Asymmetric hydrogenation of allylic alcohols using ir?N,P-Complexes

Article abstract of DOI:10.1021/acscatal.6b02456

In this study, a series of γ,γ-disubstituted and β,γ-disubstituted allylic alcohols were prepared and successfully hydrogenated using suitable N,P-based Ir complexes. High yields and excellent enantioselectivities were obtained for most of the substrates studied. This investigation also revealed the effect of the acidity of the N,P?Ir-complexes on the acid-sensitive allylic alcohols. DFT ΔpK_a calculations were used to explain the effect of the N,P-ligand on the acidity of the corresponding Ir-complex. The selectivity model of the reaction was used to accurately predict the absolute configuration of the hydrogenated alcohols.

Full text of DOI:10.1021/acscatal.6b02456

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Article
Asymmetric hydrogenation of allylic alcohols using Ir-N,P-complexes.
Jia-Qi Li, Jianguo Liu, Suppachai Krajangsri, Napasawan
Chumnanvej, Thishana Singh, and Pher G. Andersson
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.6b02456 • Publication Date (Web): 31 Oct 2016
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Asymmetric hydrogenation of allylic alcohols using Ir-N,P-
complexes.
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JiaꢀQi Li,[a] Jianguo Liu,[b] Suppachai Krajangsri,[b] Napasawan Chumnanvej,[b] Thishana Singh[b] and
Pher G. Andersson*[b]
[a] Department of Applied Chemistry, China Agricultural University, Beijing, 100193, China (jiaqili@cau.edu.cn)
[b] Department of Organic Chemistry, Stockholm University, 106 91, Stockholm, Sweden. (Pher.Andersson@su.se)
KEYWORDS asymmetric synthesis • γ,γ-disubstituted allylic alcohols • β,γ-disubstituted allylic alcohols • DFT • iridium •
hydrogenation
ABSTRACT: In this study, a series of γ,γꢀdisubstituted and β,γꢀdisubstituted allylic alcohols were prepared and successfully hyꢀ
drogenated using suitable N,Pꢀbased Irꢀcomplexes. High yields and excellent enantioselectivities were obtained for most of the
substrates studied. This investigation also revealed the effect of the acidity of the N,PꢀIrꢀcomplexes on the acid sensitive allylic
alcohols. DFT ꢀpKa calculations was used to explain the effect of the N,Pꢀligand on the acidity of the corresponding Irꢀcomplex.
The selectivity model of the reaction was used to accurately predict the absolute configuration of the hydrogenated alcohols.
Introduction
observed as a competitive process when using Rh, Ru and Irꢀ
complexes in the hydrogenation, especially at low pressure.16
Overall, allylic alcohols remain challenging substrates in tranꢀ
sitionꢀmetal catalysed asymmetric hydrogenation.
Enantioenriched alcohols provide a valuable feedstock for
the synthesis of bioactive natural products1 and pharmaceutiꢀ
cals2 since the hydroxyl group can be readily transformed to
other functional groups, most often in a high stereospecific
manner.3 Furthermore derivatives of alcohols bearing stereoꢀ
genic centers on the βꢀ and or γꢀcarbon also exist widely in
natural products,4 pharmaceuticals,5 agrochemicals6 and fraꢀ
grances.7 Transitionꢀmetal catalyzed asymmetric hydrogenaꢀ
tion has emerged as one of the most powerful tools for the
preparation of chiral compounds in both academic research
and industrial production. Some attractive features of this
transformation include high enantioselectivity, low catalyst
loadings, high yields, mild reaction conditions and nearꢀ
perfect atom economy.8
The N,Pꢀligated Irꢀcomplexes have recently proved to be
effective catalysts for the asymmetric hydrogenation of alꢀ
kenes having little or no functionality.8a,17 It has been shown
that alkenes bearing Lewis basic substituents can coordinate to
Ir and this effect may influence the performance of catalysts in
the hydrogenation process.18 It is wellꢀknown that Crabtree's
