167, 1033, 875, 8181 cm–1. HRMS (ESI): calcd. for
C9H11ClNO [M + H]+ 184.0529; found 184.0524.
(S)-(2-Chloro-5,6,7,8-tetrahydroquinolin-8-yl)methanol (3b): Ob-
tained in 87% yield. [α]2D5.0 = 8.2 (c = 1.0, CHCl3). 1H NMR
(500 MHz, CDCl3): δ = 7.35 (d, J = 8.0 Hz, 1 H), 7.09 (d, J =
8.0 Hz, 1 H), 3.82–3.76 (m, 2 H), 2.99 (m, 1 H) 2.77–2.66 (m, 2 H),
1.98–1.91 (m, 2 H), 1.71 (m, 1 H), 1.47 (m, 1 H) ppm. 13C NMR
(S)-8-(Iodomethyl)-2-phenyl-5,6,7,8-tetrahydroquinoline (5b): Ob-
tained in 90% yield. [α]2D5 = 31.1 (c = 1.0, CHCl3). 1H NMR
(500 MHz, CDCl3): δ = 8.00 (d, J = 7.5 Hz, 2 H), 7.52 (d, J =
8 Hz, 1 H), 7.47–7.42 (m, 3 H), 7.39 (m, 1 H), 3.96 (dd, J = 3,
6.5 Hz, 1 H), 3.81 (t, J = 9 Hz, 1 H), 3.11 (m, 1 H), 2.80–2.77 (m,
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FULL PAPER
2 H), 2.09 (m, 1 H), 1.92–1.89 (m, 2 H), 1.81 (m, 1 H) ppm. 13C (c = 1.00, CHCl3). 1H NMR (300 MHz, CDCl3): δ = 8.29 (dd, J =
NMR (75 MHz, CDCl3): δ = 156.9, 154.7, 139.5, 137.8, 131.3, 8.1, 14.1 Hz, 1 H), 7.98 (m, 2 H), 7.82 (dd, J = 7.8, 12.3 Hz, 1 H),
128.8, 128.6, 126.9, 118.4, 42.6, 29.9, 29.2, 20.8, 14.9 ppm. IR 7.52–7.11 (m, 11 H), 3.88 (t, J = 15.6 Hz, 1 H), 3.11 (m, 1 H), 2.77
(neat): ν = 2937, 1558, 1459, 1448, 1178, 831, 758, 689 cm–1
.
(m, 2 H), 2.40 (m, 1 H), 2.24 (s, 3 H), 2.10 (s, 3 H), 1.87 (m, 2 H),
1.6801.57 (br. m, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ =
154.4, 142.9 (d, J = 4.2 Hz), 142.0 (d, J = 6.3 Hz), 138.0, 134.9,
132.4 (d, J = 12.0 Hz), 132.0 (d, J = 8.3 Hz), 131.8 (d, J = 8.3 Hz),
131.6 (d, J = 2.3 Hz), 131.0 (d, J = 2.3 Hz), 128.8, 126.8, 126.7,
˜
HRMS (ESI): calcd. for C16H17IN [M + H]+ 350.0406; found
350.0400.
Preparation of Borane-Protected N,P-Ligands 6a–6d: nBuLi (2.5 m
in hexane; 1.5 equiv.) was added to a solution of Ar2P(BH3)H (Ar
= Ph or o-Tol; 0.5 mmol) in dry THF (15 mL) at –78 °C under an
argon atmosphere. The solution was stirred for 10 min at –78 °C,
and then for a further 1 h at room temperature. Substrate 5a or
5b (0.4 mmol) was dissolved in THF, and the solution was added
dropwise to the reaction mixture at 0 °C. The resulting mixture was
stirred at 0 °C for a further 1 h. After the addition was complete,
the reaction mixture was allowed to warm to room temperature
and stirred overnight. When the reaction was complete, NaHCO3
(saturated aqueous solution) was added, and the aqueous phase
was extracted with dichloromethane. The combined organic ex-
tracts were washed with brine, dried with MgSO4, and filtered. The
solvent was removed under vacuum, and the residue was purified
by flash column chromatography (pentane/diethyl ether = 10:1) to
give the pure product.
126.53 (d, J = 1.5 Hz), 118.1, 37.3, 30.5, 29.9, 29.1, 21.9 (d, JCP
=
4.3 Hz), 20.6 ppm. 31P NMR: δ = 18.0 ppm. IR (neat): ν = 3057.
˜
2927, 2380, 1458, 1064, 909, 741 cm–1. HRMS (ESI): calcd. for
C30H34BNP [M + H]+ 449.2480; found 449.2440.
