Enantioselective platinum-catalyzed tandem hydroarylation- cycloisomerization of 1,6-enynes

Article abstract of DOI:10.1002/adsc.200800446

The platinum(II) chloride/silver hexafluoroantimonate (PtCl ₂/AgSbF₆) catalytic system associated with atropisomeric ligand Ph-BINEPINE promotes a stereoselective tandem hydroarylation (Friedel-Crafts-type addition) of electron-rich aromatic and heteroaromatic derivatives to unactivated alkenes followed by a C-C bond cyclization reaction (ee up to 96%). Some evidence shows that the catalytic species responsible for the highest enantiomeric excesses might reasonably be an L₃Pt ²⁺ species, L being a monodentate ligand.

Full text of DOI:10.1002/adsc.200800446

FULL PAPERS
DOI: 10.1002/adsc.200800446
Enantioselective Platinum-Catalyzed Tandem Hydroarylation–
Cycloisomerization of 1,6-Enynes
Patrick Yves Toullec,a Chung-Meng Chao,a Qian Chen,a Serafino Gladiali,b
Jean-Pierre GenÞt,a and VØronique Micheleta,*
a
Laboratoire de Synth›se SØlective Organique et Produits Naturels, Ecole Nationale SupØrieure de Chimie de Paris, UMR
7573, 11 rue Pierre et Marie Curie, 75231 Paris Cedex 05, France
Fax : (+33)-1-4407-1062; e-mail: veronique-michelet@enscp.fr
Dipartimento di Chimica, Università di Sassari, Via Vienna 2, 07100 Sassari, Italy
b
Fax : (+39)-079-212-069
Received: July 21, 2008; Published online: October 10, 2008
Abstract:
hexafluoro
The
antimonate
platinum(II)
chloride/silver tion reaction (ee up to 96%). Some evidence shows
G
(PtCl2/AgSbF6)
catalytic that the catalytic species responsible for the highest
system associated with atropisomeric ligand Ph-BI- enantiomeric excesses might reasonably be an L3Pt2+
NEPINE promotes a stereoselective tandem hydro- species, L being a monodentate ligand.
arylation (Friedel–Crafts-type addition) of electron-
rich aromatic and heteroaromatic derivatives to un- Keywords: asymmetric catalysis; atom economy; cy-
À
activated alkenes followed by a C C bond cycliza- cloisomerization; platinum; tandem reactions
Introduction
matic systems.[7] In the latter case, the diastereoselec-
tive tandem hydroarylation/cyclization of 1,6-enynes
Recent years have witnessed a tremendous growth in catalyzed by cationic Au(I) species offers the opportu-
the number of transition metal-catalyzed enyne cyclo- nity to create two carbon-carbon bonds and introduce
isomerization reactions.[1] Indeed, these transforma- an aromatic ring[8] in a very selective manner related
tions illustrate ideally the atom-economy concept al- to the Friedel–Crafts reaction.[9] Considering the large
lowing the synthesis of complex and functionalized occurrence of natural products containing five-mem-
cyclic structures with high efficiency under mild con- bered rings found throughout the chemical literature
ditions.[2] Whereas a flurry of synthetic methodologies
using a variety of transition metals have appeared
during the last two decades, the ability of noble third
row transition metals, such as gold and platinum, to
act as catalytic carbophilic p-acids has resulted in a
major change of perspective in this field.[3] The gener-
al mechanism of the reaction of 1,6-enynes involving
these acids[4] proceeds through initial h2-coordination
of the metal to the alkyne (intermediate A) and sub-
sequent intramolecular addition of the alkene leading
to cyclopropylcarbene B (Scheme 1). In the presence
of an external nucleophile, ring opening of the cyclo-
propylcarbene and rearrangement to cyclized vinyl-
metal complex C is observed. Protodemetalation com-
pletes the catalytic cycle. Whereas this synthetic
methodology was first put on evidence with oxygen
nucleophiles such as water or alcohols leading respec-
tively to hydroxy- and alkoxycyclization reactions,[5]
recent studies have demonstrated the possibility to
extend the scope of this reaction to other classes of
nucleophiles such as amines[6] and electron-rich aro- Scheme 1.
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Table 1. Ligand screening on platinum-catalyzed asymmetric
hydroarylation/cycloisomerization of 1a.
