High iso Aldehyde Selectivity in the Hydroformylation of Short-Chain Alkenes

Article abstract of DOI:10.1002/anie.201811888

The hydroformylation of propene to give predominantly iso-butanal has been achieved; class-leading selectivity is possible even at higher temperatures that deliver fast conversion. Racemic rhodium complexes of bidentate phospholane phosphites derived from tropos-biphenols and unusual solvent systems are the key to the selectivity observed.

Full text of DOI:10.1002/anie.201811888

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
Chemie
International Edition
www.angewandte.org
Accepted Article
Title: High iso aldehyde selectivity in the hydroformylation of short-
chain alkenes.
Authors: Leo Iu, Jose A. Fuentes, Mesfin E. Janka, Kevin J Fontenot,
and Matthew L. Clarke
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201811888
Angew. Chem. 10.1002/ange.201811888
Link to VoR: http://dx.doi.org/10.1002/anie.201811888
http://dx.doi.org/10.1002/ange.201811888

10.1002/anie.201811888
Angewandte Chemie International Edition
COMMUNICATION
High iso aldehyde selectivity in the hydroformylation of short-
chain alkenes
Leo Iu,[a] José A. Fuentes,[a] Mesfin E. Janka,[b] Kevin J. Fontenot,[b] Matthew L. Clarke*[a]
Abstract: The hydroformylation of propene to give predominantly
iso-butanal has been achieved; class-leading selectivity is possible
even at higher temperatures that deliver fast rates. Racemic Rh
complexes of bidentate phospholane phosphites derived from
tropos-biphenols and unusual solvent systems are the key to the
selectivity observed.
is 63% (n: iso = 0.59); however, this was observed at 19 oC
where rates are not sufficiently high for commodity chemicals
production.[10a] The same catalyst at higher temperatures (80 oC)
delivers lower iso selectivity below 50%.[10a,d] An alternative
benchmark is 56% (n:iso = 0.79) observed at more typical
industrial reaction temperatures (Scheme 1).[8c,d] Surprisingly, we
have now found a combination of reaction conditions and
racemic Rh / phospholane-phosphite catalysts that can deliver
unprecedented iso-butanal selectivity from propene and report
this discovery here.
Rh-catalysed hydroformylation is a reaction of high importance
in the production of a variety of chemicals. Millions of tonnes of
aldehydes are produced in this way each year.[1]
Hydroformylation of terminal ‘alkyl’ alkenes shows a preference
towards linear aldehyde formation and with the correct ligands
near-perfect linear selectivity can be obtained.[1-5] This is used at
large scale and in organic synthesis. There are also some very
significant chemicals that require a branched-aldehyde selective
hydroformylation of a terminal alkene for an efficient synthesis.
Sometimes this can be achieved by substrate control.[6,7]
However, arguably the most industrially important branched
aldehyde is iso-butanal, which requires the very challenging
(branched) iso-selective hydroformylation of an unbiased alkyl
O
+
O
Me
n
iso
encapsulated Rh catalysts formed
from metal porphyrin
and pyridyl phosphine (ref. 10a and 10d)
At 25 °C, n:iso = 0.59 (63% iso).
N
N
N
At 70 °C, n:iso = 1.1 (47% iso).
P
M
N
N
3
alkene, propene.[8-10]
Global demand for iso-butanal can be
estimated to be over half a million tonnes in 2014.[11] Rhodium
catalysts derived from ligand (Rax,R,R)-1, (nicknamed
BOBPHOS and illustrated in Scheme 2), are extremely unusual
in being able to transform simple terminal alkenes into branched
aldehydes with good regioselectivity and up to 93% e.e.; the
Rh catalyst formed from
tBu
Ph
N
Me
O
P
PPh2
Fe
O
Me
tBu
smallest
terminal
alkene
reported
was
hex-1-ene.[9]
(ref. 8d)
Unfortunately, using either the typical published conditions for
operating this catalyst, or the typical temperatures and
pressures used in propene hydroformylation, Rh/ BOBPHOS
catalysts do not give satisfactory results in the hydroformylation
of propene (see supporting information, Table S1).
Me
At 90 °C, n: iso = 0.79 (56% iso)
Initial attempts (see ESI) using Rh BOBPHOS or its epimers
under standard conditions: n: iso = 0.6-1.2 (48-62% iso).
