The application of pyranoside phosphite-pyridine ligands to enantioselective Ir-catalyzed hydrogenations of highly unfunctionalized olefins

Article abstract of DOI:10.1016/j.tetasy.2012.06.025

Eight (biaryl)phosphite/pyridine ligands 1-2a-d have been prepared by the modular functionalization of positions C-2 and C-3 of two d-glucopyranoside backbones. The chiral ligands were examined in the iridium-catalyzed asymmetric hydrogenation of poorly functionalized alkenes, as a function of the relative position of the coordinating groups and the geometric properties of the biaryl phosphite moieties. Enantiomeric excesses of up to 90% were achieved in the hydrogenation of E-2-(4-methoxyphenyl)-2-butene by using 1a and 1c, which seemingly combine the beneficial effect of the phosphite at the 2-position with the matching (R_ax)-configuration of their encumbered biaryl substituents. The results of the hydrogenation of more challenging substrates, such as Z-trisubstituted alkenes, alkenes with a neighboring polar group or demanding 1,1-di-substituted alkenes, generally confirmed this trend, and in some significant cases, the chiral hydrogenated products were isolated with ees of 65-79%. 2012 Elsevier Ltd.

Full text of DOI:10.1016/j.tetasy.2012.06.025

Tetrahedron: Asymmetry 23 (2012) 945–951
Contents lists available at SciVerse ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
The application of pyranoside phosphite-pyridine ligands to enantioselective
Ir-catalyzed hydrogenations of highly unfunctionalized olefins
Jessica Margalef a, Matteo Lega b,c, Francesco Ruffo b,c, , Oscar Pàmies a, , Montserrat Diéguez a,
⇑
⇑
⇑
a Departament de Química Física i Inorgànica, Universitat Rovira i Virgili, Campus Sescelades, C/Marcelꢀlí Domingo, s/n. 43007 Tarragona, Spain
b Dipartimento di Scienze Chimiche, Università degli Studi di Napoli ‘Federico II’, Complesso Universitario di Monte S. Angelo, Via Cintia, I-80126 Napoli, Italy
c Consorzio Interuniversitario di Reattività Chimica e Catalisi, via Celso Ulpiani 27, I-70126 Bari, Italy
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 15 May 2012
Accepted 29 June 2012
Eight (biaryl)phosphite/pyridine ligands 1–2a–d have been prepared by the modular functionalization of
positions C-2 and C-3 of two -glucopyranoside backbones. The chiral ligands were examined in the irid-
D
ium-catalyzed asymmetric hydrogenation of poorly functionalized alkenes, as a function of the relative
position of the coordinating groups and the geometric properties of the biaryl phosphite moieties. Enan-
tiomeric excesses of up to 90% were achieved in the hydrogenation of E-2-(4-methoxyphenyl)-2-butene
by using 1a and 1c, which seemingly combine the beneficial effect of the phosphite at the 2-position with
the matching (Rax)-configuration of their encumbered biaryl substituents. The results of the hydrogena-
tion of more challenging substrates, such as Z-trisubstituted alkenes, alkenes with a neighboring polar
group or demanding 1,1-di-substituted alkenes, generally confirmed this trend, and in some significant
cases, the chiral hydrogenated products were isolated with ees of 65–79%.
Ó 2012 Elsevier Ltd. All rights reserved.
1. Introduction
gands that tolerate a broader range of substrates remained a chal-
lenge. Some years ago we discovered that the presence of biaryl-
The increasing demand for enantiomerically pure pharmaceuti-
cals, agrochemicals, flavors, and other fine chemicals has advanced
the field of asymmetric catalytic technologies. Asymmetric hydro-
genation utilizing molecular hydrogen to reduce prochiral olefins
has become one of the most reliable catalytic methods for the
preparation of optically active compounds.1 Over many years the
scope of this reaction has gradually been extended in terms of
the reactant structure and catalyst efficiency. Nowadays, an
impressive number of chiral phosphine ligands have been devel-
oped and successfully applied to Rh- and Ru-catalyzed hydrogena-
tions.1 However, the range of olefins that can be hydrogenated
with high enantiomeric excess is limited, because rhodium and
ruthenium catalysts require the presence of a coordinating group
next to the C@C bond.1 With minimally functionalized olefins
these catalysts generally show low reactivity and unsatisfactory
enantioselectivity.1 In this context, Pfaltz has introduced a new
class of hydrogenation catalysts, iridium complexes with chiral
N,P ligands, which overcome these limitations.2–4 The first set of
successful P,N ligands5 contained a phosphine or phosphinite
moiety as the P-donor group and either an oxazoline,5b,g,j oxa-
zole,5d thiazole,5i or pyridine5c as the N-donor group. However,
these iridium-phosphine/phosphinite, N catalysts were still highly
substrate-dependent and the development of efficient chiral li-
phosphite moieties in these P,N-ligands provides greater substrate
versatility than previous Ir-phosphine/phosphinite,
N catalyst
systems.6
In our efforts to expand upon the range of ligands and improve
performance, we herein report the first application of phosphite-
pyridine ligands in the Ir-catalyzed asymmetric hydrogenation of
minimally functionalized olefins (Fig. 1). These ligands combine a
priori the advantages of both types of successful ligands for this
process (phosphite and pyridine). Ligands 1–2a–d also have the
advantage of carbohydrates and phosphite ligands, such as their
availability at a low price from readily available alcohols, facile
modular constructions, and high resistance to oxidation.7 There-
fore, with these ligands we fully investigated the effects of system-
atically varying the position of the phosphite group at either C-2
(ligands 1) or C-3 (ligands 2) of the pyranoside backbone, as well
as the effects of different substituents and configurations in the
biaryl phosphite moiety a–d with the aim of maximizing the cata-
lyst performance.
2. Results and discussions
2.1. Synthesis of phosphite-pyridine ligands
The new ligands 1–2a–d were synthesized efficiently in one
step from the corresponding pyridyl-alcohols 4 and 7, which were
easily prepared on a large scale from methyl-a-D-glucopyranoside
⇑
Corresponding authors.
E-mail address: montserrat.dieguez@urv.cat (M. Diéguez).
0957-4166/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetasy.2012.06.025

946
J. Margalef et al. / Tetrahedron: Asymmetry 23 (2012) 945–951
R1
R2
tBu
O
O
Ph
Ph
O
O
O
O
O
O
O
O
O
O
O
O
O
P
O
HN
OMe
O
OBn
O
=
O
P
O
N
O
N
R1
R2
tBu
2
1
a R1 = R2 = tBu
c (R)ax
d
(S)ax
b R1 = SiMe3; R2 = H
Figure 1. Carbohydrate-based phosphite-pyridine ligands 1–2a–d.
3 and N-acetyl-
D
-glucosamine 5, respectively, using standard pro-
acterized by elemental analysis and 1H, 13C, and 31P NMR spectros-
copy. The spectroscopic assignments were based on data from
cedures (Scheme 1).8 The reaction of 4 and 7 with 1 equiv of the
O
Ph
O
O
HO
HO
Ph
O
O
P
Cl
O
O
O
(a)
O
O
O
O
O
HO
O
HO
OMe
O
OH
OMe
(d)
OMe
P
N
3
N
4
1a-d
O
O
P
Cl
HO
HO
O
O
Ph
Ph
O
Ph
O
O
(b)
O
(c)
O
O
O
O
O
HO
O
O
HO
HO
(d)
P
OH
HN
OBn
O
HN
OBn
O
NHAc
H2N
OBn
O
2a-d
7
5
6
N
N
Scheme 1. Synthesis of phosphite-pyridine ligands 1–2a–d. Reagents (a) Ref8a; (b) Ref8b; (c) DMAP, picolinic acid, DCC; (d) ClP(OR)2; (OR)2 = a–d/Py/toluene (yields: 18–59%).
corresponding phosphorochloridite in dry toluene under argon
and in the presence of pyridine, provided the desired ligands 1–
2a–d. All of the ligands were stable during purification on neutral
alumina under an argon atmosphere and could be isolated in mod-
erate yields as white solids. Rapid ring inversions (tropoisomeriza-
tion) in the biphenyl-phosphorus moieties a–b occurred on the
NMR timescale since the expected diastereoisomers were not de-
tected by low-temperature 31P NMR.9
1H–1H and 13C–1H correlation measurements and were as expected
for these C1 iridium complexes. The elemental analysis of C, H, and
N matched the stoichiometry [Ir(cod)(P–N)]n(BArF)n.
