Design and development of cyclohexane-based P,N-ligands for transition metal catalysis

Article abstract of DOI:10.1021/ol026249y

(Matrix presented) R₁ = H, Pht R₂ = Ph, Cy A new class of cyclohexane-based P,N-ligands is readily obtained through aziridine ring opening with suitable phosphorus nucleophiles under acidic conditions. tran-1-Amino-2-diphenylphosphin

Full text of DOI:10.1021/ol026249y

ORGANIC
LETTERS
2
002
Vol. 4, No. 15
597-2600
Design and Development of
Cyclohexane-Based P,N-Ligands for
Transition Metal Catalysis
2
Aldo Caiazzo, Shadi Dalili, and Andrei K. Yudin*
DaVenport Research Laboratories, Department of Chemistry, UniVersity of Toronto,
80 St. George Street, Toronto, Ontario, Canada M5S 3H6
ayudin@chem.utoronto.ca
Received May 28, 2002
ABSTRACT
A new class of cyclohexane-based P,N-ligands is readily obtained through aziridine ring opening with suitable phosphorus nucleophiles under
acidic conditions. trans-1-Amino-2-diphenylphosphinocyclohexane is resolved with tartaric acid to give the final product in >99% ee. The new
ligands show high stability toward oxidation at the phosphorus atom.
Bidentate ligands are ubiquitous components of many
transition-metal-based catalysts. Among them, chiral P,N-
character of the softer phosphorus site. On the other hand,
high oxidation states are better stabilized by the harder
1
2d,4
ligands have found applications in a variety of asymmetric
processes ranging from allylic substitution to hydrogenation
nitrogen site. This combination of complementary proper-
ties of nitrogen and phosphorus has been explored in a
number of carbocyclic environments. For instance, in a recent
2
,3
of ketones. From the reactivity standpoint, a P,N-ligand
contains a combination of hard (nitrogen) and soft (phos-
phorus) centers.2 Within this environment, metal ions can
be stabilized in their low oxidation states by the π-accepting
5
example reported by Jones, the hemilabile character of
c
(dialkylphosphino)-dialkylaminoethane was found to be
crucial for the catalytic activity of the derived platinum
complexes. The formation of putative five-membered met-
allacycles in this system was not observed in the presence
of chelating diphosphine ligands.
(1) For recent developments in bidentate ligands chemistry, see: (a)
Pfaltz, A. Chimia 2001, 55, 708-714. (b) McCarthy, M.; Guiry, P. J.
Tetrahedron 2001, 57, 3809-3844. (c) Van Leeuwen, P. W. N. M.; Kamer,
P. C. J.; Reek, J. N. H.; Dierkes, P. Chem. ReV. 2000, 100, 2741-2769.
See also: (d) Noyori, R. (ed.) Asymmetric Catalysis in Organic Synthesis;
J. W. Wiley & Sons: New York, 1994.
We were puzzled by the absence of examples of P,N-
ligands based on the trans-1,2-cyclohexane fragment. The
cyclohexane template is present in a number of useful chiral
(2) For general reviews on P,N-ligands, see: (a) Braunstein, P.; Naud,
F. Angew. Chem., Int. Ed. 2001, 40, 680-699. (b) Gavrilov, K. N.;
Polosukhin, A. I. Russ. Chem. ReV. 2000, 69, 661-682. (c) Slone, C. S.;
Weinberger, D. A.; Mirkin, C. A. Prog. Inorg. Chem. 1999, 48, 233-350.
6
ligands for asymmetric catalysis as a result of its ability to
(
5
d) Espinet, P.; Soulantica, K. Coord. Chem. ReV. 1999, 193-195; 499-
rigidify the trans configuration of substituents.
56.
We therefore viewed this as an opportunity to explore new
catalytic activity. In this paper we describe our efforts toward
(
3) For allylic substitution, see: (a) Pfaltz A. Chimia 2001, 55, 708-
7
14. (b) Helmchen, G.; Pfaltz, A. Acc. Chem. Res. 2000, 33, 336-345. (c)
Haughton, L.; Williams, J. M. J. J. Chem. Soc., Perk. Trans. 1 2000, 3335-
3
349. For Heck reaction, see: (d) Loiseleur, O.; Hayashi, M.; Keenan, M.;
Schmees, N.; Pfaltz, A. J. Organomet. Chem. 1999, 576, 16-22. For
hydrosilylation, see: (e) Nishiyama, H. In ComprehensiVe Asymmetric
Catalysis; Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer: Berlin,
Chem. 1995, 488, C20-C22. For transfer hydrogenation to ketones, see:
(i) Braunstein, P.; Naud, F.; Pfaltz, A.; Rettig, S. J. Organometallics 2000,
19, 2676-2683. (j) Braunstein, P.; Graiff, C.; Naud, F.; Pfaltz, A.;
Tiripicchio, A. Inorg. Chem. 2000, 39, 4468-4475.
(4) Schnyder, A.; Hintermann, L.; Togni, A. Angew. Chem., Int. Ed. Engl.
1995, 34, 931-933.
1
999; Vol. I, p 267. For hydroboration, see: (f) Kwong, F. Y.; Yang, Q.;
Mak, T. C. W.; Chan, A. S. C.; Chan, K. S. J. Org. Chem. 2002, 67, 2769-
777 and references therein. For hydroformylation, see: (g) Abu-Gnim,
2
C.; Amer, I. J. Organomet. Chem. 1996, 516, 235-243. (h) Basoli, C.;
Botteghi, C.; Cabras, M. A.; Chelucci, G.; Marchetti, M. J. Organomet.
(5) M u¨ ller, C.; Lachicotte, R. J.; Jones, D. W. Organometallics 2002,
21, 1118-1123.
1
0.1021/ol026249y CCC: $22.00 © 2002 American Chemical Society
Published on Web 07/02/2002