This work: n: iso down to 0.22 (82% iso),
n: iso selectivity of 0.3-0.4 retained at 75 o
C
The small size of propene renders it less influenced by steric
barriers, and possibly reduces attractive interactions as well. A
review of the patent and open literature reveals that despite
research over decades, iso-selective hydroformylation is very
much an unsolved problem, especially at typical reaction
temperatures employed in industry. The best selectivity obtained
Scheme 1. Iso-selective hydroformylation of propene is highly desired but an
extreme challenge.
The unusual regioselectivity observed for Rh catalysts derived
from (Rax,R,R)-1 in the hydroformylation of allyl benzene utilises
subtle interactions that prevent the linear Rh-alkyl intermediate
being formed; an attractive interaction between the phospholane
Ph substituents and the substrate stabilises an unproductive C-
H forming process, on the wrong side of a steric barrier between
the transition state and linear Rh-alkyl.[9d] Even subtle changes
to the ligand structure might reduce branched selectivity, yet a
racemic ligand would be preferable, since it reduces ligand cost
very significantly. We speculated that swapping the
[a]
[b]
Dr Leo Iu, Dr J. A. Fuentes, Prof. M. L. Clarke
EaStCHEM School of Chemistry, University of St Andrews,
Purdie Building, North Haugh, St Andrews, KY16 9ST, United
Kingdom
E-mail: mc28@st-andrews.ac.uk
Dr Mesfin E. Janka, Dr Kevin J. Fontenot
Eastman Chemical Company, 200 South Wilcox Drive, Kingsport,
Tennessee, 37660, USA
enantiomerically pure atropos diol for
a configurationally
unstable tropos diol could deliver a phosphite unit that while
interconverting freely as a ligand would set itself in a single
preferred conformation upon coordination to rhodium (Scheme 2,
Supporting information for this article is given via a link at the end of
the document.((Please delete this text if not appropriate))
This article is protected by copyright. All rights reserved.

10.1002/anie.201811888
Angewandte Chemie International Edition
COMMUNICATION
top).[12] We hoped that this would be an analogous conformation
to that observed with (Rax,R,R)-1, rather than its diastereomer,
(Sax,R,R)-1, (although this could not be predicted in advance). If
the tropos-R,R system were to behave more like (Rax,R,R)-1, it
solvent octafluorotoluene, which we previously had observed to
offer very marginal gains (1-3%) in branched selectivity,[8d]
actually leads to very significantly higher selectivity for this
industrially important reaction relative to the state of the art
(Table 1). This effect is observed using the new tropos ligands
and (Rax,R,R)-BOBPHOS itself. In a variety of studies using
these types of catalysts, we have observed that while using L:Rh
ratios of 1.25:1 can work well, larger L:Rh ratios are sometimes
needed under certain conditions and a ligand to Rh ratio of 2:1 is
recommended here (Table 1, entries 1 and 2 and supporting
information Table S1).
The use of fluorinated solvents has attracted interest for a
variety of reasons.[13] Lattanzi et al examined the use of
hexafluorobenzene as additive in catalytic asymmetric Michael
addition reactions and discovered that only 5 – 10 equivalents of
hexafluorobenzene relative to the substrates were required to
achieve comparable results to those using hexafluorobenzene
as the solvent.[13d] The equivalents needed were substrate-
dependent, suggesting the presence of interactions between the
substrate and hexafluorobenzene. In this case an experiment
can also be envisaged that utilising
a
racemic, trans
diastereomer of phospholane to partner the tropos diol would
lead to two species forming upon coordination that had a similar
ligand shape to (Sax,S,S)-1 and (Rax,R,R)-1, but not its
diastereomers.
Ph
P
O
tBu
Ph
P
O
tBu
O
O
P
O
P
O
O
O
fast
Ph
Ph
O
O
tBu
O
tBu
(pseudo-Sax,R,R)
(pseudo-Rax,R,R)
tBu
O
tBu
Ph
P
Ph
O
using
a
mixture of toluene and 2205 equivalents of
O
O
O
O
O
P
P
P
octafluorotoluene w.r.t Rh does not maintain the high selectivity,
and hence we believe this is a solvent effect on these reactions
(Table 1, Entry 6 and 7).