For all complexes, variable temperature NMR measurements
(from +40 °C to ꢁ80 °C) indicated that only one isomer was pres-
ent in solution. In this context, the 31P NMR spectra showed one
sharp signal. The 1H and 13C NMR showed four signals for the
olefinic protons and four signals for the olefinic carbon atoms
of the coordinated cyclooctadiene, as expected for C1-symmetri-
cal complexes. Two of the four signals, those located trans to the
phosphorus atom, appeared shifted to a lower field. The 13C NMR
spectra also showed the expected four signals of the methylenic
carbons of the cyclooctadiene, except for complexes containing
ligands 1c and 2c in which only three signals were observed.
This is probably due to an overlap of the signals. The signals
from the phosphite-pyridine ligands in these complexes pro-
2.2. Synthesis of the Ir-catalyst precursors
The catalyst precursors were made by refluxing a dichlorometh-
ane solution of the appropriate ligand in the presence of 0.5 equiv
of [Ir(l-Cl)cod]2 for 1 h and then exchanging the counterion with
sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (NaBArF)
(1 equiv), in the presence of water (Scheme 2).
Cl
P
1) 1-2a-d/ CH2Cl2
Ir
Ir
2
BArF
+ 2 NaCl
Ir
2) NaBArF / H2O
Cl
N
Scheme 2. Synthesis of catalyst precursors [Ir(cod)(1–2a–d)]BArF (yields: 93–98%).
All complexes were isolated as air-stable orange solids and
were used without further purification. The complexes were char-
duced the expected 1H and 13C NMR pattern for the gluco-pyran-
oside nucleus.

J. Margalef et al. / Tetrahedron: Asymmetry 23 (2012) 945–951
947
2.3. Asymmetric hydrogenation
when using ligand 1b (Table 1, entry 2) can be explained by the
lack of appropriate substituents at the para-position of the biphe-
nyl moiety to prevent the tropoisomerization of the biphenyl unit.
The best enantioselectivities (ee’s of up to 88%; Table 1, entry 1)
were obtained when using ligand 1a, which has the appropriate
combination of ligand parameters. The enantioselectivity can also
be improved by controlling not only the structural, but also the
reaction parameters. In this case, the enantioselectivity was further
improved (ee’s up to 90%) with Ir-1a catalyst precursor by lowering
In a first set of experiments, we used the Ir-catalyzed hydroge-
nation of E-2-(4-methoxyphenyl)-2-butene S1 to study the poten-
tial of phosphite-pyridine ligands 1–2a–d. Substrate S1 was chosen
as a model for the hydrogenation of trisubstituted olefins because
it has already been reduced with a wide range of ligands, which en-
able the efficiency of the various ligand systems to be compared di-
rectly.2 The results, which are summarized in Table 1, indicate that
Table 1
Results for the Ir-catalyzed hydrogenation of S1 using ligands 1–2a–da
[Ir(cod)(L)]BArF / 100 bar H2
CH2Cl2, rt, 4 h
*
S1
E-
MeO
MeO
Ligand
S2
Z-
Entry
Ligand
Substrate
Convb (%)
eeb (%)
Entry
Substrate
Convb (%)
eeb (%)
1
2
3
4
5
1a
1b
1c
1d
2a
2c
2d
1a
S1
S1
S1
S1
S1
S1
S1
S1
100
100
100
100
82
75
62
100
88 (S)
15 (S)
79 (S)
11 (R)
2 (R)
15 (R)
3 (S)
88 (S)
9d
10
11
12
13
14
15
16
1a
1a
1b
1c
1d
2a
2c
2d
S1
S2
S2
S2
S2
S2
S2
S2
89
100
100
84
90 (S)
0
0
23 (S)
38 (R)
2 (S)
0
69e
28
6
7
85f
43g
8c
0
a
b
c
d
e
f
Reactions carried out using 0.5 mmol of substrate and 2 mol % of Ir-catalyst precursor.
Conversion and enantiomeric excesses determined by chiral GC.
Reaction carried out at 0.5 mol % of Ir-catalyst precursor.
Reaction carried out at 5 °C.
9% of S1 observed.
15% of S1 observed.
g
23% of S1 observed.
the enantioselectivities are highly affected by the position of the
phosphite moiety at either C-2 (ligands 1) or C-3 (ligands 2) of
the pyranoside backbone as well as the substituents/configuration
of the biaryl phosphite moiety.
the reaction temperature to 5 °C (Table 1, entry 9). We also per-
formed the reaction at a low catalyst loading (0.5 mol %) using
the Ir-1a catalyst precursor (entry 8) and the high enantioselectiv-
ity and activity were maintained.
With ligands 1 and 2, we studied how the position of the phos-
phite moiety affected the product outcome. The results indicate an
important effect on both the activity and enantioselectivity. There-
fore, ligands 1 with the phosphite group attached at C-2 generally
provided higher activities and enantioselectivities than when li-
gands 2 were used (Table 1, entries 1–4 vs 5–7).
In order to assess the potential of ligands 1–2a–d for the more
demanding Z-isomers, which are usually hydrogenated with less
enantioselectivity than the corresponding E-isomers, we chose Z-
2-(4-methoxyphenyl)-2-butene S2 as the model substrate. How-
ever, low enantioselectivities were obtained (Table 1, entries 10–
16). A plausible explanation for this could be the competition be-
tween direct hydrogenation versus Z/E-isomerization of the sub-
strate. The hydrogenation of the E-isomer produces the opposite
configuration of the hydrogenated product to that when the Z-iso-
mer is hydrogenated,2 which results in low enantioselectivity. This
is supported by the presence of high amounts of S1 in the reaction
mixture (i.e. 23% of S1 was observed when using the Ir-2d catalytic
system after 4 h). In this respect we next decided to evaluate these
ligands in the hydrogenation of 7-methoxy-4-methyl-1,2-dihydro-
naphthalene S3 (Scheme 3), which has a Z-configuration and for
We next investigated the effect of the substituents/configura-
tion at the biaryl phosphite moiety. We found that for ligands 1,
in which the phosphite moiety is attached to C-2, the presence of
bulky tert-butyl groups at the para-positions of the biphenyl phos-
phite moiety is crucial for high enantioselectivity (Table 1, entry 1
vs 2). We also observed a cooperative effect between the position
of the phosphite moiety (at either C-3 or C-2) and the configuration
of the biaryl phosphite group (Table 1, entries 3, 4, 6, and 7). This
effect was seen for ligand 1c, which contains an (R)-biaryl phos-
phite moiety attached to C-2 (Table 1, entry 3). Moreover, by com-
paring the results of tropoisomeric ligands a–b with those of
enantiopure ones c–d, we can conclude that if enantioselectivity
has to be high, tropoisomerization has to be avoided upon coordi-
nation in the active species. For instance, ligands 1 efficiently con-
trol the tropoisomerization of the biaryl phosphite moiety when
bulky tert-butyl substituents at both the ortho- and para-positions
of the biaryl phosphite moiety are present. The biphenyl moiety
adopts an (R)-configuration in the active species (Table 1, entries
1 vs 3 and 4). In a similar way, the low enantioselectivity obtained
[Ir(cod)(1d)]BArF (2 mol%)
100 bar H2
*
CH2Cl2, rt, 4 h
MeO
MeO
S3
Conv: 98%
ee: 65 % (S)
Scheme 3. Asymmetric hydrogenation of S3.

948
J. Margalef et al. / Tetrahedron: Asymmetry 23 (2012) 945–951
Table 2
which Z/E-isomerization is not possible. Enantioselectivities of up
to 65% were obtained when using the Ir-1d catalyst precursor.
We next studied the asymmetric hydrogenation of trisubsti-
tuted olefins S4–S6 containing a neighboring polar group. These
substrates are interesting because they allow for further function-
alization and are therefore important synthons for the synthesis of
more complex chiral molecules. The results are summarized in
Scheme 4. The reduction of these substrates follows the same trend
as those observed for the previous E-trisubstituted substrate S1.