Scheme 2.
and our interest in the development of catalytic
tandem and atom-economical reactions,[10] we envi-
sioned that platinum chiral catalysts should offer a
unique opportunity to develop an unprecedented
enantioselective version of the tandem hydroaryla-
tion/cycloisomerization reaction.
Although impressive progress has been made in the
development of enantioselective Au(I)-catalyzed
transformations,[11] most catalytic systems described so
far for alkyne electrophilic activation show either a
moderate level of enantioselection or limited sub-
strate scope.[12] We reasoned that this situation is the
consequence of the linear geometry of the ligand-
metal-alkyne intermediate D (Scheme 2), which is in-
volved in the activation step of the alkyne function by
Au(I) complexes.[3a,5n,13] As cationic platinum com-
plexes have recently been shown to exhibit high cata-
lytic activities for the hydroarylation of alkynes[14] and
alkenes,[15] we speculated that square planar Pt-based
complexes possessing a single empty coordination site
(complex E) could provide the right combination for
a high activity and a high degree of enantiocontrol to
be met in the nucleophilic attack on the coordinated
Entry
Ligand
T [8C]
Yield[a] [%]
ee[b] [%]
(configuration)
1
2
3
4
5
6
7
(R)-L1
(R)-L2
(R)-L3
(S)-L4
(R)-L5
(R)-L5
(R)-L5
90
90
90
90
90
60
23
81
75
94
51
73
96
45
37 (À)
33 (À)
20 (+)
21 (À)
84 (À)
95 (À)
96 (À)
[a]
Isolated yield.
Determined by HPLC analysis.
[b]
alkyne. Following our previous observations on enan- action at 608C with L5 increased the ee to 95% (96%
tioselective alkoxycyclization reactions,[5f] we also en- yield) (Table 1, entry 6). Lowering further the temper-
visaged that an “optimum” chiral environment ature to room temperature led to a lower yield (45%)
around the metal could be attained by the aid of ax- and an equivalent level of enantioselectivity (96% ee)
ially chiral monodentate P donor ligands.
(Table 1, entry 7).
Using the optimized catalytic conditions, we exam-
ined at first the scope of the 1,6-enyne partner
(Table 2, Scheme 3). Changing the malonate substitu-
tion pattern from methyl to bulkier groups such as
Results and Discussion
Initially, we examined the reaction of enyne 1a with isopropyl, tert-butyl or benzyl groups led to lower ee
1-methylindole (3 equiv.) in the presence of 5 mol% (Table 2, entries 1–3). One may notice that there was
of PtCl2, 12.5 mol% AgSbF6 and 16 mol% of ligand no pronounced Thorpe–Ingold effect as the ees were
(L1–L5) in dioxane at 908C (Table 1). We chose some all in the same range. The reaction is tolerant towards
monodentate phosphorus ligands such as phosphor- a rather large variety of electron-rich aromatic and
ACHTREUNG
amidite L1 and L2,[16] BINAP monooxide[17] L3, heteroaromatic nucleophile partners: 1,3-dimethoxy-
MeO-MOP L4[18] and Ph-BINEPINE L5[19] ligands to benzene, 1,3,5-trimethoxybenzene, 2- and 5-substitut-
build up in situ the catalytic species. We were pleased ed indoles and pyrrole can be successfully introduced.
to find that all tested catalysts allowed complete con- The enantioselectivity depends on the structure of the
versions within 16 h to carbocyclic compound 2a. aryl nucleophile and apparently it suffers from an in-
While modest stereoselectivities of a similar range crease in the steric hindrance as in the case of 2-sub-
(20–37%) were promoted by ligands L1–L4 (Table 1, stituted indoles (compare, entry 6 of Table 1 and en-
entries 1–4), the catalyst formed from L5 allowed the tries 4–6 of Table 2). Similar enantiomeric excesses
formation of product 2a with 73% yield and 84% en- were obtained in the case of the introduction of dime-
antiomeric excess (Table 1, entry 5). Running the re- thoxy- and trimethoxybenzene (Table 2, entries 7 and
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Enantioselective Platinum-Catalyzed Tandem Hydroarylation–Cycloisomerization
Table 2. Substrate scope of platinum-catalyzed asymmetric hydroarylation/cycloisomerization reaction.[a]
FULL PAPERS
Entry
1
Enyne
Nucleophile
Product
Yield[b] [%]
ee[c] [%]
82 (À)
1b
1-methylindole
2b
75
2
3
4
5
1c
1d
1a
1a
1-methylindole
2c
2d
2e
2f
77
70
85
58
83 (À)
80 (À)
89 (À)
74 (À)
1-methylindole
1,2-dimethylindole
1-methyl-2-phenylindole
6
1a
1a
1-methyl-5-methoxyindole
1,3-dimethoxybenzene
2g
2h
95
53
87 (À)
80 (+)
7[d]
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Patrick Yves Toullec et al.