Rh
(L)n
Rh
(L)n
Ph
Ph
O
tBu
O
tBu
Commercial production of butanal isomers does not make use of
volatile organic solvents, since they would be too expensive;
non-volatile solvents that dissolve the catalyst and enable the
products to be distilled away, while catalyst and solvent are
recycled again and again are preferred. An alternative to the use
of volatile octafluorotoluene is therefore likely to be needed for
large-scale application. We therefore decided to produce a new
solvent that maintains the properties of octafluorotoluene in this
reaction, but is no longer volatile.
Pentafluorophenyl n-octyl ether (PFPOE), which has never been
used as a synthesis solvent before[14] was chosen since it could
be made in one step from two simple chemicals and would have
a high enough boiling point to not be stripped away from the
catalyst. We were delighted to find that using this new solvent,
even after increasing reaction temperature to 75 oC, enabled the
desired high proportion of iso-butanal, but this time with the
improved turnover frequencies (TOF) possible at 75 oC. (Table 1,
entries 12 and 13, and further results in supporting information).
We note also that n: iso ratios below 0.5 are possible even at 90
oC in PFPOE (see supporting information). The protio analogue
phenyl octyl ether, while giving lower selectivity than the
fluorinated variant still enables an impressive iso-butanal yield
(see the supporting information).
(pseudo-Sax,R,R) (Rh)
(pseudo-Rax,R,R) (Rh)
tBu
Ph
Ph
Me
MeO
MeO
tBu
R
R
P
P
Me
Me
O
O
O
O
P
O
P
O
rac
Ph
Ph
tBu
(Rax,R,R)-1
Me
tBu
tropos,rac-2
atropos
tropos
Me
tBu
R1
Ph
Ph
tBu
R
P
P
O
O
O
O
P
O
P
O
R
rac
Ph
Ph
Me
tBu
tropos,rac-3
R1
tBu
R1 = OMe: (tropos,R,R)-2
R1 = Me: (tropos,R,R)-3
tropos
tropos
Scheme 2. (top): proposed interconversion of tropos phosphite in free ligands
and formation of one atropos isomer on coordination to rhodium; (bottom)
ligands used in this study.
A promising solution to the long-standing and commercially
important problem of obtaining significantly higher proportions of
iso-butanal than n-butanal in propene hydroformylation is now in
place. The new ligands are cheaper to make than the ligand that
inspired them, which is also desirable for such relatively low
value-high volume commodity chemicals. Both catalyst and
solvents will need long term stability to be viable in a commercial
process, and these studies and other elements of process
development are now underway.
In order to test this hypothesis, ligands
2 and 3 were
synthesised (see supporting information). Relative to the parent
BOBPHOS ligand, 1 these new derivatives reduce the cost of
synthesis as neither the resolution of the racemic phospholane
ring, nor the resolution of the diol to produce
atropisomer is required.
Depending on the borane-protected phospholane used, the
(R,R) and tropos,rac analogues of the tropos ligands 2 and 3
were synthesised. With the new ligands in hand, a range of
variables such as pressure, temperature and solvents were
examined. The key finding was the use of the rather unusual
a single
This article is protected by copyright. All rights reserved.

10.1002/anie.201811888
Angewandte Chemie International Edition
COMMUNICATION
Table 1. Hydroformylation of propene in fluorinated solvents.
enantiomer during catalysis. NMR analysis of the catalyst resting
state [Rh(H)(R,R)-2)(CO)2] appears to be a single species in
agreement with this (see supporting information for NMR
spectra).
[Rh(acac)(CO)2] [0.25 mM]
CHO
Ligand (L / Rh = 1.25 or 2: 1)
CHO
H2 / CO
Solvent
iso
n
Table 2. Enantioselective Hydroformylation of allyl benzene and but-1-ene.
