Extending the substrate scope of bicyclic p-oxazoline/thiazole ligands for ir-catalyzed hydrogenation of unfunctionalized olefins by introducing a biaryl phosphoroamidite group

Article abstract of DOI:10.1002/chem.201405361

This study identifies a series of Ir-bicyclic phosphoroamidite-oxazoline/thiazole catalytic systems that can hydrogenate a wide range of minimally functionalized olefins (including E- and Z-tri- and disubstituted substrates, vinylsilanes, enol phosphinates, tri- and disubstituted alkenylboronic esters, and ?±,?2-unsaturated enones) in high enantioselectivities (ee values up to 99%) and conversions. The design of the new phosphoroamidite-oxazoline/thiazole ligands derives from a previous successful generation of bicyclic N-phosphane-oxazoline/thiazole ligands, by replacing the N-phosphane group with a p-acceptor biaryl phosphoroamidite moiety. A small but structurally important family of Ir-phosphoroamidite-oxazoline/thiazole precatalysts has thus been synthesized by changing the nature of the Ndonor group (either oxazoline or thiazole) and the configuration at the biaryl phosphoroamidite moiety. The substitution of the N-phosphane by a phosphoroamidite group in the bicyclic N-phosphane-oxazoline/thiazole ligands extended the range of olefins that can be successfully hydrogenated.

Full text of DOI:10.1002/chem.201405361

DOI: 10.1002/chem.201405361
Full Paper
&
Ligand Design
Extending the Substrate Scope of Bicyclic P-Oxazoline/Thiazole
Ligands for Ir-Catalyzed Hydrogenation of Unfunctionalized
Olefins by Introducing a Biaryl Phosphoroamidite Group
Maria Biosca,[a] Alexander Paptchikhine,[b] Oscar Pꢀmies,[a] Pher G. Andersson,*[b] and
Montserrat Diꢁguez*[a]
Abstract: This study identifies a series of Ir-bicyclic phos-
phoroamidite–oxazoline/thiazole catalytic systems that can
hydrogenate a wide range of minimally functionalized ole-
fins (including E- and Z-tri- and disubstituted substrates, vi-
nylsilanes, enol phosphinates, tri- and disubstituted alkenyl-
boronic esters, and a,b-unsaturated enones) in high enantio-
selectivities (ee values up to 99%) and conversions. The
design of the new phosphoroamidite–oxazoline/thiazole li-
gands derives from a previous successful generation of bicy-
clic N-phosphane–oxazoline/thiazole ligands, by replacing
the N-phosphane group with a p-acceptor biaryl phosphor-
oamidite moiety. A small but structurally important family of
Ir-phosphoroamidite–oxazoline/thiazole precatalysts has
thus been synthesized by changing the nature of the N-
donor group (either oxazoline or thiazole) and the configura-
tion at the biaryl phosphoroamidite moiety. The substitution
of the N-phosphane by a phosphoroamidite group in the bi-
cyclic N-phosphane–oxazoline/thiazole ligands extended the
range of olefins that can be successfully hydrogenated.
Introduction
line ligands (PHOX); cod=1,5-cyclooctadiene) to a limited
range of minimally functionalized olefins.[5] Pfaltz and other
groups then focused on Ir catalysts based on a wide range of
new ligands (mainly P,N compounds), which significantly
broadened the substrate scope. Most of the ligand designs
were based on replacing the phosphane moiety in previous
PHOX ligands with a phosphinite or a carbene group,[6] and
the oxazoline moiety with other nitrogen groups such as pyri-
dine,[7] thiazole,[8] oxazole,[9] and imidazole.[10,11] The latest
breakthrough in the design of ligands for Ir-catalyzed hydroge-
nation was the substitution of the phosphinite/phosphane
group by a p-acceptor biaryl phosphite moiety. In this context,
it was recently shown that the presence of biaryl-phosphite
groups in the ligand increases activity and substrate versatili-
ty.[12] Several mixed phosphite-nitrogen compounds have thus
emerged as extremely effective ligands that provide better
substrate versatility than earlier Ir-phosphinite/phosphane-N
systems and higher activities and enantioselectivities for many
largely unfunctionalized E/Z-trisubstituted and 1,1-disubstitut-
ed olefins. Although Ir-PN catalysts are powerful tools for re-
ducing minimally functionalized olefins and they complement
Rh/Ru catalysts, their activity and selectivity for some signifi-
cant substrates still need to be improved if they are to be
used to synthesize more complex molecules. Therefore, novel,
easy to handle, readily accessible, and highly efficient chiral li-
gands that enhance the application range still need to be
found. Here, we report the successful application of a small
but structurally valuable library of phosphoroamidite–oxazo-
line/thiazole ligands L1–L4 (Figure 1) in the Ir-catalyzed hydro-
genation of a large number of minimally functionalized al-
Chirality is a fundamental property of a wide variety of techno-
logically and biologically interesting products. Enormous ef-
forts are being made to discover enantioselective routes that
can be used to create stereogenic centers.[1] Of these routes,
asymmetric hydrogenation is one of the most efficient, sustain-
able, and straightforward. This approach can be used to ach-
ieve high selectivity, has perfect atom economy, and is opera-
tionally simple.[1,2] For this process, the use of Rh/Ru-PP based
catalysts is well known, but it normally requires substrates with
a good coordination group close to the C=C double bond to
achieve high selectivity.[1–3] To address this limitation, the asym-
metric reduction of olefins with chiral Ir-PN catalysts has
emerged as an effective and straightforward method for pro-
ducing complex chiral compounds from simple olefins.[4] In
1998, Pfaltz et al. reported the first successful application of an
[Ir(PN)(cod)]BArF chiral catalyst library (PN=phosphane–oxazo-
[a] M. Biosca, Dr. O. Pꢀmies, Prof. M. Diꢁguez
Departament de Quꢂmica Fꢂsica i Inorgꢀnica
Universitat Rovira i Virgili, Campus Sescelades
C/Marcel·lꢂ Domingo, s/n. 43007 Tarragona (Spain)
E-mail: montserrat.dieguez@urv.cat
[b] Dr. A. Paptchikhine, Prof. P. G. Andersson
Department of Organic Chemistry, Arrhenius Laboratory
Stockholm University, 106 91, Stockholm (Sweden)
E-mail: phera@organ.su.se
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201405361.
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Scheme 1. Synthetic route used for the synthesis of new phosphoroamidite–
oxazoline/thiazole ligands L1–L4: a) p-NO2-CbzCl, NaOH, dioxane/H2O, RT
(86% yield); b) EDC, HOBt, 2-amino-2,2-diphenylethanol, CH2Cl2, RT (83%
yield); c) MsCl, NEt3, CH2Cl2, 08C (79% yield); d) Pd/C, H2, EtOH, RT (61%
yield); e) Boc2O, THF/H2O, RT (72% yield); f) NH4HCO3, Py, dioxane (90%
yield); g) Lawesson’s reagent, THF, RT (87% yield); h) phenacyl bromide,
CaCO3, MeOH, reflux (80% yield); i) HCl, THF, RT (97% yield); j) ClP(OR)2, NEt3,
toluene, 808C (36–64% yield).
