Indene Derived Phosphorus-Thioether Ligands for the Ir-Catalyzed Asymmetric Hydrogenation of Olefins with Diverse Substitution Patterns and Different Functional Groups

Article abstract of DOI:10.1002/adsc.202100069

A family of phosphite/phosphinite-thioether ligands have been tested in the Ir-catalyzed asymmetric hydrogenation of a range of olefins (50 substrates in total). The presented ligands are synthesized in three steps from cheap indene and they are air-stable solids. Their modular architecture has been crucial to maximize the catalytic performance for each type of substrate. Improving most Ir-catalysts reported so far, this ligand family presents a broader substrate scope, covering different substitution patterns with different functional groups, ranging from unfunctionalized olefins, through olefins with poorly coordinative groups, to olefins with coordinative functional groups. α,β-Unsaturated acyclic and cyclic esters, ketones and amides werehydrogenated in enantioselectivities ranging from 83 to 99% ee. Enantioselectivities ranging from 91 to 98% ee were also achieved for challenging substrates such as unfunctionalized 1,1′-disubstituted olefins, functionalized tri- and 1,1′-disubstituted vinyl phosphonates, and β-cyclic enamides. The catalytic performance of the Ir-ligand assemblies was maintained when the environmentally benign 1,2-propylene carbonate was used as solvent. (Figure presented.).

Full text of DOI:10.1002/adsc.202100069

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DOI: 10.1002/adsc.202100069
Indene Derived Phosphorus-Thioether Ligands for the
Ir-Catalyzed Asymmetric Hydrogenation of Olefins with Diverse
Substitution Patterns and Different Functional Groups
Jèssica Margalef,a,* Maria Biosca,a Pol de la Cruz-Sánchez,a Xisco Caldentey,b
Carles Rodríguez-Escrich,b Oscar Pàmies,a Miquel A. Pericàs,b, c,* and
Montserrat Diégueza,*
a
Departament de Química Física i Inorgànica,
Universitat Rovira i Virgili, C/Marcel·lí Domingo 1, 43007 Tarragona, Spain
Phone: (+34)977558780
fax: (+34)955559563
E-mail: jessica.margalef@urv.cat; montserrat.dieguez@urv.cat
Institute of Chemical Research of Catalonia (ICIQ),
b
The Barcelona Institute of Science and Technology,
Av Països Catalans 16, 43007 Tarragona, Spain
Phone: (+34)977 920 200
E-mail: mapericas@iciq.es
Departament de Química Inorgànica i Orgànica, Universitat de Barcelona,
c
08028 Barcelona, Spain.
Manuscript received: January 18, 2021; Revised manuscript received: March 8, 2021;
Version of record online: ■■■, ■■■■
Supporting information for this article is available on the WWW under https://doi.org/10.1002/adsc.202100069
Abstract: A family of phosphite/phosphinite-thioether ligands have been tested in the Ir-catalyzed asymmetric
hydrogenation of a range of olefins (50 substrates in total). The presented ligands are synthesized in three steps
from cheap indene and they are air-stable solids. Their modular architecture has been crucial to maximize the
catalytic performance for each type of substrate. Improving most Ir-catalysts reported so far, this ligand family
presents a broader substrate scope, covering different substitution patterns with different functional groups,
ranging from unfunctionalized olefins, through olefins with poorly coordinative groups, to olefins with
coordinative functional groups. α,β-Unsaturated acyclic and cyclic esters, ketones and amides were
hydrogenated in enantioselectivities ranging from 83 to 99% ee. Enantioselectivities ranging from 91 to 98%
ee were also achieved for challenging substrates such as unfunctionalized 1,1’-disubstituted olefins,
functionalized tri- and 1,1’-disubstituted vinyl phosphonates, and β-cyclic enamides. The catalytic performance
of the Ir-ligand assemblies was maintained when the environmentally benign 1,2-propylene carbonate was
used as solvent.
Keywords: phosphorus-thioether ligands; asymmetric hydrogenation; iridium; α-β unsaturated compounds; β-
cyclic enamides
Introduction
genation (AH) of olefins has become a key process in
asymmetric catalysis.[1] The structural diversity of
One major goal in the fine chemicals industry is to prochiral olefins that can be used make this reaction
develop synthetic methodologies that produce chiral even more interesting since it allows the preparation of
target compounds with high enantioselectivities and very diverse chiral compounds with a range of
with a minimum environmental impact. Chemical functionalities. However, the versatility and broad
transformations with high atom economy are therefore applicability of chiral catalysts in this process remains
highly desirable. In this respect, the asymmetric hydro- an issue. Rh- and Ru-complexes have been established
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as the optimal catalysts for the reduction of olefins
bearing coordinating functional groups.[2] They are
used, for example, in the synthesis of optically active
α-amino acids and many pharmaceutically relevant
compounds. Their efficiency relies in the chelating
ability of the substrate which is key in transferring the
chiral information from the catalyst to the product.[2]
However, these catalysts behave in a less efficient
manner and with poor enantiocontrol in the hydro-
genation of substrates lacking coordinating groups
adjacent to the double bond. Pioneered by Pfaltz
et al.,[3] Ir-complexes of the type [Ir(cod)(P,N)*]BArF
(BArF =tetrakis[3,5-bis(trifluoromethyl)phenyl]borate)
were developed for the AH of unfunctionalized
olefins.[4] Compared with functionalized olefins, the
reduction of unfunctionalized substrates is less mature
Figure 1. Examples of chiral carboxylic acid derivatives with
biological activity.
and has less synthetic utility. Essentially, most Ir- scope, usually require long reaction times and produce
catalysts are still specific for a type of olefins with the enantiopure materials in low yields.[10] In contrast,
limited substitution patterns. For example, the most the AH of α,β-unsaturated esters is a highly atom
successful cases have been reported for E-trisubstituted economic approach that allows the synthesis of a broad
alkenes and to a lesser extent for Z-trisubstituted and range of chiral carboxylic derivatives. The use of esters
1,1’-disubstituted.[4] The most used P,N-ligands have instead of the free acids is a better alternative, since
been phosphine/phosphinite-oxazoline ligands. Several they are easier to handle and can be later converted to
modifications of their chiral backbone and coordinat- the desired target molecule. The reduction of α,β-
ing groups have led to the discovery of other good unsaturated ketones and amides also gives access to
performing ligands such as P-oxazole/imidazole/thia- highly valuable building blocks,[1f,11] and their AH
zole, P-pyridine and carbene-oxazoline/pyridine opens a direct, atom efficient path for preparing
ligands.[4] Among them, our research group found that optically pure ketones and amides, whose synthesis up
the introduction of a biaryl phosphite moiety improved to now has mainly relied on non-catalytic methods
the scope of successful substrates.[5,6] More recently, with a limited substrate scope. For the AH of these
we also showed that phosphinite/phosphite-thioether three types of poorly coordinating substrates, Ir-
ligands exhibit excellent performance in this trans- catalysts have proved to be superior to Rh- and Ru-
formation, providing enantioselectivities comparable to catalysts.[4e] However, the efficiency of those Ir-
the best ones reported with IrÀ P,N catalysts.[7] From a catalysts is still highly dependent on the substitution
common simple backbone, the right combination of pattern and the geometry of the substrates.[12,13,14] The
ligand parameters provided P,S-ligands that were discovery of a family of catalysts with a wide substrate
appropriate in the AH of unfunctionalized trisubsti- scope remains a central task in AH of this type of
tuted olefins and the more challenging unfunctional- olefins.
ized 1,1’-disubstituted olefins.
To sum up, research is still needed to increase the
Along the path from absolutely non-functionalized synthetic utility of the AH of olefins, by searching for
olefins to analogues bearing coordinating functional catalysts able to efficiently perform the reduction of
groups, there is a broad range of interesting alkene prochiral olefins with functional groups with varying
substrates with intermediate coordinating properties. coordinating abilities. For this purpose, further devel-
α,β-Unsaturated esters, amides and ketones, among opment in the area of chiral ligands is a key task.
others, are examples of olefins containing functional Moreover, to be industrially interesting these ligands
groups that in most of the cases do not form stable should be synthesized in few steps, from readily
chelate rings with the metal. Consequently, enantiose- available materials and be easy to handle (preferably
lectivity is more difficult to control in these solid and air stable). As said above, P,thioether-ligands
substrates.[4e,f] Remarkably, their hydrogenated prod- have proved to be excellent for the AH of olefins. The
ucts showcase interesting properties. For instance, thioether moiety imparts higher stability with respect
many carboxylic acid derivatives with a stereogenic to commonly used phosphines and oxazolines, and
center at the α- or β-position exhibit biological activity involves the introduction of an additional chiral center
(Figure 1).[1f,8] However, most of the methods used to close to the metal with a different steric environment
prepare such compounds produce large amounts of around the sulfur than the trivalent phosphorus.[15,7f]
chemical waste.[9] Enzyme-mediated reactions of race-
To continue the improvement of Ir-catalysts with
mic starting materials have also been used, although air-stable and readily available ligands, we would like
most of the reported methods are limited in substrate to disclose here the study of a simple but modular P,S-
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ligand family (Figure 2, ligands L1-L8a-f) for the AH NMR spectroscopy. The spectral assignments were
1
1
1
of olefins. These ligands are easily synthesized in only made using HÀ H and 13CÀ H correlation measure-
three steps from unexpensive indene.[16] The substrates ments, which were in agreement with what expected
studied cover different substitution patterns with differ- for these C1-symmetric iridium complexes. Variable-
ent functional groups, ranging from unfunctionalized temperature (VT) NMR spectra in CD2Cl2 (+35 to
°
olefins, through olefins with poorly coordinative À 85 C) indicated that only one isomer was present,
groups to olefins with a coordinative functional group except for ligands L3 that showed two isomers in
that can also anchor the substrate to the metal. As a solution, and for ligands L1d–e, L5d and L6b that
result, a broad range of α,β-unsaturated esters, ketones depicted broad NMR signals, which may be indicative
and amides have been hydrogenated with enantioselec- of rapid exchange between the two possible diaster-
tivities up to 99% ee. In addition, the modularity of eomers formed upon coordination of the thioether
these P,S-ligands allowed us to identify highly moiety to the metal atom (note that the coordinated S
enantioselective catalytic systems (up to 98% ee) for atom is a stereogenic center), to the interconversion of
other challenging substrates: unfunctionalized 1,1’- the different conformers of the six-membered chelate
disubstituted olefins, functionalized tri- and 1,1’-disub- ring, or to both phenomena taking simultaneously
stituted vinyl phosphonates and β-cyclic enamides.
