Tunable ligands for asymmetric catalysis: Readily available carbohydrate-derived diarylphosphinites induce high selectivity in the hydrovinylation of styrene derivatives

Article abstract of DOI:10.1021/ja0172013

Only a limited number of ligands have been successfully employed for the Ni-catalyzed asymmetric hydrovinylation reaction. Diarylphosphonites prepared from readily available carbohydrates in conjunction with a highly dissociated counterion ([3,5-(CF₃

Full text of DOI:10.1021/ja0172013

Published on Web 12/15/2001
Tunable Ligands for Asymmetric Catalysis: Readily Available
Carbohydrate-Derived Diarylphosphinites Induce High Selectivity in the
Hydrovinylation of Styrene Derivatives
Haengsoon Park and T. V. RajanBabu*
Department of Chemistry, 100 West 18th AVenue, The Ohio State UniVersity, Columbus, Ohio 43210
Received October 1, 2001; Revised Manuscript Received November 9, 2001
The asymmetric hydrovinylation of olefins is one of a handful
of catalytic asymmetric reactions that uses a feedstock carbon source
for the synthesis of potentially valuable fine chemical intermediates.1
In 1998 we reported2 a new protocol for this remarkable reaction
that gave a nearly quantitative yield of the product.3 In our initial
Figure 1. Selected8 monophosphinites and phosphines for hydrovinylation
of styrene (yield and ee of 3-phenyl-1-butene is shown in brackets).
efforts to find a broadly applicable asymmetric version of this
reaction, we considered the requirement of a coordination site for
ethylene on the putative cationic nickel hydride intermediates, and
chose (R)-2-diphenylphosphino-2′-alkoxy-1,1′-binaphthyl (3, MOP)
in which the -OR group would play the role of a hemilabile ligand.
Further we showed that there is a strong synergistic relationship
between such a ligand and the counterion that is used.4 For example,
AgOTf additive, which gave in many cases, isolated yields >95%
Figure 2. Prototypical ligands8 that gave low (<5%) turnover in the
hydrovinylation.
with Ph3P as a ligand, gave low yields in the hydrovinylation
reactions using the hemilabile ligands such as MOP (3) or the
phospholane 4. In sharp contrast, the use of Na+ -B[3,5-(CF3)2-
C6H3)]4 (Na+ -BARF) fully restored the activity of the catalyst
giving isolated yields up to 97% for various vinyl arenes (eq 1).4
Beneficial effects of highly dissociated counterions in hydroviny-
lation of styrene using the original Wilke’s azaphospholene ligand
(5)5 in supercritical CO2 have since been reported by Leitner et
al.6 Even though the initial studies with MOP (3) and 1-aryl-2,5-
phospholane (4) ligands provided a number of useful parameters
to optimize the efficiency of the catalyst, the enantioselectivity in
the hydrovinylation of styrene derivatives remained modest (best:
50%, using phospholane 4).
basic groups (e.g., 10-13, Figure 2),8 were found to be totally
ineffective. On the basis of these studies, diarylphosphinites from
2-acetamido-2-deoxyglycopyranoside were chosen for further de-
velopment. Two practical considerations make this an obvious
choice among the ligands we tested: (a) the modular construction
of the ligand allows sufficient flexibility to fine-tune the steric and
electronic properties of the ligating atom(s), and (b) the configu-
ration of the ring carbons could be changed either through
diastereoselective functional group manipulations or by choosing
alternate sugars to build the scaffold.
The hydrovinylation of styrene was carried out as follows. The
catalyst precursor was prepared by mixing stoichiometric amounts
(1:1 Ni/L) of allyl nickel bromide dimer and the ligand in CH2Cl2,
followed by exchanging the bromide ion by addition of Na BARF.
The precipitated salts were removed by filtration through Celite.
Oxygen-free ethylene was introduced into the flask after cooling
the Ni-complex to the appropriate temperature (-70 to -55 °C),
followed by the substrate dissolved in CH2Cl2. After ∼2 h, the
reaction was quenched with ammonium chloride and the product
isolated, by evaporation of the solvent. Selectivity factors were
determined by NMR spectroscopy, GC and HPLC. Table 1 shows
the yield, selectivity, and enantiomeric excess obtained when various
â-acylaminophosphinites are used as ligands for hydrovinylation
of styrene.8 In general, outstanding selectivity for the primary
product, 3-phenyl-1-butene is observed with these ligands. Among
this set of ligands, an R-glycoside appears to give better yields than
a â-glycoside (entry 1 vs 2). Whether a 3,5-bis-CH3-C6H3-
substituent or a 3,5-bis-CF3-C6H3-substituent on phosphorus is better
depends on the configuration of the carbon to which is attached
the diarylphosphinite moiety (entries 2 and 3). In the gluco-series
(entry 2) the CF3-aromatic substituent is better, whereas in the allo-
series (entry 3) the CH3-aromatic substituent is better. For higher
enantioselectivity the allo-configuration (entry 3) is clearly superior
as compared to the gluco-derivative (entry 2). Finally, the acyl group
In continued efforts to improve the selectivity, we have screened a
large number of ligands, and recently discovered that easily
accessible carbohydrate-derived phosphinites7 serve as excellent
ligands for this exacting reaction. The details of these investigations
are reported in this communication.
From our initial survey of ligands, we discovered that simple
diarylphosphinites (for example, 6-8, Figure 1)8 were viable ligands
for the nickel-catalyzed hydrovinylation of styrene (isolated yield
and ee of product shown in brackets). Not unexpectedly,4 several
others (including some phosphines), some carrying good Lewis
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734 VOL. 124, NO. 5, 2002 J. AM. CHEM. SOC.
10.1021/ja0172013 CCC: $22.00 © 2002 American Chemical Society