0.4 % [Rh(acac)(CO)2]
CHO
Entry[a]
Ligand
Solvent
TOF
TON
% iso
T
Ligand (L / Rh = 2: 1)
CHO
oC
R
H2 / CO (5 bar)
solvent
R
R
1
tropos,rac-3
tropos,rac-3
(tropos,R,R)-3
(tropos,R,R)-2
tropos,rac-2
(Rax,R,R)-1
50
50
50
50
50
50
50
C7F8
C7F8
C7F8
C7F8
C7F8
C7F8
42
51
42
37
36
49
51
670
820
670
590
570
790
810
53.8
74.2[c]
73.4
69.5
71.9
76.7
56.5
n
iso
(R = Ph or Me)
2[b]
3
Entry[a]
Ligand
‘R’
Conversion
% iso
e.r.[b]
4
1
(R/S,S,S)-1
(tropos,R,R)-2
(tropos,R,R)-3
(tropos,R,R)-2
(Rax,R,R)-1
Ph
Ph
Ph
Ph
Ph
Ph
Me
>99
66
39
71
70
77
72
86
86
50/50
5
2
80/20 (R)
80/20 (R)
85/15 (R)
96/4 (R)
96/4 (R)
96/4
6
3[c]
4
>99
>99
86
C7F8 +
C7H8
(8:92)
7
(Rax,R,R)-1
5[c]
6
8
(Rax,R,R)-1
(Rax,R,R)-1
tropos,rac-2
tropos,rac-2
(Rax,R,R)-1
(tropos,R,R)-2
30
75
75
75
75
75
C7F8
12
460
350
340
500
670
750
82.0
78.3
72.2
60.3
70.3
67.0
(Rax,R,R)-1
97
9[b,d]
C7F8
350
340
500
670
750
7[d]
(Rax,R,R)-1
86
10 [b,d]
11 [b,d]
12[b,e]
13[b,e]
C7F8
[a] Catalyst preformed from [Rh(acac)(CO)2] (4 x 10-3 mmol) and ligand (8 x
10-3 mmol) by stirring at 8 bar CO/H2 at reaction temperature for 1 hour in
octafluorotoluene solvent prior to running reaction at 50 oC, for 16 hours using
C7F8
PFPOE
PFPOE
5
bar CO/H2. Conversion and regioselectivity determined by NMR
spectroscopy using 1-methylnaphthalene as an internal standard. [b] e.r.
determined by HPLC from alcohols obtained after NaBH4 reduction except
entry 7). [c] Toluene used as solvent in place of octafluorotoluene. [d] 2.5 bar,
19 oC, 64h; e.r determined by conversion into regiochemically pure N-(4-
chlorobenzyl)-2-methylbutan-1-amine by reductive amination in 57% yield from
but-1-ene (see supporting information)
[a] Catalyst preformed from [Rh(acac)(CO)2] (5.12 x 10-3 mmol) and ligand
(6.40 x 10-3 or 10.24 x 10-3 mmol) by stirring at 8 bar CO/H2 at reaction
temperature for 1 hour in C7F8 (19.35 mL + 0.65 mL toluene) prior to running
reaction at 50 oC, for 16 hours using propene/CO/H2 in1:4.5:4.5 ratio (8 bar
initial pressure). Rh concentration = 2.52 x 10-4 mol dm-3. Product determined
by GC using 1-methylnaphthalene as an internal standard. TOF = average
TurnOver Frequency in mol prod/mol cat/hr; TON = TurnOver Number in mol
prod/mol cat.. [b] Ligand / Rh ratio of 2:1.[c] i.e. n: iso = 0.35. [d] Initial
Pressure = 18bar, reaction time 1 hour. [e] PFPOE = pentafluorophenyl n-octyl
ether as solvent, 20 bar, reaction time 1 hour.
An additional aspect discovered here is the higher branched
selectivity in asymmetric hydroformylation in octafluorotolene, so
these conditions are also a synthetically useful improvement for
asymmetric hydroformylation using the Rh / BOBPHOS catalyst.
For example highly enantioselective hydroformylation of allyl
benzene improved from 72% regioselectivity to 86% branched
selective under otherwise identical conditions but swapping
toluene for octafluorotoluene as solvent (compare Table 2,
entries 5 and 6). Unprecedented highly enantioselective and
regioselective hydroformylation of but-1-ene was also achieved
with 86% iso-selectivity (Table 2 entry 7). The conversion of this
aldehyde to a chiral secondary amine with e.r. of 96:4 and
isolated as a single regioisomer was also achieved.
In summary we have discovered tropos, racemic ligands that
under specific conditions can deliver unprecedentedly high
selectivity for iso-butanal in the hydroformylation of propene,
with useful rates. The ligands used for this process are more
economic to make than the ligand they are inspired from, and
hence more suited for development for industrial iso-selective
hydroformylation in the future. The fact that the (tropos,rac)-
ligands/Rh catalysts show comparable results to the Rh /
BOBPHOS catalyst supports the hypothesis that the tropos part
It seems likely that our hypothesis regarding the dynamic
behaviour of the tropos ligands was at least partially correct.
