A highly strained planar-chiral platinacycle for catalytic activation of internal olefins in the Friedel-crafts alkylation of indoles

Article abstract of DOI:10.1002/anie.200804944

(Chemical Equation Presented) Activation by deformation: A planar-chiral platinacycle readily prepared by diastereoselective cycloplatination enables the enantioselective intramolecular hydroarylation of indoles having disubstituted Z olefins (see scheme;

Full text of DOI:10.1002/anie.200804944

Communications
DOI: 10.1002/anie.200804944
Platinum Catalysis
A Highly Strained Planar-Chiral Platinacycle for Catalytic Activation
of Internal Olefins in the Friedel–Crafts Alkylation of Indoles**
Haoxi Huang and Renꢀ Peters*
Platinum(II)[1] and gold(I)[1a,2] catalysis have experienced
significant growth over the past five years, as these late
transition metals have the ability to catalyze atom economical
reactions of unactivated alkynes, olefins, or allenes, creating a
significant increase in the molecular complexity of a single
synthetic step by using simple starting materials. The catalysts
are compatible with most functional groups because of their
low oxophilicity, and they are usually robust towards moisture
or air. Platinum(II)–olefin complexes are reported to be
highly reactive toward outer-sphere attack by nucleophiles,
and the resulting platinum(II)–alkyl complexes undergo rapid
protonolysis[3] with Brønsted acids rather than b-hydride
elimination, which is the preferred pathway for palladi-
um(II)–alkyl complexes. In contrast, p-ligand exchange is
relatively slow for platinum(II) complexes.[1] Catalysts allow-
ing a more rapid ligand exchange could lead to enhanced
activity of this expensive metal and potentially expand the
scope of the reaction to additional applications. Due to the
reactivity issue and despite considerable progress made in this
field, the asymmetric activation of p ligands by gold or
platinum complexes is still an area with the potential for
development.[1]
Recently we found that ferrocene imidazoline mono- and
bispalladacycle complexes have the ability to efficiently
differentiate enantiotopic olefin faces.[4] The homologous
platinacycles could have similar properties. We hypothesized
that a ligand exchange acceleration might be achieved by
structural distortion of the square planar geometry around
platinum(II) (ground-state destabilization). To develop a
platinum(II) complex with increased activity, we designed the
monoplatinacycle complex 2 in which the PtII center binds to
two imidazoline units (Scheme 1): one connected to the same
Cp plane as the metal, and the second one connected to the
Scheme 1. Formation of the strained complex 2 by diastereoselective
cycloplatination.
Cp’ ligand, potentially resulting in severe structural distortion
by coordination.
When [(dmso)2PtCl2] was used it resulted in negligible
product formation, cycloplatination[5] of bisimidazoline 1[6]
occurred—accompanied by partial ferrocene oxidation—
=
upon treatment with K[(H2C CH2)PtCl3], initially forming
an inseparable mixture of monomer 2 and a major product,
which is likely to be represented by a Cl-bridged dimer (cis/
trans isomers around the Pt square plane). Treatment of the
reaction mixture with Na(acac) (acac = acetylacetonate)
completely converts both the monomer and the dimer into
the same monomeric acac complex, which provides the
diastereomerically pure 2 after treatment with LiCl and
HCl. To our knowledge, this is the first example of a highly
diastereoselective, direct cycloplatination of an enantiopure
ferrocene derivative.[7] The constitution and configuration of
2
were confirmed by X-ray crystallographic analysis
(Figure 1).[8] Both imidazoline units coordinate to the same
Pt center in a trans fashion, resulting in a unique geometry in
which the C atom connected to the metal center is strongly
pyramidalized (angle between the upper Cp plane in
À
Scheme 1 and the Cp Pt bond: 1598, deviation of the Pt
atom from the upper Cp plane in Scheme 1: 0.74 ꢀ). The
central metal adopts a distorted square planar geometry
having a close contact distance between Pt and Fe of 3.19 ꢀ.
This complex can be described as a planar-chiral pincer
complex as it has a terdentate monoanionic ligand.
