Platinum(II) catalysts for highly enantioselective 1,6-enyne cycloisomerizations. Synthetic, structural, and catalytic studies

Article abstract of DOI:10.1021/ol900724z

A new family of cyclometalated (N-heterocyclic carbene)-Pt^ll complexes bearing monodentate phosphines as ancillary ligands has been designed for use as precatalysts In 1,6-enyne cyclolsomerlzatlon reactions. Highly enantioselective skeletal rea

Full text of DOI:10.1021/ol900724z

ORGANIC
LETTERS
2009
Vol. 11, No. 10
2137-2139
Platinum(II) Catalysts for Highly
Enantioselective 1,6-Enyne
Cycloisomerizations. Synthetic,
Structural, and Catalytic Studies
Delphine Brissy, Myriem Skander, He´le`ne Jullien, Pascal Retailleau, and
Angela Marinetti*
Institut de Chimie des Substances Naturelles, CNRS UPR 2301, 1 aV. de la Terrasse,
91198 Gif-sur-YVette, France
angela.marinetti@icsn.cnrs-gif.fr
Received April 6, 2009
ABSTRACT
A new family of cyclometalated (N-heterocyclic carbene)-PtII complexes bearing monodentate phosphines as ancillary ligands has been designed
for use as precatalysts in 1,6-enyne cycloisomerization reactions. Highly enantioselective skeletal rearrangements of allylpropargyl-tosylamide
derivatives have been developed by using (S)-Ph-Binepine as the chiral auxiliary. Enantiomeric excesses up to 97% have been obtained.
Transition-metal-promoted enyne cycloisomerizations have
emerged as highly useful tools for the synthesis of func-
tionalized cyclic and heterocyclic compounds. Among them,
a well-known class of reactions involves activation of the
acetylenic moiety of the substrates by highly electrophilic
metal derivatives, intramolecular addition of the olefin, and
subsequent skeletal rearrangements to cyclic products, with
no loss or gain of any atoms.1 Owing to the outstanding
synthetic potential of these transformations, the development
of enantioselective protocols is a valuable challenge2 that
has met so far with limited success, at least as far as platinum
catalysts are concerned.3 With the aim of setting enantiose-
lective variants of these enyne cycloisomerization reactions,
we first envisioned the use as precatalysts of ligand-modified,
square planar platinum(II) complexes bearing a single
coordination site potentially available for substrate coordina-
tion.4 These first-generation chiral catalysts were cationic
platinum(II) complexes ((NHC)Pt(diphosphine)I+I-) com-
(2) Review: (a) Fairlamb, I. J. S. Angew. Chem., Int. Ed. 2004, 43, 1048–
1052. For additional examples, see: (b) Cao, P.; Zhang, X. Angew. Chem.,
Int. Ed. 2000, 39, 4104–4106. (c) Mikami, K.; Yusa, Y.; Hatano, M.;
Wakabayashi, K.; Aikawa, K. Chem. Commun. 2004, 98. (d) Shibata, T.;
Kobayashi, Y.; Maekawa, S.; Toshida, N.; Takagi, K. Tetrahedron 2005,
61, 9018–9024. (e) Corkey, B. K.; Toste, F. D. J. Am. Chem. Soc. 2007,
129, 2764–2765, and references therein.
(3) Chiral platinum catalysts have been applied so far only to cyclization
reactions involving addition of nucleophiles to the enyne substrates: (a)
Paz-Mun˜oz, M.; Adrio, J.; Carretero, J. C.; Echavarren, A. M. Organome-
tallics 2005, 24, 1293–1300. (b) Toullec, P. Y.; Chao, C. M.; Chen, Q.;
Gladiali, S.; Geneˆt, J.-P.; Michelet, V. AdV. Synth. Catal. 2008, 350, 2401–
2408, and references therein.
(1) (a) Aubert, C.; Buisine, O.; Malacria, M. Chem. ReV. 2002, 102,
813–834. (b) Lloyd-Jones, G. C. Org. Biomol. Chem. 2003, 1, 215–236.
