Synthesis, complexation behavior and catalytic performance of chelating bisphosphite ligands based on 9,10-brigded 9,10-dihydroanthracenes in Rh catalyzed hydroformylation of 4-pentenal

Article abstract of DOI:10.1016/j.molcata.2016.07.049

In the present work the modular synthesis of new chelating bisphosphite ligands based on 9,10-brigded 9,10-dihydroanthracenes as ligand backbones is presented. The complexation behavior of these ligands in rhodium metal complexes as well as mechanistic studies of the preformation step of the rhodium-catalysed hydroformylation is investigated. Ratio of coordination isomers in the Rh complexes of these ligands has been determined using NMR based calculation technique. Modular synthesis route was established allowing for a variety of ligands to be synthesized in a standard procedure The new ligands were tested in the hydroformylation of 4-pentenal under optimized conditions to give adipic aldehyde a promising starting material for the polyamide nylon-6,6. Ligand L3 showed the best selectivity towards adipic aldehyde with selectivity of 10.2/1 n/iso aldehyde.

Full text of DOI:10.1016/j.molcata.2016.07.049

Accepted Manuscript
Title: Synthesis, complexation behavior and catalytic
performance of chelating bisphosphite ligands based on
9,10-brigded 9,10-dihydroanthracenes in Rh catalyzed
hydroformylation of 4-pentenal
ˇ ´
Author: Bojan P. Bondzic Frank Rominger Peter Hofmann
PII:
S1381-1169(16)30308-9
DOI:
Reference:
http://dx.doi.org/doi:10.1016/j.molcata.2016.07.049
MOLCAA 9983
To appear in:
Journal of Molecular Catalysis A: Chemical
Received date:
Revised date:
Accepted date:
17-6-2016
25-7-2016
26-7-2016
ˇ ´
Please cite this article as: Bojan P.Bondzic, Frank Rominger, Peter Hofmann,
Synthesis, complexation behavior and catalytic performance of chelating
bisphosphite ligands based on 9,10-brigded 9,10-dihydroanthracenes in Rh catalyzed
hydroformylation of 4-pentenal, Journal of Molecular Catalysis A: Chemical
http://dx.doi.org/10.1016/j.molcata.2016.07.049
This is a PDF file of an unedited manuscript that has been accepted for publication.
As a service to our customers we are providing this early version of the manuscript.
The manuscript will undergo copyediting, typesetting, and review of the resulting proof
before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that
apply to the journal pertain.

Synthesis, complexation behavior and catalytic performance of chelating
bisphosphite ligands based on 9,10-brigded 9,10-dihydroanthracenes in Rh
catalyzed hydroformylation of 4-pentenal
Bojan P. Bondžić†*, Frank Rominger,‡ and Peter Hofmann‡*,
‡Organisch-Chemisches Institut, University of Heidelberg, Im Neuenheimer Feld 270, D-69120
Heidelberg, Germany
†Catalysis Research Laboratory (CaRLa), University of Heidelberg, Im Neuenheimer Feld 584, D-
69120 Heidelberg, Germany,
Current Address: Center for Chemistry ICTM, University of Belgrade, P.O. Box 815, 11000 Belgrade,
Serbia
In memory of late professor Peter Hofmann

Graphical abstract
Ph
H
O
H
OC
H
O
P
OC
P
Rh
Ph
P
P
Rh
Rh
OC
OC
Ph
OC
O
P
OC
ee
P
ea
O
O
O
2JP-H = 2 Hz
2JP-H = 106 Hz
JRh-H = 6 Hz
Ph
1 mol% Rh(acac)(CO)2
5 mol% Ligand
10 bar CO/H 2
O
H
O
H
H
Toluene,
temperature, time
O
Highlights