Figure 1. Phosphoroamidite–oxazoline/thiazole ligands L1–L4.
kenes, with the addition of concrete examples with neighbor-
ing polar groups.
The new ligands are based on a first successful generation
of bicyclic N-phosphane–oxazoline/thiazole ligands[6h,8g] in
which the N-phosphane group is replaced by a p-acceptor
biaryl phosphoroamidite moiety. The previous generation of bi-
cyclic N-phosphane–oxazoline/thiazole ligands was one of the
best-performing ligand families developed for Ir-catalyzed hy-
drogenation, and they proved to be highly efficient in the hy-
drogenation of many minimally functionalized aryl–alkyl E-tri-
substituted olefins.[6h,8g,13] Despite this, the enantioselectivity
achieved by using these ligands for such important substrates
as Z-analogues, 1,1-disubstituted olefins, and some com-
pounds containing weakly coordinating groups still needs to
be improved. With the simple biaryl phosphoroamidite–oxazo-
line/thiazole design introduced here (Figure 1), we expect to
increase substrate versatility in the hydrogenation of largely
unfunctionalized olefins. Interestingly, in addition to having the
fundamental advantages of the p-acceptor properties of the
phosphoroamidite moiety, ligands L1–L4 are also more robust
to air and other oxidizing agents than phosphanes and phos-
phinites and they are easily synthesized from readily available
alcohols. Although phosphoroamidite-based ligands have been
successfully used in other enantioselective reactions,[14] their
potential as a source of highly effective chiral ligands in Ir-cata-
lyzed hydrogenation remains unexplored.[15]
presence of triethylamine provided direct access to the desired
phosphoroamidite–oxazoline/thiazole ligands L1–L4. All li-
gands were stable during purification on neutral silica under
an atmosphere of argon and all were isolated as white solids.
The ligands were stable in air and very stable to hydrolysis, so
further manipulation/storage was carried out in air. Elemental
analyses and HRMS-ESI spectra were consistent with the as-
signed structure. The ligands were also characterized by
1
31P{1H}, H, and 13C{1H} NMR spectroscopy. The spectral assign-
1
ments, based on H–1H and 13C–1H correlation measurements,
were as expected for these C1-symmetric ligands.
Synthesis of Ir catalyst precursors
The Ir catalyst precursors were prepared in a two-step, one-pot
procedure (Scheme 2). First, [{Ir(m-Cl)(cod)}2] reacts with one
Results and Discussion
Scheme 2. Synthetic route used for the synthesis of catalyst precursors
[Ir(cod)(L1–L4)]BArF.
Synthesis of ligands
The sequence of ligand synthesis is summarized in Scheme 1.
Ligands L1–L4 were synthesized very efficiently from the ap-
propriate, easily accessible amino-oxazoline 1 and amino-thia-
zole 2 compounds.[8g,16] Compounds 1 and 2 were prepared in
four and five steps, respectively, by following previously report-
ed procedures from (1S,3R,4R)-2-azabicyclo[2.2.1]heptane-3-car-
boxylic acid (3),[17] which is readily available on a multigram
scale from a stereoselective aza-Diels–Alder reaction. The last
step of the synthesis is the same for all ligands (Scheme 1,
step j). Treating compounds 1 and 2 with one equivalent of
the appropriate phosphorochloridite formed in situ[18] in the
À
equivalent of the appropriate ligand. Then, ClÀ/BArF counter-
ion exchange was achieved by reaction with NaBArF in the
presence of water. The iridium catalyst precursors were isolat-
ed in pure form as air-stable orange solids in excellent yields
(92–96%) after simple extraction workup. No further purifica-
tion was required. The elemental analyses were consistent with
the assigned structures. The HRMS-ESI spectra of [Ir(cod)(L1–
L4)]BArF displayed the m/z signals for the heaviest ions that
correspond to the loss of the BArF anion from the molecular
species. The H, 13C, and 31P NMR spectra show the expected
1
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pattern for these C1-complexes. Variable-temperature (VT) NMR
spectra in CD2Cl2 (+35 to À858C) showed that only one
isomer was present in solution. In all cases, one singlet in the
31P-{1H} NMR spectra was observed.
Asymmetric Ir-catalyzed hydrogenation of trisubstituted
substrates
The asymmetric hydrogenation of minimally functionalized tri-
substituted olefins is highly dependent on the olefin geome-
try.[4] In this respect, Z-trisubstituted olefins are commonly hy-
drogenated less enantioselectively than the corresponding E
isomers. To evaluate the efficiency of ligands L1–L4 in the hy-
drogenation of olefins with different geometry, we initially
tested the ligands in the asymmetric reduction of the model
substrate S1 and the hydrogenation of Z-substrate S2
(Table 1). In general, the enantioselectivities were found to be
Table 1. Ir-catalyzed hydrogenation of S1 and S2 using ligands L1–L4.[a]
Entry
Ligand
Conv. [%][b]
ee [%][c]
Conv. [%][b]
ee [%][c]
1
2
3
4
5[d]
L1
L2
L3
L4
L3
100
100
100
100
100
92 (R)
37 (R)
95 (R)
95 (R)
95 (R)
100
100
100
100
100
82 (S)
3 (S)
97 (S)
56 (S)
97 (S)
Figure 2. Selected results for the hydrogenation of trisubstituted olefins S3–
S22 by using [Ir(cod)(L1–L4)]BArF catalyst precursors. Reaction conditions:
Catalyst precursor (2 mol%), CH2Cl2, H2 (50 bar), 4 h.
[a] Reaction conditions: Substrate (0.5 mmol), Ir catalyst precursor
(2 mol%), H2 (50 bar), CH2Cl2 (2 mL), RT; [b] conversion measured by
1H NMR spectroscopic analysis after 2 h; [c] enantiomeric excess deter-
mined by GC analysis; [d] reaction carried out at 0.25 mol% of Ir catalyst
precursor for 3 h.
tion). We again found that the ligand components must be se-
lected to suit each substrate to obtain the highest enantiose-
lectivity. With the aim of comparing these results with the first
generation of ligands and the state-of-art catalytic systems for
each substrate, we have collected the results in Table SI-3 in
the Supporting Information.
highly dependent on the configuration of the biaryl phosphor-
oamidite group. Reactions conducted with ligands containing
an S-binaphthyl phosphoroamidite group proceeded with the
highest enantioselectivities for both substrates (Table 1, en-
tries 1 vs. 2). However, whereas for substrate S1 the nature of
the N-donor group had little effect on enantioselectivity, for
the more demanding substrate S2, the presence of the thia-
zole group had a positive effect on enantioselectivity. Of the
four ligands, phosphoroamidite–thiazole ligand L3 provided
excellent activities and enantioselectivities for both substrate
types (ee values up to 97%; Table 1, entry 3), thus overcoming
one of the limitations encountered with the parent N-phos-
phane–oxazoline/thiazole ligands in the reduction of Z-olefin
S2 (ee values up to 83%[19]). We also studied these reactions at
a low catalyst loading (0.25 mol%) using ligand L3, which had
provided the best results, and the excellent enantioselectivities
were maintained (Table 1, entry 5).