iridium catalyst often shows a high tendency to coordinate to
alcohol groups in the substrate resulting in highly diastereoseꢀ
lective hydrogenations. This was studied by Stork and coꢀ
workers where it was discovered that there was coordination
to Ir in the hydrogenation of both homoallylic and allylic
alcohols
using
Crabtree’s
catalyst
The enantioselective reduction of allylic alcohols constitutes
a useful and practical route affording the corresponding optiꢀ
cally active alcohols in a single step.9 Originally, Rhꢀ and Ruꢀ
diphosphine complexes were utilized and high enantioselectivꢀ
ities have been obtained. Rhꢀcomplexes generally result in
high ees for the asymmetric hydrogenation of allylic alcohols
bearing at least one aryl group on the γꢀcarbon.10 When Rh
complexes are employed as catalysts, high catalyst loading
and often long reaction times are required.11 Despite the high
enantioselectivities achieved using Ru catalysts, the scope of
the reaction, especially considering substrates bearing aliphatꢀ
ic substituents is quite limited.12 Highly diastereoselective
hydrogenations of allylic alcohols have also been achieved
using Nꢀheterocyclic carbenes (NHCs), Nꢀbased Irꢀ
complexes.13 For asymmetric hydrogenation using Irꢀ
complexes, only a few catalysts have been shown to give high
enantioselctivities14 and the reduction often resulted in comꢀ
plex mixtures.15 Notably, the isomerization of C=C is often
[(PCy)3(Pyridine)Ir(COD)]+[PF6]ꢀ.19 However there exists no
clear evidence for this coordination in asymmetric iridiumꢀ
catalysed hydrogenations, where the monodentate phosphine
and pyridine ligands have been replaced by a bulky, bidentate
chiral N,Pꢀligand. In a computational study carried out by
Burgess and coꢀworkers, it was found that a 2ꢀsubstituted
allylic alcohol (2ꢀmethylbutꢀ2ꢀenꢀ1ꢀol) did not coordinate to Ir
during the hydrogenation.20 Also, recent studies by Pfaltz did
not provide any evidence for strong coordination between the
hydroxyl group and Ir.14d,21
Successful examples of asymmetric hydrogenations of alꢀ
lylic alcohols with Irꢀcomplexes do exist.14,17b,22 There are
numerous derivatives of (E)ꢀcinnamyl alcohols that have been
hydrogenated with high enantioselectivity, but the (Z)ꢀ
cinnamyl alcohols usually gave lower reactivities and selectivꢀ
ities.14d Dialkylsubstituted allylic alcohols were also difficult
to hydrogenate in high enantioselectivities.23 In fact, it has
been shown in the Irꢀcatalyzed asymmetric hydrogenation, that
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high enantioselectivities are easy to obtain for alkenes bearing enantioselectivities and yields. Substrates 4ꢀ6 gave excellent
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at least one aryl substituent on the prochiral carbon. This is
partially attributed to πꢀπ interaction between the aryl ring and
the catalyst.24 Pure alkyl substituted alkenes usually result in
low ees in this transformation. This is possibly due to the
similar size of the substituents and the lack of interaction
between the substrate and catalyst resulting in the difficulty to
ees and over 95% isolated yields.
Chiral diarylmethine compounds are present in numerous
natural products and bioactive compounds.28 The diarylꢀ subꢀ
stituted allylic alcohol 729 was employed in the hydrogenation
and produced excellent results: 96% yield and 95% ee.
Table 1. Asymmetric hydrogenation of γ-substituted cin-
0b
distinguish the Re and Si faces in the hydrogenation process.1
namyl alcohols[a]
Overall, the substrate scope in the Irꢀcatalyzed asymmetric
hydrogenation of allylic alcohols is still limited. Moreover,
dialkyl and (Z)ꢀallylic alcohols remain difficult substrates in
transitionꢀmetal catalyzed asymmetric hydrogenation. Thus,
there is still room to explore new complexes for the efficient
hydrogenation of diverse allylic alcohols.