synthesis of new chelating bisphosphite ligands based on 9,10-brigded 9,10-
dihydroanthracenes
 Complexation behavior of newly synthesized ligands
 NMR examination of the resting state
 Catalytic performance in hydroformylation of 4-pentenal
Abstract
In the present work the modular synthesis of new chelating bisphosphite ligands based on 9,10-
brigded 9,10-dihydroanthracenes as ligand backbones is presented. The complexation behavior of
these ligands in rhodium metal complexes as well as mechanistic studies of the preformation step of
the rhodium-catalysed hydroformylation is investigated. Ratio of coordination isomers in the Rh
complexes of these ligands has been determined using NMR based calculation technique. Modular
synthesis route was established allowing for a variety of ligands to be synthesized in a standard
procedure The new ligands were tested in the hydroformylation of 4-pentenal under optimized
conditions to give adipic aldehyde a promising starting material for the polyamide nylon-6,6. Ligand
L3 showed the best selectivity towards adipic aldehyde with selectivity of 10.2/1 n/iso aldehyde.
Key words: Hydroformylation; phosphite ligands; Rh catalysis; Aldehydes; mechanism investigation

1. Introduction
The hydroformylation reaction is defined as the reaction of an olefin with carbon monoxide
and hydrogen, affected by a late transition metal catalyst to give a homologous aldehyde. Since its
discovery by Otto Roelen[1] the hydroformylation reaction has become a useful tool for the synthesis
of aldehydes, representing one of the most important chemical manufacturing processes today with
capacity amounting to more than 10 million tons of hydroformylated products worldwide per year.[2] In
most cases the resulting aldehyde is not the desired product but is converted to more valuable
compounds such as carboxylic acids, alcohols, amines, or other downstream products. An industrially
very important product is polyamide nylon-6,6, which is made via cocondensation of adipic acid and
hexamethylenediamine.[3]
A
promising starting material for both adipic acid and
hexamethylenediamine is adipic aldehyde, which can either be oxidized to the acid or reductively
aminated to the amine. Several groups worked on the selective double hydroformylation of 1,3-
butadiene toward adipic aldehyde but only reached selectivities below 30%.[4]
In our previous studies we presented a new ligand system which gave the highest selectivity of
adipic aldehyde to date, starting from butadiene 50% adipic aldehyde was obtained (the rest being
mixture of aldehydes and isomerised enals, overall aldehyde selectivity of 90%).[5] However, from the
industrial viewpoint, these values are still unsatisfactory. Another potential starting material for the
synthesis of adipic aldehyde is 4-pentenal, which can be produced from readily available starting
materials.[6] Over the last years we have worked on the development of highly n-selective and highly
active modular ligand systems for the hydroformylation of terminal olefins. Ligand that showed the
highest selectivity (50%) in the double hydroformylation of 1,3-butadiene to adipic aldehyde as well
as highest selectivity in hydroformylation of 4-pentenal [7] was the tMe-Rucaphosphite (L1, Figure 1),
a symmetric bisphosphite ligand with a 9,10-bridged 9,10-dihydroantracene -derived backbone and
tetramethylbiphenol wingtips.[5] In the hydroformylation reaction of 4-pentenal this ligand showed
excellent conversion rate of 95% with 96% selectivity towards desired adipic aldehyde. L1 is similar
to BIPHEPHOS (Figure 1), a highly n-selective ligand for the hydroformylation of terminal and
internal olefins.[8] We previously reported that by the use of unsubstituted biphenols instead of
tetramethylbiphenols as wingtips the selectivity of hydroformylation of 4-pentenal drops significantly
(see Figure 1).[7]
Based on these observations we wanted to synthesize bulkier congeners of ligand L1, (ligands
L2 and L3), and to test them in the hydroformylation reaction of 4-pentenal en route to adipic
aldehyde. It was expected that introduction of Aryl groups at 3 and 3’ positions of biphenol core
would impose additional steric pressure on the transition state of the reaction, and possibly improve
the selectivity of the reaction. Also improved lipofilicity and increased stacking possibilities were
important to examine.[5]
2. Experimental
2.1.General Experimental Details
Unless otherwise noted, all reactions and manipulations were carried out under an Ar atmosphere
using standard Schlenk and high-vacuum-line techniques or in a Braun inert-atmosphere glovebox
(Ar) at ambient temperature. Solvents were dried using an MBraun solvent purification system,
degassed by several freeze−pump−thaw cycles, and stored over a molecular sieve (4 Å) under argon.
Unless otherwise noted, all reagents were purchased from commercial suppliers and used without
further purification.Deuterated solvents were purchased from Deutero GmbH or Aldrich. Deuterated
solvents were dried over sodium (C6D6, toluene-d8) vacuum distilled, and stored over a molecular
sieve under argon.