Again, the highest enantioselectivities were obtained when using
the Ir-1a catalyst precursor. High enantioselectivities were ob-
Results for the Ir-catalyzed hydrogenation of S7–S11 using phosphite-pyridine
ligands 1–2a–da
[Ir(cod)(L)]BArF / 1 bar H2
R1
R1
*
CH2Cl2, rt, 4 h
R2
R2
S7
S8
S9
R1= tBu; R2= H
R1= Et; R2= 4-OMe
R1= Et; R2= 4-CF3
S10 R1= iBu; R2= H
S11 R1= Bu; R2= H
tained in the hydrogenation of
a,b-unsaturated ester S4 (ee’s of
Entry
Ligand
Substrate
Convb (%)
eeb (%)
up to 79%). Conversely, the reduction of allylic alcohol S5 and
allylic acetate S6 gave lower enantioselectivities (ee’s of up to 48%).
1
2
3
4
5
6
7
8
1a
1b
1c
1d
2a
2c
2d
1c
1d
2c
2d
1d
1d
1d
S7
S7
S7
S7
S7
S7
S7
S8
S8
S8
S8
S9
S10
S11
100
100
100
100
100
100
100
38 (S)
31 (S)
65 (S)
15 (R)
33 (S)
38 (S)
72 (R)
16 (R)
20 (S)
3 (R)
COOEt
OH
OAc
99c
9
98d
78e
S5
S4
10
11
12
13
14
S6
96f
3 (R)
100% Conv
100% Conv
100g
99h
16 (S)
20 (S)
23 (S)
100% Conv
48% (R)
79% (R)
46% (R)
100i
Scheme 4. Selected hydrogenation results of other trisubstituted olefins using the
[Ir(cod)(1a)]BArF catalyst precursor. Reaction conditions: 2 mol % catalyst precur-
sor, CH2Cl2 as solvent, 100 bar H2, 4 h.
a
Reactions carried out using 0.5 mmol of substrate and 2 mol % of Ir-catalyst
precursor.
b
Conversion and enantiomeric excesses determined by chiral GC.
60% of S1 observed.
60% of S1 observed.
64% of S1 observed.
c
d
e
f
Next, we screened ligands 1–2a–d in the asymmetric hydroge-
nation of more demanding terminal olefins. Enantioselectivity was
more difficult to control in these substrates than in trisubstituted
olefins. There are two main reasons for this:2d,e (a) the two substit-
uents in the substrate can easily exchange positions in the chiral
environment formed by the catalysts, thus reversing the facial
selectivity; and (b) the terminal double bond can isomerize to form
the more stable internal alkene, which usually leads to predomi-
nant formation of the opposite enantiomer of the hydrogenated
product.
Initially we used the Ir-catalyzed hydrogenation of 3,3-di-
methyl-2-phenyl-1-butene S7. The results using ligands 1–2a–d
are shown in Table 2. Enantioselectivities were again affected by
the position of the phosphite moiety at either the C-2 or C-3 posi-
tion of the pyranoside backbone as well as the substituents/config-
uration of the biaryl phosphite moiety. However, the effect of these
ligand parameters was different from the effect observed in the
reduction of trisubstituted olefins. Thus, the presence of an enan-
tiopure biaryl phosphite moiety has a very positive effect on the
enantioselectivity (ee’s increased from 38% for Ir-1a to 65% for Ir-
1c; Table 2, entries 1 vs 3). The cooperative effect between the po-
sition of the phosphite and the configuration of the biaryl group is
also present, but in this case, both enantiomers of the hydroge-
nated product can be obtained in good enantioselectivities [ligand
1c affords 65% (S) and ligand 2d affords 72% (R)]. The best enanti-
oselectivities were therefore obtained using the catalyst precursor
Ir-2d (ee’s up to 72%, Table 2, entry 7).
67% of S1 observed.
g
h
i
59% of internal olefin observed.
41% of internal olefin observed.
48% of internal olefin observed.
3. Conclusions
This work substantiates a versatile strategy aimed at preparing
chiral ligands through immediate functionalization of common
carbohydrates. Eight ligands 1–2a–d were prepared, whose ready
availability along with an intrinsic modular nature allowed us to
refine the structures by switching the coordinating functions be-
tween C-2 and C-3, and by introducing biaryl(phosphite) moieties
with different geometric properties. The application of these li-
gands in the enantioselective Ir-catalyzed hydrogenation of mini-
mally functionalized alkenes disclosed
a
well-balanced
combination in 1a and 1c, which seemingly couple the beneficial
effect of the phosphite in position 2 with the matching (Rax)-con-
figuration of their encumbered biaryl substituents. In this case,
the hydrogenation of E-2-(4-methoxyphenyl)-2-butene yielded
the chiral product in 90% ee, and analogous beneficial synergy
was generally recognized in the hydrogenation of more challenging
substrates. Use of these ligands will be assessed also in other asym-
metric reactions of relevant synthetic interest.
4. Experimental
4.1. General
Finally, we investigated the asymmetric hydrogenation of other
1,1-disubstituted aryl-alkyl substrates with ligands containing the
enantiopure biphenyl moieties 1–2c–d. The results indicated that
enantioselectivity is highly affected by the nature of the alkyl chain
(ee’s ranging from 16% to 72%, Table 2, entry 7 vs 12) and less af-
fected by the electronic nature of the aryl ring (Table 2, entry 9
vs 12). One plausible explanation for this could be the competition
between the direct hydrogenation versus isomerization for the dif-
ferent substrates. This is supported by the high amounts of isomer-
ized internal olefin observed in all cases for substrates S8–S11.
All reactions were carried out using standard Schlenk tech-
niques under an argon atmosphere. Solvents were purified and
dried by standard procedures. Compounds 4 and 6 were prepared
as previously described.8 1H, 13C{1H}, and 31P{1H} NMR spectra
were recorded using a 400 MHz spectrometer. Chemical shifts
are relative to those of SiMe4 (1H and 13C) as the internal standard

J. Margalef et al. / Tetrahedron: Asymmetry 23 (2012) 945–951
949
or H3PO4
(
31P) as the external standard. 1H and 13C assignments
(d, 1H, H-1, 3J1–2 = 3.2 Hz), 4.89 (m, 1H, H-2), 5.09 (s, 1H, H-7), 6.34
(m, 1H, H-3), 6.5–8.4 (m, 11H, CH@). 13C NMR (C6D6), d: 16.9 (CH3),
were made on the basis of 1H–1H gCOSY and 1H–13C gHSQC exper-
iments. All catalytic experiments were performed three times.
t
t
17.0 (CH3), 20.6 (CH3), 20.7 (CH3), 32.0 (CH3, Bu), 32.1 (CH3, Bu),
35.3 (C, tBu), 35.4 (C, tBu), 55.1 (CH3–O), 63.2 (C-5), 69.3 (C-6),
72.2 (C-3), 73.3 (C-2), 80.4 (C-4), 100.4 (C-1), 101.9 (C-7), 125–
165 (aromatic carbons). Anal. calcd (%) for C44H52NO9P: C 68.65,
H 6.81, N 1.82; found: C 68.68, H 6.82, N 1.80.
4.2. Synthesis of the intermediate 7
Intermediate 6 (0.715 g, 2.00 mmol) was dissolved in dry DCM,
then DMAP (0.024 g, 0.20 mmol), picolinic acid (0.234 g, 1.90 mmol),
and DCC (0.516 g, 2.50 mmol) were added. The system was stirred at
rt overnight, then the mixture was filtered. The product was purified
by chromatography (EtOAc/PE = 3/2) and precipitation (DCM/PE).