place. To provide some light on the origin of these
isomers, DFT calculations for [Ir(cod)L3e]BArF were
performed (Figure 3). The population of isomers
obtained by DFT calculation agree to that found by
NMR spectroscopy. These DFT calculation also
indicates that both isomers arise from the different
Results and Discussion
Synthesis of the Ir-Catalyst Precursors
The catalyst precursors were prepared in a two-step, coordination of the thioether group and different
one pot procedure. First, 0.5 equivalent of [Ir(μ- conformers of the chelate-ring. Thus, the major
Cl)(cod)]2 reacts with one equivalent of thÀe appropriate diastereoisomer shows an R-configuration of the S
P,S-ligand (L1-L8a-f). Then, ClÀ /BArF counterion atom with a chair conformation of the chelate ring
exchange was performed by reaction with sodium (Figure 3). On the other hand, the minor isomer adopts
tetrakis[3,5-bis(trifluoromethyl)phenyl]borate
(Na- an S-configuration of the S atom with a boat
BArF; 1 equiv) in the presence of water (Scheme 1). conformation of the chelate ring (Figure 3). Unfortu-
1
The Ir-catalyst precursors were isolated in pure form as nately due to signal overlap in the H-NMR spectrum,
air-stable red-orange solids in high yields (typically these studies could not be validated by NOE experi-
above 90%) after a simple extraction workup. Advan- ments.
tageously, no further purification was required.
The HRMS-ESI spectra of these materials were in
agreement with the assigned structures showing the
Catalytic Experiments
heaviest ions at m/z values corresponding to the loss of In a first set of experiments the efficiency of
the BArF anion from the molecular species. The phosphite/phosphinite-thioether ligands L1-L8a-f was
1
complexes were also characterized by 31P, H and 13C evaluated in the AH of olefins with relevant poorly
coordinative groups. We initially chose two ester
substrates with different structural diversity, the α,β-
unsaturated acyclic ester S1 ((E)-3-phenylbut-2-enoate)
and the α,β-unsaturated lactone with an exocyclic
Figure 2. A readily available phosphite/phosphinite-thioether
ligand library L1–L8a–f.
Figure 3. DFT-calculated structures for [Ir(cod)L3e]BArF com-
Scheme 1. Synthesis of [Ir(cod)(PÀ S)]BArF (PÀ S=L1–L8a–f).
plex. Hydrogen atoms have been omitted for simplicity.
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double bond S2 ((E)-3-benzylidenetetrahydro-2H- the α,β-unsaturated acyclic ester S1 the highest
pyran-2-one). Although less studied,[12e,i,13f] the hydro- enantioselectivity was achieved with Ir–L8e containing
genation of substrates like S2 is important because it an anthracyl thioether group (entry 19, ee up to 94%),
gives access to cyclic carbonyl compounds with an α- precatalyst Ir–L3e, containing a tert-butyl thioether
chiral center.[1f,8a] To compare our results with the state group, was the best for cyclic substrate S2 (L3e,
of the art, we used the same optimal reaction entry 8, 94% ee). Enantioselectivities were maintained
conditions found in previous studies with other IrÀ P,S when the reaction was performed at low catalyst
catalytic systems.[7b] The results (Table 1) indicated loading (0.5 mol%, entries 20 and 21) or when
that although the configuration of the phosphite moiety dichloromethane was replaced by the environmentally
affects enantioselectivity (being better with an S- friendly solvent 1,2-propylene carbonate[17] (PC; en-
configuration for S1 and the R-configuration for S2), tries 22 and 23).
the best enantioselectivities were achieved with the o-
Encouraged by these initial results, we investigated
tolyl phosphinite moiety (e) for both substrates. In Ir–L8e and Ir–L3e in the reduction of a broad range of
addition, a bulky thioether moiety is needed to max- acyclic and cyclic α,β-unsaturated esters (S3–S13)
imize enantioselectivity, although each substrate re- with different substitution patterns and geometries
quires a different thioether substituent. Thus, while for (Figure 4). Advantageously, for acyclic α,β-unsaturated
esters (S3–S7) the enantioselectivities were quite
independent of the steric nature of the alkyl substituent
Table 1. Ir-catalyzed asymmetric hydrogenation of S1 and S2
using L1–L8a–f.[a]
in the substrate (S1 and S5–S7, ee’s up to 98%) and
the electronic properties of the phenyl ring (S1 and
S3–S4, ee’s up to 95%). The Ir–L8e catalytic system
also provided high enantioselectivities independently
of the geometry of the olefin substrate. Thus, high
enantioselectivities were also attained in the reduction
of the more challenging Z-analogue ((E)-S7 vs (Z)-S7).
Interestingly, the hydrogenation of acyclic ester S8
containing substituents at both α and β positions also
provided 98% of enantioselectivity. The scope was
then extended to other cyclic α,β-unsaturated esters
(lactones, S9–S13). Remarkably, with Ir–L3e all α,β-
Entry
Ligand
% ee[b]
% ee[b]
1
2
3
4
5
6
7
8
L1a
L1b
L1c
L1d
L1e
L2b
L3b
L3e
L4b
L5b
L5c
L5d
L5e
L6b
L7b
L8b
L8c
L8d
L8e
L3e
L8e
L3e
L8e
20 (S)
7 (S)
17 (S)
28 (S)
2 (R)
25 (S)
30 (S)
11 (S)
11 (S)
13 (S)
86 (S)
21 (S)
22 (S)
43 (S)
77 (S)
84 (S)
19 (S)
20 (S)
26 (S)
49 (S)
90 (S)
94 (S)
85 (S)
94 (S)
86 (S)
93 (S)
32 (S)
38 (S)
21 (S)
25 (S)
94 (S)
28 (S)
29 (S)
3 (S)
40 (S)
50 (S)
22 (S)
21 (S)
19 (S)
6 (R)[c]
48 (S)
62 (S)
94 (S)[e]
62 (S)[f]
94 (S)
61 (S)
9
10
11
12
13
14
15
16
17
18
19
20[d]
21[d]
22[g]
23[g]
[a] Reaction conditions: substrate (0.5 mmol), Ir-catalyst pre-
cursor (2 mol%), H2 (100 bar), CH2Cl2 (2 mL), rt for 4 h
(substrate S1) or 20 h (substrate S2). Full conversions were
achieved in all cases unless otherwise stated.
[b] Enantiomeric excesses determined by HPLC analysis.
[c] 27% conversion.
Figure 4. Substrate scope of the asymmetric hydrogenation of
trisubstituted acyclic and cyclic α,β-unsaturated esters S3–S13
with [Ir(cod)(L1–L8a–f)]BArF catalyst precursors. Reaction
conditions: catalyst precursor (2 mol%), CH2Cl2, rt, H2
(100 bar), 4 h for S3–S8 or 20 h for S9–S13. Full conversions
were achieved in all cases.
[d] Reactions carried out using 0.5 mol% of catalyst precursors.
[e] Reaction carried out during 32 h.
[f] 98% conversion after 32 h.
[g] Reactions carried out using PC (1,2-propylene carbonate) as
solvent.
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unsaturated lactones with an exocyclic double bond ketone S21 and lactams S22–S27 are challenging
were reduced with comparable high enantioselectivities substrates whose hydrogenation has been usually
(ee’s up to 98%) regardless of the substitution pattern overlooked[12e,i,13f,19] despite these frameworks are part
on the aryl moiety.
of several natural products and have numerous
We then tested whether high enantioselectivities synthetic utilities.[1f,8a] For the challenging cyclic
could also be achieved with olefins containing ketone S21 enantioselectivity was as high as 88%. Rh/
relevant, poorly coordinative groups other than the Ru-catalysts have usually failed in affording high
alkoxycarbonyl. For that purpose, we selected repre- enantioselectivities for lactams. A possible reason is
sentative sets of substrates and found that enantiose- the exocyclic nature of the double bond, which cannot
lectivities were also high for a range of α,β-unsaturated rotate towards the carbonyl oxygen, and this hampers
ketones (S14–S21), lactams (S22–S27) and the α,β- the chelation of such substrates to the metal. Gratify-
unsaturated amide S28. The results of these AH ingly, high asymmetric induction (up to 99% ee) was
reactions are shown in Figure 5. We again found that also achieved in the reduction of several valuable
the ligand components must be selected for each lactams S22–S27 but, unlike ketones, using the Ir–L8e
particular substrate type in order to obtain the highest catalytic system. Other challenging substrates are α,β-
enantioselectivity. Up to 87% enantiomeric excess unsaturated amides,[12j,13c,14a] which can give access to
could be obtained for a range of α,β-unsaturated important subunits in natural products. Ir–L8e catalyst
ketones (substrates S14–S18) independently of the was also able to reduce substrate S28 yielding the
nature of the alkyl substituent and the electronic nature corresponding amide with an α-stereogenic center with
of the phenyl ring, with the Ir–L3e catalytic system. In 84% ee.
addition, higher enantioselectivities of up to 92% ee
Interestingly, we also found that the IrÀ P,S catalysts
were achieved with more challenging β,β’-disubstituted are able to hydrogenate trisubstituted and 1,1’-disub-
enones S19 and S20, even in the reduction of substrate stituted olefins lacking any extra functional group in
S19 containing two β,β’-substituents with different ee’s as high as 98% (substrates S29–S38, Figure 6).
size.[18] Like the lactone S2, cyclic α,β-unsaturated While the best enantioselectivity in the reduction of
the unfunctionalized trisubstituted olefin S29 is again
achieved with phosphinite-based ligands (ligand L8e),
for 1,1’-disubstituted olefins a phosphite moiety with a
R-configuration is needed to maximize enantioselectiv-
ity (ligand L5c). 1,1’-Disubstituted substrates are less
hindered than the trisubstituted olefins, so they are
more easily hydrogenated but, in turn, face-selectivity
Figure 6. Selected results for the hydrogenation of trisubstituted
and 1,1’-disubstituted olefins S29–S38 with [Ir(cod)(L1–L8a–
f)]BArF catalyst precursors. Reaction conditions: catalyst pre-
Figure 5. Substrate scope of the asymmetric hydrogenation of
trisubstituted acyclic and cyclic α,β-unsaturated enones S14–
S21, lactams S22–S27 and amide S28 with [Ir(cod)(L1–L8a–f)]
BArF catalyst precursors. Reaction conditions: catalyst precur-
sor (2 mol%), CH2Cl2, rt, H2 (100 bar), 4 h for S14–S21 or 20 h
for S22–S28. Full conversions were attained in all cases.
cursor (2 mol%), CH2Cl2, H2 (100 bar S29 and 1 bar for S30–
S38), rt, 4 h. Full conversions were achieved in all cases. The
a
reaction using 1,2-propylene carbonate as solvent yielded the
b
hydrogenation product in 96% ee. The reaction using 1,2-
propylene carbonate as solvent yielded the hydrogenation
product in 98% ee.