(c) Nieto-Oberhuber, C.; Lo´pez, S.; Jime´nez-Nu´n˜ez, E.; Echavarren, A. M.
Chem.sEur. J. 2006, 12, 5916–5923. (d) Fu¨rstner, A.; Davies, P. W. Angew.
Chem. Int. Ed. 2007, 46, 3410–3449. (e) Michelet, V.; Toullec, P. Y.; Geneˆt,
J.-P. Angew. Chem., Int. Ed. 2008, 47, 4268–4315. (f) Jime´nez-Nu´n˜ez, E.;
Echavarren, A. Chem. ReV. 2008, 108, 3326–3350. (g) Lee, S. I.; Chatani,
N. Chem. Commun. 2009, 371–384.
(4) The use of tri-coordinated platinum complexes in the related
enantioselective diene cycloisomerization reactions has been introduced by
Gagne´ et al.: Feducia, J. A.; Campbell, A. N.; Doherty, M. Q.; Gagne´,
M. R. J. Am. Chem. Soc. 2006, 128, 13290–13297.
10.1021/ol900724z CCC: $40.75
Published on Web 04/17/2009
 2009 American Chemical Society

1
bining a monodentate imidazolylidene (NHC) and a chiral
bidentate phosphine ligand.5 Based on an analogous strategy,
we disclose here the newly designed PtII complexes 3 as the
first highly enantioselective platinum catalysts for 1,6-enyne
cycloisomerization processes.
range as that of 3a (2JC-P ≈ 147 Hz and JP-Pt ≈ 2750 Hz).
The solid-state structure of complex 3a displays a dihedral angle
of 49° between the imidazolylidene moiety and the coordination
plane with a δ-conformation of the six-membered platinacycle.
Owing to this peculiar coordination mode of the unsymmetrical
NHC moiety, the square planar complex 3a displays axial
chirality,8 which combined with the presence of the enantio-
merically pure phosphepine ligand is expected to generate
diastereomeric pairs. Thus, the observed isomers of complexes
3a-c can be tentatively assigned as epimeric complexes with
opposite axial configurations.
The suitability of the new NHC/phosphine-ligated com-
plexes as precatalysts for cycloisomerization reactions has
been demonstrated at first by using the triphenylphosphine
complex 2 as promoter for the 6-endo-dig skeletal rearrange-
ment of N-tosyl allyl(3-phenylpropynyl)amine 4a leading to
the 3-azabicyclo[4.1.0]hept-4-ene 5a9 (Scheme 2 and Table
The new PtII complexes, 2 and 3 in Scheme 1, display a
six-membered metallacyclic structure made of both a N-
Scheme 1
.
Synthesis of Cyclometalated NHC-Phosphine-PtII
Complexes
Scheme 2
.
Cycloisomerization Reactions Promoted by the PtII
Complexes 2 and 3
heterocyclic carbene-Pt and a σ-aryl-Pt bond. A monodentate
phosphane occupies the third coordination site, while an
arguably labile halide ion is the fourth platinum ligand. For
the synthesis of the metallacyclic moieties we have envi-
sioned intramolecular oxidative addition reactions on the
N-(o-iodobenzyl)-imidazolylidene-Pt(0)(dvtms) complexes 1,
which are easily available by adapting known methods.6
Heating of 1a-c in the presence of either PPh3 or (S)-Ph-
Binepine7 in THF led to the desired complexes 2 and 3,
respectively, in good yields.
Complexes 3 were obtained as nonseparable mixtures of
two isomers in approximate 8:2 ratios. An X-ray diffraction
study on complex 3a allowed unambiguous assignment of a
trans relative arrangement of the phosphine and carbene
ligands (Figure 1).