However, to shed light on this, we also studied the
enantioselective hydroformylation of allyl benzene using the
tropos ligands derived from an (R,R)-phospholane (Table 2). It
can be seen that the use of the mixture of diastereomers derived
from an atropos racemic biphenol leads to no enantioselectivity
in these reactions, and much lower iso selectivity (Table 2, entry
1). If the tropos ligands formed two atropisomeric isomers on
coordination, similar results to this might be expected. What is
observed is
a
significant contrast; the tropos ligands,
(Tropos,R,R)-2 and (Tropos,R,R)-3 selectively form one
enantiomer with selectivity towards the R enantiomer of 80 to
85% (Table 2, entries 2-4), not quite matching the results
obtained using the desired single enantiomer (Rax,R,R)-
BOBPHOS/ Rh catalyst, but clearly showing that at least to a
significant extent, the tropos diol is behaving more like a single
This article is protected by copyright. All rights reserved.

10.1002/anie.201811888
Angewandte Chemie International Edition
COMMUNICATION
Organic Synthesis, Vol. 342 (Eds.: M. Taddei, A. Mann), Springer Berlin
Heidelberg, 2013, pp. 79-115.
of the ligand settles into a conformation that is very similar to the
single enantiomer BOBPHOS ligands (although it cannot quite
be definitively ruled out that one conformation is much more
reactive than the other). It may be tempting to speculate about
the origin of this effect, but for such a subtle effect, with a critical
role for the solvent choice, a definitive answer is outside the
reach of DFT calculations or other mechanistic techniques, to
our knowledge. Evidently, the reasons for iso-selectivity studied
initially for BOBPHOS are either enhanced in the solvents used,
or are actually less attenuated than they are by common
solvents like toluene, enlarging the scope of substrate that can
be used. Finally, the new conditions were also found to improve
enantioselective hydroformylation regioselectivity, with highly
enantioselective and regioselective hydroformylation of but-1-
ene exemplifying this improvement.
[7]
(a) M. Leight Abrams, F. Foarta, C. R. Landis, J. Am. Chem. Soc. 2014,
136, 14583-14588; (b) A. H. Hoveyda, D. A. Evans, G. C. Fu, Chem.
Rev. 1993, 93, 1307-1370; (c) C. U. Grünanger, B. Breit, Angew. Chem.
Int. Ed. 2008, 47, 7346-7349; (d) A. D. Worthy, C. L. Joe, T. E.
Lightburn, K. L. Tan, J. Am. Chem. Soc. 2010, 132, 14757-14759; (e) B.
Breit, Acc. Chem. Res. 2003, 36, 264-275; (f) P. Dydio, W. I. Dzik, M.
Lutz, B. de Bruin, J. N. H. Reek, Angew. Chem. Int. Ed. 2011, 50, 396-
400; (g) C. Schmitz, K. Holthusen, W. Leitner, G. Franciò, ACS Catal.
2016, 6, 1584-1589.
[8]
(a) R. A. Baber, M. L. Clarke, K. M. Heslop, A. C. Marr, A. G. Orpen, P.
G. Pringle, A. Ward, D. E. Zambrano-Williams, Dalton Trans. 2005,
1079-1085; (b) E. Zuidema, P. E. Goudriaan, B. H. G. Swennenhuis, P.
C. J. Kamer, P. W. N. M. van Leeuwen, M. Lutz, A. L. Spek,
Organometallics 2010, 29, 1210-1221; (c) R. C. How, M. L. Clarke, R. T.
Hembre, J. A. Ponasik, G. S. Tolleson, (Eastman Chemical Company),
US 9308527 B2, 2016; (d) R. C. How, R. Hembre, J. A. Ponasik, G. S.
Tolleson, M. L. Clarke, Catal. Sci. Technol., 2016, 6, 118-124; (e) R. C.
How, P. Dingwall, R. T. Hembre, J. A. Ponasik, G. S. Tolleson, M. L.