[*] Prof. Dr. R. Peters
Institut fꢀr Organische Chemie, Universitꢁt Stuttgart
Pfaffenwaldring 55, 70569 Stuttgart (Germany)
Fax: (+49)711-685-64321
E-mail: rene.peters@oc.uni-stuttgart.de
Dr. H. Huang, Prof. Dr. R. Peters
Laboratorium fꢀr Organische Chemie, ETH Zꢀrich
Wolfgang-Pauli-Str. 10, 8093 Zꢀrich (Switzerland)
To establish proof of principle for the enhanced reactivity
of such a distorted catalyst system, the intramolecular
Friedel–Crafts alkylation using unactivated olefins was
selected. Atom economical hydroarylation reactions of ole-
fins provide an attractive platform to prepare partially
saturated poly(hetero)cyclic aromatic compounds. Asymmet-
ric transition-metal-catalyzed methodologies are rare. Ellman
et al. described efficient rhodium(I)-catalyzed intramolecular
[**] This work was financially supported by the ETH research grant TH-
01/07-1 and F. Hoffmann-La Roche. We thank Priv.-Doz. Dr. Martin
Karpf and Dr. Paul Spurr (both from F. Hoffmann-La Roche,
Synthesis and Process Research, Basel) for carefully reading this
manuscript and Paul Seiler and Dr. W. Bernd Schweizer (both from
ETHZ) for X-ray crystal structure analysis.
hydroarylations by using an imine directing group on the
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.200804944.
[9]
À
aromatic substrates for C H activation. Widenhoefer et al.
604
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Angew. Chem. Int. Ed. 2009, 48, 604 –606

Angewandte
Chemie
Table 1: Intramolecular Friedel–Crafts alkylation of indoles.
#
4
R
X
Y
Z
Yield [%][a] ee [%][b]
1
2
3
4
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
CO2Me
CO2Bn
CO2tBu
Et
Et
Et
Me
Me
Me
Me
H
H
H
H
H
H
H
H
H
H
H
F
95
90
85
68
92
90
45
70
92
90
50
85
70
85
82
86
90
78
88
89
89
84
92
85
83
92
85
80
80
CH2OC(O)tBu Et
5[c]
6
CO2tBu
CO2tBu
CO2tBu
CO2tBu
CO2tBu
CO2tBu
CO2Me
CO2tBu
CO2tBu
CO2tBu
CO2tBu
Me Me
nPr Me
iBu Me
7
8
9
10
Ph
Et
Et
Et
Et
Et
Et
Et
Me
Et
iPent
allyl
Me
Me
Me
Me
11
12
13[d]
14
Cl
Me
OMe 92
15
[a] Yield of isolated products. 30 mg scale (entries 2–15) and 200 mg
scale (entry 1). [b] Determined by HPLC methods. [c] 3:1 mixture of Z/E-
3e. [d] Reaction temperature of 608C.
Figure 1. X-ray crystal structure of the strained platinacycle 2.
developed a conceptually different approach,[10] in which a
cationic platinum(II)–bisphosphine complex activated a ter-
minal olefin for the nucleophilic outer-sphere attack by an
indole moiety to provide biologically interesting, partially
saturated carbazole derivatives.[11] Previously, internally dis-
ubstituted alkenes failed to undergo platinum-catalyzed
enantioselective hydroarylations of indoles,[12] therefore,
these challenging substrates were investigated herein.
Platinacycle 2 is in fact sufficiently active to catalyze this
hydroarylation process (Table 1). The optimization of the
reaction conditions for Z-configured internal olefin substrate
3a, bearing an ethyl group (X) on the olefin, revealed a strong
solvent influence (see the Supporting Information). The
highest reactivity was obtained in 2,2,2-trifluoroethanol
whereas either no or poor conversion was obtained in
common solvents such as MeOH, CH2Cl2, 1,4-dioxane,
acetone, or nitromethane. Catalyst activation by a silver salt
increased the activity but had almost no impact on the
enantioselectivity of the reaction. The highest reactivity was
obtained by activating 2 in situ using AgO2CC3F7, which
delivered the target product, after 60 h at 508C, in 95% yield
and with 82% ee (Table 1, entry 1). In contrast, E-3a did not
react at all under the same conditions, implying that geo-
metrically pure substrates are not necessary to obtain high
enantioselectivities. The corresponding platinacycle with only
one imidazoline unit provided 4a in poor yield, albeit with
74% ee under identical reaction conditions.
on the enantioselectivity: Me (Z/E 3:1),[13] Et, nPr, and iso-
butyl gave nearly identical ee values (88–90%, Table 1,
entries 3, 5–7), whereas a Ph group resulted in a slight
decrease (Table 1, entry 8). Similarly, variation of the indole
N-alkyl substituent was tolerated (Table 1, entries 9–10) with
the exception of an allyl group (Table 1, entry 11) which led to
significantly lower activity presumably as a result of catalyst
inhibition by competing olefin coordination. Both electron-
withdrawing and electron-donating substituents Z on the
aromatic core afforded smooth conversions and similar
enantioselectivity (Table 1, entries 12–15) despite the pro-
jected difference in the indole nucleophilicity, which might
À
indicate that C C bond formation is not the rate-determining
step.