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Table 2. (Continued)
Entry
Enyne
Nucleophile
Product
Yield[b] [%]
ee[c] [%]
79 (+)
8[d]
1a
1,3,5-trimethoxybenzene
2i
90
9
1e
1a
1-methylindole
pyrrole
2j
78
79 (À)
70 (+)
10
2k
46[e,f]
[a]
PtCl2 (5 mol%), L5 (16 mol%), AgSbF6 (12.5 mol%), nucleophile (3 equiv.), dioxane (0.5M), 608C.
Isolated yield.
Determined by HPLC analysis.
Reaction time: 4 h.
Reaction run at 408C.
[b]
[c]
[d]
[e]
[f]
9% of the C-3 isomer was also obtained.
8). A benzodioxolane-substituted enyne was also en-
Other carbon tethered substrates, such as the sulfo-
gaged with success in the tandem process: the corre- nated enynes 1f and g were then engaged in the
sponding heterocyclic derivative 2j was isolated in tandem process (Scheme 3). The corresponding ary-
78% yield and 79% enantiomeric excess (Table 2, lated derivatives 2l–2n resulting from the addition of
entry 9). The introduction of pyrrole was possible and 2,5-dimethylfuran, 1,3-dimethoxybenzene and 1-meth-
afforded the corresponding 2-substituted cyclic deriv- ylindole were isolated in moderate yields (21–61%).
ative 2k in a modest yield and in 70% enantiomeric Nevertheless, a beneficial substrate effect was appar-
excess (Table 2, entry 10). For all substrates investi- ent in the case of 2m as the observed enantiomeric
gated, carbocyclic compounds 2a–2n were formed in excess (91%) was some ten points higher than in the
>19:1 syn:anti diastereoselectivity.
case of 1a (Table 2, entry 7). Furthermore, product 2n
containing a quaternary carbon center was obtained
with 93% ee.
With the aim to get some clue into the exact nature
of the active species, the enyne 1a and 1-methylindole
have been reacted at a Pt/L5 ratio of 2 (Scheme 4).
Product 2a was obtained in 99% yield but in racemic
form. Inspired by the work of GagnØꢁs group on
asymmetric Pt-catalyzed bicyclopropane synthesis,[20]
we envisaged that a stereoselective tandem reaction
might be accomplished even by a combination of a
chiral and an achiral ligand. Indeed, a catalyst formed
from PtCl2 (5 mol%), dppe (diphenylphosphano-
ethane) (5 mol%), L5 (5 mol%) and AgSbF6 (12.5
mol%) lead to the formation of product 2a in 62%
yield and in 91% ee. Taken together, these last results
are in keeping with the involvement of L3Pt2+ species
in the catalytic process.
Scheme 3. Platinum-catalyzed asymmetric hydroarylation/cy-
cloisomerization reaction of sulfonated enynes.
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Enantioselective Platinum-Catalyzed Tandem Hydroarylation–Cycloisomerization
FULL PAPERS
Diisopropyl 2-(3-phenylprop-2-enyl)-2-(prop-2-ynyl)malo-
nate (1b): TLC (cyclohexane/ethyl acetate: 98/2): Rf =0.13;
1H NMR (300 MHz, CDCl3): d=1.24 (d, J=6.3 Hz, 6H),
1.25 (d, J=6.3 Hz, 6H), 2.04 (t, J=2.5 Hz, 1H), 2.82 (d, J=
2.6 Hz, 2H), 2.94 (dd, J=7.7, 0.9 Hz, 2H), 5.09 (hept, J=
6.3 Hz, 2H), 6.03 (dt, J=15.7, 7.8 Hz, 1H), 6.51 (d, J=
15.7 Hz, 1H), 7.20–7.34 (m, 5H); 13C NMR (75 MHz,
CDCl3): d=21.5, 21.6, 22.8, 35.6, 69.2, 71.4, 79.1, 123.4,
126.2, 127.4, 128.5, 134.4, 137.0, 169.2; CI-MS (NH3): m/z=
360 [M+NH4]+, 343 [M+H]+.