We first considered the reduction of substrates S3 and S4,
which differ from S1 in the substituent in the aryl ring and the
substituents trans to the aryl group. For both substrates, Ir-L3
also provided excellent enantioselectivities (up to 98%). For
the more demanding dihydronaphthalenes S5–S7, enantiose-
lectivities were as high as 70% but, unlike (Z)-S2, using the Ir/
L1 catalytic system. Remarkably, the Ir/L3 catalyst also provid-
ed high enantioselectivities in the reduction of triaryl-substitut-
ed substrates S8 and S9 (ee values up to 91%), surpassing the
enantioselectivities obtained by using the first generation of li-
gands. This latter substrate class has received little atten-
tion,[8f,11c,12e] although it provides an easy entry point to diary-
lmethine chiral centers, which are present in several important
drugs.[20] We then looked into the hydrogenation of a broad
range of key trisubstituted olefins with neighboring polar
groups. Hydrogenation of these olefins is of particular interest
because they can be further functionalized and become impor-
tant intermediates for more complex chiral molecules. Interest-
ingly, the reduction of allylic alcohol S10 and vinylsilane S11
To further establish the versatility of the reaction with the
new ligands L1–L4, we selected a representative family of sub-
strates, some of which contained poorly coordinative groups;
the most noteworthy results are shown in Figure 2 (for a com-
plete series of results, see Table SI-1 in the Supporting Informa-
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with Ir/L3 proceeded with higher enantioselectivities than
those achieved when the first generation of bicyclic N-phos-
phane–oxazoline/thiazole ligands was used.[8g,13a] The Ir/L1 cat-
alytic system can also hydrogenate the sterically demanding
enol phosphinates S12–S16 with high enantioselectivities that
were comparable to those achieved with the first generation
of ligands, which constitute the state-of-art for this substrate
class.[13b] The effective hydrogenation of this type of substrate
opens up an appealing route to chiral organophosphinates,
which can be easily transformed into high-value compounds
such as alcohols and phosphanes. The excellent results ob-
tained up to this point encouraged us to test the hydrogena-
tion of a,b-unsaturated enones S17–S20, for which the related
N-phosphane–oxazoline/thiazole counterparts provided low
enantiocontrol.[21] Although hydrogenation of this type of sub-
strate is an elegant path to ketones with a stereogenic center
in the a-position to the carbonyl moiety, such substrates have
been less studied and less successfully hydrogenated than
other trisubstituted olefins.[6i,w] We found that a range of
enones could be hydrogenated with excellent enantioselectivi-
ties that were comparable to the best values previously report-
ed. Interestingly, all four of the tested ligands provided similar
high enantioselectivities (96–98% ee for substrate S17; see the
Supporting Information) irrespective of the configuration of
the biaryl phosphoroamidite group and the nature of the N-
donor group. This indicates that the backbone of the bicyclic
phosphoroamidite–N ligand is particularly well suited to the
specific electronic and steric requirements of a,b-unsaturated
enones. We also found that hydrogenation of S17–S20 yields
products with opposite configuration to those achieved with
the other E-trisubstituted olefins studied. This behavior has
been observed previously and has been attributed to the
strong polarization of the double bond.[4h,8i]
Asymmetric Ir-catalyzed hydrogenation of 1,1-disubstituted
substrates
Unlike trisubstituted olefins, 1,1-disubstituted olefins have not
been successfully hydrogenated until very recently.[4e,h] This is
because the catalyst has the added difficulty of controlling not
only the face selectivity coordination (only two substituents
compared with the three of trisubstituted olefins), but also the
isomerization of the olefins to form the more stable E-trisubsti-
tuted substrates, which are hydrogenated to form the opposite
enantiomer.[4e,h] To estimate how effective systems with ligands
L1–L4 are at reducing this type of substrate, we first studied
the hydrogenation of substrates S23 and S24, which have dif-
ferent steric requirements at the alkyl chain (Table 2). In addi-
tion, whereas substrate S23 is prone to isomerization, S24
cannot isomerize. In all cases, full conversions were achieved
by using 1 bar of H2.[24]
Table 2. Ir-catalyzed hydrogenation of S23 and S24 using ligands L1–
L4.[a]
Entry
Ligand
Conv. [%][b]
ee [%][c]
Conv. [%][b]
ee [%][c]
1
2
3
4
5[d]
L1
L2
L3
L4
L1
100
100
100
100
100
13 (R)
3 (S)
65 (S)
40 (S)
12 (R)
100
100
100
100
100
93 (S)
69 (S)
76 (S)
68 (S)
93 (S)
[a] Reaction conditions: substrate (0.5 mmol), Ir catalyst precursor
(2 mol%), H2 (1 bar), CH2Cl2 (2 mL), RT; [b] conversion measured by
1H NMR spectroscopic analysis after 2 h; [c] enantiomeric excess deter-
mined by GC analysis; [d] reaction carried out with 0.25 mol% of Ir cata-
lyst precursor for 3 h.
We finally turned our attention to the asymmetric reduction
of alkenylboronic esters. Among the existing methods for pre-
paring chiral organoboron compounds, this is one of the most
sustainable and most straightforward. The synthesis of chiral
organoboron compounds has recently received considerable
attention; they are valuable organic intermediates because the
CÀB bond can be readily transformed into chiral CÀN, CÀO,
and CÀC bonds. In this field, the reduction of alkenylboronic
esters has been less investigated, and only a few catalytic sys-
tems have been used effectively.[11d,13c,22] Our results show that
by correctly choosing the N-donor group (thiazole rather than
oxazoline) and the configuration of the biaryl group (R for S21
and S for S22) of the ligand, excellent enantioselectivities can
be achieved for the reduction of two types of alkenylboronic
esters containing either one or two (pinacolato)boron groups.
The enantioselectivities achieved are among the best reported,
and they surpass those obtained with the first generation of li-
gands.[11d,13c,22]
We found that the effect of the ligand parameters on enan-
tioselectivity is different for the two substrates. Whereas for
S23 the effect is like that observed for S1 and S2 (the enantio-
selectivity was highest with phosphoroamidite–thiazole ligand
L3), the enantioselectivity for S24 was best with the phosphor-
oamidite–oxazoline ligand L1. We also found that enantioselec-
tivities are highly dependent on the nature of the alkyl chain
of the substrate (Table 2). Whereas enantioselectivities up to
93% can be achieved with S24, only moderate enantiocontrol
was obtained in the reduction of S23 (up to 65% ee). This sug-
gests that competition between isomerization and direct hy-
drogenation may be responsible for the moderate enantiose-
lectivities achieved by using S23. However, face selectivity
issues cannot be excluded.
To address this point, we performed deuterium labeling ex-
periments (Scheme 3). For this purpose we performed the re-
duction of S1 and S23 with deuterium. In contrast to S1, the
reduction of S23 with deuterium led to the incorporation of
deuterium not only at the expected positions (direct addition
to the double bond) but also at the allylic position, which is in-
dicative of the presence of a competing isomerization process.
