Asymmetric synthesis of monodentate phosphine ligands based on chiral η6-Cr[arene] templates

Article abstract of DOI:10.1021/ol990929s

(formula presented) Optically active Cr-complexed arylphosphines are presented as a new class of chiral monodentate phosphine ligand for use in asymmetric catalysis. Asymmetric synthesis of the chiral phosphine ligands 9 is achieved in three steps from the achiral Cr[arene] precursor 3. A variety of ligand structures are accessed from a common synthesis intermediate. The utility of these phosphine ligands in asymmetric catalysis is highlighted in Pd(II)-catalyzed allylic alkylation reactions.

Full text of DOI:10.1021/ol990929s

ORGANIC
LETTERS
1999
Vol. 1, No. 9
1379-1382
Asymmetric Synthesis of Monodentate
Phosphine Ligands Based on Chiral
η6-Cr[arene] Templates
Scott G. Nelson* and Mark A. Hilfiker
Department of Chemistry, UniVersity of Pittsburgh, Pittsburgh, PennsylVania 15260
sgnelson+@pitt.edu
Received August 10, 1999
ABSTRACT
Optically active Cr-complexed arylphosphines are presented as a new class of chiral monodentate phosphine ligand for use in asymmetric
catalysis. Asymmetric synthesis of the chiral phosphine ligands 9 is achieved in three steps from the achiral Cr[arene] precursor 3. A variety
of ligand structures are accessed from a common synthesis intermediate. The utility of these phosphine ligands in asymmetric catalysis is
highlighted in Pd(II)-catalyzed allylic alkylation reactions.
Multidentate ligand-metal binding is a common prerequisite
for metal-based catalysts that mediate highly stereoselective
organic transformations. However, multidentate ligands are
incompatible with metal complexes in which catalytic activity
is exclusive to complexes possessing monodentate ligands
or to catalysts that retain only a single ligand during the
critical bond-forming event. Realizing high levels of asym-
metric induction under these circumstances requires chiral
monodentate ligands that, despite the conformational mobility
associated with univalent metal-ligand attachment, ef-
fectively relay chirality to the pertinent bond construction.1
Chiral, nonracemic monodentate phosphine ligands satisfying
these requirements are relatively rare compared to the
numerous examples of bidentate phosphine ligands employed
widely in asymmetric catalysis. As a contribution to the
development of optically active monophosphine ligands, a
modular strategy for the asymmetric synthesis of monoden-
tate phosphine ligands 1 based on chiral η6-Cr[arene]
scaffolds is presented herein (Scheme 1). Crystal structure
data for the derived Pd(0)-phosphine complex 2 and Pd(0)-
catalyzed allylic alkylations employing these monodentate
Scheme 1
phosphines highlight the potential utility of these ligands in
asymmetric catalysis.
Catalyst optimization routinely necessitates access to a
variety of ligand structures. A strategy for efficiently
preparing a variety of ligand architectures from a common
synthetic pathway was, therefore, considered essential in
designing the phosphine ligand synthesis. These consider-
ations led to a modular ligand synthesis based on an optically
active η6-Cr[arene] core that would provide access to a
variety of ligand structures from a common synthesis
10.1021/ol990929s CCC: $18.00 © 1999 American Chemical Society
Published on Web 10/02/1999

