Asymmetric hydroformylation of vinyl acetate with BINAP-rhodium(I) complexes

Article abstract of DOI:10.1016/S0957-4166(99)00312-2

Complexes of (R)-BINAP (BINAP=2,2'-bis(diphenylphosphino)-1,1'-binaphthyl) derived from the available rhodium precursors Rh(acac)(CO)₂ and [Rh(μ-OMe)(cod)]₂ are used for the asymmetric hydroformylation of vinyl acetate. Enantiomeric excesses of up to 60% are achieved with regioselectivities of up to 99%. Only a BINAP/Rh ratio of 2 is required. Effects of pressure and temperature on catalyst stability, enantio- and chemoselectivity are discussed.

Full text of DOI:10.1016/S0957-4166(99)00312-2

Pergamon
Tetrahedron: Asymmetry 10 (1999) 3039–3043
Asymmetric hydroformylation of vinyl acetate with
BINAP–rhodium(I) complexes
Dirk Hoegaerts and Pierre A. Jacobs ∗
Centre for Surface Science and Catalysis - K.U. Leuven, Kardinaal Mercierlaan 92, 3001 Heverlee, Belgium
Received 16 July 1999; accepted 27 July 1999
Abstract
Complexes of (R)-BINAP (BINAP=2,20-bis(diphenylphosphino)-1,10-binaphthyl) derived from the available
rhodium precursors Rh(acac)(CO)2 and [Rh(µ-OMe)(cod)]2 are used for the asymmetric hydroformylationof vinyl
acetate. Enantiomeric excesses of up to 60% are achieved with regioselectivities of up to 99%. Only a BINAP/Rh
ratio of 2 is required. Effects of pressure and temperature on catalyst stability, enantio- and chemoselectivity are
discussed. © 1999 Elsevier Science Ltd. All rights reserved.
1. Introduction
Hydroformylation is one of the most versatile methods for the functionalization of C_C bonds.1 It is
evident that the asymmetric variant represents a potentially powerful synthetic tool for the preparation
of optically active aldehydes. In a one-step reaction, the carbon skeleton of an olefin is extended by
one C atom and a stereocenter is created. These chiral molecules play an important role in the context of
biological activity and are therefore valuable as precursors for drugs, agrochemicals and food additives in
enantiomerically pure form.2 For example, 2-arylpropionic acids, which can be synthesized by oxidation
of the corresponding aldehydes, represent an important class of nonsteroidal anti-inflammatory agents.
The development of efficient catalytic systems, that could provide both a high regioselectivity (bran-
ched/normal aldehyde ratio) and enantioselectivity, has attracted a lot of research in recent years.3 The
major breakthrough in the rhodium asymmetric hydroformylation was made in 1993 by Takaya and co-
workers.4 They were the first to use BINAPHOS 1 (Fig. 1), a phosphane-phosphite ligand. Rhodium(I)
complexes of this ligand gave the highest ees so far reported in the hydroformylation of a broad variety of
olefins. Furthermore, excellent chemo- (hydroformylation vs hydrogenation) and regioselectivities were
obtained. Although no better catalyst system has yet been discovered, the rather complex synthesis of
this kind of ligand is a considerable drawback for practical use.
∗
Corresponding author. Tel: ++32-16321610; fax: ++32-16321998; e-mail: pierre.jacobs@agr.kuleuven.ac.be
0957-4166/99/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(99)00312-2

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D. Hoegaerts, P. A. Jacobs / Tetrahedron: Asymmetry 10 (1999) 3039–3043
Figure 1.
Instead of synthesizing new and complex chiral ligands, we were interested in the application of
existing, commercially available ligands used in other types of chiral reactions. In this paper, we report the
use of BINAP 2 (BINAP=2,20-bis(diphenylphosphino)-1,10 -binaphthyl, Fig. 1) for the rhodium catalyzed
conversion of vinyl acetate 3 into 2-acetoxypropanal 4 (Scheme 1). This atropisomeric ligand has already
proven to be outstandingly efficient for asymmetric isomerization and hydrogenation reactions.5
Scheme 1.
Surprisingly, BINAP was only tested once as a ligand for this reaction, with rather moderate success.
Enantiomeric excesses did not exceed 47% and yields were impractically low (6%).6 By changing
the catalyst precursor and by modifying the reaction conditions, we could substantially improve these
results and provide higher ees than previously reported for any other simple diphosphane rhodium
hydroformylation catalyst.
2. Results and discussion
Initially, Rh(acac)(CO)2 (acac=acetylacetonate) was used as the catalyst precursor for the asymmetric
hydroformylation of vinyl acetate. In all experiments (except run 11, Table 1), an excess of diphosphane
was used to exclude the formation of [RhH(CO)4]. The latter is a highly active achiral hydroformylation
catalyst and forms predominantly linear aldehydes.7 No hydrogenation or isomerization products were
observed (except run 8, Table 1). The results are given in Table 1.
In all cases, using (R)-BINAP leads to the formation of an excess of (R)-2-acetoxypropanal. A
substrate/catalyst ratio of 250 seems best to provide acceptable yields. Higher reaction temperatures cause
a decrease in ee after longer reaction times (runs 6, 13 and 15). When decreasing the phosphane/rhodium
ratio, comparable ees are obtained after 24 h (runs 9 and 10). Longer reaction times, however, result in a
loss of enantioselectivity, probably due to racemization of the branched aldehydes.
Using a 1:1 mixture of CO and H2 and thereby decreasing the total pressure causes a significant
enhancement of the reaction rate in the pressure range of 50 to 10 atm (runs 2–4). However, no significant
change in the regio- or enantioselectivity is observable within this range. It is known that carbon
monoxide and the chelating diphosphane ligand can compete for coordination around the rhodium metal