In summary, the simple substitution of the N-phosphane by
a phosphoroamidite group in the bicyclic N-phosphane–oxazo-
line/thiazole ligands extended the range of hydrogenated tri-
substituted olefins and led to enantioselectivities that, for
most of the substrates, were among the best reported so far
(see Table SI-3 in the Supporting Information).[23]
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Scheme 3. Deuterium labeling experiments with substrates S1 and S23. The
percentage of incorporation of deuterium atoms is shown in parentheses.
It has been suggested that this isomerization process can pro-
ceed either through the formation of Ir-p-allyl intermediates or
through protonation of the double bond at the terminal posi-
tion, which gives a stabilized carbocation.[6d,25] Accordingly, the
mass spectra data of the resulting deuterated products, in the
deuterium addition to S23, indicated the presence of reduced
species with more than two deuterium atoms incorporated
into the product.
We also studied these reactions at low catalyst loading
(0.25 mol%) and found that the catalytic performance was
maintained (Table 2, entry 5).
Figure 3. Selected results for the hydrogenation of 1,1-disubstituted olefins
S25–S41 by using [Ir(cod)(L1–L4)]BArF catalyst precursors. Reaction condi-
tions: Catalyst precursor (2 mol%), CH2Cl2, H2 (1 bar), 4 h. [a] Reactions car-
ried out for 8 h; [b] reaction carried out at 50 bar H2 for 12 h.
In line with the observed isomerization, similar moderate
enantioselectivities were achieved in the hydrogenation of
substrates S25–S28 irrespective of the steric demands of the
alkyl substituents (Figure 3).
trolled, thus facilitating the reduction of a broad range of 1,1-
disubstituted substrates with high enantioselectivities that
were comparable for most of the substrates (except for olefins
prone to isomerization) to the best reported so far. Once
again, the introduction of the biaryl phosphoroamidite group
was also advantageous compared with related bicyclic N-phos-
phane–oxazoline/thiazole counterparts that have been effi-
ciently applied in the hydrogenation of very few 1,1-disubsti-
tuted substrates.[8g,13b,c,26a] See Table SI-4 in the Supporting In-
formation to compare these results with the first generation of
ligands and the state of art systems for each substrate.
We then focused on evaluating how the electronic and
steric properties of the aryl group of the substrate affected the
catalytic performance. For this purpose, a wide range of a-tert-
butylstyrene type substrates (S29–S35) were tested (Figure 3).
Advantageously, we found that enantioselectivity (ee values up
to 98%) is relatively insensitive to changes in the electronic
and steric properties of the aryl group. However, the highest
enantioselectivity of the series was achieved in the hydrogena-
tion of substrates containing either electron-withdrawing
groups at the para-position (S29) or substituents at the ortho-
position (S34 and S35) of the aryl group.
Conclusion
Finally, we also investigated the hydrogenation of relevant
1,1-disubstituted olefins containing neighboring polar groups
(Figure 3, substrates S36–S41). We were again able to fine
tune the ligand to obtain high to excellent enantioselectivities
(ee values up to 98%). The results are among the best reported
for each substrate, even in the reduction of such highly ap-
pealing substrates as enol phosphinates S38 and S39[26] and
pinacolatoboron-containing substrates S40[27] and S41,[28] for
which only very few catalytic systems have provided high
enantioselectivities. It should be noted that although S41 is
prone to isomerization, it has been hydrogenated with high
enantioselectivity.
We have identified new Ir-bicyclic phosphoroamidite–oxazo-
line/thiazole catalytic systems that can hydrogenate a wide
range of minimally functionalized olefins (including E- and Z-
tri- and disubstituted substrates, vinylsilanes, enol phosphi-
nates, tri- and disubstituted alkenylboronic esters and a,b-un-
saturated enones) with enantioselectivities up to 99% and
with high conversions. These catalytic systems were derived
from a previous successful generation of Ir-bicyclic N-phos-
phane–oxazoline/thiazole catalysts, by replacing the N-phos-
phane group of the ligand with a p-acceptor biaryl phosphor-
oamidite moiety. The simple substitution of the N-phosphane
by a phosphoroamidite group extended the range of olefins
that could be successfully hydrogenated, and furnished enan-
tioselectivities that were comparable, for most of the sub-
In summary, although isomerization was not completely sup-
pressed by introducing a biaryl phosphoroamidite group, the
face coordination mode of the substrate was successfully con-
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633.2307; elemental analysis calcd (%) for C41H33N2O3P: C 77.83, H
5.26, N 4.43; found: C 77.81, H 5.24, N 4.39.
strates, to the best reported so far. In this respect, the new Ir-
phosphoroamidite–oxazoline/thiazole catalysts have been able
to efficiently hydrogenate not only minimally functionalized
model olefins (i.e., S1, S2, S4, and S10), but also a wide range
of demanding olefins (S5–S9 and S11–S41) that have recently
received a great deal of attention because the resulting hydro-
genated compounds can be easily stereoselectively trans-
formed into high-value organic compounds. Therefore, the ef-
fective hydrogenation of these substrates with the Ir-bicyclic
phosphoroamidite–oxazoline/thiazole catalysts reported in the
present study opens up an appealing route that is more effi-
cient, straightforward, sustainable, and selective than alterna-
tive methods.[29] Another important advantage of the new li-
gands over previous bicyclic N-phosphane–oxazoline/thiazole
ligands, is that they are solid and stable to air. The ligands are
therefore easier to handle and can be manipulated and stored
in air.
Ligand L2: Yield: 114 mg (36%); [a]2D3 =À112.24 (c=0.1 in CH2Cl2);
31P NMR (161.9 MHz, C6D6, 258C): d=146.2 ppm (s); 1H NMR
2
(400 MHz, C6D6, 258C): d=0.56 (d, J(H,H)=10.0 Hz, 1H; CH2), 0.85
(m, 1H; CH2), 1.10 (m, 2H; CH2), 1.72 (m, 1H; CH2), 1.82 (b, 1H;
CH2) 2.46 (b, 1H; CH), 3.63 (b, 1H; CH), 3.97 (s, 1H; CH), 4.47 (d,
2
2J(H,H)=8.8 Hz, 1H; CH2), 4.56 (d, J(H,H)=8.8 Hz, 1H; CH2), 6.86–
7.67 ppm (m, 12H, CH=); 13C NMR (100.6 MHz, C6D6, 258C): d=28.7
(CH2), 33.6 (CH2), 43.6 (CH), 46.1 (CH2), 54.1 (C), 57.6 (CH), 62.5 (d,
2J(C,P)=19.2 Hz; CH), 81.4 (CH2), 123.1–168.5 ppm (Ar); TOF-MS
(ESI+): m/z calcd for C41H33N2O3P: 633.2307 [M+H]+; 633.2304; ele-
mental analysis calcd (%) for C41H33N2O3P: C 77.83, H 5.26, N 4.43;
found: C 77.80, H 5.24, N 4.37.