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is more difficult to control. Probably for this reason, genation of ketones) and phosphines.[22] The Ir–L8e
the effective AH of a large range of 1,1’-disubstituted catalytic system can hydrogenate trisubstituted enol
olefins has only been achieved quite recently, and with phosphinates (S39–S41) in high enantioselectivities
a few catalytic systems.[4e,20] It is to note that excellent (ee’s up to 94%). Remarkably, high enantioselectivities
enantioselectivities, comparable to the best ones (ee’s up to 97%) can also be achieved in the reduction
reported previously, have been achieved with the of 1,1’-disubstituted enol phosphinates S42 and S43
present set of P-thiother ligands for a broad range of but, unlike trisubstituted enol phosphinates, using the
terminal olefins (S30–S37), independently of the Ir–L1f catalytic system. Among these results it should
electronic and steric properties of the substituents in be noted that the efficient reduction of purely alkyl-
the aryl moiety of the substrate (ee’s up to 98%). Like substituted enol phosphinates (tri- and disubstituted
in other cases reported in the literature, the hydro- substrates S40 and S42, respectively) is a plausible
genation of the α-alkylstyrene derivative S38 pro- alternative to the AH of prochiral alkyl-alkyl ketones
ceeded with a lower enantioselectivity than that of the to chiral alcohols by Rh/Ru-catalysts, which remains a
analogue S29.[20] This result is in agreement with a challenging reaction due to the difficulty in differ-
competing isomerization pathway that was corrobo- entiating enantiofaces involving two alkyl groups.[23]
rated by studying the incorporation of deuterium in
Finally, we focused on the reduction of cyclic β-
S38 (Scheme 2).[21] It was found that deuterium was enamides, which is another challenging type of
not only inserted in the double bond but also at the functionalized olefins. While the enantioselective
allylic position. Again, the results were maintained by reduction of α-enamides can be carried out with
using 1,2-propylene carbonate as solvent.
success,[2] the AH of β-enamides remains a puzzling
To further establish the potential of the P,S-ligands transformation, albeit the corresponding reduction
L1–L8a–f we studied the AH of substrates bearing products are key units in biologically active natural
strongly coordinating groups. We first considered the products and drugs such as rotigotine,[24] alnespirone[25]
[26]
reduction of challenging tri- and di-substituted enol and robalzotan.
Most of the currently available
phosphinates (S39–S43, Figure 7). The hydrogenation catalysts, predominantly based on Rh and Ru, provide
of both types of substrates opens up an interesting unsatisfactory enantioselectivities in reducing cyclic β-
route for obtaining chiral organophosphinates, which enamides.[27] More recently, it has been shown that
can be easily transformed into high-value compounds IrÀ P,X (X=N or S) catalysts can reduce cyclic β-
such as alcohols (an alternative route to the hydro- enamides with higher enantioselectivities than the Rh/
Ru-catalysts.[28] We first studied the reduction of the
benchmark N-(3,4-dihydronaphthalen-2-yl)acetamide
S44 (Table 2) under previously reported conditions.[28c]
Like for disubstituted olefins S30–S37, the presence of
a phosphite group instead of a phosphinite moiety had
a positive effect on the enantioselectivity (e.g. entries 2
and 11 vs 4 and 13). Regarding the effect of the
thioether group, the bulkiness of the thioether group
and its electronic nature had an important role on the
enantioselectivity. The presence of an electron-poor
Scheme 2. Deuterium labeling study of substrate S38 with
[Ir(cod)(L5c)]BArF catalyst precursor. The percentages of
incorporation of deuterium in different positions are shown in
brackets.
thioether group worsened enantioselectivity (entry 14
(L6b) vs 15 (L7b)). The bulkiness of the thioether
substituents has a different effect depending on the
configuration of the phosphite group. While for ligands
with less bulky thioether substituents the presence of
(R)-biaryl phosphite moieties resulted in a matched
combination (e.g. L1b–c, entry 2 vs 3), for ligands
containing bulkier thioether substituents, the best
enantioselectivity was achieved with (S)-biaryl
phosphite moieties (e.g. L5 and L8, entries 10 and 16
vs 11 and 17). As expected, the highest enantioselec-
tivity of the series (91% ee, entry 6) is therefore
provided with ligand L2b, which contains the optimal
bulkiness of the thioether substituent in combination
with the optimal configuration of the phosphite moiety.
Advantageously, high enantioselectivities were still
attained by lowering the hydrogen pressure to 10 bar
of H2 (entry 20). We were also pleased to find out that
Figure 7. Asymmetric hydrogenation of tri- and 1,1’-disubsti-
tuted enol phosphinates S39–S43 with [Ir(cod)(L1–L8a–f)]
BArF catalyst precursors. Reaction conditions: catalyst precur-
sor (2 mol%), CH2Cl2, H2 (100 bar for S39–S41 and 50 bar for
S42–S43), rt, 4 h.
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Table 2. Ir-catalyzed asymmetric hydrogenation of S44 using
L1–L8a–f.[a]
Entry
Ligand
% Conv[b]
% ee[b]
1
2
3
4
5
6
7
8
L1a
L1b
L1c
L1d
L1e
L2b
L3b
L3e
L4b
L5b
L5c
L5d
L5e
L6b
L7b
L8b
L8c
L8d
L8e
L2b
L2b
20
35
18
70
100
85
70
80
50
100
100
41
62
34
33 (S)
88 (S)
39 (R)
64 (S)
83 (S)
91 (S)
61 (S)
17 (R)
57 (S)
66 (S)
77 (R)
70 (R)
63 (R)
21 (S)
73 (S)
30 (S)
74 (R)
21 (R)
65 (R)
92 (S)
91 (S)
Figure 8. Asymmetric hydrogenation of functionalized olefins
S45–S50 with [Ir(cod)(L2b)]BArF catalyst precursors. Reaction
conditions: Catalyst precursor (2 mol%), CH2Cl2, H2 (50 bar),
rt, 18 h.
9
10
11
12
13
14
15
16
17
18
19
20[c]
21[c,d]
Conclusion
The asymmetric hydrogenation of diversely substituted
olefins bearing variably coordinating functional groups
is in no case a problem that can be addressed with a
single catalyst. Bearing this consideration in mind, the
design of modular, easy-to-assemble ligands that can
adapt to manifold substrates becomes a fundamental
task towards the development of efficient and widely
applicable AH methodologies. In an effort towards this
end, we have shown the utility of an indene-based
phosphite/phosphinite-thioether ligand library for the
Ir-catalyzed asymmetric hydrogenation of a broad
range of substrates (50 olefins in total). The high
modularity of these ligands helped us to identify highly
enantioselective catalysts for AH of substrates cover-
ing different substitution patterns with different func-
tional groups and coordination abilities, ranging from
unfunctionalized olefins, through olefins with poorly
coordinative groups, to olefins with coordinative func-
57
100
100
100
100
98
86
[a] Reaction conditions: Substrate (0.5 mmol), Ir-catalyst pre-
cursor (1 mol%), H2 (50 bar), CH2Cl2 (2 mL), rt, 18 h.
[b] Conversion measured by 1H-NMR and enantiomeric excesses
determined by HPLC.
[c] Reaction carried out using 10 bar of H2 for 24 h.