intermediate.2,3 The carbamate-substituted arene complex 3
was targeted as an intermediate that could be elaborated to
the desired optically active arylphosphine complexes via a
three-step sequence (Scheme 2): (1) enantioselective arene
mediate with 1,2-dibromo-1,1,2,2-tetrachloroethane afforded
the optically active o-bromo carbamate 6 in 84% yield (62%
ee) and 95-97% ee after a single recrystallization (48%
overall yield).4,5 This reaction sequence defines the optically
active Cr[arene] ligand scaffold with concomitant introduc-
tion of an easily interchanged ortho substituent.
The enantiomerically enriched o-bromo carbamate com-
plex 6 provides a platform for accessing an array of ligand
structures by exploiting bond constructions based on the
activation and coupling of aryl halides. To maximize the
dissymmetry within the targeted phosphine ligands, aryl
residues were selected for coupling to the Cr[arene] fragment
as a means of introducing substituents with well-defined
spatial displacements. Thus, Suzuki coupling of bromide 6
with a series of aryl boronic acids was accomplished under
the reaction conditions developed by Uemura (Scheme 4).6
Scheme 2
Scheme 4
lithiation and ensuing derivatization to provide the optically
active Cr[arene] 4, (2) incorporation of structural diversity
by interconversion of the ortho substituent X, and (3)
installation of the phosphine moiety via SNAr2 displacement
of the carbamate function.
Synthesis of the targeted arylphosphine ligands was
initiated by asymmetric ortho lithiation of the Cr-complexed
aryl carbamate 3 (Scheme 3). Deprotonation of aryl carbam-
Scheme 3
Chiral biaryl complexes incorporating aryl substituents
possessing electron-donating (entry b) and electron-with-
drawing groups (entry d) as well as ortho substitution (entries
a-c) were obtained in 63-75% yield with complete retention
of optical purity (Table 1). Chromium-arenes 7a-c can adopt
ate 3 using the lithioamide 5 developed by Ku¨ndig and
reaction of the resulting optically active aryllithium inter-
Table 1. Suzuki Coupling and Phosphine SNAr2 Reactions
(1) For examples of optically active monodentate phosphine ligands and
their use in asymmetric catalysis, see: (a) Morrison, J. D.; Burnett, R. E.;
Aguiar, A. M.; Morrow, C. J.; Phillips, C. J. Am. Chem. Soc. 1971, 93,
1301-1303. (b) Knowles, W. S.; Sabacky, M. J.; Vineyard, B. D. J. Chem.
Soc., Chem. Commun. 1972, 10-11. (c) Bogdanovic, B. Angew. Chem.,
Int. Ed. Engl. 1973, 12, 954-964. (d) Hayashi, T. In Ferrocenes; Togni,
A., Hayashi, T., Eds.; VCH: Weinheim, Germany, 1995; p 105. (e) Hamada,
Y.; Seto, N.; Ohmori, H.; Hatano, K. Tetrahedron Lett. 1996, 37, 7565-
7568. (f) Hayashi, T.; Kawatsura, M.; Uozumi, Y. J. Chem. Soc., Chem.
Commun. 1997, 561-562. (g) Zhu, G.; Chen, Z.; Jiang, Q.; Xiao, D.; Cao,
P.; Zhang X. J. Am. Chem. Soc. 1997, 119, 3836-3837. (h) Chen, Z.; Jiang,
Q.; Zhu, G.; Xiao, D.; Cao, P.; Guo, C.; Zhang, X. J. Org. Chem. 1997,
62, 4521-4523. (i) Hayashi, T.; Kawatsura, M.; Uozumi, Y. J. Am. Chem.
Soc. 1998, 120, 1681-1687. (j) Hayashi, T. J. Organomet. Chem. 1999,
576, 195-202 and references therein. (k) Dai, X. D.; Virgil, S. Tetrahedron
Lett. 1999, 40, 1245-1248. (l) Graf, C. D.; Malan, C.; Harms, K.; Knochel,
P. J. Org. Chem. 1999, 64, 5581-5588.
conformations placing the ortho substituent of the auxiliary
aryl ring in an endo or exo orientation relative to the Cr(CO)3
fragment. Placing the ortho substituents in the naphthyl (7a)
and o-tolyl (7b) complexes adjacent to the metal fragment
(2) For syntheses of phosphine ligands incorporating η6-Cr[arene] units,
see: (a) Uemura, M.; Miyake, R.; Nishimura, H.; Matsumoto, Y.; Hayashi,
T. Tetrahedron: Asymmetry 1992, 3, 213-216. (b) Hayashi, Y.; Sakai, H.;
Kaneta, N.; Uemura, M. J. Organomet. Chem. 1995, 503, 143-148. (c)
Ariffin, A.; Blake, A. J.; Li, W.-S.; Simpkins, N. S. Synlett 1997, 1453-
1455.
(3) For a review of syntheses of optically active Cr[arene] complexes,
see: Bolm, C.; Mun˜iz, K. Chem. Soc. ReV. 1999, 28, 51-59.
(4) Ku¨ndig, E. P.; Quattropani, A. Tetrahedron Lett. 1994, 35, 3497-
3500.
1380
Org. Lett., Vol. 1, No. 9, 1999