C O M M U N I C A T I O N S
Table 1. Hydrovinylation of Styrene Using Sugar-Phosphinite
matograpic analysis of 24 using Chirasil-L-val column revealed
baseline separation, with a diastereomeric excess of 89% for the
(R)-ibuprofen ester. This confirms the overall selectivity and the
absolute configuration of the primary product of hydrovinylation.
Finally, studies with 4-isobutylstyrene serve as a reminder that
a single ligand is unlikely to have broad applicability and that further
fine-tuning may be needed before practical levels of asymmetric
induction can be achieved for individual substrates. The most
promising ligand, 16A, produced a very efficient catalyst (1 mol
% loading, >99% yield and selectivity) for the hydrovinylation of
this substrate, albeit with a modest 74% ee for the product.8
Nonetheless, this represents one of the highest overall selectivity
in the synthesis of this key intermediate.13
Ligands1
In summary, discovery of a new, tunable ligand class for efficient
asymmetric hydrovinylation of vinyl arenes is reported. Also
disclosed are the highest overall yields and selectivities for the
hydrovinylation of 4-bromostyrene and 4-isobutylstyrene, two
important precursors for the synthesis of commercially important
2-arylpropionic acids. Further studies are in progress.
1 See eq 1. A Ar ) 3,5-(CH3)2-C6H3; B Ar ) 3,5-(CF3)2-C6H3. 2 Isolated
yield of 3-phenyl-1-butene. 3 Percentage of 3-phenyl-1-butene among all
products. 4 Determined by HPLC. 5 Conversion >99%.
Acknowledgment. We acknowledge the financial assistance by
the U.S. National Science Foundation (CHE 0079948).
Scheme 1. Synthesis of Ibuprofen via Asymmetric Hydrovinylation
Supporting Information Available: Details of the synthesis of
ligands and characterization and analytical data of products including
GC and HPLC data for key compounds (PDF). This material is available
free of charge via the Internet at http://pubs.acs.org.
References
(1) (a) Jolly, P. W.; Wilke, G. In Applied Homogeneous Catalysis with
Organometallic Compounds; Cornils, B., Herrmann, W. A., Eds.; VCH:
New York, 1996; p 1024 and references therein. (b) RajanBabu, T. V.;
Nomura, N.; Jin, J.; Radetich, B.; Park, H.; Nandi, M. Chem. Eur. J. 1999,
5, 1963.
(2) (a) Nomura, N.; Jin, J.; Park, H.; RajanBabu, T. V. J. Am. Chem. Soc.
1998, 120, 459. (b) For the use of propylene: Jin, J.; RajanBabu, T. V.
Tetrahedron 2000, 56, 2145.
(3) For recent reports on asymmetric hydrovinylation, see: (a) Bayersdo¨rfer,
R.; Ganter, B.; Englert, U.; Keim, W.; Vogt, D. J. Organomet. Chem.
1998, 552, 187. (b) Albert, J.; Cadena, M.; Granell, J.; Muller, G.; Ordinas,
J. I.; Panyella, D.; Puerta, C.; Sanudo, C.; Valerga, P. Organometallics
1999, 18, 3511. (c) Englert, U.; Haerter, R.; Vasen, D.; Salzer, A.;
Eggeling, E. B.; Vogt, D. Organometallics 1999, 18, 4390. (d) Reference
6 below.
on nitrogen showed a pronounced effect on the selectivity of the
reaction (entry 4). All are exceptionally good ligands (>99% con-
version), with the N-CH3CO-ligand giving the best selectivity (entry
3, A). The N-COPh and N-COCF3 derivatives promote concomitant
isomerization of the initially formed 3-phenyl-1-butene to a mixture
of 2-phenyl-2-butenes under the reaction conditions, reducing the