Dibenzyl
2-(3-phenylprop-2-enyl)-2-(prop-2-ynyl)malo-
nate (1c): TLC (cyclohexane/ethyl acetate: 90/10): Rf =0.46;
1H NMR (300 MHz, CDCl3): d=2.06 (t, J=2.7 Hz, 1H),
2.91 (d, J=2.7 Hz, 2H), 3.02 (d, J=7.8 Hz, 2H), 5.16 (d, J=
12.3 Hz, 2H), 5.19 (d, J=12.3 Hz, 2H), 5.92 (dt, J=15.6,
7.8 Hz, 1H), 6.46 (d, J=15.6 Hz, 1H), 7.21–7.35 (m, 15H);
13C NMR (75 MHz, CDCl3): d=22.9, 35.8, 57.3, 67.4, 71.8,
78.8, 122.9, 126.3, 127.5, 128.3, 128.4, 128.4, 128.5, 134.7,
135.2, 136.9, 169.4; CI-MS (NH3): m/z=456 [M+NH4]+, 439
[M+H]+.
Scheme 4. Pt-catalyzed arylation of enyne 1a.
Conclusions
Di(tert-butyl)
2-(3-phenylprop-2-enyl)-2-(prop-2-ynyl)-
In summary, we have extended the methodology de-
veloped for Au to Pt allowing the enantioselective in-
termolecular tandem hydroarylation/cycloisomeriza-
tion of 1,6-enynes with a variety of electron-rich aro-
matic and heteroaromatic nucleophiles under mild
conditions. The corresponding functionalized cyclic
derivatives were isolated in good to excellent yields
and up to 96% enantiomeric excesses were obtained.
We have also provided evidence that the catalytic spe-
cies responsible for the highest enantiomeric excesses
might reasonably be an L3Pt2+ species, L being a
malonate (1d): TLC (cyclohexane/ethyl acetate: 98/2): Rf =
0.21; H NMR (300 MHz, CDCl3): d=1.46 (s, 18H), 2.04 (t,
1
J=2.7 Hz, 1H), 2.74 (d, J=2.7 Hz, 2H), 2.87 (dd, J=7.6,
1.2 Hz, 2H), 6.04 (dt, J=15.7, 7.6 Hz, 1H), 6.51 (d, J=
15.7 Hz, 1H), 7.20–7.35 (m, 5H); 13C NMR (75 MHz,
CDCl3): d=22.8, 27.9, 35.6, 57.7, 71.2, 79.4, 81.8, 123.8,
126.2, 127.3, 128.5, 134.1, 137.2, 168.9; ESI-MS (NH3): m/z=
393 [M+Na]+.
Dimethyl 2-[3-(3’,4’-methylenedioxy)phenylprop-2-enyl]-
2-(prop-2-ynyl)malonate (1e): TLC (cyclohexane/ethyl ace-
1
tate: 80/20): Rf =0.41; H NMR (300 MHz, CDCl3): d=2.06
(t, J=2.7 Hz, 1H), 2.69 (d, J=2.6 Hz, 2H), 2.91 (dd, J=7.7,
1.0 Hz, 2H), 3.73 (s, 6H), 5.81 (dt, J=15.5, 7.7 Hz, 1H), 5.90
(m, 2H), 6.40 (d, J=15.5 Hz, 1H), 6.68–6.79 (m, 2H), 6.84
(s, 1H); 13C NMR (75 MHz, CDCl3): d=22.9, 35.8, 52.8,
57.2, 71.6, 78.8, 101.0, 105.6, 108.2, 120.8, 121.2, 131.5, 134.2,
147.2, 148.0, 170.1; ESI-MS (Na): m/z=353 [M+Na]+.
monoACHTREUNGdentate ligand. This process paves the way for
further applications in enantioselective tandem nucle-
ophile addition/cycloisomerization reactions. Current
efforts are focused on expanding the scope of this
methodology to other classes of substrates such as
1,5-enynes and to develop an enantioselective intra-
molecular version of the transformation.