Compound 1d Yield: 315 mg (41%). 31P NMR (C6D6), d: 137.7. 1H
NMR (C6D6), d: 1.54 (s, 3H, CH3), 1.62 (s, 9H, CH3, tBu), 1.65 (s, 3H,
CH3), 1.67 (s, 9H, CH3, tBu), 2.02 (s, 6H, CH3), 3.03 (s, 3H, CH3, CH3–
O), 3.35 (m, 1H, H-6), 3.56 (m, 1H, H-4), 3.89 (m, 1H, CH, H-5), 4.02
Yield: 0.647 g (70%). 1H NMR (CDCl3), d: 8.60 (dd, 1H, CH@, JH–
(dd, 1H, H-6’, 3J6 –6 = 10.0 Hz, 3J6 –5 = 4.8 Hz), 4.55 (m, 1H, H-2), 4.91
(d, 1H, H-1, 3J1–2 = 3.6 Hz), 5.09 (s, 1H, H-7), 6.34 (m, 1H, H-3), 6.5–
8.4 (m, 11H, CH@). 13C NMR (C6D6), d: 16.9 (CH3), 20.7 (CH3), 20.8
(CH3), 31.9 (d, CH3, tBu, JC–P = 8.5 Hz), 32.4 (CH3, tBu), 35.3 (C, tBu),
35.7 (C, tBu), 55.4 (CH3–O), 63.2 (C-5), 69.2 (C-6), 71.2 (d, C-3,
JC–P = 9.8 Hz), 75.0 (d, C-2, JC–P = 11.2 Hz), 80.3 (C-4), 100.0 (C-1),
101.9 (C-7), 125–165 (aromatic carbons). Anal. calcd (%) for
3
0
0
H = 4.7 Hz, 3JH–H = 0.8 Hz), 8.49 (d, 1H, NH, JNH-2 = 10.0 Hz), 8.17 (d,
3
3
3
3
1H, CH@, JH–H = 7.8 Hz), 7.84 (td, 1H, CH@, JH–H = 7.7 Hz, JH–
H = 1.6 Hz), 7.55–7.20 (m, 10H, CH@), 5.58 (s, 1H, H-7), 4.99 (d, 1H,
H-1, 3J1–2 = 3.9 Hz), 4.78 (d, 1H, CH2-Ph, 2JH–H = 12.1 Hz), 4.57 (d, 1H,
2
3
3
CH2-Ph, JH–H = 12.1 Hz), 4.42 (td, 1H, H-2, J2–1 = 3.9 Hz, J2–3 = 3J2-
2
3
0
NH = 10.0 Hz), 4.27 (dd, 1H, H-6, J6–6 = 10.2 Hz, J6–5 = 4.9 Hz), 3.79
(t, 1H, H-3, J3–4 = 3J3–2 = 10.0 Hz), 3.96 (td, 1H, H-5, J5–6 = 4.9 Hz,
C
44H52NO9P: C 68.65, H 6.81, N 1.82; found: C 68.69, H 6.82, N 1.79.
3
3
3
J5–4 = 3J6–6 = 10.2 Hz), 3.79 (t, 1H, H-6’, 2J6 –6 = 3J6 –5 = 10.2 Hz), 3.68
(m, 1H, H-4); 13C NMR (CDCl3), d: 165.1 (C@O), 149.1–122.6 (17 C,
aromatics), 102.0 (C-7), 97.3(C-1), 82.1 (C-4),70.5 (C-3), 69.9(CH2Ph),
68.9 (C-6), 62.7 (C-5), 54.2 (C-2).
Compound 2a Yield: 156 mg (18%). 31P NMR (C6D6), d: 147.7. 1H
0
0
0
NMR (C6D6), d: 1.21 (s, 9H, CH3, tBu), 1.23 (s, 9H, CH3, tBu), 1.54 (s,
9H, CH3, tBu), 1.56 (s, 9H, CH3, tBu), 3.53 (m, 1H, H-6), 3.79 (m, 1H,
H-4), 4.07 (m, 2H, H-5 and H-6’), 4.15 (d, 1H, CH2–Ph,
2JH–H = 12.0 Hz), 4.41 (d, 1H, CH2–Ph, JH–H = 12.0 Hz), 4.79 (m,
2
3
4.3. Typical procedure for the preparation of [Ir(cod)(L)]BArF
1H, H-3), 5.13 (m, 1H, H-2), 5.31 (d, 1H, H-1, J1–2 = 3.6 Hz), 5.42
(s, 1H, H-7), 6.53 (m, 1H, CH@), 6.9–7.1 (m, 10 H, CH@), 7.22 (d,
1H, CH@, J = 2.4 Hz), 7.54 (dd, 1H, CH@, J = 10.8 Hz, J = 2.8 Hz),
The corresponding phosphorochloridite (1.1 mmol) produced
10
3
in situ
was dissolved in toluene (5 mL), after which pyridine
7.69 (d, 1H, CH@, JH–H = 7.2 Hz), 7.88 (m, 1H, NH), 8.01 (d, 1H,
3
3
(0.3 mL, 3.9 mmol) was added. The corresponding pyridine-hydro-
xyl compound (1 mmol) was azeotropically dried with toluene
(3 ꢂ 2 mL) and then dissolved in toluene (5 mL) to which pyridine
(0.3 mL, 3.9 mmol) was added. The alcohol solution was trans-
ferred slowly to a solution of phosphorochloridite. The reaction
mixture was stirred at 80 °C for 90 min, after which the pyridine
salts were removed by filtration. Evaporation of the solvent gave
a white foam, which was purified by flash chromatography in alu-
mina (toluene/NEt3 = 100/1) to produce the corresponding ligand
as a white solid.
CH@, JH–H = 8.0 Hz), 8.82 (d, 1H, CH@, JH–H = 8.4 Hz). 13C NMR
(C6D6), d: 31.6 (CH3, tBu), 31.7 (CH3, tBu), 31.8 (CH3, tBu), 31.9
(CH3, tBu), 34.8 (C, tBu), 34.9 (C, tBu), 36.0 (C, tBu), 54.9 (C-3),
64.2 (C-4), 69.3 (C-6), 70.4 (CH2–Ph), 72.8 (d, C-2, JC–P = 16.8 Hz),
81.5 (C-5), 99.3 (C-1), 102.1 (C-7), 122–165 (aromatic carbons).
Anal. calcd (%) for C54H65N2O8P: C 71.98, H 7.27, N 3.11; found: C
72.03, H 7.29, N 3.08.
Compound 2c Yield: 144 mg (18%). 31P NMR (C6D6), d: 140.1. 1H
NMR (C6D6), d: 1.44 (s, 9H, CH3, tBu), 1.59 (s, 9H, CH3, tBu), 1.61 (s,
3H, CH3), 1.66 (s, 3H, CH3), 1.91 (s, 3H, CH3), 2.02 (s, 3H, CH3), 3.44
(m, 1H, H-6), 3.83 (m, 1H, H-4), 4.08 (m, 2H, H-5, and H-6’), 4.17 (d,
Compound 1a Yield: 489 mg (59%). 31P NMR (C6D6), d: 144.7. 1H
2
2
NMR (C6D6), d: 1.25 (s, 9H, CH3, tBu), 1.29 (s, 9H, CH3, tBu), 1.57 (s,
1H, CH2-Ph, JH–H = 12.4 Hz), 4.35 (d, 1H, CH2-Ph, JH–H = 12.4 Hz),
t
t
9H, CH3, Bu), 1.63 (s, 9H, CH3, Bu), 2.89 (s, 3H, CH3, CH3–O), 3.41
(m, 1H, H-6), 3.66 (m, 1H, H-4), 3.95 (m, 1H, H-5), 4.04 (dd, 1H, H-
4.92 (m, 1H, H-3), 5.08 (m, 1H, H-2), 5.12 (s, 1H, H-7), 5.29 (d,
3
1H, H-1, J1–2 = 3.2 Hz), 6.53 (m, 1H, CH@), 6.9–7.2 (m, 11H,
3
3
3
0
0
6’, J6 –6 = 10.0 Hz, J6 –5 = 4.8 Hz), 4.13 (d, 1H, H-1, J1–2 = 3.1 Hz),
5.02 (m, 1H, H-2), 5.05 (s, 1H, H-7), 6.43 (m, 1H, H-3), 6.5–8.4
(m, 13H, CH@). 13C NMR (C6D6), d: 31.0 (CH3, tBu), 31.1 (CH3,
CH@), 7.53 (m, 2H, CH@), 8.04 (m, 1H, NH), 8.23 (d, 1H, CH@,
3
3JH–H = 8.0 Hz), 8.82 (d, 1H, CH@, JH–H = 8.4 Hz). 13C NMR (C6D6),
t
d: 16.2 (CH3), 16.5 (CH3), 19.9 (CH3), 20.0 (CH3), 31.2 (CH3, Bu),
t
t
t
t
t
t
t
tBu), 31.1 (CH3, Bu), 31.2 (CH3, Bu), 34.3 (C, Bu), 34.4 (C, Bu),
31.3 (CH3, Bu), 34.6 (C, Bu), 34.7 (C, Bu), 54.7 (C-3), 63.7 (C-4),
68.5 (C-6), 69.5 (CH2-Ph), 72.6 (d, C-2, JC–P = 19.1 Hz), 80.3 (C-5),
97.3 (C-1), 101.5 (C-7), 121–165 (aromatic carbons). Anal. calcd
(%) for C50H57N2O8P: C 71.07, H 6.80, N 3.32; found: C 71.12, H
6.83, N 3.28.