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We have previously shown the highly enantioselective hyꢀ
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drogenation of functionalized olefins using IrꢀN,P catalysts.2
As an extension of our study, we now report the asymmetric
hydrogenation of a wide range of disubstituted allylic alcohols
with the intention to study the substrate scope in the Irꢀ
catalyzed asymmetric hydrogenation.
Figure 1. Catalysts used in this study.26
Results and Discussion
The asymmetric hydrogenation of γꢀsubstituted cinnamyl
alcohol was chosen for the initial study (Table 1). In the hyꢀ
drogenation of (E)ꢀallylic alcohol 1, catalyst A (Figure 1) gave
an excellent ee of 98% and a high isolated product yield was
also obtained. No isomerization product, 3ꢀphenylbutanal, was
1
detected by H NMR under the reaction conditions used. The
impact of steric and electronic effects on the enantioselectivity
is often a problem in the Irꢀcatalyzed asymmetric reaction27
and we were pleased to see that significant structure variation
in the substituents on C=C was tolerated without affecting the
ee in this hydrogenation. Electron donating or withdrawing
groups at the para position of the aryl ring only affected the
hydrogenation slightly (substrates 2 and 3). The resulting
chiral saturated alcohols were obtained with excellent yields
and enantioselectivities. Sterically bulkier substituents (ethyl,
isopropyl and cyclohexyl) had no significant influence on
[a] Reaction conditions: 0.25 mmol of substrate, 1.0 mol % cataꢀ
lyst, 2 mL of CH2Cl2, 50 bar H2. 17h, r.t. [b] Isolated product
yields. [c] Determined by chiral GC or HPLC analysis, see Supꢀ
porting Information for details. [d] Assignment of absolute conꢀ
figuration is based on literature reference. [e] Absolute configuraꢀ
tion of the hydrogenated product was tentatively assigned based
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on elution order. [f] Reaction carried out under 100 bar H2. [g]
ly demanding cyclohexyl group as the substituent (substrate
Conversion determined by 1H NMR.
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17) resulted in a much lower enantioselectivity. In the asymꢀ
metric hydrogenation of (Z)ꢀcrotyl alcohols, complex C was
found to be the most selective catalyst. Only the neopentyl
substituted allylic alcohol 21 gave a poor ee. Interestingly,
when the steric hindrance of the substituent became smaller
(ethyl, 2ꢀphenylethyl and benzyl) or larger (cyclohexyl), exꢀ
cellent enantioselectivities (over 90% ees) were obtained
(substrates 18, 19, 20 and 22).
When compared to a similar study of the hydrogenation of
diarylꢀsubstituted allylic alcohols using an imidazole catalyst,
this hydrogenation does not need a special solvent, α,α,αꢀ
trifluorotoluene, and was carried out at 50 bar H2 instead of
100 bar H2.14a Recently, Ding and coꢀworkers reported a Rhꢀ
catalysed asymmetric hydrogenation of β,βꢀdiarylpropionic
acids prepared from the hydroxylation of 3,3ꢀdiarylacrylates.
Similar enantioselectivities (up to 96% ee) were achieved,
however, in that case a mixedꢀligand approach had to be used
in order to obtain enough activity and morpholine had to be
used as base.30
Table 2. Asymmetric hydrogenation of dialkyl substituted
allylic alcohols[a]
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The influence of the stereochemistry of the C=C on both reacꢀ
tivity and enantioselectivities are frequently observed in hyꢀ
drogenation reactions. In contrast to (E)ꢀconfigured alkenes,
the corresponding (Z)ꢀalkenes are usually more difficult to
hydrogenate and generally result in lower enantioselectivities
in the Irꢀcatalysed asymmetric hydrogenation.21 However,
substituted (Z)ꢀconfigured cinnamyl alcohols were also sucꢀ
cessfully hydrogenated. Higher catalyst loading, H2 pressure
or longer reaction time were not required to achieve full conꢀ
version when using the same substrate concentration and temꢀ
perature as (E)ꢀolefins. Instead, enantioselectivities were
found to be sensitive to the steric bulk of the substituent close
to the C=C. In the hydrogenation of (Z)ꢀallylic alcohols 8 and
9, complex C was found to be the most selective catalyst. The
methyl substituted substrate 8 gave an excellent ee of 95%,
whereas only 86% ee was obtained for the ethyl derivative 9.