Clarke, Molecular Catalysis, 2017, 434, 116-122; (f) A. Phanopoulos
and K. Nozaki, ACS Catal. 2018, 8, 5799-5809.
Acknowledgements
The authors thank the Eastman Chemical Company for funding
(LI, and later JAF) and permission to publish. The EPSRC
(EP/M003868/1) is also acknowledged for funding (JAF).
[9]
(a) G. M. Noonan, J. A. Fuentes, C. J. Cobley, M. L. Clarke, Angew.
Chem., Int. Ed. 2012, 51, 2477-2480; (b) G. M. Noonan, C. J. Cobley. T.
Mahoney, M. L. Clarke, Chem. Commun. 2014, 50, 1475-1477; (c) R.
Pittaway, J. A. Fuentes, M. L. Clarke, Org. Lett. 2017, 19, 2845-2848;
(d) P. Dingwall, J. A. Fuentes, L. Crawford, A. M. Z. Slawin, M. Bühl, M.
L. Clarke, J. Am. Chem. Soc. 2017, 139, 15921-15932; (d) (S,S,S-
BOBPHOS is commercially available from Strem Chemicals.
Keywords: Hydroformylation • rhodium • fluorinated solvents •
enantioselective catalysis • phosphorus ligands
[10] (a) D. W. Norman, J. N. H. Reek, T. R. M. L. Besset, (Eastman
Chemical Company), US 8710275 B2, 2014; (b) n: iso of 0.66 for oct-1-
ene at higher T:, T. Besset, D. W. Norman, and J. N. H. Reek, Adv.
Synth. Catal. 2013, 355, 348-352. c) V. F. Slagt, P. C. J. Kamer, P. W.
N. M. van Leeuwen, J. N. H. Reek, J. Am. Chem. Soc. 2004, 126,
1526-1536; d) n:iso of 0.84 at 25 oC, 1.1 at 70 oC: X. Wang, S. Nurttila,
W. I. Czik, R. Becker, J. Rodgers, J. N. H. Reek, Chem. Eur. J. 2017,
23, 14769-14777.
[1]
(a) P. W. N. M. van Leeuwen, in Rhodium Catalyzed Hydroformylation,
Vol. 22 (Eds.: P. W. N. M. van Leeuwen, C. Claver), Springer
Netherlands, 2002, pp. 1-13; (b) R. Franke, D. Selent, A. Börner, Chem.
Rev. 2012, 112, 5675-5732, (c) A. Börner, R. Franke, in
Hydroformylation. Fundamentals, Processes, and Applications in
Organic Synthesis; Wiley-VCH Verlag GmbH & Co. KGaA, 2016.
(a) L. Gonsalvi, A. Guerriero, E. Monflier, F. Hapiot, M. Peruzzini, in
Hydroformylation for Organic Synthesis, Vol. 342 (Eds.: M. Taddei, A.
Mann), Springer Berlin Heidelberg, 2013, pp. 1-47.
[2]
[3]
[11] Grand View Research, Mar 2016, Isobutanol Market Analysis By
Product (Synthetic, Bio-Based), Application (Oil & Gas, Solvents &
Coatings, Chemical Intermediates) And Segment Forecasts To 2022,
https://www.grandviewresearch.com/industry-analysis/isobutanol-
market
(a) T. J. P. Devon, G. W.; Puckette, T. A.; Stavinoha, J. L.; Vanderbilt, J.
J. (Eastman Kodak Company), US 4694109 A, 1987; (b) T. J. P. Devon,
G. W.; Puckette, T. A.; Stavinoha, J. L.; Vanderbilt, J. J. (Eastman
Kodak Company), US 5332846 A, 1994. (c) C. P. Casey, E. L. Paulsen,
E. W. Beuttenmueller, B. R. Proft, L. M. Petrovich, B. A. Matter, D. R.
Powell, J. Am. Chem. Soc. 1997, 119, 11817-11825; (d) C. P. Casey, E.
L. Paulsen, E. W. Beuttenmueller, B. R. Proft, B. A. Matter, D. R.
Powell, J. Am. Chem. Soc. 1999, 121, 63-70.
[12] (a) K. Aikawa, K. Mikami, Chem. Commun. 2012, 48, 11050-11069; P.