35.3 (C, tBu), 35.3 (C, tBu), 54.3 (CH3–O), 62.6 (C-5), 68.7 (C-6),
3
71.5 (d, C-3, JC–P = 4.2 Hz), 72.7 (C-2), 79.7 (C-4), 99.5 (C-1),
101.3 (C-7), 124–164 (aromatic carbons). Anal. calcd (%) for
C
48H60NO9P: C 69.80, H 7.32, N 1.70; found: C 69.78, H 7.30, N 1.69.
Compound 1b Yield: 265 mg (36%). 31P NMR (C6D6), d: 146.6. 1H
Compound 2d Yield: 109 mg (13%). 31P NMR (C6D6), d: 140.8. 1H
NMR (C6D6), d: 1.45 (s, 3H, CH3), 1.52 (s, 9H, CH3, tBu), 1.66 (s, 3H,
CH3), 1.67 (s, 9H, CH3, tBu), 1.83 (s, 3H, CH3), 2.01 (s, 3H, CH3), 3.55
(m, 1H, H-6), 3.80 (m, 1H, H-4), 4.03 (m, 1H, H-5), 4.08 (m, 1H, H-
NMR (C6D6), d: 0.48 (s, 9H, CH3–Si), 0.50 (s, 9H, CH3–Si), 2.82 (s, 3H,
CH3–O), 3.37 (m, 1H, H-6), 3.72 (m, 1H, H-4), 3.94 (m, 1H, H-5), 4.03
3
3
3
0
0
(dd, 1H, H-6’, J6 –6 = 10.0 Hz, J6 –5 = 4.8 Hz), 4.24 (d, 1H, H-1, J1–
2 = 3.5 Hz), 4.88 (m, 1H, H-2), 5.05 (s, 1H, H-7), 6.40 (m, 1H, H-3),
6.5–8.4 (m, 13H, CH@). 13C NMR (C6D6), d: ꢁ0.1 (CH3–Si), ꢁ0.2
2
6’), 4.13 (d, 1H, CH2-Ph, JH–H = 12.4 Hz), 4.37 (d, 1H, CH2-Ph,
2JH–H = 12.4 Hz), 4.85 (m, 1H, H-3), 5.07 (m, 1H, H-2), 5.14 (d, 1H,
3
3
(CH3–Si), 54.5 (CH3–O), 62.6 (C-5), 68.6 (C-6), 71.3 (d, C-3, JC–P
= 4.3 Hz), 72.6 (d, C-2, JC–P = 3.7 Hz), 79.7 (C-4), 99.7 (C-1), 101.3
H-1, J1–2 = 3.6 Hz), 5.49 (s, 1H, H-7), 6.52 (m, 1H, CH@), 6.9–7.2
2
3
(m, 11H, CH@), 7.78 (m, 2H, CH@), 7.94 (d, 1H, CH@, JH–H
3
(C-7), 124–165 (aromatic carbons). Anal. calcd (%) for C38H44NO9P-
Si2: C 61.19, H 5.95, N 1.88; found: C 61.21, H 5.98, N 1.86.
= 8.0 Hz), 8.05 (m, 1H, NH), 8.56 (d, 1H, CH@, JH–H = 8.8 Hz). 13C
NMR (C6D6), d: 16.2 (CH3), 16.3 (CH3), 19.9 (CH3), 20.0 (CH3),
t
t
t
Compound 1c Yield: 261 mg (34%). 31P NMR (C6D6), d: 138.6. 1H
NMR (C6D6), d: 1.56 (s, 9H, CH3, tBu), 1.62 (s, 9H, CH3, tBu), 1.65 (s,
3H, CH3), 1.70 (s, 3H, CH3), 2.01 (s, 3H, CH3), 2.04 (s, 3H, CH3), 2.84
(s, 3H, CH3, CH3–O), 3.35 (m, 1H, H-6), 3.62 (m, 1H, H-4), 3.91 (m,
31.3 (d, CH3, Bu, JC–P = 5.0 Hz), 31.5 (CH3, Bu), 34.6 (C, Bu), 34.8
t
(C, Bu), 53.5 (C-3), 63.4 (C-4), 68.5 (C-6), 69.4 (CH2-Ph), 71.8 (d,
C-2, JC–P = 10.9 Hz), 81.2 (C-5), 97.8 (C-1), 101.2 (C-7), 125–165
(aromatic carbons). Anal. calcd (%) for C50H57N2O8P: C 71.07, H
6.80, N 3.32; found: C 71.13, H 6.83, N 3.29.
1H, CH, H-5), 4.01 (dd, 1H, H-6’, 3J6 –6 = 10.4 Hz, 3J6 –5 = 4.8 Hz), 4.38
0
0

950
J. Margalef et al. / Tetrahedron: Asymmetry 23 (2012) 945–951
4.4. Typical procedure for the preparation of [Ir(cod)(L)]BArF
77.8 (b, C-2), 80.1 (C-4), 99.9 (C-1), 101.4 (C-7), 101.9 (b, CH@,
cod), 103.9 (b CH@, cod), 117.6 (b, CH@, BArF), 120–134 (aromatic
carbons), 135.0 (b, CH@, BArF), 136–158 (aromatic carbons), 161.9
The corresponding ligand (0.037 mmol) was dissolved in CH2Cl2
1
(2.5 mL) and [Ir(l-Cl)cod]2 (12.5 mg, 0.0185 mmol) was added. The
(q, C-B, BArF, JC–B = 49.5 Hz), 166.7 (C@O). Anal. calcd (%) for
reaction was refluxed at 45 °C for 1 h. After 5 min at room temper-
ature, NaBArF (38.6 mg, 0.041 mmol) and water (2.5 mL) were
added and the reaction mixture was stirred vigorously for 30 min
at room temperature. The phases were separated and the aqueous
phase was extracted twice with CH2Cl2. The combined organic
phases were filtered through a Celite plug, dried over MgSO4 and
the solvent was evaporated to give the product as an orange solid.
C84H76BF24IrNO9P: C 52.18, H 3.96, N 0.72; found: C 52.17, H
3.92, N 0.71.