Standard Catalytic Procedure
A mixture of PtCl2 (5 mol%) and (R)-BINEPINE[19a] (16
mol%) in degassed dioxane (0.5M) was stirred under an
argon atmosphere at 608C for 30 min. The formation of a
white precipitate was observed. The reaction mixture was
cooled down to room temperature and AgSbF6 (12.5 mol%)
was added. The reaction was stirred at room temperature
for 15 min. The aromatic nucleophile (3 equiv.) was then
added and the mixture was stirred for 3 min. The enyne
(1 equiv.) was finally added and the mixture was warmed to
608C and stirred until completion of the reaction monitored
by TLC. The mixture was filtered through a short pad of
silica (cyclohexane/EtOAc, 50/50) and the solvents were
evaporated under reduced pressure. The crude product was
purified by silica gel flash chromatography using eluent con-
ditions reported for TLC.
Experimental Section
General Remarks
PtCl2 was obtained from Johnson–Matthey. AgSbF6 was pur-
chased from Acros. All manipulations were carried out
1
under argon. H NMR and 13C NMR spectra were recorded
on a Bruker AV 300 instrument. All signals are expressed as
ppm (d) and internally referenced to residual protio solvent
signals. Coupling constants (J) are reported in Hz and refer
to apparent peak multiplicities. Mass spectrometric analyses
(direct introduction by chemical ionization with ammonia or
electrospray) were performed at the Ecole Nationale SupØr-
ieure de Chimie de Paris. High resolution mass spectra were
performed on a Varian MAT311 instrument at the Ecole
Normale SupØrieure (Paris). Enynes 1a, 1f and 1g were pre-
pared according to published procedures.[4b,5d] Enynes 1b, 1c,
1d and 1e were prepared in analogy with published proce-
dures.[7a]
Dimethyl 3-[1-(1-methyl-1H-indol-3-yl)-phenylmethyl]-4-
1
methylenecyclopentane-1,1-dicarboxylate (2a): H, 13C NMR
and mass spectroscopic data for compound 2a were identical
to literature values.[2] The product ratio was determined by
HPLC using a Chiralcel OD-H (hexane/2-propanol: 98/2,
1 mLminÀ1). The retention times for the two enantiomers
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Patrick Yves Toullec et al.
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were 21.7 and 24.9 min; [a]D À7.3 (CHCl3, c 0.45) at 95%
ee.
(m, 9H); 13C NMR (75 MHz, CDCl3): d=10.8, 29.5, 39.6,
41.8, 45.1, 48.2, 52.6, 52.7, 57.9, 108.7, 109.4, 113.7, 119.0,
119.4, 120.3, 125.7, 126.6, 128.1, 128.2, 133.1, 136.7, 145.0,
150.2, 172.2, 172.3; CI-MS (NH3): m/z=432 [M+H]+; HR-
MS: m/z=432.2177, calcd. for C27H30O4N: 432.2175. The
product ratio was determined by HPLC using a Chiralcel
AS-H (hexane/2-propanol: 98/2, 1 mLminÀ1). The retention
times for the two enantiomers were 12.3 and 14.7 min; [a]D:
À8.9 (CHCl3, c 1.02) at 89% ee.
Diisopropyl 3-[1-(1-methyl-1H-indol-3-yl)-phenylmethyl]-
4-methylenecyclopentane-1,1-dicarboxylate (2b): TLC (pe-
troleum ether/ethyl acetate: 95/5): Rf =0.13; 1H NMR
(300 MHz, CDCl3): d=1.21 (d, J=6.3 Hz, 3H), 1.17–1.23
(m, 9H), 1.94 (dd, J=13.6, 8.6 Hz, 1H), 2.73 (dd, J=13.6,
7.8 Hz, 1H), 2.87 (d, J=16.0 Hz, 1H), 3.11 (dq, J=15.9,
1.9 Hz, 1H), 3.50–3.58 (m, 1H), 3.76 (s, 3H), 4.12 (s, 1H),
4.16 (d, J=10.5 Hz, 1H), 4.78 (s, 1H), 4.97 (hept, J=6.3 Hz,
1H), 5.06 (hept, J=6.3 Hz, 1H), 7.00–7.35 (m, 8H), 7.56 (d,
J=8.0 Hz, 1H); 13C NMR (75 MHz, CDCl3): d=21.5, 32.7,
39.7, 41.7, 46.9, 48.0, 58.5, 68.7, 68.9, 109.1, 109.6, 117.3,
118.8, 119.5, 121.5, 125.9, 126.2, 127.6, 128.0, 128.4, 136.9,
144.7, 149.4, 171.2, 171.4; CI-MS (NH3): m/z=474 [M+H]+;
HR-MS (CI-CH4): m/z=474.2633, calcd. for C30H36O4N:
474.2644. The product ratio was determined by HPLC using
a Chiralcel AD-H (hexane/2-propanol: 98/2, 1 mLminÀ1).