An excellent ee of 93% was obtained in the hydrogenation of
nꢀBu substituted allylic alcohol 10. Complex D was the most
selective catalyst for the hydrogenation of sterically more
demanding substrates (substrates 11 and 12). Perfect selectiviꢀ
ty (98% ee) was obtained for the hydrogenation of cyclohexyl
substituted substrate 12. The reduction of (Z)ꢀconfigured subꢀ
strates 8ꢀ12 was very clean with excellent isolated product
yields of between 92ꢀ98% being attained. No double bond
isomerization products, aldehydes or (E)ꢀconfigured allylic
alcohols were detected under the reaction conditions used.
Diol 13 was also successfully hydrogenated. As the synthetic
equivalent of 2ꢀsubstituted succinic acid derivatives, the hyꢀ
drogenation product can function as valuable and important
building blocks in the syntheses of biologically active comꢀ
pounds and natural products.38
With a few exceptions, high enantioselectivities have previꢀ
ously only been reported for alkenes bearing aryl groups on
C=C. Pure alkyl substituted alkenes are still considered chalꢀ
lenging substrates in the asymmetric hydrogenation using Irꢀ
N,Pꢀcomplexes.8a,17 High enantioselectivities and diastere-
oselectivities have been achieved in the hydrogenation of
allylic alcohols bearing two or more C=C bonds8a e.g. farnesol
and with a stereogenic center adjacent to the C=C bond.13
However, the diversity of substrates was quite limited. In a
previous study on the hydrogenation of γ,γꢀdialkylsubstituted
allylic alcohols, (E)ꢀ and (Z)ꢀ3ꢀmethylꢀ5ꢀphenylpentꢀ2ꢀenꢀ1ꢀol,
gave only moderate enantioselectivities (64% ee for (E)ꢀ
configured isomer and 69% ee for the (Z)ꢀisomer) using Irꢀ
PHOX complex.23 In the asymmetric hydrogenation of (E)ꢀ 3ꢀ
methylꢀ5ꢀphenylpentꢀ2ꢀenꢀ1ꢀol 14, catalyst B proved to be the
best catalyst in the catalyst screening. Substrates 14ꢀ16, bearꢀ
ing 3ꢀphenylpropyl, benzyl and neopentyl on C=C, gave good
to excellent enantioselectivities (78ꢀ91% ees). A more stericalꢀ
[a]ꢀ[e] See the corresponding footnotes in Table 1. [f] Absolute
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configuration of the hydrogenated product was tentatively asꢀ
Table 3. Correlation of observed and predicted absolute
configurations.
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signed based on specific optical rotation. [g] Absolute configuraꢀ
tion of the hydrogenated product was tentatively assigned based
on elution order and specific optical rotation. [h] Reaction carried
out with 1.5 mol % catalyst under 100 bar H2. [i] Reaction carried
out under 100 bar H2. [j] Conversion determined by 1H NMR.
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Nevertheless, the asymmetric hydrogenation of all dialkylsubꢀ
stituted substrates gave the corresponding saturated alcohols in
excellent isolated yields. For substrates 23, 24 and 25, the
substituent was varied from ethyl to isopropyl and cyclohexyl.
Both the yield and ee for 24 decreased however for the larger
cyclohexyl 25, it increased. The cyclic allylic alcohol 26 gave
high ee whereas the more strained 5ꢀmembered substrate 27
was hydrogenated with a lower yield and ee which is also
consistent with previous findings.48 Hydrogenation of two β,γꢀ
dialkyl substituted allylic alcohols was also attempted. Comꢀ
plex J was the most selective catalyst for substrate 28 and
catalyst C gave the best results for allylic alcohol 29. The
resulting saturated alcohols of these two aliphatic allylic subꢀ
strates has numerous applications.49 Hydrogenation of geraniol
and nerol was also attempted under the standard hydrogenaꢀ
tion conditions. (See Supporting Information for details.)