D. Hoegaerts, P. A. Jacobs / Tetrahedron: Asymmetry 10 (1999) 3039–3043
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Table 1
Hydroformylation of vinyl acetate using Rh(acac)(CO)2 as rhodium precursora
and can afford different species.3 In our case, a higher CO partial pressure obviously slows down the
reaction rate (run 7). This inverse dependence was also observed by Horiuchi et al, when studying the
mechanistic effects of the rhodium catalyzed hydroformylation of olefins, using BINAPHOS as the chiral
ligand.8 Not surprisingly, as BINAP is a typical hydrogenation ligand, increasing the hydrogen partial
pressure results in a predominant reduction of the substrate into ethyl acetate (65% yield) (run 8). Only a
small amount of 2-acetoxypropanal was formed (4%).
In a second series of experiments, [Rh(µ-OMe)(cod)]2 (cod=cycooctadiene) was used as rhodium
precursor. The results are summarized in Table 2.
Compared to the results shown in Table 1, Table 2 shows that this catalyst provides significantly higher
yields to 2-acetoxypropanal, while maintaining the same regio- and enantioselectivities. Furthermore,
using [Rh(µ-OMe)(cod)]2 as the precursor allows the use of only a small excess of phosphane relative to
rhodium (runs 19 and 20). Only a small decrease in activity is observed. Moreover, the catalyst seems to
be more stable than when Rh(acac)(CO)2 is used as precursor (runs 9 and 10). However, longer reaction
times still result in a slight decrease of ee in the case of a 1.2/1 ratio (run 20). Similar temperature and
pressure effects are observable as in the case of Rh(acac)(CO)2. Low pressures are favorable for the
catalytic activity and using higher temperatures results in a small loss of enantioselectivity at longer
reaction times (runs 17 and 18).
In a final experiment, we tested (R)-tolBINAP as a chiral hydroformylation ligand ((R)-tolBINAP=
2,20-bis(di-p-tolylphosphino)-1,10 -binaphthyl). Although enantio-, chemo- and regioselectivities are
comparable to those achieved with (R)-BINAP, yields were rather low.

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Table 2
Hydroformylation of vinyl acetate using [Rh(µ-OMe)(cod)]2 as rhodium precursora
3. Conclusion
BINAP–rhodium(I) complexes are active catalysts in the asymmetric hydroformylation of vinyl
acetate. These chiral phosphanes provide a better enantioselectivity than previously reported for any
other chiral diphosphane–rhodium system. Enantiomeric excesses of up to 60% are achieved. Applying
10 bar of a 1:1 CO:H2 mixture seems appropriate in order to obtain good activities and selectivities.
Furthermore, the reaction rate is inversely dependent on the CO partial pressure, while increasing the
H2 partial pressure leads to an important hydrogenation of the substrate. In addition, using [Rh(µ-
OMe)(cod)]2 as rhodium precursor allows to work at a lower BINAP:Rh ratio (2:1). (R)-tolBINAP, a
derivative of BINAP, is far less active but also provides good regio-, chemo- and enantioselectivities.
4. Experimental
4.1. General
The diphosphanes (R)-BINAP and (R)-tolBINAP, and the Rh(acac)(CO)2 precursor were of commer-
cial origin. The [Rh(µ-OMe)(cod)]2 complex was prepared using standard literature methods.9 Vinyl
acetate was obtained from Acros Organics. Solvents were distilled before use. Gas chromatographic
analyses were carried out on a Hewlett–Packard Model 5890 gas chromatograph. This instrument was
equipped with a FID detector and a 30 m×0.32 mm Astec Chiraldex G-TA (G: γ-cyclodextrin; TA:
trifluoroacetyl) column. Hydroformylation experiments were performed in home-made stainless steel 10
ml autoclaves with magnetic stirring. The reactors are equipped with a heating control unit, a ‘micro-
sampling’ unit and an analogue manometer.
4.2. General procedure for the asymmetric hydroformylation of vinyl acetate
A solution of the substrate (typically 6.25 mmol), the catalyst precursor (0.025 mmol) and the
phosphorus compound (in the appropriate ratio) in anhydrous toluene (5 ml) was introduced into the
reactor. After flushing three times with nitrogen, the autoclave was heated. When the desired temperature

D. Hoegaerts, P. A. Jacobs / Tetrahedron: Asymmetry 10 (1999) 3039–3043
3043
was reached, the premixed gas mixture was introduced. The reaction progress was followed by GC
analysis.
Acknowledgements
This work was supported by the Belgian Federal Government in the frame of an IUAP–PAI project
on Supramolecular Catalysis. We are indebted to ‘Het Vlaams Instituut voor de Bevordering van het
Wetenschappelijk-Technologisch Onderzoek in de Industrie’ (I.W.T.) for a PhD grant to D.H.
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