2.2.Instrumental
All NMR chemical shifts are reported as δ in parts per million (ppm). 1H NMR spectra were
referenced to residual protiated solvent, and chemical shifts are reported in parts per million downfield
from tetramethylsilane. 31P{1H} NMR spectra are reported relative to trimethyl phosphate as the
external standard. 13C{1H} NMR spectra were referenced to the solvent. Gas chromatographic
analysis was performed on an Agilent Technologies 6890N Network GC system equipped with a 30 m
BGB-5 column (5% diphenylpolysiloxane, 95% dimethylpolysiloxane). Since the use of syngas is a
potential hazard, the following measures were taken: The syngas bottle was stored outside the lab and
permanently connected to a gas distribution system equipped with magnetic safety valves. The valves
were connected to CO sensors inside the lab. Additionally, personal CO sensors were used while
working with syngas.
CCDC 1483399 (L2) contains the supplementary crystallographic data for this paper. These
data can be obtained free of charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
2.3. General procedure for the hydroformylation reaction
To an autocalave placed in a glove box were added Rh(acac)(CO)2 (13.05 mg, 0.05mmol, 1 mol%)
and Ligand (65 mg, 0.06 mmol, 1.25 mol%) followed by 20 ml of dry toluene and 4-pentenal (0.5 ml,
5mmol, 1 equiv) and n-nonane as an internal standard was added via syringe. Autoclave was sealed
and pressurized with 10 bar syn gas (CO/H2= 1/1) and heated at designated temperature for designated
period of time. After completion of reaction autoclave was depresurized and taken into glovebox.
Reaction was analyzed by GC measurement. The He flow rate was kept at 2.0 mL/min. The column
temperature was initially held at 40 °C for 1 min, then ramped at 4 °C/min to 90 °C, followed by an
immediate temperature ramp of 30 °C/min to 200 °C, and held at this temperature for 5 min. Peak
assignments were confirmed with samples of commercially available or independently synthesized
compounds. GC calibration curves were constructed for all of the compounds.
3. Results and discussion
3.1.Ligand synthesis
In order to synthesize symmetrical biphenyl compound 4 possessing Ph groups at 3 and 3’ positions of
biphenol core, we envisaged synthesis starting from 2-Bromo-4-methyl-phenole 1 (Scheme 1) which
upon DHP protection, Suzuki coupling and subsequent cleavage gave compound 3 in 85% yield over 3
steps. However oxidative coupling of compound 3 failed to give reasonable yield of desired biphenyl
compound 4 under various conditions applied. Low yields or mixtures of different compounds were
obtained in all cases.
Since above strategy failed, direct oxidative coupling of 2-bromo-4-methyl-phenole 1 was performed
in order to obtain common intermediate 5 (Scheme 2). To our delight we were able to obtain
compound 5 in 50% yield in a reasonably clean reaction in the presence of catalytic amount of Fe(II)
salt and stoichiometric amount of oxidant (Na2S2O8). In order to synthesize biphenol 4, free phenol
groups of common intermediate 5 were MOM protected and crude compound 6 was submitted to