Ligand L3: Yield: 182 mg (64%); [a]2D3 = +188.18 (c=0.11 in
CH2Cl2); 31P NMR (161.9 MHz, C6D6, 258C): d=155.5 ppm (s);
1H NMR (400 MHz, C6D6, 258C): d=0.65 (d, 2J(H,H)=10.0 Hz, 1H;
CH2), 0.80 (m, 1H; CH2), 1.10 (m, 1H; CH2), 1.22 (m, 1H; CH2), 1.80
3
(b, 2H; CH2), 2.45 (b, 1H; CH), 3.40 (b, 1H; CH), 4.63 (d, J(H,P)=
4.0 Hz, 1H; CH), 6.82–7.98 ppm (m, 13H; CH=); 13C NMR
(100.6 MHz, C6D6, 258C): d=28.3 (CH2), 32.5 (CH2), 36.2 (CH2), 46.4
(CH), 59.1 (CH), 66.3 (d, 2J(C,P)=24.2 Hz; CH), 133.7–176.4 ppm
(Ar); TOF-MS (ESI+): m/z calcd for C35H27N2O2PS: 571.1609 [M+H]+;
found: 571.1599; elemental analysis calcd (%) for C35H27N2O2PS: C
73.67, H 4.77, N 4.91, S 5.62; found: C 73.69, H 4.76, N 4.87, S 5.57.
Experimental Section
General considerations
All reactions were carried out by using standard Schlenk tech-
niques under an argon atmosphere. Solvents were purified and
dried by standard procedures. Phosphorochloridites were easily
prepared in one step from the corresponding binaphthols.[18] Inter-
mediate amine–oxazoline/thiazole compounds 1[16] and 2[8g] were
prepared as reported previously. Neutral silica (pH 7, 0.040–
Ligand L4: Yield: 163 mg (57%); [a]2D3 =À133.64 (c=0.11 in
CH2Cl2); 31P NMR (161.9 MHz, C6D6, 258C): d=147.5 ppm (s);
1H NMR (400 MHz, C6D6, 258C): d=0.76 (d, 2J(H,H)=10.0 Hz, 1H;
CH2), 1.10 (m, 1H; CH2), 1.23 (m, 1H; CH), 1.78 (m, 1H; CH2), 1.98
2
(d, J(H,H)=10.0 Hz, 1H; CH2), 2.40 (b, 1H; CH), 3.84 (b, 1H; CH),
4.78 (d, 3J(C,P)=3.2 Hz, 1H; CH), 6.86–8.07 ppm (m, 13H; CH=);
13C NMR (100.6 MHz, C6D6, 258C): d=28.2 (CH2), 33.5 (CH2), 36.7
(CH2), 46.7 (CH), 58.7 (CH), 65.4 (d, 2J(C,P)=17.4 Hz; CH), 113.3–
175.8 ppm (Ar); TOF-MS (ESI+): m/z calcd for C35H27N2O2PS:
571.1609 [M+H]+; found: 571.1602; elemental analysis calcd (%)
for C35H27N2O2PS: C 73.67, H 4.77, N 4.91, S 5.62; found: C 73.64, H
4.75, N 4.87, S 5.59.
0.063 mm) was purchased from Merck. H, 13C, and 31P NMR spectra
1
were recorded with a 400 MHz spectrometer. Chemical shifts are
relative to that of SiMe4 (1H and 13C) as internal standard or H3PO4
(31P) as external standard. 1H and 13C assignments were made
based on the results of 1H-1H gCOSY and 1H-13C gHSQC experi-
ments.
Preparation of phosphoroamidite–oxazoline/thiazole ligands
L1–L4: General procedure
General procedure for the preparation of [Ir(cod)(L1–
L4)]BArF
The corresponding phosphorochloridite (0.5 mmol) produced in
situ was dissolved in toluene (2 mL), and triethylamine (0.3 mL,
2.15 mmol) was added. The amino-oxazoline/thiazole compound
(0.5 mmol) was azeotropically dried with toluene (3ꢃ3 mL) and
then dissolved in toluene (2 mL) to which triethylamine (0.3 mL,
2.15 mmol) was added. The phosphorochloridite solution was then
transferred slowly to the amino-oxazoline/thiazole solution. The re-
action mixture was stirred at 808C for 2 h, after which the triethyla-
mine salts were removed by filtration. Evaporation of the solvent
gave a white foam, which was purified by flash chromatography
on neutral silica (dichloromethane as eluent) to produce the corre-
sponding ligand as a white solid.
The corresponding ligand (0.074 mmol) was dissolved in CH2Cl2
(5 mL), and [{Ir(m-Cl)(cod)}2] (25.0 mg, 0.037 mmol) was added. The
reaction mixture was heated to reflux at 408C for 1 h. After 5 min
at RT, NaBArF (77.2 mg, 0.080 mmol) and water (5 mL) were added
and the reaction mixture was stirred vigorously for 30 min at RT.
The phases were separated and the aqueous phase was extracted
twice with CH2Cl2. The combined organic phases were dried with
MgSO4, filtered through a plug of Celite, and the solvent was
evaporated to give the product as an orange solid.
[Ir(cod)(L1)]BArF: Yield: 127 mg (96%); 31P NMR (161.9 MHz, CDCl3,
1
258C): d=112.0 ppm (s); H NMR (400 MHz, CDCl3, 258C): d=1.26
(s, 7H; CH2 and CH), 1.56 (m, 4H; CH2, cod), 1.90 (m, 2H; CH2, cod),
2.04 (m, 1H; CH2, cod), 2.27 (m, 1H; CH2, cod), 2.43 (m, 1H; CH),
3.91 (m, 1H; CH=, cod), 4.35 (m, 1H; CH), 4.49 (b, 1H; CH=, cod),
4.61 (d, 2J(H,H)=9.2 Hz, 1H; CH=, cod), 5.21 (d, 2J(H,H)=9.2 Hz,
2H; CH2), 6.68–8.02 ppm (m, 32H, CH=); 13C NMR (100.6 MHz,
CDCl3, 258C): d=22.9 (b; CH2, cod), 27.2 (CH2), 27.4 (b; CH2, cod),
29.9 (CH), 30.6 (CH2), 31.0 (b; CH2, cod), 34.1 (CH2), 38.7 (b; CH2,
cod), 57.6 (CH=, cod), 58.5 (CH), 62.0 (CH=, cod), 62.4 (CH), 82.6
(CPh2), 86.6 (CH2), 97.7 (CH=, cod), 101.3 (CH=, cod), 119.5–133 (Ar),
Ligand L1: Yield: 118 mg (37%); [a]2D3 = +102.41 (c=0.1 in CH2Cl2);
31P NMR (161.9 MHz, C6D6, 258C): d=153 ppm (s); 1H NMR
2
(400 MHz, C6D6, 258C): d=0.70 (d, J(H,H)=10.0 Hz, 1H; CH2,), 0.75
(m, 1H; CH2), 1.0 (m, 2H; CH2), 1.65 (m, 1H; CH2), 1.9 (b, 1H; CH2),
2.40 (b, 1H; CH), 3.35 (b, 1H; CH), 3.80 (b, 1H; CH), 4.47 (d,
2
2J(H,H)=8.4 Hz, 1H; CH2), 4.56 (d, J(H,H)=8.4 Hz, 1H; CH2), 6.80–
8.81 ppm (m, 12H; CH=); 13C NMR (100.6 MHz, C6D6, 258C): d=27.6
(CH2), 34.4 (CH2), 36.8 (CH2), 42.1 (CH), 53.5 (C), 58.2 (CH), 61.4 (d,
2J(C,P)=20.4 Hz; CH,), 80.6 (CH2), 122.3–167.4 ppm (Ar); TOF-MS
(ESI+): m/z calcd for C41H33N2O3P: 633.2307 [M+H]+; found:
1
135.0 (b; CH=, BArF), 136–149 (Ar), 162.0 (q, J(C,B)=49.8 Hz; C-B,
BArF,), 173.0 ppm (C=N); TOF-MS (ESI+): m/z calcd for
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C81H57BF24IrN2O3P: 933.2797 [MÀBArF]+; found: 933.2795; elemen-
tal analysis calcd (%) for C81H57BF24IrN2O3P: C 54.16, H 3.20, N 1.56;
found: C 54.13, H 3.16, N 1.53.