The generally observed high enantioselectivity can be
rationalized by the mechanistic proposal depicted in
Scheme 2. The stereoselectivity depends at least in part on
the enantiofacial selectivity of the alkene coordination. In
analogy to our palladacycle catalysts, the olefin moiety is
expected to bind trans to the upper imidazoline moiety
(trans effect)[4,6] thereby releasing the catalyst strain.[14] Coor-
dination at this position may, in principal, afford four different
isomers, assuming the stereoelectronically preferred perpen-
dicular orientation of the alkene to the platinum(II) square
plane. In the coordination mode shown, steric repulsion
between both olefin substituents and the ferrocene moiety is
minimized. Outer-sphere attack by the indole core results in
the formation of Pt–alkyl complex 5. It is not yet clear if the
imidazoline moiety liberated by the olefin coordination is
involved in the subsequent proton transfer, possibly acting as
a shuttle by abstracting the acidic proton on the C atom
To facilitate the substrate formation, the indoles 3 were
prepared by sequential malonate alkylation (see the Support-
ing Information). By using 3c, derived from di-tert-butyl
malonate, the product was formed with a slightly higher
ee value of 90% and in a yield of 85% (Table 1, entry 3).
Variation in the alkene substituent X had almost no influence
=
adjacent to the C N double bond and transferring it to the
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Communications
Chem. Int. Ed. 2006, 45, 5694; b) D. F. Fischer, Z.-q. Xin, R.
Peters, Angew. Chem. 2007, 119, 7848; Angew. Chem. Int. Ed.
2007, 46, 7704; c) Z.-q. Xin, D. F. Fischer, R. Peters, Synlett 2008,
1495; d) R. Peters, Z.-q. Xin, D. F. Fischer, W. B. Schweizer,
Organometallics 2006, 25, 2917; for the first preparation of chiral
ferrocenyl imidazolines, see: e) R. Peters, D. F. Fischer, Org.
Lett. 2005, 7, 4137; for selected recent applications of imidazo-
lines in asymmetric catalysis, see for example: f) S. Bhor, G.
Anilkumar, M. K. Tse, M. Klawonn, C. Dobler, B. Bitterlich, A.
Grotevendt, M. Beller, Org. Lett. 2005, 7, 3393; g) K. Ma, J. You,
Chem. Eur. J. 2007, 13, 1863; h) T. Arai, T. Mizukami, A.
Yanagisawa, Org. Lett. 2007, 9, 1145; i) S. Enthaler, B. Hage-
mann, S. Bhor, G. Anilkumar, M. K. Tse, B. Bitterlich, K. Junge,
G. Erre, M. Beller, Adv. Synth. Catal. 2007, 349, 853; for recent
reviews about palladacycles, see: j) I. P. Beletskaya, A. V.
Cheprakov, J. Organomet. Chem. 2004, 689, 4055; k) J.
Dupont, C. S. Consorti, J. Spencer, Chem. Rev. 2005, 105, 2527.
[5] a) C. Lꢃpez, A. Caubet, S. Pꢂrez, X. Solans, M. Font-Bardꢄa, E.
Molins, Eur. J. Inorg. Chem. 2006, 3974, and references therein;
b) review on Pt-pincer complexes: M. Albrecht, G. van Koten,
Angew. Chem. 2001, 113, 3866; Angew. Chem. Int. Ed. 2001, 40,
3750.
Scheme 2. Proposed mechanism for the intramolecular Friedel–Crafts
alkylation of indoles.
[6] a) S. Jautze, P. Seiler, R. Peters, Angew. Chem. 2007, 119, 1282;
Angew. Chem. Int. Ed. 2007, 46, 1260; b) S. Jautze, P. Seiler, R.
Peters, Chem. Eur. J. 2008, 14, 1430; c) S. Jautze, R. Peters,
Angew. Chem. 2008, 120, 9424; Angew. Chem. Int. Ed. 2008, 47,
9284.
[7] Cycloplatination of racemic Ugi-amine: a) P. R. R. Ranatunge-
Bandarage, B. H. Robinson, J. Simpson, Organometallics 1994,
13, 500.