[d] Reaction carried out using 1,2-propylene carbonate as
solvent.
the enantioselectivity using 1,2-propylene carbonate tional groups. A range of α,β-unsaturated esters,
remained as high as those observed with dichloro- ketones, even the much less studied lactones and
methane (entry 21).
lactams, and α,β-unsaturated amides were hydrogen-
We subsequently tested the scope of the Ir/L2b ated with enantioselectivities up to 99%. The best
catalytic system in the reduction of a range of cyclic β- enantioselectivities were obtained with ligands contain-
enamides derived from tetralones (Figure 8; substrates ing an o-tolyl phosphinite moiety (e) and bulky
S45–S49). The high catalytic performance of this thioether groups (ligand L8e for acyclic α,β-unsatu-
catalyst was maintained independently of the different rated esters, lactams and amides and ligand L3e for
substitution pattern of the 3,4-dihydronaphthalene core cyclic esters and α,β-unsaturated ketones). Enantiose-
(92–94% ee). In addition, it could also effectively lectivities up to 98% ee were also achieved for other
hydrogenate enamide S50, derived from 3-chroma- challenging substrates such as unfunctionalized 1,1’-
none, in high enantioselectivity (95% ee). Among all disubstituted olefins, functionalized tri- and 1,1’-disub-
these results, it is to note the high enantioselectivity stituted vinyl phosphonates and β-cyclic enamides.
achieved in the AH of S49 and S50, whose hydro- While for the functionalized tri- and 1,1’-disubstituted
genated products are key intermediates for the syn- vinyl phosphonates the best enantioselectivities are still
thesis of rotigotine and alnespirone. The former is a achieved with phosphinite-based ligands L8e and L1f,
dopamine agonist used for the treatment of Parkinson’s respectively, for unfunctionalized 1,1-disubstituted
disease,[24] while alnespirone is a selective 5-HT1 A substrates and cyclic β-enamides a phosphite moiety is
receptor with antidepressant and anxiolytic properties. needed to maximize enantioselectivities (ligands L5c
[25]
and L2b, respectively). Usefully, friendly 1,2-
propylene carbonate can be used with no loss of
Adv. Synth. Catal. 2021, 363, 1–15
7
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asc.wiley-vch.de
t
CDCl3): δ=1.36 (s, 9H, CH3, Bu), 1.37 (s, 9H, CH3, tBu), 1.49
enantioselectivity. These results open up the use of air
stable, readily available and modular ligands to
advance in the AH of a broad type of substrates with
diverse functional groups with different coordination
abilities and with different substitution patterns.
t
t
i
(s, 9H, CH3, Bu), 1.55 (s, 9H, CH3, Bu), 1.63 (d, 6H, CH3, Pr,
3JH-H =6.8 Hz), 1.91-2.10 (m, 5H, CH2, cod), 2.22-2.27 (m, 3H,
2
3
CH2, cod), 3.02 (dd, 1H, CH2, JH-H =14.8 Hz, JH-H =9.6 Hz),
3.26 (dd, 1H, CH2, JH-H =15.2 Hz, JH-H =7.6 Hz), 3.68–3.75
2
3
i
3
(m, 1H, CH, Pr), 4.25 (d, 1H, CHÀ S, JH-H =18.8 Hz), 4.47 (b,
1H, CH=, cod), 4.76 (b, 1H, CH=, cod), 4.98–5.07 (m, 1H, CH-
OP), 5.09 (b, 1H, CH=cod), 5.43 (b, 1H, CH=, cod), 7.16–7.71
(m, 20H, CH=). 13C NMR (100.6 MHz, CDCl3): δ=24.6 (CH3,
Experimental Section
iPr), 25.6 (CH3, Pr), 28.4 (b, CH2, cod), 29.9 (CH2, cod), 30.9
i
General Considerations
(b, CH2, cod), 31.3 (CH3, tBu), 31.5 (CH3, tBu), 31.8 (CH3, tBu),
All reactions were carried out using standard Schlenk techni-
ques under an argon atmosphere. Solvents were purified and
dried by standard procedures. Phosphorochloridites are easily
prepared in one step from the corresponding biaryls.[29]
Phosphite/phosphinite-thioether ligands L1-L8a-f were pre-
pared as previously reported.[16] Substrates S1,[30] S2,[12e] S3–
S4,[30] S5–S7,[12g] S8,[31] S9–S10,[32] S11,[33] S12,[32] S13,[33]
S14,[34] S15–S18,[13b] S19,[35] S20,[13a] S21,[36] S22,[37] S28,[6g]
S29,[38] S30–S37,[6g] S38,[39] S39–S43,[22b] S44,[40] S45–S46,[27j]
S47,[41] S48,[27j] S49,[27i] S50[27a] were prepared following the
reported procedures. 1H, 13C and 31P NMR spectra were
recorded using a 400 MHz spectrometer. Chemical shifts are
relative to that of SiMe4 (1H and 13C) as internal standard or
t
t
t
33.6 (b, CH2, cod), 35.0 (C, Bu), 35.5 (C, Bu), 35.6 (C, Bu),
3
i
37.5 (d, CH2, JC-P =7.6 Hz), 48.3 (b, CH, Pr), 55.0 (CHÀ S),
75.7 (b, CH=, cod), 78.4 (b, CH=, cod), 82.5 (CH-OP), 100.8
(b, CH=, cod), 104.3 (b, CH=, cod), 117.6-149.1 (aromatic
1
carbons), 161.9 (q, CÀ B, BArF, JC-B =49.7 Hz). MS HR-ESI
[found 947.4136 C48H67IrO3PS (M)+ requires 947.4172].
[Ir(cod)(L1b)]BArF: Yield: 60 mg (93%). 31P NMR
(161.9 MHz, CDCl3): δ=108.8 (s). 1H NMR (400 MHz,
i
3
CDCl3): δ=1.03 (d, 3H, CH3, Pr, JH-H =6.4 Hz), 1.41 (s, 9H,
CH3, Bu), 1.50 (d, 3H, CH3, Pr, JH-H =6.8 Hz), 1.54 (s, 9H,
CH3, Bu), 1.78 (s, 3H, CH3), 1.79 (s, 3H, CH3), 1.93–2.15 (m,
t
i
3
t
6H, CH2, cod), 2.25 (b, 2H, CH2, cod), 2.27 (s, 6H, CH3), 2.89
1
H3PO4 (31P) as external standard. H, 13C and 31P assignments
(dd, 1H, CH2, 2JH-H =15.2 Hz, 3JH-H =8.8 Hz), 3.35 (dd, 1H,
1
1
1
13
CH2, 2JH-H =15.6 Hz, 3JH-H =8.4 Hz), 3.61–3.77 (m, 1H, CH,
were made on the basis of HÀ H gCOSY, HÀ C gHSQC and
31
1HÀ P gHMBC experiments.
iPr), 3.86 (b, 1H, CH=, cod), 4.53 (d, 1H, CHÀ S, JH-H
=
3
11.2 Hz), 4.97 (b, 1H, CH=, cod), 5.06–5.13 (m, 2H, CHÀ OP,
CH=, cod), 5.37 (b, 1H, CH=, cod), 7.20-7.70 (m, 18H, CH=).
13C NMR (100.6 MHz, CDCl3): δ=16.5 (CH3), 16.8 (CH3),
Computational Details
i
i
All calculations were performed using the Gaussian 16
program.[42] Optimizations of [Ir(cod)L3e]BArF complexes were
performed employing the B3LYPÀ D3[43] density functionaland
the 6–31G(d)[44] basis set for all elements except for Ir for which
SDD[45] was used. Solvation correction was applied in the
course of the optimizations using the PCM model with the
default parameters for dichloromethane.[46] The complexes were
treated with charge +1 and in the singlet state. No symmetry
constraints were applied. The energies were further refined by
performing single-point calculations using the above-mentioned
parameters, with the exception that the density functional used
was PBEÀ D2[47,48] and the basis set was 6–311+G**[49] for all
elements except for iridium. All energies reported are Gibbs
20.3 (CH3), 20.4 (CH3), 24.7 (CH3, Pr), 24.9 (CH3, Pr), 28.9
t
t
(CH2, cod), 30.0 (CH2, cod), 31.8 (CH3, Bu), 32.1 (CH3, Bu),
32.3 (CH2, cod), 32.5 (d, CH2, cod, JC-P =4.6 Hz), 34.7 (C, tBu),
t
3
i
34.8 (C, Bu), 38.2 (d, CH2, JC-P =6.8 Hz), 44.7 (CH, Pr), 55.1
(CHÀ S), 71.9 (CH=, cod), 79.2 (CH-OP), 81.5 (CH=, cod),
98.0 (d, CH=, cod, JC-P =16.9 Hz), 106.7 (d, CH=, cod, JC-P
=
13.2 Hz), 117.4-145.0 (aromatic carbons), 161.7 (q, CÀ B, BArF,
1JC-B =49.7 Hz). MS HR-ESI [found 891.3519, C44H59IrO3PS
(M)+ requires 891.3546].
[Ir(cod)(L1c)]BArF: Yield: 62 mg (95%). 31P NMR
(161.9 MHz, CDCl3): δ=111.1 (s). 1H NMR (400 MHz,
t
CDCl3): δ=1.43 (s, 9H, CH3, Bu), 1.56 (s, 9H, CH3, tBu), 1.60
i
3
i
3
(d, 3H, CH3, Pr, JH-H =6.8 Hz), 1.63 (d, 3H, CH3, Pr, JH-H
6.8 Hz), 1.77 (s, 3H, CH3), 1.82 (s, 3H, CH3), 1.82-1.91 (m, 2H,
CH2, cod), 2.03-2.15 (m, 4H, CH2, cod), 2.22 (b, 2H, CH2, cod),
=
free energies at 298.15 K and calculated as ΔGreported =ΔGB3LYP/6-
31G(d) +(ΔEPBE-D2/6-311+G(d,p)À ΔEB3LYP/6-31G(d)).
2
3
2.28 (s, 6H, CH3), 3.09 (dd, 1H, CH2, JH-H =15.2 Hz, JH-H
=
General Procedure for the Preparation of [Ir-
(cod)(L1-L8a-f)]BArF
9.2 Hz), 3.28 (dd, 1H, CH2, 2JH-H =15.6 Hz, 3JH-H =8.0 Hz),
i
3.63–3.70 (m, 1H, CH, Pr), 3.85 (b, 1H, CH=, cod), 4.22 (d,
3
1H, CHÀ S, JH-H =8.8 Hz), 4.86 (b, 1H, CH=, cod), 4.92–4.98
The corresponding ligand (0.037 mmol) was dissolved in
CH2Cl2 (2 mL) and [Ir(μ-Cl)(cod)]2 (12.5 mg, 0.0185 mmol)
(m, 1H, CH-OP), 5.03 (b, 1H, CH=cod), 5.41 (b, 1H, CH=,
cod), 7.22–7.72 (m, 18H, CH=). 13C NMR (100.6 MHz,
°
was added. The reaction mixture was refluxed at 50 C for 1 h.
i
CDCl3): δ=16.5 (CH3), 20.3 (CH3), 24.0 (CH3, Pr), 25.6 (CH3,
After 5 min at room temperature, NaBArF (38.6 mg,
0.041 mmol) and water (2 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 dried
with MgSO4, filtered through a plug of celite and the solvent
was evaporated to give the product as red-orange solids.
iPr), 28.1 (CH2, cod), 29.7 (CH2, cod), 30.6 (CH2, cod), 31.2
t
t
(CH3, Bu), 32.0 (CH3, Bu), 33.3 (d, CH2, cod, JC-P =4.0 Hz),
t
3
i
34.7 (C, Bu), 37.4 (d, CH2, JC-P =8.9 Hz), 48.2 (CH, Pr), 54.4
(CHÀ S), 72.5 (CH=, cod), 79.9 (CH=, cod), 83.0 (d, CH-OP,
3JC-P =5.5 Hz), 99.3 (d, CH=, cod, JC-P =17.2 Hz), 104.6 (d,
CH=, cod, JC-P =10.8 Hz), 117.4-144.7 (aromatic carbons),
161.7 (q, CÀ B, BArF, 1JC-B =50.0 Hz). MS HR-ESI [found
891.3518, C44H59IrO3PS (M)+ requires 891.3546].