sat. NH4Cl (20 mL) was added and the mixture was extracted with
diethyl ether (3ꢃ25 mL). The organic phases were dried over anhy-
drous MgSO4. Removal of solvents gave a crude product, which
was purified by flash column chromatography on silica gel (100%
petroleum ether) to afford the corresponding 1,1’-disubstituted
olefin as a colorless oil.
[Ir(cod)(L2)]BArF: Yield: 123 mg (93%); 31P NMR (161.9 MHz, CDCl3,
1
258C): d=102.9 ppm (s); H NMR (400 MHz, CDCl3, 258C): d=1.21
(s, 7H; CH2 and CH), 1.59 (m, 4H; CH2, cod), 1.85 (m, 2H; CH2, cod),
2.01 (m, 1H; CH2, cod), 2.35 (m, 1H; CH2, cod), 3.50 (m, 1H; CH),
3.69 (m, 1H; CH), 4.27 (b, 1H; CH=cod), 4.58 (b, 1H; CH=cod), 4.68
(b, 1H; CH=cod), 4.95 (d, 2J(H,H)=9.2 Hz, 1H; CH2), 5.22 (d,
2J(H,H)=9.2 Hz, 1H; CH2), 5.29 (b, 1H; CH=cod), 7.0–8.3 ppm (m,
32H; CH=); 13C NMR (100.6 MHz, CDCl3, 258C): d=24.5 (b; CH2,
cod), 25.7 (CH2), 28.7 (b; CH2, cod), 29.4 (CH), 31.7 (CH2), 32.0 (b;
CH2, cod), 38.3 (CH2), 39.3 (b; CH2, cod), 57.5 (CH=, cod), 58.5 (CH),
62.3 (CH=, cod), 65.9 (CH), 82.9 (CPh2), 86.3 (CH2), 93.8 (CH=, cod),
100.5 (CH=, cod), 117.7 (b; CH=, BArF), 119–131 (Ar), 135.0 (b; CH=,
1-(3,3-Dimethylbut-1-en-2-yl)-4-methoxybenzene (S24): Yield:
695 mg (59%); 1H NMR (400 MHz, CDCl3, 258C): d=1.10 (s, 9H),
2
2
3.81 (s, 3H), 4.74 (d, J(H,H)=1.6 Hz, 1H), 5.14 (d, J(H,H)=1.6 Hz,
1H), 6.81–7.26 ppm (m, 4H); 13C NMR (100.6 MHz, CDCl3, 258C): d=
29.7, 36.2, 55.1, 111.6, 112.7, 130.0, 135.9, 158.1, 159.4 ppm; TOF-
MS (ESI+): m/z calcd for C13H18O: 191.1391 [M+H]+; found:
191.1390.
1-(3,3-Dimethylbut-1-en-2-yl)-4-(trifluoromethyl)benzene (S29):
Yield: 862 mg (61%); 1H NMR (400 MHz, CDCl3, 258C): d=1.18 (s,
9H), 4.80 (d, 2J(H,H)=1.6 Hz, 1H), 5.25 (d, 2J(H,H)=1.6 Hz, 1H),
7.23–7.61 ppm (m, 4H); 13C NMR (100.6 MHz, CDCl3, 258C): d=29.6,
36.1, 112.3, 124.4, 124.8 (q, 1J(C,F)=6.0 Hz), 129.3, 130.2,
158.7 ppm; TOF-MS (ESI+): m/z calcd for C13H15F3: 229.1159
[M+H]+; found: 229.1161.
1
BArF), 136–150 (Ar), 161.9 (q, J(C,B)=49.8 Hz; C-B, BArF), 173.3 ppm
(C=N); TOF-MS (ESI+): m/z calcd for C81H57BF24IrN2O3P: 933.2797
[MÀBArF]+; found: 933.2792; elemental analysis calcd (%) for
C81H57BF24IrN2O3P: C 54.16, H 3.20, N 1.56; found: C 54.12, H 3.16, N
1.52.
[Ir(cod)(L3)]BArF: Yield: 119 mg (93%); 31P NMR (161.9 MHz, CDCl3,
1-(3,3-Dimethylbut-1-en-2-yl)-4-methylbenzene
(S30):
Yield:
1
755 mg (70%); 1H NMR (400 MHz, CDCl3, 258C): d=1.17 (s, 9H),
258C): d=104.3 ppm (s); H NMR (400 MHz, CDCl3, 258C): d=1.26
2
2
(s, 7H; CH2 and CH), 1.36 (m, 2H; CH2, cod), 1.63 (m, 2H; CH2, cod),
1.73 (m, 2H; CH2, cod), 2.11 (m, 1H; CH2, cod), 2.25 (m, 1H; CH2,
cod), 2.77 (m, 1H; CH), 2.98 (m, 1H; CH), 3.36 (m, 1H; CH=cod),
4.39 (b, 1H; CH=cod), 4.47 (b, 1H; CH=cod), 4.84 (b, 1H; CH=cod),
5.00 (s, 1H; CH=), 6.7–8.2 ppm (m. 27H; CH=); 13C NMR
(100.6 MHz, CDCl3, 258C): d=25.3 (b; CH2, cod), 28.3 (CH2), 29.8 (b;
CH2, cod), 31.3 (CH), 31.7 (CH2), 32.9 (b; CH2, cod), 37.7 (CH2), 40.9
(b; CH2, cod), 53.7 (CH), 60.0 (CH), 62.3 (CH=, cod), 65.2 (CH=), 65.4
(CH=, cod), 94.5 (d, J(C,P)=21.3 Hz; CH=, cod), 103.6 (d, J(C,P)=
11.4 Hz; CH=, cod), 116.7 (C), 117.7 (b; CH=, BArF), 119–131 (Ar),
2.40 (s, 3H), 4.80 (d, J(H,H)=1.6 Hz, 1H), 5.21 (d, J(H,H)=1.6 Hz,
1H), 7.08–7.15 ppm (m, 4H); 13C NMR (100.6 MHz, CDCl3, 258C): d=
21.1, 29.7, 36.2, 111.5, 128.0, 128.9, 135.7, 140.6, 159.8 ppm; TOF-
MS (ESI+): m/z calcd for C13H18: 175.1442 [M+H]+; found:
175.1440.