The retention times for the two enantiomers were 10.6 and
11.2 min; [a]D: À9.7 (CHCl3, c 0.48) at 82% ee.
Dimethyl 3-[1-(1-methyl-2-phenyl-1H-indol-3-yl)-phenyl-
methyl]-4-methylenecyclopentane-1,1-dicarboxylate
(2f):
1
TLC (cyclohexane/ethyl acetate: 80/20): Rf =0.45; H NMR
(300 MHz, CDCl3): d=1.90 (dd, J=13.8, 9.3 Hz, 1H), 2.57
(dd, J=13.8, 9.3 Hz, 1H), 2.99 (s, 2H), 3.49 (s, 3H), 3.68 (s,
3H), 3.76 (s, 3H), 3.90–4.00 (m, 1H), 4.12 (s, 1H), 4.72 (s,
1H), 7.05–7.97 (m, 14H); 13C NMR (75 MHz, CDCl3): d=
30.7, 40.0, 41.7, 45.0, 48.1, 52.6, 52.7, 57.9, 109.3, 109.4, 115.4,
119.5, 120.5, 121.4, 125.7, 126.3, 127.9, 128.2, 128.4, 131.2,
132.2, 137.2, 138.5, 144.9, 149.8, 172.2, 172.3; CI-MS (NH3):
m/z=494 [M+H]+; HR-MS: m/z=494.2327, calcd. for
C32H32O4N: 494.2331. The product ratio was determined by
HPLC using a Chiralcel OD-H (hexane/2-propanol: 99/1,
1 mLminÀ1). The retention times for the two enantiomers
were 10.4 and 11.7 min; [a]D: +35.0 (CHCl3, c 0.68) at 74%
ee.
Dibenzyl 3-[1-(1-methyl-1H-indol-3-yl)-phenylmethyl]-4-
methylenecyclopentane-1,1-dicarboxylate (2c): TLC (petro-
leum ether/ethyl acetate: 95/5): Rf =0.08; 1H NMR
(300 MHz, CDCl3): d=2.03 (dd, J=13.2, 8.0 Hz, 1H), 2.78
(dd, J=13.6, 7.9 Hz, 1H), 2.95 (d, J=15.8 Hz, 1H), 3.16 (dd,
J=16.0, 1.9 Hz, 1H), 3.48–3.57 (m, 1H), 3.72 (s, 3H), 4.14–
4.17 (m, 2H), 4.78 (s, 1H), 4.99 (d, J=12.3 Hz, 1H), 5.10 (d,
J=12.3 Hz, 1H), 5.12 (s, 2H), 6.94 (s, 1H), 7.01–7.32 (m,
13H), 7.53 (d, J=7.9 Hz, 1H); 13C NMR (75 MHz, CDCl3):
d=32.7, 39.8, 41.8, 47.9, 58.6, 67.2, 109.1, 110.0, 117.1, 118.9,
119.4, 121.5, 126.0, 126.1, 127.6, 127.9, 128.0, 128.1, 128.2,
128.4, 135.4, 135.5, 136.9, 144.6, 148.9, 171.4, 171.5; CI-MS
(NH3): m/z=587 [M+NH4]+, 570 [M+H]+; HR-MS (CI-
CH4): m/z=570.2645, calcd. for C38H36O4N: 570.2644. The
product ratio was determined by HPLC using a Chiralcel
OD-H (hexane/2-propanol: 98/2, 1 mLminÀ1). The retention
times for the two enantiomers were 36.4 and 53.9 min; [a]D:
À3.2 (CHCl3, c 0.50) at 83% ee.