À
Pt C bond. The suggested mechanism is in line with the
absolute configuration of a sulfonate derivative prepared
from 4a as determined by X-ray crystal structure analysis (see
the Supporting Information).[8]
In summary, we have developed a platinum(II) catalyst
which enables the enantioselective intramolecular Friedel–
Crafts alkylation of indoles having disubstituted internal
olefins. Adequate reactivity was accomplished through the
design of a highly strained planar-chiral platinacycle, presum-
ably providing an accelerated olefin coordination step. The
catalyst was prepared by the first highly diastereoselective
cycloplatination of an enantiopure ferrocene affording the
first highly enantioselective application of a platinacycle in
catalysis, in particular for olefin activation.[14] Application of
this new catalyst to other reactions involving olefin and
alkyne p-bond activation is currently being investigated.
[8] CCDC 698461 (2) and 698460 (a derivative prepared from 4a)
contain 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.
[9] a) R. K. Thalji, J. A. Ellman, R. G. Bergman, J. Am. Chem. Soc.
2004, 126, 7192; b) S. J. OꢅMalley, K. L. Tan, A. Watzke, R. G.
Bergman, J. A. Ellman, J. Am. Chem. Soc. 2005, 127, 13496;
c) R. M. Wilson, R. K. Thalji, R. G. Bergman, J. A. Ellman, Org.
Lett. 2006, 8, 1745.
[10] a) C. Liu, X. Han, X. Wang, R. A. Widenhoefer, J. Am. Chem.
Soc. 2004, 126, 3700; b) X. Han, R. A. Widenhoefer, Org. Lett.
2006, 8, 3801; c) C. Liu, C. F. Bender, X. Han, R. A. Widenhoe-
fer, Chem. Commun. 2007, 3607. Pioneering studies on the use of
stoichiometric amounts of PdII in intramolecular Friedel–Crafts-
type alkylations of indoles for alkaloid syntheses (desethylibog-
amine and ibogamine): d) B. M. Trost, J. P. GenÞt, J. Am. Chem.
Soc. 1976, 98, 8516; and e) B. M. Trost, J. P. GenÞt, J. Am. Chem.
Soc. 1978, 100, 3930. Catalytic amounts of PdII in related
asymmetric Fujiwara–Moritani cyclizations: f) J. A. Schiffner,
A. B. Machotta, M. Oestreich, Synlett 2008, 2271.
Received: October 9, 2008
Published online: December 15, 2008
Keywords: alkylation · hydroarylation · metallacycles ·
.
olefin activation · platinum
[11] J. E. Saxton, Nat. Prod. Rep. 1997, 14, 559.
[12] C. Liu, R. A. Widenhoefer, Org. Lett. 2007, 9, 1935.
[13] Although isomerically pure E-3e did not react, the 3:1 Z/E
isomeric mixture gave a significantly higher yield than 75%
(checked twice). Similarly, a 1:1 mixture gave a yield of 55%.
[14] Selected applications of previous enantiopure platinacycle
complexes: aldol additions: a) F. Gorla, A. Togni, L. M. Venanzi,
A. Albinati, F. Lianza, Organometallics 1994, 13, 1607; b) J. M.
Longmire, X. Zhang, M. Shang, Organometallics 1998, 17, 4374;
c) Y. Motoyama, H. Kawakami, K. Shimozono, K. Aoki, H.
Nishiyama, Organometallics 2002, 21, 3408; Diels–Alder reac-
tions: d) W.-C. Yeo, J. J. Vittal, L. L. Koh, G.-K. P. H. Tan,
Leung, Organometallics 2004, 23, 3474.
[1] a) A. Fꢁrstner, P. W. Davies, Angew. Chem. 2007, 119, 3478;
Angew. Chem. Int. Ed. 2007, 46, 3410; b) A. R. Chianese, S. J.
Lee, M. R. Gagnꢂ, Angew. Chem. 2007, 119, 4118; Angew. Chem.
Int. Ed. 2007, 46, 4042; c) selected example of recent asymmetric
applications: C. A. Mullen, A. N. Campbell, M. R. Gagnꢂ,
Angew. Chem. 2008, 120, 6100; Angew. Chem. Int. Ed. 2008,
47, 6011.
[2] A. S. K. Hashmi, Chem. Rev. 2007, 107, 3180.
[3] F. P. Fanizzi, F. P. Intini, L. Maresca, G. Natile, J. Chem. Soc.
Dalton Trans. 1992, 309.
[4] a) M. E. Weiss, D. F. Fischer, Z.-q. Xin, S. Jautze, W. B.
Schweizer, R. Peters, Angew. Chem. 2006, 118, 5823; Angew.
606
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