1-(3,3-Dimethylbut-1-en-2-yl)-3-methylbenzene
(S32):
Yield:
486 mg (45%); 1H NMR (400 MHz, CDCl3, 258C): d=1.11 (s, 9H),
2
2
2.35 (s, 3H), 4.75 (d, J(H,H)=1.6 Hz, 1H), 5.15 (d, J(H,H)=1.6 Hz,
1H), 6.93–7.26 ppm (m, 4H); 13C NMR (100.6 MHz, CDCl3, 258C): d=
21.5, 29.7, 36.1, 111.3, 126.1, 126.9, 127.1, 129.7, 136.7, 143.4,
159.9 ppm; TOF-MS (ESI+): m/z calcd for C13H18: 175.1442 [M+H]+;
found: 175.1441.
1
135.0 (b; CH=, BArF), 136–148 (Ar), 161.9 (q, J(C,B)=49.8 Hz; C-B,
BArF), 170.8 ppm (C=N); TOF-MS (ESI+): m/z calcd for
C75H51BF24IrN2O2PS: 871.2090 [MÀBArF]+; found: 871.2087; elemen-
tal analysis calcd (%) for C75H51BF24IrN2O2PS: C 51.94, H 2.96, N 1.62,
S 1.85; found: C 54.89, H 2.94, N 1.59, S 1.81.
2-(3,3-Dimethylbut-1-en-2-yl)naphthalene (S33): Yield: 808 mg
(62%); 1H NMR (400 MHz, CDCl3, 258C): d=1.29 (s, 9H), 4.98 (d,
2J(H,H)=1.6 Hz, 1H), 5.38 (d, 2J(H,H)=1.6 Hz, 1H), 7.41–7.94 ppm
(m, 7H); 13C NMR (100.6 MHz, CDCl3, 258C): d=29.9, 36.5, 112.1,
125.6, 126.0, 126.7, 127.4, 127.7, 128.0, 128.1, 132.2, 133.0, 141.2,
159.9 ppm; TOF-MS (ESI+): m/z calcd for C16H18: 211.1442 [M+H]+;
found: 211.1443.
[Ir(cod)(L4)]BArF: Yield: 122 mg (95%); 31P NMR (161.9 MHz, CDCl3,
1
258C): d=102.5 ppm (s); H NMR (400 MHz, CDCl3, 258C): d=1.27
(s, 7H; CH2 and CH), 1.39 (m, 2H; CH2, cod), 1.56 (m, 2H; CH2, cod),
1.89 (m, 2H; CH2, cod), 2.07 (m, 1H; CH2, cod), 2.23 (m, 1H; CH2,
cod), 3.41 (m, 1H; CH=cod), 4.46 (b, 1H; CH=cod), 3.62 (m, 1H;
CH), 4.03 (b, 1H; CH=cod), 4.93 (m, 1H; CH), 5.00 (b, 1H; CH=cod),
5.35 (s, 1H; CH=), 7.1–8.3 ppm (m, 27H; CH=); 13C NMR
(100.6 MHz, CDCl3, 258C): d=24.9 (b; CH2, cod), 27.0 (CH2), 28.1 (b;
CH2, cod), 29.9 (CH), 31.2 (CH2), 32.8 (b; CH2, cod), 37.6 (CH2), 42.2
(b; CH2, cod), 58.7 (CH), 65.5 (CH), 65.9 (CH=), 66.0 (CH=, cod), 68.3
(CH=, cod), 97.6 (CH=, cod), 105.7 (CH=, cod), 117.2 (C), 117.7 (b;
CH=, BArF), 119–131 (Ar), 135.0 (b; CH=, BArF), 136–150 (Ar), 161.9
(q, 1J(C,B)=49.8 Hz; C-B, BArF), 172.6 ppm (C=N); TOF-MS (ESI+):
m/z calcd for C75H51BF24IrN2O2PS: 871.2090 [MÀBArF]+; found:
871.2084; elemental analysis calcd (%) for C75H51BF24IrN2O2PS: C
51.94, H 2.96, N 1.62, S 1.85; found: C 54.90, H 2.94, N 1.60, S 1.83.
1-(3,3-Dimethylbut-1-en-2-yl)-2-methylbenzene
(S34):
Yield:
518 mg (48%); 1H NMR (400 MHz, CDCl3, 258C): d=1.17 (s, 9H),
2
2
2.30 (s, 3H), 4.81 (d, J(H,H)=1.6 Hz, 1H), 5.34 (d, J(H,H)=1.6 Hz,
1H), 7.09–7.22 ppm (m, 4H); 13C NMR (100.6 MHz, CDCl3, 258C): d=
20.6, 29.9, 36.9, 112.3, 124.4, 126.4, 129.4, 129.9, 135.8, 142.6,
157.8 ppm; TOF-MS (ESI+): m/z calcd for C13H18: 175.1442 [M+H]+;
found: 175.1441.
1-(3,3-Dimethylbut-1-en-2-yl)naphthalene (S35): Yield: 730 mg
(56%); 1H NMR (400 MHz, CDCl3, 258C): d=1.20 (s, 9H), 4.98 (d,
2
2J(H,H)=1.6 Hz, 1H), 5.57 (d, J(HÀH)=1.6 Hz, 1H), 7.26–8.04 ppm
(m, 7H); 13C NMR (100.6 MHz, CDCl3, 258C): d=30.1, 37.0, 133.9,
124.6, 125.3, 125.4, 126.2, 126.8, 127.2, 128.0, 132.8, 133.6, 140.7,
156.6 ppm; TOF-MS (ESI+): m/z calcd for C16H18: 211.1442 [M+H]+;
found 211.1441.
General procedure for the preparation of substrates S24,
S29, S30, S32–S35
In a flame-dried Schlenk flask, methyltriphenylphosphonium bro-
mide (9.2 mmol) was stirred in anhydrous THF (40 mL). The solu-
tion was cooled to 08C and nBuLi (1.6m in hexane, 5.4 mL,
8.6 mmol) was added slowly. The reaction was stirred at 08C for
30 min, then aryl tert-butyl ketone[30] (6.2 mmol) in anhydrous THF
(6 mL) was added. The mixture was warmed to RT and, after 18 h,
General 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. The apparatus was pressurized to the desired
pressure and, after the required reaction time, the autoclave was
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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
TOF-MS (ESI+): m/z calcd for C13H20: 177.1599 [M+H]+; found:
177.1597.
1-(3,3-Dimethylbutan-2-yl)naphthalene (from S35): Enantiomeric
excess determined by GC analysis using a Chiraldex B-DM column
(100 kPa H2, 608C for 30 min, 38CminÀ1 until 1758C): tR =60.7 (S),
1
HPLC analysis and conversions were determined by H NMR spec-
troscopic analysis. The enantiomeric excesses of hydrogenated
products from S1 and S2,[9] S3,[31] S4 and S5,[9] S6 and S7,[32] S8
and S9,[8f] S10,[9] S11,[13a] S12–S16,[13b] S17,[6i] S18–S20,[33] S21,[13c]
S22,[22] S23,[9] S25 and S26,[31] S27 and S28,[12c] S31,[9] S36,[9] S37,[34]
S38,[26a] S39,[13b] and S40 and S41[22] were determined under the
conditions described previously.