[Ir(cod)(L1a)]BArF: Yield: 67 mg (92%). 31P NMR
(161.9 MHz, CDCl3): δ=114.1 (s). 1H NMR (400 MHz,
Adv. Synth. Catal. 2021, 363, 1–15
8
© 2021 Wiley-VCH GmbH
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asc.wiley-vch.de
[Ir(cod)(L1d)]BArF: Yield: 54 mg (93%). 31P NMR
(161.9 MHz, CDCl3): δ=107.7 (s). 1H NMR (400 MHz,
1H, CH=, cod), 4.78 (m, 1H, CHÀ S), 4.95 (m, 1H, CH=, cod),
5.24 (m, 1H, CH=, cod), 5.48 (m, 1H, CH=, cod), 5.67 (m, 1H,
CH-OP), 7.20–7.80 (m, 18H, CH=). 13C NMR (100.6 MHz,
CDCl3): δ=16.5 (CH3), 16.7 (CH3), 20.3 (b, CH3), 28.4–33.0
i
3
CDCl3): δ=1.37 (d, 6H, CH3, Pr, JH-H =6.8 Hz), 1.95 À 2.15
i
(m, 8H, CH2, cod), 2.72 (b, 1H, CH, Pr), 3.34 (dd, 1H, CH2,
2JH-H =15.2 Hz, 3JH-H =9.5 Hz), 3.52–3.57 (m, 2H, CH2,
CH=cod), 3.83 (b, 1H, CH=, cod), 4.20 (b, 1H, CHÀ S), 4.96 (b,
1H, CH=, cod), 5.11 (b, 1H, CH-OP), 5.23 (b, 1H, CH=, cod),
7.32–7.74 (m, 26H, CH=). 13C NMR (100.6 MHz, CDCl3): δ=
(CH2, cod), 31.6–34.0 (CH3, Bu), 34.5–35.2 (C, Bu), 38.4
(CH2), 58.9 (CHÀ S), 68.9 (CH=, cod), 79.4 (CH=, cod), 81.0
(CH-OP), 99.4 (d, CH=, cod, JC-P =14.3 Hz), 110.5 (d, CH=,
cod, JC-P =18.2 Hz), 117.4–135.9 (aromatic carbons), 161.6 (q,
t
t
i
i
1
24.5 (CH3, Pr), 24.8 (CH3, Pr), 29.5 (CH2, cod), 30.5 (CH2,
CÀ B, BArF, JC-B =49.7 Hz). Minor isomer (35%): 31P NMR
3
cod), 31.9 (CH2, cod), 32.7 (CH2, cod), 38.0 (d, CH2, JC-P
=
(161.9 MHz, CDCl3): δ=105.6 (s). 1H NMR (400 MHz,
i
t
10.6 Hz), 48.5 (b, CH, Pr), 57.2 (CHÀ S), 98.2 (b, CH=, cod),
101.0 (bs, CH=, cod), 117.7-136.9 (aromatic carbons), 161.8 (q,
CÀ B, BArF, 1JC-B =49.7 Hz). MS HR-ESI [found 693.1915,
C32H37IrOPS (M)+ requires 693.1926].
CDCl3): δ=1.41 (s, 9H, CH3, Bu), 1.48 (s, 9H, CH3, tBu), 1.58
t
(s, 9H, CH3, Bu), 1.77 (s, 3H, CH3), 1.80 (s, 3H, CH3), 2.00–
2.40 (m, 8H, CH2, cod), 3.12 (s, 3H, CH3), 3.27 (s, 3H, CH3),
3.12 (m, 1H, CH2), 3.27 (m, 1H, CH2), 4.12 (m, 1H, CHÀ S),
4.48 (m, 1H, CH=, cod), 4.56 (m, 1H, CH=, cod), 4.94 (m, 1H,
CH-OP), 5.48 (m, 1H, CH=, cod), 6.02 (m, 1H, CH=, cod),
7.20–7.80 (m, 18H, CH=). 13C NMR (100.6 MHz, CDCl3): δ=
16.5 (CH3), 16.7 (CH3), 20.3 (b, CH3), 28.4–33.0 (CH2, cod),
[Ir(cod)(L1e)]BArF: Yield: 54 mg (92%). 31P NMR
(161.9 MHz, CDCl3): δ=116.0 (s). 1H NMR (400 MHz,
CDCl3): δ=1.42 (m, 6H, CH3, iPr and CH3, o-Tol), 1.57 (s, 3H,
CH3, o-Tol), 1.63 (d, 3H, CH3, iPr, 3JH-H =5.2 Hz), 1.78 (b, CH2,
cod), 2.05–2.36 (m, 6H, CH2, cod), 2.85 (b, 1H, CH=, cod),
t
t
31.6–34.0 (CH3, Bu), 34.5–35.2 (C, Bu), 36.5 (CH2), 49.9
(CHÀ S), 68.9 (CH=, cod), 81.3 (CHÀ OP), 82.9 (CH=, cod),
93.5 (b, CH=, cod), 95.7 (b, CH=, cod), 117.4-135.9 (aromatic
i
2.97 (b, 1H, CH, Pr), 3.18–3.24 (m, 1H, CH2), 3.41–3.44 (m,
1H, CH2), 3.82 (b, 1H, CH=, cod), 3.92 (b, 1H, CHÀ S), 3.99 (b,
1H, CH=, cod), 4.62–4.83 (b, 1H, CH=, cod), 5.09 (b, 1H, CH-
OP), 5.35 (b, 1H, CH=, cod), 6.52–8.34 (m, 24H, CH=). 13C
NMR (100.6 MHz, CDCl3): δ=21.5 (CH3, o-Tol), 22.2 (CH3,
1
carbons), 161.6 (q, CÀ B, BArF, JC-B =49.7 Hz). MS HR-ESI
[found 905.3711, C45H61IrO3PS (M)+ requires 905.3703].
[Ir(cod)(L3e)]BArF: Yield: 52.6 mg (89%). Major isomer
i
i
1
o-Tol), 24.2 (CH3, Pr), 24.4 (CH3, Pr), 27.5 (CH2, cod), 29.8
(85%): 31P NMR (161.9 MHz, CDCl3): δ=116.0 (s). H NMR
t
(CH2, cod), 32.2 (CH2, cod), 34.2 (CH2, cod), 37.5 (CH2), 49.8
(400 MHz, CDCl3): δ=1.37 (s, 9H, CH3, Bu), 1.70–2.40 (m,
i
(b, CH, Pr), 57.6 (CHÀ S), 75.9 (CH=, cod), 77.2 (b, CH-OP),
8H, CH2, cod), 2.27 (s, 3H, CH3, o-Tol), 2.72 (s, 3H, CH3, o-
2
87.4 (b, CH=, cod), 93.6 (b, CH=, cod), 101.0 (b, CH=, cod),
Tol), 2.92 (b, 1H, CH=, cod), 3.28 (dd, 1H, CH2, JH-H
=
1
117.4-143.1 (aromatic carbons), 161.7 (q, CÀ B, BArF, JC-B
=
14.8 Hz, 3JH-H =7.6 Hz), 3.42 (dd, 1H, CH2, 2JH-H =14.8 Hz,
3JH-H =9.6 Hz), 3.93 (b, 1H, CH=, cod), 4.21 (d, 1H, CHÀ S,
3JH-H =9.6 Hz), 4.82 (b, 1H, CH=, cod), 5.08 (m, 1H, CH-OP),
5.47 (b, 1H, CH=, cod), 6.42 (m, 1H, CH=), 7.00-7.80 (m, 22H,
49.7 Hz). MS HR-ESI [found 721.2243, C34H41IrOPS (M)+
requires 721.2240].