Suzuki coupling reaction with PhB(OH)2. Coupling product was deprotected in situ by the addition of
conc. HCl to give desired biphenol 4 in 80% yield over 3 steps (Scheme 2).
In order to synthesize biphenol 8, compound 6 was submitted to Suzuki and Negishi coupling
conditions with appropriate substrates, however, either no reaction or several products were obtained
respectively. Subsequently, protecting group was changed; free phenol groups of 5 were methylated to
give 7, which was submitted to Negishi coupling reaction with ArZn species obtained in situ. Obtained
coupling product 7 was deprotected by the addition of BBr3 to give desired biphenol 8 in 67% yield
over 2 steps (Scheme 2). Synthesized biphenols 4 and 8 were used for the synthesis of the desired
ligands L2 and L3 respectively by coupling them with the PCl3 and by subsequent reaction of
obtained chloro phosphites with 1,8-Dihydroxy-9,10-ethano-9,10- dihydroanthracene 9 to give desired
compounds (Scheme 2).
3.2.Complexation behavior
To elucidate the coordination behavior of the bidentate phosphite ligand L2, complexation
experiments in high pressure NMR tubes were performed. Four- and five-coordinate rhodium(I)-
species (Figure 2) representing corresponding four- and five-coordinate complexes postulated in the
dissociative Wilkinson mechanism of hydroformylation were expected.
[(L2)Rh(acac)(CO)]
H2/CO (1:1)
Toluene, t(°C)
-CO
-CO
[cis-(L2)Rh(acac)]
Figure2. Postulated intermediates in dissociative Wilkinson mechanism
+CO
[(ee/ea-L2)RhH(CO)2]
resting state
[Rh(acac)(CO)2] + L2
t(°C), Toluene
Bisphosphite ligand L2 and Rh(acac)(CO)2 catalyst were mixed in the high pressure NMR tube,
dissolved in deuterated solvent, pressurized with syn-gas and heated at designated temperature
(Scheme 4).
After 2h of reaction 3 different species are observable in the solution: starting ligand L2, intermediate
L2(acac)Rh 10 and resting state, pentacoordinate catalyst 11. Reaction clearly shows slow
interconversion of starting Rh complex to the resting state i.e. active hydroformylation catalyst via
four coordinate complex 10.
There are two possible coordination modes of these chelating ligands: ee (equatorial-
equatorial) or ea (equatorial-axial).By high pressure NMR-experiments, two coordination isomers of
the resting state cannot be detected, both isomers exist in a fast dynamic equilibrium in the catalytic
system. Both complexes of the formula [(chelatephosphite)RhH(CO)2] show a bipyramidal geometry
with the chelate ligand binding through an ee-coordination for one isomer and an ea-coordination for
the other isomer. Even at low temperatures it is not possible to completely freeze out this fast dynamic
process but only to slow it down. [9] However, extent of ee and ea coordination can be predicted based
on NMR coupling constants.[10,11,12]
Ligand L2 has a 2JP-H coupling constant of 14.3 Hz, which can be interpreted as the averaged coupling
constant for equilibrating trans and cis phosphite P-coordination in ae and ee isomers. Typical
coupling constants in these types of complexes are around 106 Hz for axial phosphites and around 2
Hz for equatorial phosphorus ligands.[13,14,15] These coupling constants can be used as “ideal” coupling