Preparation of Iridium Complexes 7a–7d: The borane-protected
N,P-ligand (1 mmol) was dissolved in Et2NH (10 mL for 1 mmol
of substrate), and the mixture was stirred at room temperature un-
der argon overnight. The Et2NH was removed under vacuum, the
residue was filtered through a short column of deactivated silica
gel (pentane/diethyl ether, 1:1), and then the solvent was removed.
The free N,P-ligand and [Ir(COD)Cl]2 were dissolved in dichloro-
methane under argon. This solution was heated to reflux for 1 h.
The mixture was allowed to cool to room temperature, and then
water and NaBArF·3H2O were added, and the resulting mixture
was stirred vigorously for 2 h at room temperature. The organic
phase was separated and washed with brine, dried with MgSO4,
and filtered. The solvent was removed under vacuum, and the resi-
due was purified by flash column chromatography (pentane/di-
chloromethane = 3: 2) to give the pure product.
(S)-7-[(Diphenylphosphanyl)methyl]-2-phenyl-6,7-dihydro-5H-cyclo-
penta[b]pyridine Borane Adduct (6a): Obtained in 91% yield. [α]2D5
1
= 17.5 (c = 1.00, CHCl3). H NMR (300 MHz, CDCl3): δ = 8.06
(d, J = 12.0 Hz, 2 H), 7.94 (m, 2 H), 7.78 (m, 2 H), 7.55–7.43 (m,
11 H), 3.61 (m 1 H), 3.46 (m, 1 H), 2.80 (m, 2 H), 2.43 (m, 1 H),
1.67 (m, 1 H), 1.4–0.6 (br. m, 3 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 166.3 (d, J = 13.6 Hz), 155.7, 139.7, 135.1, 132.9, 132.5
(d, J = 8.7 Hz), 131.3 (d, J = 2.7 Hz), 129.1, 128.9, 128.8, 128.7,
126.9, 118.6, 41.1, 33.0, 30.2 (d, J = 3.8 Hz), 29.1 ppm. 31P NMR:
Complex 7a: Obtained in 76% yield. [α]2D5 = 2.9 (c = 0.75, CHCl3).
1H NMR (300 MHz, CDCl3): δ = 7.71–7.43 (m, 27 H), 7.24–7.17
(m, 2 H), 4.35 (m, 2 H), 4.16 (m, 1 H), 3.06 (m, 2 H), 2.84 (m, 4
H), 2.22–1.61 (m, 8 H), 1.24 (m, 2 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 166.7 (d, J = 2.0 Hz), 161.9 (dd, J = 50.0 Hz), 160.4,
139.4, 138.3, 136.4, 134.9, 133.7, 132.5, 132.4, 132.1, 131.6, 131.3,
130.6 (d, J = 10.0 Hz), 130.1, 129.8, 129.7, 129.4, 129.3, 129.2,
128.8 (m), 128.4, 126.4 (d, J = 20.0 Hz), 125.5, 122.9, 119.3, 117.6,
92.6 (d, J = 7.5 Hz), 83.6 (d, J = 17.3 Hz), 68.6, 66.6, 46.7 (d, J =
5.5 Hz), 36.6 (d, J = 4.8 Hz), 34.6, 30.0, 29.8, 29.3, 28.8, 28.7, 28.1,
δ = 16.6 ppm. IR (neat): ν = 2379, 1587, 1435, 1107, 1061, 736,
˜
693 cm–1. HRMS (ESI): calcd. for C27H27BNP [M + H]+ 406.2010;
found 406.1890.
(S)-7-[(Di-o-tolylphosphanyl)methyl]-2-phenyl-6,7-dihydro-5H-cyclo-
penta[b]pyridine Borane Adduct (6b): Obtained in 60% yield. [α]2D5
1
24.4 ppm. 31P NMR: δ = 12.7 ppm. IR (neat): ν = 2924, 1610,
= 3.3 (c = 1.00, CHCl3). H NMR (300 MHz, CDCl3): δ = 8.18–
˜
1454, 1437, 1352, 1272, 1115, 885, 836, 744, 712, 694, 681 cm–1.
HRMS (ESI): calcd. for C35H36IrNP [M – BArF]+ 694.2215; found
694.2211.