[Ir(cod)(L2b)]BArF: Yield: 62 mg (93%). 31P NMR
CH=), 8.24 (dd, 1H, JH-H =17.6 Hz, JH-H =7.2 Hz). 13C NMR
(100.6 MHz, CDCl3): δ=22.4 (CH3, o-Tol), 22.5 (CH3, o-Tol),
27.3 (CH2, cod), 29.7 (CH2, cod), 30.0 (CH2, cod), 31.5 (CH2,
3
3
(161.9 MHz, CDCl3): δ=107.9 (s). 1H NMR (400 MHz,
3
CDCl3): δ=0.98 (t, 3H, CH3, Pr, JH-H =6.8 Hz), 1.42 (s, 9H,
t
t
CH3, Bu), 1.55 (s, 9H, CH3, Bu), 1.57–1.67 (m, 2H, CH2, Pr),
1.78 (s, 3H, CH3), 1.82 (s, 3H, CH3), 1.94–1.99 (m, 2H, CH2,
cod), 2.04 (m, 2H, CH2, cod), 2.18 (m, 2H, CH2, cod), 2.22–
2.30 (m, 2H, CH2, cod), 2.28 (s, 3H, CH3), 2.29 (s, 3H, CH3),
t
t
3
cod), 31.9 (CH3, Bu), 34.0 (C, Bu), 37.5 (d, CH2, JC-P
=
4.2 Hz), 52.5 (CHÀ S), 74.4 (CH=, cod), 76.6 (CH=, cod), 87.4
(CH-OP), 93.6 (d, CH=, cod, JC-P =15.2 Hz), 104.0 (d, CH=,
cod, JC-P =16.0 Hz), 117.4–142.9 (aromatic carbons), 161.6 (q,
2.77–2.81 (m, 2H, CH2, Pr), 2.95 (dd, 1H, CH2, 2JH-H =15.2 Hz,
1
CÀ B, BArF, JC-B =48.8 Hz). Minor isomer (15%): 31P NMR
3
3JH-H =9.2 Hz), 3.34 (dd, 1H, CH2, 2JH-H =15.6 Hz, JH-H
=
=
(161.9 MHz, CDCl3): δ=115.6 (s). 1H NMR (400 MHz,
3
7.6 Hz), 3.44 (b, 1H, CH=, cod), 4.43 (d, 1H, CHÀ S, JH-H
t
CDCl3): δ=1.56 (s, 9H, CH3, Bu), 1.70–2.40 (m, 8H, CH2,
8.8 Hz), 4.93–5.01 (m, 2H, CH-OP and CH=cod), 5.05–5.09
(m, 1H, CH=, cod), 5.31 (b, 1H, CH=, cod), 7.22–7.70 (m,
18H, CH=). 13C NMR (100.6 MHz, CDCl3): δ=13.2 (CH3, Pr),
16.5 (CH3), 16.7 (CH3), 20.3 (CH3), 20.4 (CH3), 21.8 (CH2, Pr),
cod), 2.29 (s, 3H, CH3, o-Tol), 2.60 (s, 3H, CH3, o-Tol), 2.92 (b,
3
1H, CH=, cod), 3.12 (dd, 1H, CH2, 2JH-H =15.2 Hz, JH-H
=
8.0 Hz), 3.42 (m, 1H, CH2), 3.57 (m, 1H, CH=, cod), 4.24 (b,
1H, CHÀ S), 4.76 (b, 1H, CH=, cod), 5.09 (m, 1H, CH-OP),
5.29 (b, 1H, CH=, cod), 6.60 (m, 1H, CH=), 7.00–7.80 (m,
t
29.2 (CH2, cod), 29.6 (CH2, cod), 31.9 (CH3, Bu, CH2, cod),
32.3 (CH3, Bu), 33.1 (CH2, cod), 35.0 (C, Bu), 37.3 (CH2, Pr),
t
t
3
3
22H, CH=), 8.65 (dd, 1H, JH-H =17.6 Hz, JH-H =7.2 Hz). 13C
NMR (100.6 MHz, CDCl3): δ=22.2 (CH3, o-Tol), 22.7 (CH3,
o-Tol), 27.0 (CH2, cod), 29.3 (CH2, cod), 29.5 (CH2, cod), 30.0
3
38.1 (d, CH2, JC-P =6.8 Hz), 53.8 (CHÀ S), 70.9 (CH=, cod),
79.3 (CHÀ OP), 82.1 (CH=, cod), 98.5 (d, CH=, cod, JC-P
=
17.5 Hz), 108.8 (d, CH=, cod, JC-P =14.6 Hz), 117.4–137.0
t
t
(CH2, cod), 31.5 (CH3, Bu), 34.5 (C, Bu), 37.0 (b, CH2), 52.9
(CHÀ S), 70.6 (CH=, cod), 76.0 (CH=, cod), 86.4 (CH-OP),
94.2 (b, CH=, cod), 103.8 (b, CH=, cod), 117.4-142.9 (aromatic
1
(aromatic carbons), 161.7 (q, CÀ B, BArF, JC-B =50.5 Hz). MS
HR-ESI [found 889.3509, C44H59IrO3PS (M)+ requires
889.3523].
1
carbons), 161.6 (q, CÀ B, BArF, JC-B =48.8 Hz). MS HR-ESI
[found 735.2398, C35H43IrOPS (M)+ requires 735.2396].
[Ir(cod)(L3b)]BArF: Yield: 60.2 mg (92%). Major isomer
1
(65%): 31P NMR (161.9 MHz, CDCl3): δ=107.7 (s). H NMR
[Ir(cod)(L4b)]BArF: Yield: 61 mg (93%). 31P NMR
t
(400 MHz, CDCl3): δ=1.37 (s, 9H, CH3, Bu), 1.45 (s, 9H,
(161.9 MHz, CDCl3): δ=104.4 (s). 1H NMR (400 MHz,
t
t
CH3, Bu), 1.55 (s, 9H, CH3, Bu), 1.77 (s, 3H, CH3), 1.80 (s,
3H, CH3), 2.00–2.40 (m, 8H, CH2, cod), 2.26 (s, 3H, CH3), 2.28
(s, 3H, CH3), 2.82 (m, 1H, CH2), 3.41 (m, 1H, CH2), 3.79 (m,
t
t
CDCl3): δ=1.49 (s, 9H, CH3, Bu), 1.59 (s, 9H, CH3, Bu),
1.63-1.91 (m, 4H, CH2, cod), 1.75 (s, 3H, CH3), 1.85 (s, 3H,
CH3), 2.12-2.36 (m, 4H, CH2, cod), 2.29 (s, 6H, CH3), 2.89 (b,
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3
1H, CH=, cod), 3.00 (dd, 1H, CH2, 2JH-H =14.8 Hz, JH-H
=
CH2, 2JH-H =15.6 Hz, 3JH-H =9.6 Hz), 3.19 (dd, 1H, CH2, 2JH-H
=
9.6 Hz), 3.37 (dd, 1H, CH2, 2JH-H =15.6 Hz, 3JH-H =8.0 Hz),
4.19 (m, 1H, CH=, cod), 4.67 (m, 1H, CH=, cod), 4.81–4.91
(m, 1H, CH-OP), 5.17 (b, 1H, CH=, cod), 5.21 (d, 1H, CHÀ S,
3JH-H =9.6 Hz), 6.23-7.74 (m, 23H, CH=). 13C NMR
(100.6 MHz, CDCl3): δ=16.4 (CH3), 16.6 (CH3), 20.2 (CH3),
20.5 (CH3), 26.4 (CH2, cod), 29.9 (CH2, cod), 31.1 (CH2, cod),
31.8 (CH3, tBu), 32.8 (CH3, tBu), 34.7 (CH2, cod), 35.0 (C, tBu),
15.6 Hz, JH-H =8.0 Hz), 3.27 (m, 1H, CH=, cod), 3.41 (m, 1H,
CH=, cod), 3.88 (m, 1H, CH=, cod), 4.49–4.58 (m, 1H, CH-
3
3
OP), 5.05 (d, 1H, CHÀ S, JH-H =8.4 Hz), 5.11 (m, 1H, CH=,
cod), 6.09–7.94 (m, 29H, CH=). 13C NMR (100.6 MHz,
CDCl3): δ=23.2 (CH3), 23.6 (CH3), 27.3 (CH2, cod), 30.7
(CH2, cod), 31.0 (CH2, cod), 33.6 (CH2, cod), 38.3 (d, CH2,
3JC-P =7.6 Hz), 52.9 (CHÀ S), 69.3 (CH=, cod), 74.9 (CH=,
cod), 82.5 (CHÀ OP), 97.2 (d, CH=, cod, JC-P =10.0 Hz), 98.6
(d, CH=, cod, JC-P =13.0 Hz), 117.4–143.2 (aromatic carbons),
161.7 (q, CÀ B, BArF, 1JC-B =49.7 Hz). MS HR-ESI [found
755.2085, C37H39IrOPS (M)+ requires 755.2083].
t
3
35.2 (C, Bu), 37.8 (d, CH2, JC-P =7.4 Hz), 55.9 (CHÀ S), 67.9
(CH=, cod), 78.6 (CH=, cod), 79.4 (CH-OP), 101.2 (d, CH=,
cod, JC-P =14.5 Hz), 106.0 (d, CH=, cod, JC-P =15.3 Hz), 117.4-
1
143.6 (aromatic carbons), 161.7 (q, CÀ B, BArF, JC-B
=
50.4 Hz). MS HR-ESI [found 923.3367, C47H57IrO3PS (M)+
requires 923.3366].
[Ir(cod)(L5e)]BArF: Yield: 56 mg (96%). 31P NMR
(161.9 MHz, CDCl3): δ=118.2 (s). 1H NMR (400 MHz,
CDCl3): δ=1.68–1.85 (m, 2H, CH2, cod), 1.95–2.19 (m, 2H,
CH2, cod), 2.23 (s, 3H, CH3), 2.25–2.47 (m, 4H, CH2, cod),
2.53 (s, 3H, CH3), 2.92 (s, 4H, CH=, cod and CH3), 3.03 (dd,
1H, CH2, 2JH-H =15.6 Hz, 3JH-H =9.6 Hz), 3.15 (s, 3H, CH3),
3.15–3.20 (m, 2H, CH=cod, CH2), 3.75 (m, 1H, CH=, cod),
4.32-4.42 (m, 1H, CH-OP), 5.08 (b, 1H, CH=, cod), 5.24 (d,
1H, CHÀ S, 3JH-H =8.4 Hz), 5.89–9.06 (m, 27H, CH=). 13C
[Ir(cod)(L5b)]BArF: Yield: 64 mg (95%). 31P NMR
(161.9 MHz, CDCl3): δ=104.1 (s). 1H NMR (400 MHz,
t
t
CDCl3): δ=1.47 (s, 9H, CH3, Bu), 1.60 (s, 9H, CH3, Bu),
1.65-1.84 (m, 4H, CH2, cod), 1.76 (s, 3H, CH3), 1.86 (s, 3H,
CH3), 2.13-2.38 (m, 4H, CH2, cod), 2.29 (s, 3H, CH3), 2.30 (s,
3H, CH3), 2.56 (s, 3H, CH3), 2.72 (m, 1H, CH=, cod), 2.95 (dd,
1H, CH2, 2JH-H =15.2 Hz, 3JH-H =9.6 Hz), 3.08 (s, 3H, CH3),
3.38 (dd, 1H, CH2, 2JH-H =15.2 Hz, 3JH-H =7.6 Hz), 3.92 (m, 1H,
CH=, cod), 4.72 (m, 1H, CH=, cod), 4.89 (m, 1H, CH-OP),
3
NMR (100.6 MHz, CDCl3): δ=21.8 (CH3), 22.3 (d, CH3, JC-P
=6.9 Hz), 23.1 (CH3), 26.7 (CH2, cod), 29.9 (CH2, cod), 31.7
3
3
5.12 (d, 1H, CHÀ S, JH-H =8.8 Hz), 5.18 (b, 1H, CH=, cod),
(CH2, cod), 34.3 (CH2, cod), 38.3 (d, CH2, JC-P =7.6 Hz), 52.0
6.08-7.70 (m, 21H, CH=). 13C NMR (100.6 MHz, CDCl3): δ=
16.4 (CH3), 16.6 (CH3), 20.3 (CH3), 20.5 (CH3), 22.8 (CH3),
22.9 (CH3), 25.7 (CH2, cod), 30.5 (CH2, cod), 31.0 (CH2, cod),
31.8 (CH3, tBu), 32.7 (CH3, tBu), 35.0 (CH2, cod), 35.2 (C, tBu),
(CHÀ S), 67.9 (CH=, cod), 77.2 (CH=, cod), 81.4 (CH-OP),
96.5 (d, CH=, cod, JC-P =9.2 Hz), 96.8 (d, CH=, cod, JC-P
=
13.8 Hz), 117.4–143.5 (aromatic carbons), 161.7 (q, CÀ B, BArF,
1JC-B =49.7 Hz). MS HR-ESI [found 783.2401, C39H43IrOPS
(M)+ requires 783.2396].