Dimethyl 3-[1-(1-methyl-5-methoxy-1H-indol-3-yl)-phe-
nylmethyl]-4-methylenecyclopentane-1,1-dicarboxylate (2g):
1
TLC (cyclohexane/ethyl acetate: 80/20): Rf =0.27; H NMR
(300 MHz, CDCl3): d =1.88 (dd, J=13.6, 8.5 Hz, 1H), 2.68
(ddd, J=13.6, 7.9, 1.5 Hz, 1H), 2.80 (dd, J=15.8, 1.0 Hz,
1H), 3.03 (dq, J=15.8, 2.5 Hz, 1H), 3.36–3.43 (m, 1H), 3.56
(s, 3H), 3.64 (s, 6H), 3.72 (s, 3H), 3.99 (d, J=10.3 Hz, 1H),
4.03 (s, 1H), 4.71 (s, 1H), 6.75 (dd, J=8.9, 2.3 Hz, 1H),
6.87–6.89 (m, 2H), 7.00–7.25 (m, 6H); 13C NMR (75 MHz,
CDCl3): d=32.9, 39.9, 41.8, 46.8, 48.1, 52.6, 52.7, 55.9, 58.4,
101.6, 109.8, 109.9, 111.6, 116.6, 126.0, 126.8, 127.9, 128.1,
128.4, 132.3, 144.6, 149.0, 153.6, 172.1, 172.3; CI-MS (NH3):
m/z=448 [M+H]+; HR-MS (CI-NH3): m/z=448.2133,
calcd. for C27H30O5N [M+H]+: 448.2124. The product ratio
was determined by HPLC using a Chiralcel AD-H (hexane/
2-propanol: 90/10, 1 mLminÀ1). The retention times for the
two enantiomers were 12.5 and 14.6 min; [a]D: À19.5
(CHCl3, c 0.48) at 87% ee.
Di-tert-butyl 3-[1-(1-methyl-1H-indol-3-yl)-phenylmeth-
yl]-4-methylenecyclopentane-1,1-dicarboxylate (2d): TLC
(petroleum ether/ethyl acetate: 95/5): Rf =0.25; 1H NMR
(300 MHz, CDCl3): d=1. 29 (s, 9H), 1.35 (s, 9H), 1.76 (dd,
J=13.6, 8.7 Hz, 1H), 2.55 (ddd, J=13.6, 7.9, 1.5 Hz, 1H),
2.68 (dd, J=15.6, 1.3 Hz, 1H), 2.92 (dq, J=15.8, 2.5 Hz,
1H), 3.37–3.46 (m, 1H), 3.65 (s, 3H), 3.98 (s, 1H), 4.04 (d,
J=10.4 Hz, 1H), 4.66 (s, 1H), 6.89–7.15 (m, 7H), 7.21–7.25
(m, 2H), 7.44 (d, J=7.9 Hz, 1H); 13C NMR (75 MHz,
CDCl3): d=27.9, 32.7, 39.7, 41.8, 46.7, 48.2, 59.7, 81.0, 81.3,
109.0, 109.4, 117.3, 118.7, 119.6, 121.4, 125.9, 126.2, 127.7,
128.0, 128.5, 137.0, 144.8, 149.6, 171.0, 171.2; CI-MS (NH3):
m/z=502 [M+H]+, 446 [MÀC4H8 +H]+: HR-MS (CI-CH4):
m/z=501.2871, calcd. for C32H39O4N: 501.2879. The product
ratio was determined by HPLC using a Chiralcel OD-H
(hexane/2-propanol: 99/1, 1 mLminÀ1). The retention times
for the two enantiomers were 10.0 and 11.7 min; [a]D: À14.8
(CHCl3, c 0.54) at 80% ee.
Dimethyl
3-[1-(2,4-dimethoxyphenyl)-phenylmethyl]-4-
methylenecyclopentane-1,1-dicarboxylate (2h): H, 13C NMR
and mass spectroscopy data for compound 2h were identical
to literature values.[2] The product ratio was determined by
HPLC using a Chiralcel AS-H (hexane/2-propanol: 98/2,
1 mLminÀ1). The retention times for the two enantiomers
were 11.1 and 12.6 min; [a]D: +26.6 (CHCl3, c 1.58) at 80%
ee.