affords sufficient steric destabilization that the exo conform-
ers predominate: exo:endo ) g95:5 (7a), 91:9 (7b).7 The
o-anisyl complex 7c is obtained as a 2.3:1 mixture of exo/
endo conformers, suggesting that the methoxy substituent
does not suffer especially severe steric interactions in the
endo orientation.8
The completion of the phosphine synthesis was predicated
on developing the means for transforming the arene car-
bamate functionality to the desired arylphosphine moiety.
On the basis of the observation that chromium tricarbonyl
complexation strongly activates coordinated arenes toward
nucleophilic addition, we anticipated that this effect would
allow successful SNAr2 addition of phosphine nucleophiles
with concomitant carbamate displacement.9,10 To test this
hypothesis, the achiral carbamate complex 3 was reacted with
lithiodiphenylphosphine; standard reaction workup afforded
the desired phosphine complex 8 as an air-stable crystalline
solid in 96% yield (Scheme 5). In accord with this prelimi-
displacement reactions; phosphine complexes 9a-e are
obtained with enantiomer ratios directly reflecting the optical
purity of the carbamate starting materials.
Chromium tricarbonyl complexation to arene rings can
impart dramatic electronic perturbations to both the coordi-
nated aryl ring and the appended substituents.9,12 To evaluate
the effect these electronic properties have on metal coordina-
tion by the phosphinyl-Cr[arene] complexes, the X-ray
crystal structure of the Pd(0) complex 10, derived from
phosphine 9a, was determined. Thus, [(η3-C3H5)PdBr]2 was
reacted with phosphine 9a in CH2Cl2, with the resulting
yellow crystalline product 10 affording the X-ray crystal
structure depicted in Figure 1. The palladium-phosphorus
Scheme 5
nary observation, efficient C-P bond construction was
achieved by reacting the biaryl complexes 7a-e with
lithiodiphenylphosphine, providing the optically active mono-
phosphine ligands 9a-e in 63-87% yield (Table 1).11 No
erosion of the Cr[arene] optical purity is observed in the
(5) Arene 3 was reacted with the lithio amide 5 (1.02 equiv) in THF
(0.3 M) at -78 °C. After the mixture was stirred for 2 h, a 0.13 M solution
of 1,2-dibromotetrachloroethane (1.1 equiv) in Et2O was added and the
reaction mixture was warmed to ambient temperature. After 12 h, the
reaction mixture was filtered through a silica gel pad and purified by column
chromatography (hexanes/ethyl acetate). Recrystallization of the purified
bromide (Et2O/pentane) afforded 6 in g95% ee.
(6) (a) Uemura, M.; Nishimura, H.; Hayashi, T. J. Organomet. Chem.
1994, 473, 129-137. (b) Uemura, M.; Kamikawa, K. J. Chem. Soc., Chem.
Commun. 1994, 2697-2698. (c) Watanabe, T.; Kamikawa, K.; Uemura,
M. Tetrahedron Lett. 1995, 36, 6695-6698.
(7) The assignment of 7a-c as adopting the thermodynamically favored
exo conformation is consistent with the structure of related Cr[arene]
complexes prepared under thermodynamic control; see: Uemura, M.;
Nishimura, H.; Kamikawa, K.; Shiro, M. Inorg. Chim. Acta 1994, 222, 63-
70. The conformation of the 1-naphthyl derivative 7a was further established
by X-ray crystal structure determination of the related phosphine complex
10. See the Supporting Information for full details.
(8) The observed exo:endo ratio in 7c appears to represent the ground-
state conformer population, as the isomers can be interconverted at elevated
temperatures while cooling reestablishes the original 2.3:1 exo:endo ratio.
(9) Semmelhack, M. F. Nucleophilic Addition to Arene-Metal Com-
plexes. In ComprehensiVe Organic Synthesis; Trost; B. M., Fleming, I.,
Heathcock, C. H., Eds.; Pergamon Press: New York, 1991; Vol. 4, pp 517-
549.
(10) For an example of SNAr2 reactions of chiral Cr[arene] complexes,
see: Kamikawa, K.; Uemura, M. Tetrahedron Lett. 1996, 37, 6359-6362.
(11) Carbamates 7a-e were reacted with the lithiodiphenylphosphine
(2 equiv) in THF (0.16 M) at -78 °C. After the mixtures were stirred for
20 min, they were warmed to ambient temperature. After 12 h, the reaction
mixtures were filtered through a silica gel pad and purified by column
chromatography (hexanes/ethyl acetate). The optically active triarylphos-
phine complexes 9a-e are highly crystalline, air-stable solids.
Figure 1. X-ray crystal structure of PdII[allyl] complex 10.
bond length (2.33 Å) in 10 is nearly identical with that in
the closely related [η3-(2-CH3)C3H4]Pd(PPh3)Cl complex
(2.31 Å), suggesting that the Cr(CO)3 fragment has relatively
little impact on metal-phosphine bonding, with phosphine
9a behaving much like a chiral variant of triphenylphos-
phine.13 The crystal structure also provides insight into the
(12) (a) Davis, R.; Kane-Maguire, L. A. P. Chromium Compounds with
η2-η8 Carbon Ligands. In ComprehensiVe Organometallic Chemistry;
Wilkinson, G., Ed.; Pergamon Press: New York, 1982; Vol. 3, pp 953-
1077. (b) Morris, M. J. Arene and Heteroarene Complexes of Chromium,
Molybdenum, and Tungsten. In ComprehensiVe Organometallic Chemistry
II; Abel, E. W., Stone, F. G. A., Wilkinson, G., Eds.; Pergamon Press:
New York, 1995; Vol. 5, pp 471-549.
(13) Mason, R.; Russell, D. R. J. Chem. Soc., Chem. Commun. 1966,
26-28.
Org. Lett., Vol. 1, No. 9, 1999
1381