constants for axial and equatorial phosphorus atoms to estimate the ae/ee ratio in the equilibrium by
using eq 1 as proposed by Casey et al.[10c]
2JPH = Xee*Jee + Xea*Jea (Eq. 1)
Xee/ea is the fraction of axial and equatorial phosphorus atoms, respectively, and Jee/ea are the
corresponding estimated P−H coupling constants. When using 106 and 2 Hz as Jea and Jee,
respectively, the experimental coupling constant of 14.3 Hz in the case of resting state 11, corresponds
[10]
to the 12% of ea isomer and 88% of ee isomer (Scheme 5). According to C.P.Casey
the n-
selectivity is related to a degree of ee coordination in trigonalbipyramidal chelate complexes
[11,14]
L2RhH(CO)2. However, there is no consensus in the literature
on the importance that a specific
coordination mode has on the n-selectivity of the hydroformylation reaction.
Ligand L2 has higher extent of ee coordination compared to tMe-rucaphosphite L1 (Scheme
5) which was the best performing ligand in the hydroformylation of 4-pentenal in our previous studies.
These data suggest that it is easier for L2 to adopt conformation with higher bite angles (i.e.
equatorial) compared to axial (ea) conformation which is preferred by the tMe-rucaphosphite L1
(Scheme 5). [9] Obviously there is a massive impact of the steric properties of the newly synthesized
ligand on the complexation behavior, i.e. almost 9/1 ee/ea ratio for L2 as compared to approximately
1/1 ee/ea for benchmark ligand L1. Our initial thought that increased steric pressure at position 3,3’
would change complexation mode of the ligand with rhodium precursor turned out to be correct and
from these observations it stems that newly synthesized ligand with ee coordination isomer in excess
should theoretically produce higher n-selsctivities.
Next task was to examine catalytic behavior of these new modular chelating bisphosphite ligands in
the rhodium-catalyzed hydroformylation reaction of 4-pentenal.
3.3.Catalytic reactions
Newly synthesized ligands with bulky groups at 3,3’ positions were tested in the
hydroformylation reaction of 4-pentenal in order to test the selectivity towards the formation of n-
aldehyde (Table 1). Reaction in the presence of L2 and in a 1/1 ligand to metal ratio at 100 °C after 2h
yields only 35% conversion of starting material and approximately 1/1 n/iso ratio of products (Table
1, Entry 1). When L/M ratio is increased to 1.25 (Table 1, Entry 2) temperature lifted to 110 °C and
reaction time extended to 5h, 69% conversion is observed with improved n/iso selectivity of 2.5/1.
Under the same conditions but at reaction time of 21h (Table 1, Entry 3) partial polymerization of
adipic aldehyde is observed and n/iso ratio drops to 1.9/1. When the same reaction was performed at
room temperature (Table 1, Entry 4) for 24h only 16% conversion is observed with 2.2/1 n/iso ratio.
Hence, decrease in reaction temperature leads to a slight increase in regioselectivity of
hydroformylation, however, conversion rate was low as expected. An increase in ligand concentration
up to a metal to ligand ratio of 1:5 led to an increase in n/iso-ratio (n/iso-ratio of 8.3 with ligand L2
and 10.2 for ligand L3) which went along with a lowered conversion (from 79% to 74% for ligand L2
(Table 1, Entry 5) and 70% to 65% for L3 (Table 1, entry 8)). Further increase in ligand concentration
up to a metal to ligand ratio of 1:10 (Table 1, Entry 6) led to slight decrease in selectivity and
conversion as compared to 1:5 ratio. Reaction without any ligand was performed as well (100 °C, 2h)
and it showed scarcely any conversion (<5%) of the starting material showing that ligands are required
in order to obtain higher conversions and selectivities.
When ligand L3 was tested (Table 1, Entry 7) 70% conversion was observed after 5h of
reaction and 2.65/1 ratio of n/iso aldehyde. Increasing metal to ligand ratio to 1:5 led to decrease in