1, entry 1). At a 4 mol % catalyst loading, in the presence
of AgBF4 as the halide scavenger, quantitative conversion
Table 1. Enantioselective Platinum-Catalyzed
Cycloisomerizations of Allylpropargylamines
substrate
R1
Ar
catalyst product yield (%)a ee (%)b
1
2
3
4
5
6
7
8
9
4a
4a
4a
4a
H
H
H
H
Ph
Ph
Ph
Ph
2
5a
5a
5a
5a
5b
5b
5c
5d
5e
5e
90
88
81
90
95
78
77
51
93
98
3a
3b
3c
3a
3c
3b
3c
3b
3c
93
94
96
90
93
91
97
81
88
4b H 3,5-(Me2)C6H3
4b H 3,5-(Me2)C6H3
4c
4d H 4-NO2-C6H4
4e Me Ph
H
4-MeO-C6H4
10 4e Me Ph
a Reaction performed at 60 °C, except for entry 1 to which a reaction
temperature of 90 °C was applied. b By HPLC.
was observed after 20 h at 90 °C, with 5a being the only
product.
Based on this encouraging result, we next considered using
chiral PtII complexes in the same reaction. Following a
preliminary screening of a few monodentate phosphorus deriva-
tives,10 (S)-Ph-Binepine has been selected as the preferred chiral
ligand. The Pt-phosphepine complexes 3a-c displayed high
catalytic activity and allowed the cycloisomerization of 4a to
be performed in rather mild conditions (60 °C). They afforded
Figure 1. ORTEP view of the platinum(II) complex 3a.
The same geometry can be tentatively assigned to complex
2, as well as to both isomers of complexes 3b,c since they all
display 2JP-C(carbene) and/or 1JP-Pt coupling constants in the same
2138
Org. Lett., Vol. 11, No. 10, 2009

the expected bicyclic compound 5a in good yields, with total
product selectivity and, most significantly, in very high enan-
tiomeric excesses (entries 2-4 in Table 1).
The efficiency of the cyclometalated catalysts 3 was further
assessed by cyclization experiments on the N-Ts propyny-
lamines 4b-e, which display either substituted aryl groups
on the alkyne unit (entries 5-8) or a methyl substituent on
the allyl moiety (entries 9 and 10). Yields for the isolated
products 5b-e were typically high, and good enantiomeric
excesses (88-97%) were attained in all cases.
A few key structural features of complexes 3, relevant to
chiral induction, have been identified so far. So, the high
enantioselectivity levels can be ascribed, at least in part, to
the metallacyclic structure of the catalyst and its subsequent
restricted conformational freedom, since the analogous
acyclic complex 6 (Figure 2) afforded a racemic sample of
5a under the reaction conditions of entry 2.
lectivity levels (93-96% ee) was observed when 3a (R )
Me), 3b (R ) Et), or 3c (R ) CH2Ph) were used as catalysts
in the cycloisomerization of 4a (entries 2-4). A more
pronounced effect was noticed, however, in the cycloisomer-
ization of 4e, where ee’s of 81% and 88% were afforded by
3b and 3c, respectively (entries 9 and 10). Thus, modulation
of the N substituent is likely to be a key parameter for future
optimizations of analogous catalytic processes.
The substrate scope of this enantioselective cycloisomer-
ization reaction seems to be restricted to aryl-substituted
alkynes, since 2-butynamine derived enynes led to the
corresponding cyclized products in ee’s of <20%.
As an extension of the enantioselective approach to Pt-
promoted cycloisomerizations developed here, the cycloi-
somerization of enyne 712 bearing a cyclic olefinic moiety
has been considered (Scheme 3).
Scheme 3. Enantioselective Cycloisomerization of Enyne 7
Figure 2. Molecular structure of complex 6.
Moreover, based on the X-ray structure of 3a, it could be
anticipated that the R substituent of the imidazolylidene unit
would play a role on the stereochemical course of the
cyclization, because of its close proximity to the catalyst
reaction site.11 Only a small modulation of the enantiose-
Catalysts 3 trigger the expected conversion of 7 into the
tricyclic derivative 8 with high stereoselectivity levels (ee
up to 92%). This result shows that substantial structural
variations of the olefin function are accommodated by this
new enantioselective process.