preparation of a new family of P,N-ligands based on aziridine
ring opening chemistry.7
Our recent interest in the synthesis and applications of
8
functionalized aziridines prompted us to investigate their
ring opening with phosphine nucleophiles. Readily available
-azabicyclo[4.1.0]heptane (1)7 was subjected to nucleo-
a
7
philic ring opening with diphenylphosphine according to
Scheme 1, yielding trans-1-amino-2-diphenylphosphino cy-
Scheme 1
Figure 1. Thermal ellipsoid plot of complex 3. Selected distances
[
Å] and bond angles [deg]: Ni-N1 1.930(9), Ni-N2 1.928(9),
clohexane (2a) in 50% yield. The use of trifluoromethane-
sulfonic (triflic) acid was crucial in order to activate the
aziridine ring toward opening. When trifluoroacetic acid was
utilized in place of triflic acid, rapid oxidation of the
Ni-P1 2.197(3), Ni-P2 2.196(3), N1-Ni-P1 84.6(3), N2-Ni-
P2 85.1(3), N1-Ni-P2 175.3(3), N2-Ni-P1 172.1(3).
9
8
phosphorus center was observed.
trosynthesis recently developed in our lab. We subjected
Analogously, the opening of aziridine 1 by using dicy-
clohexylphosphine as a nucleophile led to the formation of
trans-1-amino-2-dicyclohexylphosphino-cyclohexane (2b) as
a white solid in 30% yield (Scheme 1). This opens up to the
possibility of synthesizing a wide variety of P,N-ligands with
different kinds of disubstituted phosphines.
aziridine 4 to ring opening with diphenylphosphine under
the same conditions as for 1. Accordingly, 2-{[2-(diphe-
nylphosphino)cyclohexyl]amino}-1H-isoindole-1,3(2H)-di-
one (5) was obtained in 65% yield (Scheme 2).
The trans-stereochemistry of 2a and its coordinating ability
were confirmed by X-ray analysis (Figure 1) of the bis(trans-
Scheme 2
1
-amino-2-diphenylphosphino cyclohexane) nickel(II) di-
tetrafluoroborate) (3). This complex was formed in 50%
yield during the reaction between 2 equiv of 2a and NiCl
O in the presence of lithium tetrafluoroborate. The
(
2
‚
6H
2
geometry of 3 is square planar, with a bite angle [P(1A)-
Ni(1A)-N(1A)] in the 84.6(3)°-85.1(3)° range.1
0
2
The homochiral complex, which contains a C axis, was
the only observed product. The preferred formation of the
cis complex as opposed to the trans isomer can be attributed
2
to the higher trans influence of the PPh group with respect
group.11
Using these methods, functionalized hydrazines were easily
prepared and subsequently served as precursors to more
complex ligands. For instance, the deprotection of the
phthalimide group was achieved using an excess of n-
butylamine in refluxing ethanol. This reaction resulted in the
formation of 1-[2-(diphenylphosphino)cyclohexyl]-hydrazine
to the NH
2
The results obtained in parent aziridine ring opening led
us to investigate other derivatives of cyclohexene aziridine,
such as 2-(7-azabicyclo[4.1.0]hept-7-yl)-1H-isoindole-1,3-
1
2
(2H)-dione (4), which became readily available using elec-
(
6) (Scheme 3).
The resulting hydrazine 6 was directly subjected to reaction
(
6) (a) Jacobsen, E. N. Acc. Chem. Res. 2000, 33, 421-431. (b) Trost,
B. M.; Bunt, R. C.; Lemoine, R. C.; Calkins, T. L. J. Am. Chem. Soc. 2000,
1
7
22, 5968-5976. (c) Ito, Y. N.; Katsuki, T. Bull. Chem. Soc. Jpn. 1999,
2, 603-619.
with 2,4-pentanedione to give the pyrazole-based P,N-ligand
trans-1-[2-(diphenylphosphino)cyclohexyl]-3,5-dimethyl-1H-
pyrazole (7) in 70% overall yield over two steps (Scheme
(7) (a) Christoffers, J.; Schulze, Y.; Pickardt, J. Tetrahedron 2001, 57,
1
765-1769. (b) Katagiri, T.; Takahashi, M.; Fujiwara, Y.; Ihara, H.;
Uneyama, K. J. Org. Chem. 1999, 64, 7323-7329.
3
).
The complexation of 7 with bis(benzonitrile)palladium-
(
8) Siu, T.; Yudin, A. K. J. Am. Chem. Soc. 2002, 35, 2723-2727.
(9) For cyclohexene oxide ring opening with diphenylphosphine, see:
Muller, G.; Sainz, D. J. Organomet. Chem. 1995, 495, 103-111.
10) Suzuki, T.; Morikawa, A.; Kashibawara, K. Bull. Chem. Soc. Jpn.
996, 69, 2539-2548.
11) Suzuki, T.; Rude, M.; Simonsen, K. P.; Morooka, M.; Tanaka, H.;
Ohba, S.; Galsbøl, F.; Fujita, J. Bull. Chem. Soc. Jpn. 1994, 67, 1013-
023.
(II) dichloride (1:1 ratio) in dichloromethane provided {trans-
(
1
(
(12) (a) Barz, M.; Rauch, M. U.; Thiel, W. R. J. Chem. Soc., Dalton
Trans. 1997, 2155-2161. (b) Barz, M.; Herdtweck, E.; Thiel, W. R. Angew.
Chem., Int. Ed. 1998, 37, 2262-2265.
1
2598
Org. Lett., Vol. 4, No. 15, 2002