conversion but led to marked increase in n/iso selectivity of 10.2/1(Table 1, Entry 8). tMe-
rucaphosphite remains the best performing ligand in the hydrofomylation of 4-pentenal among the
9,10-brigded 9,10-dihydroanthracenes series, as L2 and L3 showed good selectivities and moderate
activities, in this reaction. TON numbers are in all cases equal to the % of conversion since only
hydroformylation products (branched and linear) are counted under conversion. In entry 3 where 5%
aldol product is obtained steming from n-product TON number is 69 instead of 64.
It is clear that sheer ee/ea ratios in the resting state cannot be easily translated into the selectivities of
the reaction, however, good selectivities can be achieved with proper adjustment of reaction
conditions. From this study it is clear that presence of substituents at positions 3, 3’ of biphenol
wingtips is crucial for activity and selectivity in the hydroformylation of 4-pentenal. Fine tuning of
steric bulk is required in order to achieve high levels of selectivity in this industrially important
reaction. This study also gave important insight into complexation behaviour and resting state
formation of these ligands and represents important standpoint for future development of these types
of ligands and their application in both academia and industry relevant reactions.
4. Conclusion
Modular method for the synthesis of previously unavailable types of 9,10-bridged 9,10-antracene
based ligands was established, allowing introduction of variously substituted aryl groups at the 3 and
3’ positions of biphenyl core. Coordination behavior of the newly synthesized bidentate phosphite
ligands was examined, four- and five-coordinate rhodium(I)-species representing corresponding four-
and five-coordinate complexes postulated in the dissociative Wilkinson mechanism of
hydroformylation were identified. NMR spectra of these complexes implied a significant structural
flexibility. Finally these new complexes were tested in hydroformylation reaction of 4-pentenal
showing promising selectivities. Further work in the development of these types of complexes is
expected to give good candidates for a hydroformylation of butadiene towards adipic aldehyde.
Supplementary data
Electronic supplementary information (ESI) is available: Procedures and characterization of starting
materials; 1H, 13C, 31P NMR and X-ray structure of newly synthesized compounds
Acknowledgement
B.P.B and P.H. worked at CaRLa of Heidelberg University, being cofinanced by Heidelberg
University, the state of Baden-Wꢀrttemberg, and BASF SE. The support of these institutions is
gratefully acknowledged.
Appendix A. Supplementary data
Supplementary data associated with this article can be found in the online version, at http://dx.doi.org/