3
37.8 (d, CH2, JC-P =7.6 Hz), 53.7 (CHÀ S), 66.2 (CH=, cod),
77.7 (CH=, cod), 80.0 (CH-OP), 102.1 (d, CH=, cod, JC-P
=13.8 Hz), 104.6 (d, CH=, cod, JC-P =16.1 Hz), 117.4–143.8
[Ir(cod)(L6b)]BArF: Yield: 69 mg (97%). 31P NMR
(161.9 MHz, CDCl3): δ=104.1 (s). 1H NMR (400 MHz,
1
(aromatic carbons), 161.7 (q, CÀ B, BArF, JC-B =49.7 Hz). MS
t
t
CDCl3): δ=1.49 (s, 9H, CH3, Bu), 1.58 (s, 9H, CH3, Bu),
HR-ESI [found 951.3674, C49H61IrO3PS (M)+ requires
951.3679].
1.64–1.71 (m, 4H, CH2, cod), 1.76 (s, 3H, CH3), 1.85 (s, 3H,
CH3), 2.08–2.22 (m, 4H, CH2, cod), 2.29 (s, 6H, CH3), 2.99-
[Ir(cod)(L5c)]BArF: Yield: 63 mg (94%). 31P NMR
3.05 (m, 2H, CH2 and CH=, cod), 3.39 (dd, 1H, CH2, JH-H
=
2
(161.9 MHz, CDCl3): δ=108.7 (s). 1H NMR (400 MHz,
15.2 Hz, JH-H =7.6 Hz), 4.10 (m, 1H, CH=, cod), 4.76 (b, 1H,
CH=, cod), 4.84–4.92 (m, 1H, CH-OP), 5.13 (b, 1H, CH=,
3
t
t
CDCl3): δ=1.41 (s, 9H, CH3, Bu), 1.59 (s, 9H, CH3, Bu),
1.71–1.89 (m, 4H, CH2, cod), 1.71 (s, 3H, CH3), 1.73 (s, 3H,
CH3), 1.97–2.20 (m, 4H, CH2, cod), 2.21 (s, 3H, CH3), 2.22 (s,
3H, CH3), 2.24 (s, 3H, CH3), 2.75 (s, 3H, CH3), 2.99–3.08 (m,
2H, CH2 and CH=cod), 3.31 (dd, 1H, CH2, 2JH-H =15.6 Hz,
3JH-H =8.4 Hz), 4.26 (m, 1H, CH=, cod), 4.67 (m, 1H, CH=,
3
cod), 5.23 (d, 1H, CHÀ S, JH-H =9.2 Hz), 6.23–7.89 (m, 22H,
CH=). 13C NMR (100.6 MHz, CDCl3): δ=16.4 (CH3), 16.6
(CH3), 20.2 (CH3), 20.4 (CH3), 26.6 (CH2, cod), 29.8 (CH2,
t
t
cod), 31.2 (CH2, cod), 31.8 (CH3, Bu), 32.8 (CH3, Bu), 34.5
t
t
(CH2, cod), 35.0 (C, Bu), 35.2 (C, Bu), 37.7 (CH2), 56.1
3
cod), 4.74 (m, 1H, CH=, cod), 4.80 (d, 1H, CHÀ S, JH-H
(CHÀ S), 68.9 (CH=, cod), 79.3 (CH=, cod), 79.7 (CH-OP),
=8.8 Hz), 5.31-5.35 (m, 1H, CH-OP), 5.88–7.63 (m, 21H,
CH=). 13C NMR (100.6 MHz, CDCl3): δ=16.7 (CH3), 16.8
(CH3), 20.5 (CH3), 20.7 (CH3), 23.5 (CH3), 24.3 (CH3), 27.6
100.9 (d, CH=, cod, JC-P =13.7 Hz), 105.4 (d, CH=, cod, JC-P =
15.3 Hz), 117.4–143.5 (aromatic carbons), 161.7 (q, CÀ B, BArF,
1JC-B =49.7 Hz). MS HR-ESI [found 991.3222, C48H56F3IrO3PS
(M)+ requires 991.3240].
t
(CH2, cod), 29.9 (d, CH2, cod, JC-P =10.0 Hz), 31.8 (CH3, Bu),
t
32.1 (CH2, cod), 32.9 (CH3, Bu), 34.2 (CH2, cod), 35.1 (C,
[Ir(cod)(L7b)]BArF: Yield: 64 mg (95%). 31P NMR
tBu), 35.5 (C, Bu), 37.5 (d, CH2, JC-P =9.2 Hz), 56.4 (CHÀ S),
t
3
(161.9 MHz, CDCl3): δ=104.7 (s). 1H NMR (400 MHz,
2
67.3 (CH=, cod), 77.4 (CH=, cod), 86.3 (d, CH-OP, JC-P
=
t
t
CDCl3): δ=1.49 (s, 9H, CH3, Bu), 1.58 (s, 9H, CH3, Bu),
6.0 Hz), 103.4 (d, CH=, cod, JC-P =14.8 Hz), 104.7 (d, CH=,
cod, JC-P =13.9 Hz), 117.7-144.7 (aromatic carbons), 161.9 (q,
CÀ B, BArF, 1JC-B =50.1 Hz). MS HR-ESI [found 951.3641,
C49H61IrO3PS (M)+ requires 951.3679].
1.63-1.94 (m, 4H, CH2, cod), 1.75 (s, 3H, CH3), 1.85 (s, 3H,
CH3), 2.07–2.37 (m, 4H, CH2, cod), 2.29 (s, 6H, CH3), 2.86 (m,
3
1H, CH=, cod), 2.98 (dd, 1H, CH2, 2JH-H =15.2 Hz, JH-H
=
9.6 Hz), 3.36 (dd, 1H, CH2, 2JH-H =15.2 Hz, 3JH-H =8.0 Hz),
3.84 (s, 3H, CH3, MeO), 4.30–4.33 (m, 1H, CH=, cod), 4.67 (b,
1H, CH=, cod), 4.79-4.88 (m, 1H, CH-OP), 5.12 (d, 1H, CHÀ S,
3JH-H =9.2 Hz), 5.16 (b, 1H, CH=, cod), 6.31–7.71 (m, 22H,
CH=). 13C NMR (100.6 MHz, CDCl3): δ=16.4 (CH3), 16.6
(CH3), 20.2 (CH3), 20.5 (CH3), 26.3 (CH2, cod), 30.0 (CH2,
[Ir(cod)(L5d)]BArF: Yield: 55 mg (92%). 31P NMR
(161.9 MHz, CDCl3): δ=114.3 (s). 1H NMR (400 MHz,
CDCl3): δ=1.75–1.86 (m, 2H, CH2, cod), 1.93–2.01 (m, 2H,
CH2, cod), 2.10–2.15 (m, 1H, CH2, cod), 2.20–2.40 (m, 3H,
CH2, cod), 2.57 (s, 3H, CH3), 3.02 (s, 3H, CH3), 3.07 (dd, 1H,
Adv. Synth. Catal. 2021, 363, 1–15
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t
t
cod), 31.0 (CH2, cod), 31.8 (CH3, Bu), 32.8 (CH3, Bu), 34.9
[Ir(cod)(L8e)]BArF: Yield: 55 mg (43%). 31P NMR
(161.9 MHz, CDCl3): δ=119.4 (s). 1H NMR (400 MHz,
CDCl3): δ=1.42–1.47 (m, 2H, CH2, cod), 1.64–1.76 (m, 1H,
CH2, cod), 1.79–2.00 (m, 3H, CH2, cod), 2.08–2.16 (m, 1H,
CH2, cod), 2.26 (s, 3H, CH3, o-Tol), 2.31–2.39 (m, 2H, CH2,
cod), 2.97 (m, 1H, CH=, cod), 2.99 (m, 1H, CH2), 3.11 (m, 1H,
CH2), 3.13 (m, 1H, CH=, cod), 3.26 (s, 3H, CH3, o-Tol), 3.43
(m, 1H, CH=, cod), 4.50 (m, 1H, CH-OP), 5.07 (d, 1H, CH=,
3JH-H =7.8 Hz), 5.21 (m, 1H, CH=, cod), 5.51 (d, 1H, CHÀ S,
3JH-H =9.0 Hz), 6.49-9.49 (m, 32H, CH=). 13C NMR
(100.6 MHz, CDCl3): δ=21.8 (CH3, o-Tol), 22.2 (CH3, o-Tol),
26.3 (CH2, cod), 29.9 (CH2, cod), 31.4 (CH2, cod), 34.1 (CH2,
cod), 38.3 (CH2-O), 53.4 (CHÀ S), 67.8 (CH=, cod), 77.2 (CH=,
cod), 81.3 (CH-OP), 97.9 (d, CH=, cod, JC-P =9.9 Hz), 98.4 (d,
CH=, cod, JC-P =12.4 Hz), 117.4–142.9 (aromatic carbons),
161.66 (q, CÀ B, BArF, 1JC-B =50.0 Hz). MS HR-ESI [found
855.2399, C45H43IrOPS (M)+ requires 855.2396].
t
t
3
(CH2, cod), 35.0 (C, Bu), 35.2 (C, Bu), 37.8 (d, CH2, JC-P
=
8.1 Hz), 55.6 (CH3, MeO), 56.2 (CHÀ S), 67.7 (CH=, cod), 78.5
(CH=, cod), 79.4 (CH-OP), 101.3 (d, CH=, cod, JC-P =14.4 Hz),
106.0 (d, CH=, cod, JC-P =16.3 Hz), 116.2–163.4 (aromatic
1
carbons), 161.7 (q, CÀ B, BArF, JC-B =50.5 Hz). MS HR-ESI
[found 955.3512, C48H56F3IrO3PS (M)+ requires 955.3501].