4.4.4. [Ir(cod)(1d)]BArF
Yield: 68 mg (96%). 31P NMR (CD2Cl2), d: 93.6. 1H NMR (CD2Cl2),
t
t
d: 1.53 (s, 9H, CH3, Bu), 1.58 (s, 3H, CH3), 1.65 (s, 9H, CH3, Bu),),
1.69 (s, 3H, CH3), 1.86 (b, 4H, CH2, cod), 1.95 (b, 2H, CH2, cod),
1.99 (s, 6H, CH3), 2.08 (b, 2H, CH2, cod), 2.79 (s, 3H, CH3–O), 3.34
(m, H, CH@, cod), 3.38 (m, 1H, H-6), 3.48 (m, 1H, H-4), 3.53 (m,
4.4.1. [Ir(cod)(1a)]BArF
Yield: 71 mg (96%). 31P NMR (CD2Cl2), d: 96.0. 1H NMR (CD2Cl2),
d: 1.32 (s, 9H, CH3, tBu), 1.36 (s, 9H, CH3, tBu), 1.52 (s, 9H, CH3, tBu),
1.64 (s, 9H, CH3, tBu), 1.71 (b, 4H, CH2, cod), 1.98 (b, 2H, CH2, cod),
2.16 (b, 2H, CH2, cod), 2.72 (s, 3H, CH3–O), 3.39 (m, 2H, H-6, and
CH@ cod), 3.43 (m, 1H, H-4), 3.48 (m, 1H, H-2), 3.62 (m, 1H,
2H, H-2, and CH@, cod), 4.09 (d, 1H, H-1, J1–2 = 3.6 Hz), 4.46 (m,
3
2H, H-5, and CH@ cod), 4.49 (m, 1H, H-6’), 5.02 (s, 1H, H-7), 5.19
(m, 1H, H-3), 5.68 (m, 1H, CH@ cod), 6.9–7.5 (m, 21H, CH@), 7.82
(m, 1H, CH@), 8.70 (m, 1H, CH@). 13C NMR (CD2Cl2), d: 16.9
(CH3), 17.0 (CH3), 20.7 (CH3), 22.9 (b, CH2, cod), 24.6 (b, CH2,
3
t
CH@, cod), 3.91 (d, 1H, H-1, J1–2 = 3.6 Hz), 4.19 (m, 1H, H-5),
cod), 28.8 (b, CH2, cod), 30.7 (b, CH2, cod), 32.1 (CH3, Bu), 32.2
4.47 (m, 2H, H-6’, and CH@ cod), 5.08 (s, 1H, H-7), 5.24 (m, 1H,
H-3), 5.71 (m, 1H, CH@ cod), 6.9–7.5 (m, 23H, CH@), 7.81 (m, 1H,
CH@), 8.72 (m, 1H, CH@). 13C NMR (CD2Cl2), d: 24.8 (b, CH2, cod),
(CH3, tBu), 35.3 (C, tBu), 35.4 (C, tBu), 54.7 (CH3–O), 62.5 (C-5),
64.2 (CH@, cod), 68.6 (C-6), 69.3 (CH@, cod), 72.9 (C-3), 77.1 (b,
C-2), 80.0 (C-4), 99.6 (C-1), 101.3 (C-7), 102.4 (b, CH@, cod),
103.5 (b CH@, cod), 117.6 (b, CH@, BArF), 120–134 (aromatic car-
bons), 135.0 (b, CH@, BArF), 136–158 (aromatic carbons), 161.9
t
t
t
28.7 (b, CH2, cod), 31.0 (CH3, Bu), 31.1 (CH3, Bu), 31.1 (CH3, Bu),
t
t
t
31.2 (CH3, Bu), 32.0 (b, CH2, cod), 34.3 (C, Bu), 34.4 (C, Bu), 34.8
(b, CH2 cod), 35.3 (C, tBu), 54.1 (CH3–O), 62.2 (C-5), 63.7 (CH@,
cod), 68.6 (C-6), 68.9 (CH@, cod), 73.2 (b, C-3), 76.9 (b, C-2), 80.3
(C-4), 98.2 (C-1), 101.3 (C-7), 102.4 (b, CH@, cod), 106.5 (b CH@,
cod), 117.6 (b, CH@, BArF), 120–134 (aromatic carbons), 135.0 (b,
1
(q, C-B, BArF, JC–B = 49.5 Hz), 166.7 (C@O). Anal. calcd (%) for
C84H76BF24IrNO9P: C 52.18, H 3.96, N 0.72; found: C 52.16, H
3.94, N 0.70.
1
CH@, BArF), 136–158 (aromatic carbons), 161.9 (q, C-B, BArF, JC–
4.4.5. [Ir(cod)(2a)]BArF
B = 49.5 Hz), 166.7 (C@O). Anal. calcd (%) for C88H84BF24IrNO9P: C
53.12, H 4.26, N 0.70; found: C 53.09, H 4.24, N 0.67.
Yield: 71 mg (93%). 31P NMR (CD2Cl2), d: 92.4. 1H NMR (CD2Cl2),
d: 1.23 (s, 9H, CH3, 1.29 (s, 9H, CH3, tBu), 1.46 (s, 9H, CH3, tBu), 1.51
(s, 9H, CH3, tBu), 1.87 (b, 2H, CH2, cod), 2.21 (b, 2H, CH2, cod), 2.29
(b, 4H, CH2, cod), 3.09 (m, H, CH@, cod), 3.24 (m, 3H, H-5, H4, and
H-6), 3.77 (m, 1H, H-2), 3.89 (m, 1H, CH@ cod), 4.24 (m, 2H, H-6’,
4.4.2. [Ir(cod)(1b)]BArF
Yield: 69 mg (98%). 31P NMR (CD2Cl2), d: 96.5. 1H NMR (CD2Cl2),
d: 0.01 (s, 9H, CH3–Si), 0.35 (s, 9H, CH3–Si), 1.68 (b, 4H, CH2, cod),
1.95 (b, 2H, CH2, cod), 2.29 (b, 2H, CH2, cod), 2.65 (s, 3H, CH3–O),
3.45 (m, 4H, H-6, H-4, H-2, and CH@ cod)), 3.59 (m, 1H, CH@,
2
and CH@ cod), 4.61 (d, 1H, CH2-Ph, JH–H = 12.4 Hz), 4.76 (d, 1H,
2
3
CH2-Ph, JH–H = 12.4 Hz), 4.91 (m, H-3), 4.98 (d, 1H, H-1, J1–
2 = 3.6 Hz), 5.09 (s, 1H, H-7), 5.34 (m, 1H, CH@ cod), 6.19 (m, 1H,
NH), 6.87 (m, 1H, CH@), 7.0–7.9 (m, 25H, CH@), 8.81 (m, 2H,
CH@). 13C NMR (CD2Cl2), d: 16.5 (CH3), 16.7 (CH3), 20.2 (CH3),
20.9 (CH3), 25.2 (b, CH2, cod), 28.7 (b, CH2, cod), 29.9 (b, CH2,
3
cod), 3.94 (d, 1H, H-1, J1–2 = 3.2 Hz), 4.21 (m, 1H, H-5), 4.44 (m,
2H, H-6’, and CH@ cod), 5.06 (s, 1H, H-7), 5.19 (m, 1H, H-3), 5.66
(m, 1H, CH@ cod), 6.8–7.5 (m, 25H, CH@), 7.82 (m, 1H, CH@),
8.71 (m, 1H, CH@). 13C NMR (CD2Cl2), d: ꢁ0.7 (CH3–Si), 0.6 (CH3–
Si), 24.9 (b, CH2, cod), 29.4 (b, CH2, cod), 32.1 (b, CH2, cod), 37.5
(b, CH2, cod), 54.3 (CH3–O), 62.0 (C-5), 63.2 (CH@, cod), 68.5 (C-
6), 69.9 (CH@, cod), 75.0 (b, C-3), 77.8 (b, C-2), 80.8 (C-4), 97.3
(C-1), 101.8 (C-7), 107.2 (b, CH@, cod), 109.7 (b CH@, cod), 117.6
(b, CH@, BArF), 120.5–132.8 (aromatic carbons), 135.0 (b, CH@,
t
t
cod), 30.9 (CH3, Bu), 31.2 (b, CH2, cod), 32.1 (CH3, Bu), 34.3 (C,
tBu), 34.8 (C, Bu), 59.0 (C-3), 63.8 (C-4), 68.6 (b, CH@, cod), 68.8
t
(C-6), 71.2 (CH2-Ph), 75.1 (b, CH@, cod), 77.6 (C-2), 79.9 (C-5),
98.6 (C-1), 102.8 (b, CH@, cod), 103.1 (C-7), 106.2 (b, CH@, cod),
117.6 (b, CH@, BArF), 120–134 (aromatic carbons), 135.0 (b, CH@,
1
BArF), 136–158 (aromatic carbons), 161.9 (q, C-B, BArF, JC–
1
BArF), 136–156 (aromatic carbons), 161.9 (q, C-B, BArF, JC–
B = 49.5 Hz), 166.6 (C@O). Anal. calcd (%) for C94H89BF24IrN2O8P:
B = 49.5 Hz), 166.4 (C@O). Anal. calcd (%) for C78H68BF24IrNO9PSi2:
C 54.68, H 4.34, N 1.36; found: C 54.61, H 4.32, N 1.33.