.
References
[1] a) O. Roelen, Patent DE 849548, 1938/1952; b) C.D. Frohning, C.W. Kohlpainter, in: Applied
Homogeneous Catalysis with Organometallic Compounds, vol.1, (Eds.: B. Cornils, W.A.

Herrmann) Wiley-VCH, Weinheim, 1996, pp 29-52; c) P. Kalck, Y. Peres, J. Jenck, Adv.
Organomet. Chem. 32 (1991) 121.
[2] a) B. Breit, Top. Curr. Chem. 279 (2007) 139; b) H.-J. Arpe, Industrial Organic Chemistry;
Wiley-VCH, Weinheim, Germany, 2010.
[3] a) G. Bellussi, C. Perego, CATTECH 4 (2000) 4; b) R. Franke, D. Selent, A. Bꢁrner, Chem.
Rev. 112 (2012) 5675.
[4] a) J. Briggs, D. Packett, D. Bryant, A. Phillips, D. Schreck, K. Olson, E. Tjaden, A. Guram, T.
Eisenschmid, E. Bragham, WO199740001A1, 1997; b) C. Botteghi, M. Branca, A. Saba, J.
Organomet. Chem. 184 (1980) C17; c) B. Fell, P. Hermanns, H. Bahrmann, J. Prakt.
Chem./Chem.-Ztg. 340 (1998) 459; d) H. Bahrmann, B. Fell J. Mol. Catal. 8 (1980) 329; e) D.
L. Packett, U.S. Patent 5,312,996, 1994.
[5] a) S. E. Smith, T. Rosendahl, P. Hofmann, Organometallics, 30 (2011) 3643; b) S. Schmidt, E.
Barath, C. Larcher, T. Rosendahl, P. Hofmann, Organometallics, 34 (2015) 841.
[6] a) C. D. Hurd, M. A. Pollack, J. Am. Chem. Soc. 60 (1938) 1905; b) F. Merger, W. Bertleff, J.
Liebe, EP0287956A2, 1988; c) W. E. Hanford, D. L. Fuller, Ind. Eng. Chem. 40 (1948) 1171;
d) V. A. Sims, J. J. Vitcha, Ind. Eng. Chem. Prod. Res. Dev. 2 (1963) 293.
[7] J. Mormul, M. Mulzer, T. Rosendahl, F. Rominger, M. Limbach, P. Hofmann,
Organometallics, 34 (2015) 4102.
[8] a) G. D. Cuny, S. L. Buchwald, J. Am. Chem. Soc. 115 (1993) 2066; b) C. Vogl, E. Paetzold,
C. Fischer, U. Kragl, J. Mol. Catal. A: Chem. 232 (2005) 41.
[9] T. Rosendahl, Dissertation, University of Heidelberg, 2007.
[10]a) C. P. Casey, G. T. Whitecker, M. G. Melville, L. M. Petrovich, J. A. Gavney, D. R. Powell,
J. Am. Chem. Soc. 114 (1992) 5535; b) C.P. Casey, L. M. Petrovich, J. Am. Chem. Soc. 117
(1995) 6007; 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. 119 (1997) 11817.
[11] L. A. van der Veen, P. H. Keeven, G. C. Schoemaker, J. N. H. Reek, P. C. J. Kamer, P. W. N.
M. van Leeuwen, M. Lutz, A. L. Spek, Organometallics 19 (2000) 872.
[12]G. Abkai, S. Schmidt, T. Rosendahl, F. Rominger, P. Hofmann, Organometallics, 33 (2014)
3212.
[13]D. A. C. Molina, C. P. Casey, I. Mꢀller, K. Nozaki, C. Jꢂkel, Organometallics 29 (2010)
3362.
[14] L. A. van der Veen, M. D. K. Boele, F. R. Bregmann, P. C. J. Kamer, P. W. N. M. van
Leeuwen, K. Guobitz, J. Fraanje, H. Schenk, C. Bo, J. Am. Chem. Soc. 120 (1998) 11616.
[15] C. P. Casey, E. L. Paulsen, E. W. Beuttenmueller, B. R. Proft, B. A. Matter, D. R. Powell, J.
Am. Chem. Soc. 121 (1999) 63.
[16]See SI for details