However, both the C2/C3 and C6/C7 double bonds were hyꢀ
drogenated. Similar observations have been reported with Ir(I)
complexes.50
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Hence, the absolute configuration of the major product
formed in the asymmetric hydrogenation of a trisubstituted
olefin using this type of catalyst can be predicted by determinꢀ
ing if the ligand places the substituent of the Nꢀheterocycle
above or below the N–Ir–P plane (Figure 2b).
The mechanism of Irꢀcatalyzed asymmetric hydrogenation
of unfunctionalized olefins proceeding first through migratoryꢀ
insertion and then a reductiveꢀelimination sequence involving
[IrIII(H)2(alkene)(H2)(N,P)]+ and [IrV(H)3(alkyl)(N,P)]+ as the
key reactive intermediates was originally supported by Densiꢀ
ty Functional Theory (DFT) calculations51 and has recently
been investigated by an experimental study.52 In this catalytic
cycle, olefin coordination occurs cis to the chelating N, and is
followed by the migratoryꢀinsertion step. A simple quadrant
model can be derived from this coordination and rationalizes
the observed enantioselectivities based on this IrIII/IrV pathway
in which the migratoryꢀinsertion is considered as the rateꢀ and
enantioꢀdetermining step for the hydrogenation of trisubstitutꢀ
ed olefins.53 The space surrounding Ir in an IrꢀN,Pꢀcomplex is
divided into four quadrants (Figure 2a). It is clear that the
space occupied by the orthoꢀ substituent of sp2ꢀhybridized
nitrogen on the heterocyclic ring is the most hindered quadrant.
Thus, the trisubstituted olefin orients its smallest substituent, a
vinylic proton, toward the most hindered quadrant when it
coordinates to Ir.
The absolute configurations of the majority of the allylic alꢀ
cohol products are known and reported in the literature (Table
1 and 2). This data was used to evaluate the selectivity model
with a variety of substrates. By comparing the specific optical
rotation and/or GCꢀMS/HPLC elution order, it was found that
the stereochemistries of all the saturated alcohols investigated
in the asymmetric hydrogenation are consistent with the preꢀ
dicted configurations from the selectivity model (Table 3).
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Figure 2. Quadrant model for predicting the absolute configuration in the asymmetric hydrogenation of trisubstituted alkenes
using Ir-N,P-complexes. a) steric environment around Ir. b) 3-D model for asymmetric hydrogenation of allylic alcohols 10 and 12.
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Transitionꢀmetalꢀhydride complexes can be considered as
potential Lewis acids or Brønsted acids.54 There are a number
of transformations catalyzed by metalꢀhydrides based on their
acidity.55 Moreover, reactivities of these complexes and the
results of reactions they catalyze, are directly related to their
acidities which are presented as pKa values.56 The N,P and
NHCs, Nꢀbased Irꢀcomplexes are the two major types of cataꢀ
lysts that are chiral mimics of Crabtree’s catalyst and are used
in the asymmetric hydrogenation of olefins with or without
coordinating functional groups. In our previous study27a of the
asymmetric hydrogenation of some acid sensitive enol ethers
using N,P based Irꢀcomplexes, base had to be added in the
hydrogenation to avoid side reactions that may be caused by
proton generation by the Ir catalyst. Base was also required
using NHCsꢀbased Irꢀcomplexes.57 Recently, Burgess and coꢀ
workers showed that NHCsꢀbased Irꢀcomplexes are less acidic
than N,P based Irꢀcomplexes. This difference in acidity can be
explained by the electronic features of the NHCs and the
phosphine ligands. The NHCs is a superior σꢀdonor and an
inferior πꢀacceptor, this results in a more electron rich comꢀ
plex from which protons are more difficult to dissociate from
Ir.58
The pKaH of the parent 5ꢀmembered protonated heterocyꢀ
cles is as follows: imidazole has a pKaH of 7.0 and is classified
as a medium strong base; thiazole is less basic with a pKaH of
2.5 and oxazole has a pKaH of 0.8 (Figure 3a). The experiꢀ
mental pKaH were measured in dimethylsulfoxide.59
The ꢀG values for the metal hydrides in the deprotonation
reactions as depicted in the acidꢀbase relationship (Figure 3a)
was calculated and used to generate the ꢀpKa values. Since
one pKa unit corresponds to 1.37 kcal.molꢀ1 difference in free
energy,60 ꢀpKa values were calculated for the Irꢀcomplexes
(Figure 3b) in dimethylsulfoxide and dichloromethane. A
similar trend for the ꢀpKa values was observed in both solꢀ
vents. (Calculation details and XYZ coordinates with energies
are available in the Supporting Information.) The oxazole
complex I was calculated to have the lowest energy. The enerꢀ
gy differences were then measured relative to complex I
which was set to zero.