8.02 (m, 3 H), 7.89 (m, 1 H), 7.58–7.10 (m, 11 H), 3.82 (t, J =
15.0 Hz, 1 H), 3.32 (m, 1 H), 2.81 (m, 2 H), 2.36 (m, 2 H), 2.26 (s,
3 H), 2.12 (s, 3 H), 1.71 (m, 1 H), 1.7–0.8 (m, 3 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 166.5 (d, J = 14.2 Hz), 155.5, 142.3 (d, J =
5.2 Hz), 139.6, 135.2, 134.2, 132.9, 132.8, 131.9 (d, J = 8.3 Hz),
131.5 (d, J = 15 Hz), 128.7, 126.9, 126.6 (d, J = 7.5 Hz), 118.5,
40.9, 33.1, 29.6, 29.1, 21.8 (d, J = 4.5 Hz) ppm. 31P NMR: δ =
Complex 7b: Obtained in 80% yield. [α]2D5 = 24.5 (c = 2.0, CHCl3).
1H NMR (300 MHz, CDCl3): δ = 7.87–7.39 (m, 26 H), 7.12 (m, 1
H), 4.42 (m, 1 H), 4.21 (m, 2 H), 3.07 (m, 3 H), 2.95–2.40 (m, 6
H), 2.32–2.06 (m, 5 H), 2.05–1.90 (m, 3 H), 1.43–1.23 (m, 2 H),
1.23–1.00 (m, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 166.7,
162.0 (dd, J = 50.0 Hz), 160.9, 142.48, 140.51, 139.5, 138.6, 136.3,
135.0, 133.8, 133.1, 132.6, 132.2, 131.8 (d, J = 2.7 Hz), 131.4, 130.2,
129.8, 129.3, 129.01–128.86 (m), 128.53–128.42 (m), 128.18, 127.02
(d, J = 10.0 Hz), 126.6, 126.4, 122.9, 119.4, 117.7 (m), 93.9, 85.2,
67.2 (d, J = 5.0 Hz), 66.4 (m), 46.6 (d, J = 5.6 Hz), 36.9 (m), 34.4,
30.4, 30.2, 29.9, 28.7, 28.4 (m), 27.9 (m), 24.6, 23.3 (m), 23.1 ppm.
17.5 ppm. IR (neat): ν = 2373, 1585, 1442, 1135, 1061, 823, 737,
˜
693 cm–1. HRMS (ESI): calcd. for C29H32BNP [M + H]+ 436.2365;
found 436.2365.
(S)-8-[(Diphenylphosphanyl)methyl]-2-phenyl-5,6,7,8-tetrahydro-
quinoline Borane Adduct (6c): Obtained in 99% yield. [α]2D5 = 3.0 (c
1
= 1.00, CHCl3). H NMR (300 MHz, CDCl3): δ = 8.12–8.02 (m, 4
H), 7.78–7.71 (m, 2 H), 7.53–7.38 (m, 11 H), 3.76 (dt, J = 0.2,
14.7 Hz, 1 H), 3.30 (m, 1 H), 2.77 (m, 2 H), 2.28 (m, 2 H), 1.90–1.71
(m, 3 H), 1.50–0.82 (m, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ
= 158.7 (d, J = 12.7 Hz), 154.3, 139.8, 137.8, 133.0 (d, J = 8.7 Hz),
132.1 (d, J = 8.7 Hz), 131.2, 131.1, 128.9, 128.8, 128.7, 126.8, 118.0,
31P NMR: δ = 20.8 ppm. IR (neat): ν = 2925, 1610, 1452, 1436,
˜
1353, 1273, 1117, 886, 839, 745, 681 cm–1. HRMS (ESI): calcd. for
C37H40IrNP [M – BArF]+ 708.2371; found 722.2524.
Complex 7c: Obtained in 89% yield. [α]2D5 = 15.7 (c = 0.2, CHCl3).
1H NMR (500 MHz, CDCl3): δ = 7.79–7.63 (m, 10 H), 7.63–7.48
(m, 12 H), 7.48–7.39 (m, 5 H), 7.34–7.28 (m, 2 H), 4.52 (m, 1 H),
4.31 (m, 1 H), 4.10 (m, 1 H), 3.14 (m, 1 H), 2.84 (m, 2 H), 2.70
(m, 1 H), 2.55 (m, 1 H), 2.51–2.32 (m, 2 H), 2.19 (m, 1 H), 2.08–
1.84 (m, 3 H), 1.81–1.67 (m, 3 H), 1.40–1.31 (m, 1 H), 1.15–1.04
(m, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 162.6 (dd, J =
37.1 (d, J = 1.4 Hz), 31.0 (d, J = 3.6 Hz), 30.1, 28.9, 20.6 ppm. 31
P
NMR: δ = 16.8 ppm. IR (neat): ν = 3676, 2988, 2380, 1459, 1065,
˜
736, 692 cm–1. HRMS (ESI): calcd. for C28H39BNP [M + H]+
422.2209; found 422.2208.