Scheme 3
Scheme 4
ligands are precursors to active catalysts. The conversion/
time study revealed that the Suzuki coupling was complete
after 8 h.
The ligand 2a was successfully resolved using D-tartaric
acid via the formation of the tartrate salt, which was filtered
and recrystallized from water. X-ray analysis carried out on
crystals grown in 95% aqueous ethanol showed that the
enantiomer separated from the racemic mixture had (R,R)
absolute configuration.
The enantiomerically pure P,N-ligand was then recovered
by dissolving the tartrate salt in 10% sodium hydroxide
solution and extracting the mixture with dichloromethane
1
-[2-(diphenylphosphino) cyclohexyl]-3,5-dimethyl-1H-pyra-
zole} palladium(II) dichloride (8) in 80% yield as a yellow
solid. The X-ray analysis of 8 shows that the complex has a
square planar geometry, with a bite angle [N(1)-Pd(1)-
P(1)] of 83.03(11)°. The Pd-Cl bond trans to the phosphorus
atom is longer than the one trans to the nitrogen atom [Pd-
Cl1 ) 2.3743(13) Å vs Pd-Cl2 ) 2.2902(12) Å, Figure 2].
(Scheme 5). The enantiomeric excess of the recovered ligand
Scheme 5
Figure 2. Thermal ellipsoid plot of complex 8. Selected distances
[
(
(
Å] and bond angles [deg]: Pd-Cl1 2.3743(13), Pd-Cl2 2.2902-
12), Pd-N1 2.0480(4), Pd-P1 2.2389(12), Cl2-Pd-Cl1 92.94-
5), N1-Pd-P1 83.0(11), N1-Pd-Cl2 95.2(5), Cl1-Pd-P1
(
> 99%, 65% yield) was analyzed by converting it into
13
Mosher acid amide. Throughout these manipulations, the
P,N-derivatives showed considerable stability toward air
1
68.7(5), N1-Pd-Cl2 167.6(11).
3
oxidation. When a solution of 2a in CDCl was stirred under
air for 16 h, less than 4% oxidation was observed.
In summary, cyclohexane-based P,N-ligands can be pre-
pared in enantiomerically pure form from readily available
2
An equimolar mixture of ligand 7 and Pd(dba) was found
to catalyze the Suzuki coupling between sterically hindered
-bromomesitylene and phenylboronic acid in 55% yield and
8% selectivity (Scheme 4), indicating that these new P,N-
2
9
(13) Ward, D. E.; Rhee, C. K. Tetrahedron Lett. 1991, 32, 7165-7166.
Org. Lett., Vol. 4, No. 15, 2002
2599

aziridines and are precursors to active catalysts. Straightfor-
ward manipulation of the substituents on nitrogen renders
these ligands applicable in asymmetric catalysis. A particu-
larly useful property of these ligands is significant oxidative
stability of the phosphorus center. The choice of phosphine
during the ring opening step allows one to manipulate
electronic properties of the system. These and related studies
are in progress and will be reported in due course.
for Innovation, ORDCF, and the University of Toronto for
financial support. Prof. Andrei Yudin is a Cottrell Scholar
of Research Corporation. We also thank Dr. Alan Lough for
his contribution to X-ray analyses and Ms. Katherine Groom
for the help given in the resolution of compound 2a.
Supporting Information Available: Experimental pro-
cedures, characterization data and spectra for compounds
1
-10. This material is available free of charge via the
Internet at http://pubs.acs.org.
Acknowledgment. We thank the National Science and
Engineering Research Council (NSERC), Canada Foundation
OL026249Y
2600
Org. Lett., Vol. 4, No. 15, 2002