Allylic alcohols can be considered as relatively acid sensiꢀ
tive compounds. Protonation of the hydroxyl group and subseꢀ
quent elimination of water, results in the generation of an allyl
carbocation. It was assumed that the reason for the complex
mixture of reaction products that was observed in some of the
hydrogenations was due to the formation of carbocation interꢀ
mediates. Several allylic alcohols that can generate different
types of carbocations were tested in the hydrogenation using a
set of catalysts based on different heterocycles.
In this work, a number of different Nꢀheterocyclic ligand
donors have been studied which includes imidazoles (complex
F, G), thiazoles (complex A, D, E) and oxazoles (complex I).
A combination of DFT energy calculations and experimental
studies indicates that the basicity of the Nꢀheterocycles has a
significant contribution on the relative acidity of the correꢀ
sponding N,Pꢀbased Irꢀcomplexes.
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Figure 3. a) Acid-base relationship of metal hydrides. b) pKaH of the protonated heterocycles and trend depicting the decrease of
ꢀpKa values in dichloromethane as the N donors varied.
tertiary allylic alcohol 33 was used as substrate, an intramoꢀ
lecular Friedel–Crafts reaction took place instead of hydroꢀ
genation (Scheme 1).
Figure 4. Performance of Ir-complexes in hydrogenation of
acid sensitive compounds.
Scheme 1. Intramolecular Friedel–Crafts alkylation cata-
lyzed by Ir-complexes under H2
In the hydrogenation of primary allylic alcohol 30, excellent
yields (over 99%) were obtained with all catalysts. This is
possibly due to the difficulty in the formation of the primary
carbocation. When the secondary allylic alcohol 31, bearing a
methyl group on the allylic position, was applied in the hydroꢀ
genation the amount of desired hydrogenation products follow
the order F > G > E > H > I which is consistent with the deꢀ
creasing basicity of the heterocycle in the ligand (Figure 4).
Racemic 36 (determined by chiral HPLC analysis) was obꢀ
tained as the sole product and the C=C hydrogenation product
38 could not be detected by 1H NMR. The FriedelꢀCrafts
product 36 is a tetrasubstituted olefin which is usually difficult
to hydrogenate using IrꢀN,P catalysts.61 The cyclization of
allylic alcohol 33 has earlier been reported to take place using
62
strongly acidic conditions (Brønsted acid, e.g. FSO3HꢀSO2
and Lewis acid, e.g FeCl3·6H2O63) as depicted in Scheme 1.
The hydrogenation of the acid sensitive enol acetate was also
attempted. When 39 with an alkyl substituent was used as
substrate, only the imidazole complex F gave full conversion
and excellent yield. No conversions were observed using
catalyst G, E, H and I. The hydrogenation of the phenyl subꢀ
The same trend was observed for the hydrogenation of the
phenyl substituted secondary allylic alcohol 32 and resulted in
a lower yield of hydrogenated product since the generation of
the carbocation is easier when the phenyl group is in the alꢀ
lylic position. Furthermore, when the diphenyl substituted
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stituent enol acetate 40 resulted in complex mixtures with all
catalysts.
[8]
For recent reviews, see: a) Woodmansee, D. H.; Pfaltz, A. Chem.