1
Dimethyl 3-[1-(2,4,6-trimethoxyphenyl)-phenylmethyl]-4-
1
methylenecyclopentane-1,1-dicarboxylate (2i): H, 13C NMR
and mass spectroscopy data for compound 2i were identical
to literature values.[2] Product ratio was determined by
HPLC using a Chiralcel AS-H (hexane/2-propanol: 98/2,
1 mLminÀ1). The retention times for the two enantiomers
were 11.8 and 12.8 min; [a]D: + 92.1 (CHCl3, c 2.9) at 77%
ee.
Dimethyl 3-[1-(1-methyl-1H-indol-3-yl)-(3,4-methylene-
dioxy)phenylmethyl]-4-methylenecyclopentane-1,1-dicarbox-
ylate (2j): TLC (cyclohexane/ethyl acetate: 80/20): Rf =0.35;
Dimethyl 3-[1-(1-methyl-2-methyl-1H-indol-3-yl)-phenyl-
methyl]-4-methylenecyclopentane-1,1-dicarboxylate
(2e):
1
TLC (cyclohexane/ethyl acetate: 80/20): Rf =0.50; H NMR
(300 MHz, CDCl3): d=1.70–1.90 (m, 1H), 2.45 (s, 3H),
2.50–2.60 (m, 1H), 3.62 (s, 3H), 3.65 (s, 3H), 3.75 (s, 3H),
3.80–4.20 (m, 2H), 4.30 (br s, 1H), 4.70 (br s, 1H), 6.90–7.80
2406
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Enantioselective Platinum-Catalyzed Tandem Hydroarylation–Cycloisomerization
FULL PAPERS
1H NMR (300 MHz, CDCl3): d=1.92 (dd, J=13.6, 8.4 Hz,
1H), 2.75 (dd, J=13.7, 7.9 Hz, 1H), 2.88 (d, J=14.9 Hz,
1H), 3.12 (d, J=15.9 Hz, 1H), 3.39–3.47 (m, 1H), 3.63 (s,
3H), 3.70 (s, 3H), 3.73 (s, 3H), 4.05 (d, J=10.5 Hz, 1H),
4.21 (s, 1H), 4.83 (s, 1H), 5.86 (d, J=5.9 Hz, 1H), 6.67 (d,
J=8.4 Hz, 1H), 7.79 (d, J=6.4 Hz, 1H), 6.99 (s, 1H), 7.04
(t, J=7.8 Hz, 1H), 7.18 (t, J=8.0 Hz, 1H), 7.25 (d, J=
5.8 Hz, 1H), 7.52 (d, J=7.9 Hz, 1H); 13C NMR (75 MHz,
CDCl3): d=32.8, 40.0, 41.7, 47.0, 47.8, 52.6, 52.7, 58.4, 100.7,
107.7, 108.7, 109.1, 110.1, 117.2, 118.9, 119.4, 120.9, 121.5,
121.6, 126.0, 127.5, 136.9, 138.7, 145.6, 147.4, 148.8, 172.1,
172.3. CI-MS (NH3): m/z=462 [M+H]+; HR-MS (CI-NH3):
m/z=462.1932, calcd. for C27H28O6N: 462.1917. The product
ratio was determined by HPLC using a Chiralcel OD-H
(hexane/2-propanol: 90/10, 1 mLminÀ1). The retention times
for the two enantiomers were 14.6 and 18.1 min; [a]D: À7.6
(CHCl3, c 1.44) at 79% ee.
to the Minist›re de l’Education et de la Recherche for finan-
cial support. Johnson-Matthey is acknowledged for a gener-
ous loan of PtCl2. The authors also thank Professor T. Haya-
shi for a generous gift of the MeO-MOP ligand L4.
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8.7 Hz, 1H), 2.63 (dd, J=15.7, 8.7 Hz, 1H), 3.07 (d, J=
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were 41.7 and 49.1 min; [a]D: +75.0 (CHCl3, c 0.42) at 91%
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1 mLminÀ1). The retention times for the two enantiomers
were 30.6 and 36.6 min; [a]D: +6.9 (CHCl3, c 0.89) at 49% ee.
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Acknowledgements
This work was supported by the Centre National de la Re-
cherche Scientifique (CNRS). Q. C. and C.-M. C. are grateful
Adv. Synth. Catal. 2008, 350, 2401 – 2408
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
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Patrick Yves Toullec et al.
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Adv. Synth. Catal. 2008, 350, 2401 – 2408