1
61.0 min (R); H NMR (400 MHz, CDCl3, 258C): d=0.91 (s, 9H), 1.25
(d, J=6.8 Hz, 3H), 2.81 (q, J=6.8 Hz, 1H), 6.8–7.0 (m, 2H), 7.3–
8.2 ppm (m, 5H); 13C NMR (100.6 MHz, CDCl3, 258C): d=17.4, 28.6,
35.3, 41.7, 124.7, 125.3, 125.4, 125.5, 125.7, 126.7, 129.3, 133.5,
134.2, 142.6 ppm; TOF-MS (ESI+): m/z calcd for C16H20: 213.1599
[M+H]+; found: 213.1598.
1-(3,3-Dimethylbutan-2-yl)-4-methoxybenzene (from S24): Enan-
tiomeric excess determined by GC analysis using a Chiraldex B-DM
column (100 kPa H2, 608C for 30 min, 38CminÀ1 until 1758C): tR =
53.4 (S), 53.8 min (R); 1H NMR (400 MHz, CDCl3, 258C): d=0.78 (s,
9H), 1.16 (d, J=6.8 Hz, 3H), 2.42 (q, J=6.8 Hz, 1H), 3.71 (s, 3H),
6.72 (d, J=7.2 Hz, 2H), 6.94 ppm (d, J=7.2 Hz, 2H); 13C NMR
(100.6 MHz, CDCl3, 258C): d=16.0, 27.8, 33.7, 49.0, 55.2, 112.8,
129.8, 137.6, 157.6 ppm; TOF-MS (ESI+): m/z calcd for C13H20O:
193.1548 [M+H]+; found: 193.1547.
Acknowledgements
We thank the Spanish Government for providing grant
CTQ2013-40568-P, the Catalan Government for grant
2014SGR670, and the ICREA Foundation for providing M. Diꢁ-
guez and O. Pꢀmies with financial support through the ICREA
Academia awards. We also thank the Swedish Research Council
(VR), Stiftelsen Olle Engkvist Byggmꢄstare, The Swedish Energy
Agency and SYNFLOW (FP7) for supporting this work. We
thank Mr. Xu Quan for his help in the analysis of the deuterium
experiments.
1-(3,3-Dimethylbutan-2-yl)-4-(trifluoromethyl)benzene
(from
S29): Enantiomeric excess determined by GC analysis using a Chiral-
dex B-DM column (100 kPa H2, 608C for 30 min, 38CminÀ1 until
1
1758C): tR =41.1 (S), 42.0 min (R); H NMR (400 MHz, CDCl3, 258C):
d=0.83 (s, 9H), 1.14 (d, J=6.8 Hz, 3H), 2.44 (q, J=6.8 Hz, 1H), 7.27
(d, J=7.2 Hz, 2H), 7.53 ppm (d, J=7.2 Hz, 2H); 13C NMR
(100.6 MHz, CDCl3, 258C): d=15.8, 27.7, 32.9, 49.8, 124.3, 129.2,
142.1, 160.4 ppm; TOF-MS (ESI+): m/z calcd for C13H17F3: 231.1316
[M+H]+; found: 231.1317.
Keywords: asymmetric catalysis
design · iridium · P ligands
· hydrogenation · ligand
1-(3,3-Dimethylbutan-2-yl)-4-methylbenzene (from S30): Enantio-
meric excess determined by GC analysis using a Chiraldex B-DM
column (100 kPa H2, 608C for 30 min, 38CminÀ1 until 1758C): tR =
39.3 (S), 39.7 min (R); 1H NMR (400 MHz, CDCl3, 258C): d=0.82 (s,
9H), 1.23 (d, J=6.8 Hz, 3H), 2.33 (s, 3H), 2.43 (q, J=6.8 Hz, 1H),
7.06 ppm (m, 5H); 13C NMR (100.6 MHz, CDCl3, 258C): d=15.9, 21.0,
27.8, 33.9, 49.5, 128.1, 128.9. 143.2, 163.0 ppm; TOF-MS (ESI+): m/z
calcd for C13H20: 177.1599 [M+H]+; found: 177.1598.
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1-(3,3-Dimethylbutan-2-yl)-3-methylbenzene (from S32): Enantio-
meric excess determined by GC analysis using a Chiraldex B-DM
column (100 kPa H2, 608C for 30 min, 38CminÀ1 until 1758C): tR =
41.7 (S), 42.5 min (R); 1H NMR (400 MHz, CDCl3, 258C): d=0.79 (s,
9H), 1.18 (d, J=6.8 Hz, 3H), 2.26 (s, 3H), 2.44 (q, J=6.8 Hz, 1H),
6.92 (m, 3H), 7.06 ppm (m, 1H); 13C NMR (100.6 MHz, CDCl3, 258C):
d=15.9, 21.6, 27.9, 33.8, 49.8, 126.1, 126.5, 127.3, 129.9, 144.2,
162.3 ppm; TOF-MS (ESI+): m/z calcd for C13H20: 177.1599 [M+H]+;
found: 177.1598.
2-(3,3-Dimethylbutan-2-yl)naphthalene (from S33): Enantiomeric
excess determined by GC analysis using a Chiraldex B-DM column
(100 kPa H2, 608C for 30 min, 38CminÀ1 until 1758C): tR =63.5 (S),
1
63.7 min (R); H NMR (400 MHz, CDCl3, 258C): d=0.93 (s, 9H), 1.36
(d, J=6.8 Hz, 3H), 2.41 (q, J=6.8 Hz, 1H), 6.8–7.0 (m, 2H), 7.2–
7.8 ppm (m, 5H); 13C NMR (100.6 MHz, CDCl3, 258C): d=15.9, 27.9,
34.0, 50.0, 125.0, 125.6, 126.6, 127.2, 127.5, 127.7, 128.1, 132.1,
133.1, 142.9 ppm; TOF-MS (ESI+): m/z calcd for C16H20: 213.1599
[M+H]+; found: 213.1597.
1-(3,3-Dimethylbutan-2-yl)-2-methylbenzene (from S34): Enantio-
meric excess determined by GC analysis using a Chiraldex B-DM
column (100 kPa H2, 608C for 30 min, 38CminÀ1 until 1758C): tR =
39.8 (S), 40.5 min (R); 1H NMR (400 MHz, CDCl3, 258C): d=0.83 (s,
9H), 1.23 (d, J=6.8 Hz, 3H), 2.37 (s, 3H), 2.93 (q, J=6.8 Hz, 1H),
6.9–7.2 ppm (m, 5H); 13C NMR (100.6 MHz, CDCl3, 258C): d=16.7,
20.9, 27.8, 34.8, 42.9, 125.3, 127.6, 130.8, 136.2, 144.2, 166.2 ppm;
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Published online on January 7, 2015
Chem. Eur. J. 2015, 21, 3455 – 3464
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