Commun. 2011, 47, 7912ꢀ7916. b) Cadu, A.; Andersson, P. G. J. Orꢀ
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Acc. Chem. Res. 2015, 48, 1494ꢀ1502. g) Li, Y.ꢀY.; Yu, S.ꢀL.; Shen,
W.ꢀY.; Gao, J.ꢀX. Acc. Chem. Res. 2015, 48, 2587ꢀ2598.
1
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8
Conclusion
High yields and excellent enantioselectivities were obtained
for most of the substrates studied using various IrꢀN,Pꢀ
complexes. The ꢀpKa values that have been calculated for the
Irꢀcomplexes using DFT indicate that there is a trend in the
decrease of the acidity of the metal hydrides with increasing
basicity of the heterocyclic ligand. The selectivity model was
successfully used to confirm the observed and predicted absoꢀ
lute configuration of the products of hydrogenation.
[9]
Wu, R.; Beauchamps, M. G.; Laquidara, J. M.; Sowa, J. R. Angew.
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ASSOCIATED CONTENT
Supporting Information
Experimental procedures, spectroscopic and computational data.
This material is available free of charge via the Internet at
http://pubs.acs.org
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Lett. 1985, 14, 1007ꢀ1008. b) Takaya, H.; Ohta, T.; Sayo, N.;
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AUTHOR INFORMATION
Corresponding Author
[13] For a review, see: Zhu, Y.; Burgess, K. Acc. Chem. Res. 2012, 45,
Pher.Andersson@.su.se
1623ꢀ1636.
ACKNOWLEDGMENT
[14] a) Tolstoy, P.; Engman, M.; Paptchikhine, A.; Bergquist, J.; Church, T.
L.; Leung, A. W. M.; Andersson, P. G. J. Am. Chem. Soc. 2009, 131,
8855ꢀ8860. b) Lu, W.ꢀJ.; Chen, Y.ꢀW.; Hou, X.ꢀL. Adv. Synth. Catal.
2010, 352, 103ꢀ107. c) Rageot, D.; Pfaltz, A. Helv. Chim. Acta. 2012,
95, 2176ꢀ2193. d) Bernasconi, M.; Ramella, V.; Tosatti, P.; Pfaltz, A.
Chem.ꢀEur. J. 2014, 20, 2440ꢀ2444.
The Swedish Research Council (VR), Stiftelsen Olle Engkvist
Byggmastare and The Swedish Energy Agency supported this
work. All computations were carried out using the computational
cluster resources at the National Supercomputer Center based at
Linköping University, Sweden. JiaꢀQi Li thanks the National
Natural Science Foundation of China (No. 21402234) and Chiꢀ
nese Universities Scientific Fund (2014XJ034). Jianguo Liu
thanks the Guangzhou Elite Scholarship Council for the PhD
fellowship. Napasawan Chumnanvej thanks VR/SIDA for the
threeꢀmonth exchange fellowship to Stockholm University.
Thishana Singh acknowledges the NRF South Africa and the
College of Agriculture, Engineering and Science, University of
KwazuluꢀNatal, South Africa for the Postdoctoral Research Felꢀ
lowship.
[15] a) Verendel, J. J.; Andersson, P. G. Dalton Trans. 2007, 36, 5603ꢀ
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G. Adv. Synth. Catal. 2008, 350, 1168ꢀ1176.
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ABBREVIATIONS
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COD 1,5ꢀcyclooctadiene; DFT Density Functional Theory;
GC/MS Gas Chromatography Mass Spectroscopy; HPLC High
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Figure 1. Catalysts used in this study.
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Table 1. Asymmetric hydrogenation of γ-substituted cinnamyl alcohols
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Table 2. Asymmetric hydrogenation of dialkyl substitut-ed allylic alcohols
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Table 3. Correlation of observed and predicted absolute configurations.
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Figure 4. Performance of Ir-complexes in hydrogenation of acid sensitive compounds.
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Scheme 1. Intramolecular Friedel–Crafts alkylation catalyzed by Ir-complexes under H2
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Graphical Abstract
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