C 49.06, H 3.59, N 0.73; found: C 49.02, H 3.58, N 0.72.
4.4.6. [Ir(cod)(2c)]BArF
4.4.3. [Ir(cod)(1c)]BArF
Yield: 73 mg (94%). 31P NMR (CD2Cl2), d: 91.6. 1H NMR (CD2Cl2),
Yield: 66 mg (93%). 31P NMR (CD2Cl2), d: 92.5. 1H NMR (CD2Cl2),
d: 1.56 (s, 9H, CH3, tBu), 1.62 (s, 9H, CH3, tBu), 1.68 (s, 3H, CH3), 1.78
(b, 7H, CH3, and CH2, cod), 1.99 (b, 2H, CH2, cod), 2.03 (s, 3H, CH3),
2.09 (s, 3H, CH3), 2.14 (b, 2H, CH2, cod), 2.76 (s, 3H, CH3–O), 3.34
(m, 1H, H-6), 3.41 (m, H, CH@, cod), 3.52 (m, 1H, H-4), 3.56 (m,
d: 1.20 (s, 9H, CH3, tBu), 1.26 (s, 3H, CH3), 1.50 (s, 3H, CH3), 1.54 (s,
t
9H, CH3, Bu), 1.69 (s, 3H, CH3), 1.83 (s, 3H, CH3), 1.92 (b, 2H, CH2,
cod), 2.23 (b, 2H, CH2, cod), 2.35 (b, 4H, CH2, cod), 2.83 (m, H, CH@,
cod), 2.92 (m, 1H, H-4), 3.11 (m, 1H, H-6), 3.48 (m, 1H, H-5), 3.69
(m, 1H, H-2), 3.95 (m, 1H, CH@ cod), 4.05 (m, 1H, H-6’), 4.32 (m,
3
2
2H, H-2, and CH@, cod), 4.02 (d, 1H, H-1, J1–2 = 3.6 Hz), 4.32 (m,
1H, CH@ cod), 4.60 (d, 1H, CH2-Ph, JH–H = 12.4 Hz), 4.73 (d, 1H,
2
3
1H, H-5), 4.46 (m, 2H, H-6’, and CH@ cod), 5.02 (s, 1H, H-7), 5.23
(m, 1H, H-3), 5.86 (m, 1H, CH@ cod), 6.9–7.5 (m, 21H, CH@), 7.82
(m, 1H, CH@), 8.72 (m, 1H, CH@). 13C NMR (CD2Cl2), d: 16.9
(CH3), 17.0 (CH3), 20.6 (CH3), 20.7 (CH3), 23.9 (b, CH2, cod), 26.4
(b, CH2, cod), 29.9 (b, CH2, cod), 32.3 (CH3, Bu), 32.5 (CH3, Bu),
32.8 (b, CH2, cod), 35.3 (C, Bu), 35.4 (C, Bu), 54.8 (CH3–O), 62.3
CH2-Ph, JH–H = 12.4 Hz), 4.89 (m, H-3), 5.01 (d, 1H, H-1, J1–
2 = 3.2 Hz), 5.05 (s, 1H, H-7), 5.28 (m, 1H, CH@ cod), 6.22 (m, 1H,
NH), 6.28 (s, 1H, CH@CH@), 7.0–7.9 (m, 25H, CH@), 8.81 (m, 2H,
CH@). 13C NMR (CD2Cl2), d: 16.8 (CH3), 20.5 (CH3), 21.4 (CH3),
25.5 (b, CH2, cod), 29.1 (b, CH2, cod), 29.9 (b, CH2, cod), 30.5
t
t
t
t
t
t
t
t
(CH3, Bu), 31.9 (CH3, Bu), 34.3 (C, Bu), 35.0 (C, Bu), 59.1 (C-3),
(C-5), 63.9 (CH@, cod), 68.3 (C-6), 69.2 (CH@, cod), 72.3 (C-3),
63.3 (C-4), 68.4 (C-6), 68.9 (b, CH@, cod), 71.1 (CH2-Ph), 75.3 (b,

J. Margalef et al. / Tetrahedron: Asymmetry 23 (2012) 945–951
951
CH@, cod), 77.4 (C-2), 79.8 (C-5), 97.3 (C-1), 102.2 (b, CH@, cod),
References
103.4 (C-7), 107.0 (b, CH@, cod), 117.6 (b, CH@, BArF), 120–134
(aromatic carbons), 135.0 (b, CH@, BArF), 136–158 (aromatic car-
bons), 161.9 (q, C-B, BArF, 1JC–B = 49.5 Hz), 166.2 (C@O). Anal. calcd
(%) for C90H81BF24IrN2O8P: C 53.82, H 4.06, N 1.39; found: C 53.79,
H 4.05, N 1.35.
1. (a)Asymmetric Catalysis in Industrial Scale Challenges; Blaser, H. U., Schmidt, E.,
Eds.; Approaches and Solutions: Wiley, Weinheim, Germany, 2003; (b) Shang,
G.; Li, W. Zhang, X. In Catalytic Asymmetric Synthesis; Ojima, I., Ed., 3rd Edition;
John Wiley & Sons, Inc.: Hoboken, 2000; pp 343–436; (c) Brown, J. M. In
Comprehensive Asymmetric Catalysis; Jacobsen, E. N., Pfaltz, A., Yamamoto, H.,
Eds.; Springer-Verlag: Berlin, 1999; Vol. 1, pp 121–182; (d)Asymmetric Catalysis
in Organic Synthesis; Noyori, R., Ed.; Wiley: New York, 1994; (e)Applied
Homogeneous Catalysis with Organometallic Compounds; Cornils, B., Herrmann,
W. A., Eds., second ed.; Wiley-VCH: Weinheim, 2002.
2. (a) Källström, K.; Munslow, I.; Andersson, P. G. Chem. Eur. J 2006, 12, 3194; (b)
Roseblade, S. J.; Pfaltz, A. Acc. Chem. Res. 2007, 40, 1402; (c) Church, T. L.;
Andersson, P. G. Coord. Chem. Rev. 2008, 252, 513; (d) Cui, X.; Burgess, K. Chem.
Rev. 2005, 105, 3272; (e) Pàmies, O.; Andersson, P. G.; Diéguez, M. Chem. Eur. J.
2010, 16, 14232; (f) Woodmansee, D. H.; Pfaltz, A. Chem. Commun. 2011, 47,
7912.
3. Chelating oxazoline-carbene ligands, mainly developed by Burgess et al., have
also been successfully used and also to a lesser extent chiral diphosphines. For
example, see (a) Perry, M. C.; Cui, X.; Powell, M. T.; Hou, D. R.; Reibenspies, J. H.;
Burgess, K. J. Am. Chem. Soc. 2003, 125, 113; (b) Cui, X.; Burgess, K. J. Am. Chem.
Soc. 2003, 125, 14212; (c) Cui, X.; Ogle, J. W.; Burgess, K. Chem. Commun. 2005,
672; (d) Zhao, J.; Burgess, K. J. Am. Chem. Soc. 2009, 131, 13236; (e) Co, T. T.;
Kim, T. J. Chem. Commun. 2006, 3537; (f) Forman, G. S.; Ohkuma, T.; Hems, W.
P.; Noyori, R. Tetrahedron Lett. 2000, 41, 9471.
4. Very recently, the ligand scope has been extended to the use of other non-
nitrogen containing heterodonor ligands such as P,O and P,S. See (a) Rageot, D.;
Woodmansee, D. H.; Pugin, B.; Pfaltz, A. Angew. Chem., Int. Ed. 2011, 50, 9598;
(b) Coll, M.; Pàmies, O.; Diéguez, M. Chem. Commun. 2011, 47, 9215.
5. See for instance (a) Perry, M. C.; Cui, X.; Powell, M. T.; Hou, D.-R.; Reibenspies, J.
H.; Burgess, K. J. Am. Chem. Soc. 2003, 125, 5391; (b) Blankestein, J.; Pfaltz, A.
Angew. Chem., Int. Ed. 2001, 40, 4445; (c) Kaiser, S.; Smidt, S. P.; Pfaltz, A. Angew.