[Ir(cod)(L8b)]BArF: Yield: 57.1 mg (89%). 31P NMR
(161.9 MHz, CDCl3): δ=104.4 (s). 1H NMR (400 MHz,
CDCl3): δ=1.14–1.17 (m, 2H, CH2, cod), 1.66 (s, 9H, CH3,
tBu), 1.69 (s, 9H, CH3, Bu), 1.73-1.82 (m, 2H, CH2, cod), 1.79
t
(s, 3H, CH3), 1.90 (s, 3H, CH3), 2.09-2.26 (m, 2H, CH2, cod),
2.31 (s, 3H, CH3), 2.32 (s, 3H, CH3), 2.78 (m, 1H, CH=, cod),
2.93 (dd, 1H, CH2, JH-H =15.2 Hz, JH-H =9.2 Hz), 3.39 (dd,
2
3
2
3
1H, CH2, JH-H =15.6 Hz, JH-H =8.0 Hz), 3.53 (m, 1H, CH=,
cod), 4.83 (b, 1H, CH=, cod), 4.99-5.03 (m, 1H, CH-OP), 5.35
3
(d, 1H, CHÀ S, JH-H =9.2 Hz), 5.37 (b, 1H, CH=, cod), 5.50–
9.47 (m, 27H, CH=). 13C NMR (100.6 MHz, CDCl3): δ=16.5
(CH3), 16.7 (CH3), 20.3 (CH3), 20.6 (CH3), 24.9 (CH2, cod),
General Procedure for the Hydrogenation of Ole-
fins S1–S43
t
30.3 (CH2, cod), 31.0 (CH2, cod), 31.9 (CH3, Bu), 32.8 (CH3,
t
t
tBu), 35.1 (CH2, cod and C, Bu), 35.3 (C, Bu), 37.7 (CH2),
The alkene (0.5 mmol) and the corresponding catalyst precursor
[Ir(cod)(L)]BArF (2 mol%) were dissolved in the corresponding
solvent (2 mL) and placed in a high-pressure autoclave. The
autoclave was purged 4 times with hydrogen. Then, it was
pressurized at the desired pressure. After the desired reaction
time, the autoclave was depressurized and the solvent evapo-
rated off. The residue was dissolved in Et2O (1.5 ml) and
filtered through a short plug of celite. The enantiomeric excess
was determined by chiral GC or chiral HPLC and conversions
54.5 (CHÀ S), 65.8 (CH=, cod), 78.3 (CH=, cod), 79.9 (CH-
OP), 103.1 (CH=, cod, JC-P =13.7 Hz), 105.6 (CH=, cod, JC-P
=
16.0 Hz), 117.4–143.9 (aromatic carbons), 161.7 (q, CÀ B, BArF,
1JC-B =49.8 Hz). MS HR-ESI [found 1025.3706, C55H61IrO3PS
(M)+ requires 1025.3703].
[Ir(cod)(L8c)]BArF: Yield: 35 mg (24%). 31P NMR
(161.9 MHz, CDCl3): δ=106.0 (s). 1H NMR (400 MHz,
CDCl3): δ=1.53–1.61 (m, 1H, CH2, cod), 1.56 (s, 9H, CH3,
tBu), 1.75–2.09 (m, 6H, CH2, cod), 1.80 (s, 3H, CH3), 1.81 (s,
1
were determined by H NMR (see Supporting Information for
details).
t
12H, Bu and CH3), 2.30 (s, 3H, CH3), 2.32-2.36 (m, 1H, CH2,
cod), 3.01 (m, 1H, CH2), 3.14 (m, 1H, CH=, cod), 3.26 (m, 1H,
CH2), 4.46 (m, 1H, CH=, cod), 4.87 (m, 1H, CH=, cod), 4.96
(m, 1H, CH=, cod), 5.14 (d, 1H, CHÀ S, 3JH-H =8.3 Hz), 5.39 (d,
General Procedure for the Hydrogenation of Cyclic
β-Enamides S44–S50
3
1H, CH=, JH-H =7.8 Hz), 5.55 (m, 1H, CHÀ OP), 6.39-9.09 (m,
27H, CH=). 13C NMR (100.6 MHz, CDCl3): δ=16.5 (CH3),
The enamide (0.25 mmol) and the corresponding catalyst
precursor [Ir(cod)(L)]BArF (1 mol%) were dissolved in in the
corresponding solvent (1 mL) and placed in a high-pressure
autoclave, which was purged four times with hydrogen. It was
then pressurized at the desired pressure. After the desired
reaction time, the autoclave was depressurized and the solvent
evaporated off. The residue was dissolved in Et2O (1.5 ml) and
filtered through a short celite plug. Conversions were deter-
16.6 (CH3), 20.3 (CH3), 20.4 (CH3), 26.6 (CH2, cod), 30.0 (CH2,
t
t
cod), 31.7 (CH3, Bu), 32.7 (CH3, Bu), 33.0 (CH2, cod), 34.6
t
t
(CH2, cod), 34.9 (C, Bu), 35.2 (C, Bu), 37.7 (CH2-O), 53.4
(CHÀ S), 66.8 (CH=, cod), 78.5 (CH=, cod), 84.1 (CH-OP),
102.2 (b, CH=, cod), 106.6 (b, CH=, cod), 117.4-144.7
1
(aromatic carbons), 161.1 (q, CÀ B, BArF, JC-B =51.9 Hz). MS
HR-ESI [found 1025.3706, C55H61IrO3PS (M)+ requires
1025.3703].
1
mined by H NMR and enantiomeric excesses by HPLC (see
[Ir(cod)(L8d)]BArF: Yield: 75 mg (60%). 31P NMR
(161.9 MHz, CDCl3): δ=115.0 (s). 1H NMR (400 MHz,
CDCl3): δ=1.44–1.54 (m, 2H, CH2, cod), 1.78–1.89 (m, 2H,
CH2, cod), 1.97–2.03 (m, 2H, CH2, cod), 2.22–2.37 (m, 2H,
CH2, cod), 3.09 (m, 1H, CH2), 3.25 (m, 1H, CH2), 3.37 (m, 1H,
CH=, cod), 3.54 (m, 2H, CH=, cod), 4.78 (m, 1H, CH=, cod),
Supporting Information for details).
Acknowledgements
We all acknowledge MINECO for the INTECAT network
CTQ2016-81293-REDC/AEI. The URV members gratefully
acknowledge financial support from the Spanish Ministry of
Economy and Competitiveness (CTQ2016-74878-P and
PID2019-104904GBÀ I00) and European Regional Development
Fund (AEI/FEDER, UE), the Catalan Government
(2014SGR670), and the ICREA Foundation (ICREA Academia
award to M.D). The ICIQ members gratefully acknowledge
financial support from CERCA Programme/Generalitat de
Catalunya, the Spanish Ministry of Economy and Competitive-
ness (CTQ2015-69136-R, CTQ2017-87792-R, PID2019-
3
5.17 (m, 1H, CH-OP), 5.25 (d, 1H, CHÀ S, JH-H =8.7 Hz), 5.49
3
(d, 1H, CH=, JH-H =7.8 Hz), 6.58-9.05 (m, 34H, CH=). 13C
NMR (100.6 MHz, CDCl3): δ=27.4 (CH2, cod), 30.3 (CH2,
cod), 31.3 (CH2, cod), 32.8 (CH2, cod), 38.3 (CH2), 54.2
(CHÀ S), 70.7 (CH=, cod), 74.1 (CH=, cod), 83.2 (CH-OP),
97.8 (d, CH=, cod, JC-P =10.6 Hz), 99.9 (d, CH=, cod, JC-P
=
12.4 Hz), 117.4-137.8 (aromatic carbons), 161.7 (q, CÀ B, BArF,
1JC-B =49.9 Hz). MS HR-ESI [found 827.2087, C43H39IrOPS
(M)+ requires 827.2083].
Adv. Synth. Catal. 2021, 363, 1–15
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1092336RBÀ I00, AEI/MINECO/FEDER, UE and Severo Ochoa
Excellence Accreditation 2020–2023 (CEX2019-000925-S,
MIC/AEI)) and DEC Generalitat de Catalunya (Grant
2014SGR827). The CELLEX Foundation is also acknowledged
for financing the High Throughput Experimentation (HTE)
laboratory.
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Adv. Synth. Catal. 2021, 363, 1–15
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FULL PAPER
Indene Derived Phosphorus-Thioether Ligands for the Ir-
Catalyzed Asymmetric Hydrogenation of Olefins with
Diverse Substitution Patterns and Different Functional
Groups
Adv. Synth. Catal. 2021, 363, 1–15
J. Margalef*, M. Biosca, P. de la Cruz-Sánchez, X.
Caldentey, C. Rodríguez-Escrich, O. Pàmies, M. A. Pericàs*,
M. Diéguez*