(S)-8-[(Di-o-tolylphosphanyl)methyl]-2-phenyl-5,6,7,8-tetrahydro-
quinoline Borane Adduct (6d): Obtained in 54% yield, [α]2D5 = 13.2
144
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© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 140–146

Iridium Catalysts with Chiral Bicyclic Ligands
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50.0 Hz), 160.2, 141.2, 138.8, 135.0, 133.2 (d, J = 10.5 Hz), 132.6–
132.1 (m), 132.0–131.4 (m), 130.6–130.2 (m), 129.9, 129.8, 129.6,
129.5, 129.3, 128.9, 126.7, 124.8, 124.2, 123.0, 119.3, 117.7, 88.0,
69.5, 68.8, 41.0, 36.1, 35.8, 32.2, 32.1, 29.9, 29.4, 28.3, 23.6,
20.0 ppm. 31P NMR: δ = 3.7 ppm. IR (neat): ν = 2923, 1609, 1461,
˜
1436, 1353, 1274, 1118, 886, 838, 738, 712, 681, 695 cm–1. HRMS
(ESI): calcd. for C36H38IrNP [M – BArF]+ 722.2528; found
708.2367.
[5]
Complex 7d: Obtained in 87% yield. [α]2D5 = 10.0 (c = 0.3, CHCl3).
1H NMR (500 MHz, CDCl3): δ = 7.84–7.67 (m, 12 H), 7.67–7.55
(m, 3 H), 7.55–7.49 (m, 5 H), 7.49–7.26 (m, 6 H), 7.23–7.11 (m, 1
H), 4.68–4.33 (m, 2 H), 4.19 (m, 1 H), 3.01–2.67 (m, 1 H), 2.67–
2.36 (m, 4 H), 2.23–2.00 (m, 5 H), 1.95–1.83 (m, 2 H), 1.83–1.48
(m, 5 H), 1.22–0.94 (m, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ
= 161.6 (dd, J = 50 Hz), 169.0, 141.0, 139.2, 135.1, 132.7, 131.7,
131.5, 130.2, 129.8–129.3 (m), 128.5–129.0 (m), 127.1, 127.0–126.6
(m), 125.8, 123.0, 119.4, 117.7, 41.0 (d, J = 6 Hz), 36.5, 34.8, 31.8
(m), 30.8, 30.2, 29.4, 28.2, 24.0, 23.1, 22.7, 19.6 ppm. 31P NMR: δ
= 40.7 ppm. IR (neat): ν = 2951, 1609, 1461, 1353, 1272, 1115, 886,
˜
[6]
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838, 736, 712, 681, 669 cm–1. HRMS (ESI): calcd. for C38H42IrNP
[M – BArF]+ 736.2684; found 736.2681.
General Procedure for Asymmetric Hydrogenation: Ir complex
(1.0 mol-%) and substrate (0.25 mmol) were added into a vial, fol-
lowed by dichloromethane (1 mL). The vial was placed in a high-
pressure hydrogenation apparatus. The reactor was purged three
times with H2 (1 bar), then it was filled with H2 (50 bar). The reac-
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H2 pressure was released, and the solvent was removed in vacuo.
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1
versions were determined by H NMR spectroscopy, and enantio-
meric excesses were determined by GC–MS or HPLC with a chiral
column.[4]
Supporting Information (see footnote on the first page of this arti-
cle): Copies of the 1H and 13C NMR spectra for all key intermedi-
ates and final products.
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Acknowledgments
The Swedish Research Council (VR) and SYNFLOW (FP7) sup-
ported this work. The authors thank Dr. A. Paptchikhine, Dr. T.
Singh, and Dr. J-Q. Li for useful discussions.
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145

X. Quan, V. S. Parihar, M. Bera, P. G. Andersson
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Received: July 30, 2013
Published Online: October 17, 2013
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Eur. J. Org. Chem. 2014, 140–146