chiral environment created by the monodentate phosphine
ligand with the planar naphthyl substituent shielding the “top”
of the square-planar Pd(II) ion while the phosphine phenyl
groups create a “wall” perpendicular to the metal ion’s ligand
plane. Furthermore, this ligand architecture is predicted to
restrict conformational mobility about the Pd-P bond, as
significant deviation from the solid-state conformation would
induce considerable nonbonded interactions between the Pd
fragment and the naphthyl or phosphine aryl residues.
Scheme 6
Considering the structural information gained from the
Pd(II)[allyl] complex 10, reactions involving palladium-allyl
intermediates emerged as logical platforms for assaying the
effectiveness of these ligands in asymmetric catalysis.14 To
this end, the palladium(0)-catalyzed alkylation of allylic
acetates was selected as a test reaction for evaluating the
optically active triphenylphosphine surrogates.15 The palla-
dium(II) precatalyst was prepared by reacting [(η3-allyl)-
PdBr]2 with the naphthyl-substituted phosphine 9a (0.6 equiv;
phosphine:Pd(II) ) 1.2:1) in CH2Cl2. The catalyzed alkyl-
ation of 1-phenylcinnamyl acetate 11 with dimethyl malonate
was conducted using 5 mol % 10 under Trost’s alkylation
conditions (N,O-bis(trimethylsilyl)acetamide, KOAc) to af-
ford the alkylated product 12 in 90% ee and 97% yield
(Scheme 6).16,17 Reaction times and enantioselection are
nearly identical for reactions employing catalysts derived
from 1:1.2 or 1:2 metal:ligand stoichiometry. This observa-
tion in conjunction with the X-ray structure of complex 10
strongly supports a Pd(0)-monophosphine complex as the
catalytically active species in these reactions rather than a
transient bisphosphine complex derived from disproportion-
ation of 10.
Chromium-complexed arylphosphines provide optically
active equivalents of triarylphosphine ligands that are ubiqui-
tious in late transition-metal chemistry and catalysis. The
synthesis sequence described herein provides access to
numerous structural analogues of the phosphine ligands from
a single intermediate, the optically active bromide 6.
Investigations into the structural and reactivity properties of
the metal complexes incorporating these monodentate phos-
phine ligands are expected to prove valuable in the design
and development of new chiral monophosphine-derived
catalysts.
Acknowledgment. The University of Pittsburgh and the
National Science Foundation (Grant No. CHE-9875735) are
gratefully acknowledged for support of this work.
(14) For asymmetric allylic substitution reactions catalyzed by mono-
phosphine-palladium catalysts, see ref 1e,f,h-l.
(15) For reviews of catalyzed allylic substitution reactions, see: (a) Trost,
B. M.; Van Vranken, D. L. Chem. ReV. 1996, 96, 395-422. (b) Trost, B.
M. Acc. Chem. Res. 1996, 29, 355-364. (c) Helmchen, G, J. Organomet.
Chem. 1999, 576, 203-214.
(16) Trost, B. M.; Murphy, D. J. Organometallics 1985, 4, 1143-1145.
(17) Similar enantioselection is obtained in alkylation of 11 catalyzed
by 5 mol % 10 employing the sodium salt of dimethyl malonate (86% ee).
Supporting Information Available: Experimental pro-
cedures, details of compound characterization, and X-ray data
for 9c and 10 are provided. This material is available free
of charge via the Internet at http://pubs.acs.org.
OL990929S
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Org. Lett., Vol. 1, No. 9, 1999