selectivity for the former to 23 and 40%, respectively (entry 4).
In overall yield and selectivity, the diarylphosphinite 16A is one
of the best ligands for the Ni-catalyzed asymmetric hydrovinylation
of styrene.9 Most gratifyingly, ligand 16 A10 is also one of the best
ligands for the hydrovinylation of 4-bromostyrene, giving 98%
isolated yield (>99% selectiVity for the desired product) with 89%
enantiomeric excess (Scheme 1). A study of the effect of the
counteranion on this reaction shows that SbF6- is marginally better
than BARF, whereas BF4 and OTf are greatly inferior.11 The
enantiomeric excess of this key compound {([R]25D ) + 9.9 ( 0.1
(c 7.02, CHCl3)}, from which a number of 2-arylpropionic acids
could be prepared by cross-coupling chemistry (vide infra), was
determined by three independent methods, all agreeing within
experimental error. The ee’s for compound 20 (Ar ) 4-bromophe-
nyl) and the corresponding debrominated derivative, 3-phenyl-1-
butene (prepared by treatment of 20 with Mg in MeOH, >99%
yield) were determined by HPLC on a Chiralcel OJ column.
Kumada coupling of 20 and i-BuMgBr in the presence of 1 mol %
of (dppe)NiCl2 (Scheme 1) gave 21 (89%ee, HPLC). Subsequent
ozonolysis and oxidation of the resulting aldehyde12 gave ibuprofen,
whose configuration and enantiomeric excess were established by
conversion to the known (-)-menthyl esters (24).2a Gas chro-
(4) Nandi, M.; Jin, J.; RajanBabu, T. V. J. Am. Chem. Soc. 1999, 121, 9899.
(5) (a) Reference 1a. (b) Wilke, G.; Monkiewicz, J.; Kuhn, H. U.S. Patent
4,912,274, 1990; Chem. Abstr. 1991, 114, 43172.
(6) (a) Wegner, A.; Leitner, W. J. Chem. Soc., Chem. Commun. 1999, 1583.
(b) Bo¨smann, A.; Francio´, G.; Janssen, E.; Solinas, M.; Leitner, W.;
Wasserscheid, P. Angew. Chem., Int. Ed. 2001, 40, 2697.
(7) For the applications of sugar phosphinites in asymmetric catalysis: See:
(a) Selke, R. React. Kinet. Catal. Lett. 1979, 10, 135. (b) Yan, Y.-Y.;
RajanBabu, T. V. J. Org. Chem. 2001, 66, 3277 and references therein.
(e) RajanBabu, T. V.; Casalnuovo, A. L.; Ayers, T. A. Ligand Tuning in
Asymmetric Catalysis: Hydrocyanation and Hydrogenation Reactions. In
AdVances in Catalytic Processes; Doyle, M., Ed.; JAI Press: Greenwhich,
1998; Vol. 2, p 1.
(8) For a more complete list and experimental procedures see Supporting
Information.
(9) For a compilation of best practices, see ref 1b. See also ref 6a for a reaction
done in sc CO2 using 5 and BARF as a counteranion.
(10) Other related ligands gave the following yield/selectivity (for 4-aryl-1-
butene)/ee for 4-bromostyrene: 15A 88/>99/13; 15B 41/>99/47; 16B
19/>99/43.
(11) The following yield/selectivity (for 3-aryl-1-butene)/ee were obtained for
various salts when used in conjunction with 16A: AgSbF6 98/>99/89;
NaBARF 94/94/89: AgBF4 24/>99/86; AgOTf 70/>99/74.
(12) Parrinello, G.; Stille, J. K. J. Am. Chem. Soc. 1987, 109, 7122.
(13) According to our results, the [R]D values for 21 previously reported in
the literature5b,13a and the ee’s based on these numbers alone may need
reevaluation.8 We obtained a value of +6.80 ( 0.1 (c 2.09, CHCl3) for
(S)-21 of 74% ee. (a) Hayashi, T.; Konishi, M.; Fukushima, M.; Kanehira,
K.; Hioki, T.; Kumada, M. J. Org. Chem. 1983, 48, 2195.
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