In conclusion, this work highlights the first known class
of well-defined PtII complexes leading to highly enantiose-
lective cycloisomerizations of representative enyne substrates.
Further studies will explore the applications of these and
analogous catalysts in stereoselective enyne skeletal rear-
rangements leading to different structural motifs.
(5) The use of (S,S)-Chiraphos as the ligand allowed enantiomeric
excesses up to 74% to be attained in the model allylpropargylamine
cycloisomerization reaction of Scheme 2 for R1 ) H and Ar ) Ph. (a)
Brissy, D.; Skander, M.; Retailleau, P.; Marinetti, A. Organometallics 2007,
26, 5782–5785. (b) Brissy, D.; Skander, M.; Retailleau, P.; Frison, G.;
Marinetti, A. Organometallics 2009, 28, 140–151.
(6) Berthon-Gelloz, G.; Buisine, O.; Brie`re, J.-F.; Michaud, G.; Ste´rin,
S.; Mignani, G.; Tinant, B.; Declercq, J.-P.; Chapon, D.; Marko´, I. E. J.
Organomet. Chem. 2005, 690, 6156–6168.
(7) (a) Gladiali, S.; Dore, A.; Fabbri, D.; De Lucchi, O.; Manassero,
M. Tetrahedron:Asymmetry 1994, 5, 511–514. (b) Junge, K.; Oehme, G.;
Monsees, A.; Riermeier, T.; Dingerdissen, U.; Beller, M. Tetrahedron Lett.
2002, 43, 4977–4980.
Acknowledgment. We are very grateful to Dr. Thomas
Riermeier and Dr. Renat Kadyrov (Evonik Degussa GmbH,
Hanau, Germany) for a generous gift of (S)-Ph-Binepine.
(8) For discussions on the axial chirality in square-planar carbene metal
complexes, see: Enders, D.; Gielen, H. J. Organomet. Chem. 2001,
617-618, 70–80.
(9) For analogous reactions promoted by PtCl2 or platinum complexes,
see: (a) Fu¨rstner, A.; Szillat, H.; Stelzer, F. J. Am. Chem. Soc. 2000, 122,
6785–6786. (b) Fu¨rstner, A.; Stelzer, F.; Szillat, H. J. Am. Chem. Soc. 2001,
123, 11863–11869. (c) Ferrer, C.; Raducan, M.; Nevado, C.; Claverie, C. K.;
Echavarren, A. M. Tetrahedron 2007, 63, 6306–6316. Asymmetric Ir-
promoted cyclisations of analogous enyne substrates have been described
in ref 2d.
Note Added after ASAP Publication. There was an error
in Scheme 1 in the version published April 17, 2009; the
corrected version was published April 23, 2009.
Supporting Information Available: Complete experi-
mental procedures, characterization data, ee determinations,
and crystallographic data for 3a (CCDC 713409). This
material is available free of charge via the Internet at
http://pubs.acs.org.
(10) Analogous PtII complexes with (S)-Monophos as the ligand also
provide promising catalysts for the cycloisomerization reactions of Scheme
2. Compared to the phosphepine complexes 3, the Monophos complexes
display improved catalytic activities but slightly lower enantiomeric
excesses. Quantitative conversion rates (92% and 88% isolated yields) and
enantiomeric excesses of 75% and 84% have been obtained in the reactions
of entries 2 and 5 in Table 1, respectively. The enantioselectivity levels
were found to be largely temperature independent in a 40-90 °C range.
(11) With the assumption that the initial geometry is retained in the
tricoordinated intermediate formed by halide abstraction.
OL900724Z
(12) Lee, S. I.; Kim, S. M.; Choi, M. R.; Kim, S. Y.; Chung, Y. K.;
Han, W.-S.; Kang, S. O. J. Org. Chem. 2006, 71, 9366–9372.
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