Oczipka, D. Müller, W. Leitner and G. Franciò, Che. Sic. 2016, 7, 678-
683. G. Storsch and O. Trapp, Angew. Chem. Int. Ed. 2015, 54, 3580-
3586; C. Monti, c. Gennari, U. Piarulli, Chem. Commun. 2005, 5281-
5283; P. W. N. M. van Leeuwen, P. C. J. Kamer, C. Claver, O Pàmies,
M. Diéguez, Chem. Rev. 2011, 111, 2077-2118; G. T. Whiteker, A. M.
Harrison and A. H. Abatjoglou, Chem. Commun. 1995, 1805-6.
[13] (a) L. C. Clark, F. Gollan, Science 1966, 152, 1755-1756; (b) R. H. Fish,
Chem. Eur. J. 1999, 5, 1677-1680; (c) I. Colomer, A. E. R. Chamberlain,
M. B. Haughey, T. J. Donohoe, Nature Reviews Chemistry 2017, 1,
0088; (d) A. Lattanzi, C. De Fusco, A. Russo, A. Poaterb, L. Cavallo,
Chem. Commun. 2012, 48, 1650–1652; (e) C. Samojłowicz, M. Bieniek,
A. Pazio, A. Makal, K. Woźniak, A. Poater, L. Cavallo, J. Wójcik, K.
Zdanowski, K. Grela, Chem. Eur. J. 2011, 17, 12981-12993.
[4]
[5]
(a) E. Billig, A. G. Abatjoglou, D. R. Bryant, (Union Carbide) EP 213639,
1987
(a) L. A. van der Veen, M. D. K. Boele, F. R. Bregman, P. C. J. Kamer,
P. W. N. M. van Leeuwen, K. Goubitz, J. Fraanje, H. Schenk, C. Bo, J.
Am. Chem. Soc. 1998, 120, 11616-11626 and ref’s therein.
[6]
(a) I. Ojima, K. Kato, M. Okabe, T. Fuchikami, J. Am. Chem. Soc. 1987,
109, 7714-7720; (b) C. J. Cobley, K. Gardner, J. Klosin, C. Praquin, C.
Hill, G. T. Whiteker, A. Zanotti-Gerosa, J. L. Petersen, K. A. Abboud, J.
Org. Chem. 2004, 69, 4031-4040; (c) N. Sakai, S. Mano, K. Nozaki, H.
Takaya, J. Am. Chem. Soc. 1993, 115, 7033-7034; (d) G. M. Noonan,
D. Newton, C. J. Cobley, A. Suárez, A. Pizzano, and M. L. Clarke, Adv.
Synth. Catal. 2010, 352, 1047-1054; (e) Z. Yu, M. S. Eno, A. H. Annis,
J. P. Morken, Org. Lett. 2015, 17, 3264-3267; (f) F. Shibahara, K.
Nozaki, T. Hiyama, J. Am. Chem. Soc. 2003, 125, 8555-8560; (g) X.
Wang and S. L. Buchwald, J. Org. Chem. 2013, 78, 3429-3433; (h) B.
F. Perandones, C. Godard, and C. Claver, in Hydroformylation for
[14] D. Prescher, V. E. Platonov, K. V. Dvornikova, J. Schulze, O. I. Osina,G.
G. Yakobson, Journal of Fluorine Chemistry, 1985, (29), 204.
[15] The research data supporting this publication can be accessed
at https://doi.org/10.17630/6ed96377-ab54-4fb3-98c9-d2a5bc4d333e
This article is protected by copyright. All rights reserved.

10.1002/anie.201811888
Angewandte Chemie International Edition
COMMUNICATION
Entry for the Table of Contents (Please choose one layout)
Layout 1:
COMMUNICATION
Ligand = tropos-rac
Significant selectivity for the
Author(s), Corresponding
Author(s)*
Ph
P
MeO
tBu
branched or iso-aldehydes in the
hydroformylation of propene and
but-1-ene has been obtained.
R
Rh pre-cat.
Ligand
H2 / CO
Fluorinated
solvents
O
O
P
O
Page No. – Page No.
Ph
Title
MeO
tBu
CHO
CHO
R= H or Me
n
up to 86% iso
R
R
iso
Layout 2:
COMMUNICATION
Author(s), Corresponding Author(s)*
((Insert TOC Graphic here))
Page No. – Page No.
Title
Text for Table of Contents
This article is protected by copyright. All rights reserved.