MeO
But
OMe
tBu
R
R
O
O
O
O
O O
P
P
Me
Me
P
P
O
O
O
O
O
O
R
R
Me
Me
BIPHEPHOS
R = H, selectivity 80%
L1; R=Me, tMe-Rucaphosphit, selectivity 96%
L2; R= Ph
L3; R= 2,6 dimethyl phenyl
Figure 1. Structure of BIPHEPHOS and 9,10-bridged 9,10-dihydroantracene based ligands and their
selectivity in the hydroformylation of the 4-pentenal

ODHP
OH
ODHP
3 eq PhB(OH)2
5 mol% Pd(PPh3)4
Br
Br
O
Ph
2eq PPTS
CH2Cl2
2M Na2CO3
MeOCH2CH2OMe
reflux, 36h
2
1
quant
OH
OH
OH
conditions:
Ph
1. FeSO4*7H2O, Na2S2O8
2.tBuOOH, FeCl3, H2O
3. MTBAP, CH2Cl
4.VO(acac)2, CH2Cl2, O2
5. KOH, O2, 700C, H2O
oxidative Ph
coupling
Ph
HCl conc
conditions
MeOH,
60 C, 1h
4
3
82%
(over 3 steps)
Scheme 1. Convergent route to biphenol 4

OR
OR
OH
OH
OH
Br
Br
Br
Br
Br
a
b or c
d or e
5
50%
6, R=MOM
7, R=Me
quant.
1
Cl
P
OH
OH
Ar
Ar
O
O
f
Ar
Ar
4, Ar= Ph, 80% over 3 steps
8, Ar= 2,6-diMePh, 67% over 3 steps
Ar
Ar
O
O
O
O
HO
HO
9
P
O
P
O
Me
Me
3 eq NEt3, THF
-78°C-rt
Ar
Ar
Me
Me
L2 65% (from 4)
L3 38% (from 8)
a) FeSO4*7H2O, Na2S2O8, H2O. b) 3eq NaH, 3eq MOMCl, THF, rt. c) 2.5 eq Me2SO4, 3eq K2CO3, acetone. d) 1) 3 eq PhB(OH)2,
5 mol% Pd(PPh3)4, 2M Na2CO3, MeOCH2CH2OMe,2) HCl conc. e) 1) 1 eq 1-bromo-2,6-dimethylbenzene, 3 eq nBuLi, 3 eq
ZnCl2*TMEDA, 5 mol% Pd(PPh3)4, THF, -780C to r.t. 2) 3 eq BBr3, CH2Cl2, 0 °C, 2h. f) 1.3 eq PCl, 3 eq NEt3, -78°C, THF
Scheme 2. Synthesis of ligands L2 and L3 and ORTEP plot of ligand L2 (Single crystal X-ray
structure, ellipsoids shown at 50% probability level, H-atoms omitted for clarity).

Ph
O
H
O
Ph
O
OC
Ph
Ph
P
Rh
O
P
O
P
OC
Ph
O
L2, 5 bar CO/H2
benzene D6, 90 0
O
O
Rh(acac)(CO)2
Rh
O
C
P
O
O
O
O
O
Ph
Ph
Ph
10
11
resting
state
BB-HP nmr 4, 48h
3 3
3
BB-HP NMR 3, after 20h
2 2
resting
state
2
L2
BB-HP NMR 2
1 1
L2
resting
state
1
200 195
190
185 180
175
170 165
160
155
150 145
f1 (ppm)
140
135 130
125
120 115
110
105
100
95
Scheme4. Formation of catalyst resting state with ligand L2 and Rh(acac)(CO)2, 31P NMR spectra.

H
H
OC
P
P
Rh
P
Rh
OC
OC
P
OC
ee
Ph
ea
O
H
O
2JP-H = 106 Hz
JRh-H = 6 Hz
2JP-H = 2 Hz
OC
Ph
P
Rh
OC
O
Ph
P
2JP-P = 4.5 Hz
JRh-P = 210 Hz
O
O
O
Ph
2JP-H = 14.3 Hz
JRh-H = 3.3 Hz
JRh-P = 244.5 Hz
11
12 % ea- to 88 %
ee-coordination
O
O
H
OC
P
Rh
OC
O
2JP-H = 58 Hz
JRh-H = 6 Hz
2JP-P = 4.5 Hz
JRh-P = 210 Hz
P
O
O
O
55 % ea- to 45 %
ee-coordination
12
Scheme 5. Representative coupling constants and distribution of ee and ea isomers in the resting state
of catalyst 11 (with ligand L2) and catalyst 12 with tMe-rucaphosphite ligand (L1).[9]

Table 1. Hydroformylation of 4-pentenal in the presence of Rh complexes with L1 and L2
1 mol% Rh(acac)(CO)2
1.25 mol% Ligand
10 bar CO/H 2
O
O
O
O
H
+
H
H
H
H
Toluene,
temperature, time
O
adipic aldehyde
n-product
iso-product
Entrya)
Ligand
L2
L2
L2
L2
L2
L2
L3
L3
M/L ratio T (°C)
Time(h) Conversionc) n/iso ratiod) TON
1
2
3
4
5
6
7
8
1/1
100
110
110
20
110
110
110
110
2
5
35%
0.9/1.1
2.5/1
1/1.25
1/1.25
1/1.25
1/5
79%
21b)
24
5
5
5
64%
16%
74%
61%
70%
65%
1.9/1
2.2/1
8.3/1
8.2/1
2.65/1
10.2/1
1/10
1/1.25
1/5
5
a Reaction conditions: 1 mmol of 4-pentenal (167 mM), 10 bar CO/H2 (1:1), 6 mL of toluene, Rh: 1
mol %, ligand (see in table)
b Small amount (<5%) of cyclopentenecarbaldehyde detected (by intramolecular aldol condensation of
adipic aldehyde).
c Hydroformylation products, determined by gas chromatography with n-nonane as internal standard.
d Selectivity of the linear product over the branched.