Chem., Int. Ed. 2006, 45, 5194; (d) Källström, K.; Hedberg, C.; Brandt, P.; Bayer,
P.; Andersson, P. G. J. Am. Chem. Soc. 2004, 126, 14308; (e) Engman, M.; Diesen,
J. S.; Paptchikhine, A.; Andersson, P. G. J. Am. Chem. Soc. 2007, 129, 4536; (f)
Trifonova, A.; Diesen, J. S.; Andersson, P. G. Chem. Eur. J. 2006, 12, 2318; (g)
Menges, G.; Pfaltz, A. Adv. Synth. Catal. 2002, 334, 4044; (h) Drury, W. J., III;
Zimmermann, N.; Keenan, M.; Hayashi, M.; Kaiser, S.; Goddard, R.; Pfaltz, A.
Angew. Chem., Int. Ed. 2004, 43, 70; (i) Hedberg, C.; Källström, K.; Brandt, P.;
Hansen, L. K.; Andersson, P. G. J. Am. Chem. Soc. 2006, 128, 2995; (j) Franzke, A.;
Pfaltz, A. Chem. Eur. J. 2011, 17, 4131; (k) Tang, W.; Wang, W.; Zhang, X. Angew.
Chem., Int. Ed. 2003, 42, 943; (l) Hou, D.-R.; Reibenspies, J.; Colacot, T. J.;
Burgess, K. Chem. Eur. J. 2001, 7, 5391; (m) Cozzi, P. G.; Menges, F.; Kaiser, S.
Synlett 2003, 833; (n) Lightfoot, A.; Schnider, P.; Pfaltz, A. Angew. Chem., Int. Ed.
1998, 37, 2897; (o) Menges, F.; Neuburger, M.; Pfaltz, A. Org. Lett. 2002, 4, 4713;
(p) Liu, D.; Tang, W.; Zhang, X. Org. Lett. 2004, 6, 513; (q) Lu, S.-M.; Bolm, C.
Angew. Chem., Int. Ed. 2008, 47, 8920; (r) Lu, W.-J.; Chen, Y.-W.; Hou, X.-L. Adv.
Synth. Catal. 2010, 352, 103; (s) Paptchikhine, A.; Cheruku, P.; Engman, M.;
Andersson, P. G. Chem. Commun. 2009, 5996.
6. (a) Diéguez, M.; Mazuela, J.; Pàmies, O.; Verendel, J. J.; Andersson, P. G. J. Am.
Chem. Soc. 2008, 130, 7208; (b) Diéguez, M.; Mazuela, J.; Pàmies, O.; Verendel, J.
J.; Andersson, P. G. Chem. Commun. 2008, 3888; (c) Mazuela, J.; Verendel, J. J.;
Coll, M.; Schäffner, B.; Börner, A.; Andersson, P. G.; Pàmies, O.; Diéguez, M. M. J.
Am. Chem. Soc. 2009, 131, 12344; (d) Mazuela, J.; Paptchikhine, A.; Pàmies, O.;
Andersson, P. G.; Diéguez, M. Chem. Eur. J. 2010, 16, 4567; (e) Mazuela, J.;
Norrby, P.-O.; Andersson, P. G.; Pàmies, O.; Diéguez, M. J. Am. Chem. Soc. 2011,
133, 13634.
7. See for instance (a) Diéguez, M.; Pàmies, O.; Claver, C. Chem. Rev. 2004, 104,
3189; (b) Boysen, M. M. K. Chem. Eur. J. 2007, 13, 8648; (c) Benessere, V.; Del
Litto, R.; De Roma, A.; Ruffo, F. Coord. Chem. Rev. 2010, 254, 390; (d) Woodward,
S.; Diéguez, M.; Pàmies, O. Coord. Chem. Rev. 2007, 2010, 254; (e) van Leeuwen,
P. W. N. M.; Kamer, P. C. J.; Claver, C.; Pàmies, O.; Diéguez, M. Chem. Rev. 2011,
111, 2077.
4.4.7. [Ir(cod)(2d)]BArF
Yield: 75 mg (97%). 31P NMR (CD2Cl2), d: 90.9. 1H NMR (CD2Cl2),
d: 1.23 (s, 9H, CH3, tBu), 1.32 (s, 3H, CH3), 1.49 (s, 3H, CH3), 1.53 (s,
t
9H, CH3, Bu), 1.71 (s, 3H, CH3), 1.83 (s, 3H, CH3), 1.92 (b, 2H, CH2,
cod), 2.26 (b, 2H, CH2, cod), 2.33 (b, 4H, CH2, cod), 3.01 (m, 1H,
CH@, cod), 3.24 (m, 1H, H-4), 3.29 (m, 1H, H-6), 3.47 (m, 1H, H-
5), 3.69 (m, 1H, H-2), 3.97 (m, 2H, CH@ cod and H-6’), 4.39 (m,
2
1H, CH@ cod), 4.61 (d, 1H, CH2-Ph, JH–H = 12.4 Hz), 4.70 (d, 1H,
2
3
CH2-Ph, JH–H = 12.4 Hz), 4.92 (m, H-3), 5.03 (d, 1H, H-1, J1–
2 = 3.2 Hz), 5.07 (s, 1H, H-7), 5.57 (m, 1H, CH@ cod), 6.02 (m, 1H,
NH), 6.7–7.7 (m, 26H, CH@), 8.81 (m, 2H, CH@). 13C NMR (CD2Cl2),
d: 16.8 (CH3), 16.9 (CH3), 20.4 (CH3), 20.9 (CH3), 25.1 (b, CH2, cod),
26.3 (b, CH2, cod), 28.9 (b, CH2, cod), 29.3 (b, CH2, cod), 32.2 (CH3,
tBu), 32.5 (CH3, tBu), 34.4 (C, tBu), 34.6 (C, tBu), 59.0 (C-3), 63.5 (C-
4), 68.4 (C-6), 69.7(b, CH@, cod), 71.0 (CH2-Ph), 75.9 (b, CH@, cod),
77.1 (C-2), 79.6 (C-5), 98.3 (C-1), 102.9 (C-7), 103.4 (b, CH@, cod),
106.8 (b, CH@, cod), 117.6 (b, CH@, BArF), 120–134 (aromatic car-
bons), 135.0 (b, CH@, BArF), 136–158 (aromatic carbons), 161.9 (q,
1
C-B, BArF, JC–B = 49.5 Hz), 166.2 (C@O). Anal. calcd (%) for
C90H81BF24IrN2O8P: C 53.82, H 4.06, N 1.39; found: C 53.77, H
4.03, N 1.36.
4.5. Typical procedure for the hydrogenation of olefins
The alkene (0.5 mmol) and Ir complex (2 mol%) were dissolved
in CH2Cl2 (2 mL) in a high-pressure autoclave, which was purged
four times with hydrogen. Next, it was pressurized at the desired
pressure. After the desired reaction time, the autoclave was
depressurized and the solvent evaporated off. The residue was dis-
solved in Et2O (1.5 ml) and filtered through a short Celite plug. The
enantiomeric excess was determined by chiral GC or chiral HPLC
and conversions were determined by 1H NMR. The enantiomeric
excesses of the hydrogenated products were determined using
the previously described conditions.5
Acknowledgements
We would like to thank the Spanish Government for providing
Grant CTQ2010-15835, the Catalan Government for Grant
2009SGR116, and the ICREA Foundation for providing M. Diéguez
and O. Pàmies with financial support through the ICREA Academia
awards. M. Lega and F. Ruffo thank the Ministero dell’Istruzione,
dell’Università e della Ricerca (Italy) for financial support (PRIN
2009LR88XR).
8. (a) Baek, J. Y.; Shin, Y.; Jeon, H. B.; Kim, K. S. Tetrahedron Lett. 2005, 46(31),
5143; (b) Benessere, V.; De Roma, A.; Ruffo, F. ChemSusChem 2008, 1, 425.
9. Pàmies, O.; Diéguez, M.; Net, G.; Ruiz, A.; Claver, C. Organometallics 2000, 19,
1488.
10. Jongsma, T.; Fossen, D.; Challa, G.; van Leeuwen, P. W. N. M. J. Mol. Catal. 1993,
83, 17.