Cyclometalated N-heterocyclic carbene-platinum catalysts for the enantioselective cycloisomerization of nitrogen-tethered 1,6-enynes

Article abstract of DOI:10.1002/adsc.201000904

Platinum(II) complexes which combine six-membered N-heterocyclic carbene-containing metallacyclic units and monodentate chiral phosphines have been prepared. The key step of their synthesis is the intramolecular oxidative addition of N-2-iodobenzylimidazo

Full text of DOI:10.1002/adsc.201000904

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DOI: 10.1002/adsc.201000904
Cyclometalated N-Heterocyclic Carbene-Platinum Catalysts for
the Enantioselective Cycloisomerization of Nitrogen-Tethered
1,6-Enynes
Hꢀlꢁne Jullien,a Delphine Brissy,a Rꢀmy Sylvain,a Pascal Retailleau,a
Jean-Valꢁre Naubron,b Serafino Gladiali,c and Angela Marinettia,*
a
Institut de Chimie des Substances Naturelles, CNRS UPR 2301, 1 av. de la Terrasse, 91198 Gif-sur-Yvette Cedex, France
Fax : (+33)-01-6907-7247; phone: (+33)-01-6982-3036; e-mail: angela.marinetti@icsn.cnrs-gif.fr
ISM2, Universitꢀ Paul Cezanne Aix-Marseille III, av. Escadrille Normandie-Niemen, 13397 Marseille Cedex 20, France
Dipartimento di Chimica, Universitꢂ di Sassari, via Vienna 2, 07100 Sassari, Italy
b
c
Received: November 30, 2010; Revised: February 10, 2011; Published online: May 3, 2011
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.201000904.
Abstract: Platinum(II) complexes which combine configuration of the final 3-azabicycloACTHUNTGRNEUNG[4.1.0.]heptenes
six-membered N-heterocyclic carbene-containing has been established by X-ray diffraction studies.
metallacyclic units and monodentate chiral phos- The method has been extended then to the cycloiso-
phines have been prepared. The key step of their merization of dienynes with enantiotopic vinyl
synthesis is the intramolecular oxidative addition groups. An (S)-phenyl-Binepine-platinum(II) com-
of N-2-iodobenzylimidazolylidene-platinum(0)-diene plex allows total diastereoselectivity and high enan-
complexes in the presence of the chiral phosphorus tioselectivity levels to be attained in these reactions
ligands. The platinum(II) metallacycles have been (ees up to 95%) which represent the first enantiose-
used as well-defined pre-catalysts for the enantiose- lective desymetrizations achieved via enyne cycloiso-
lective cycloisomerization of nitrogen-tethered 1,6- merizations.
enynes into 3-azabicycloACTHNUTRGENUGN[4.1.0]hept-4-enes. High
enantiomeric excesses have been obtained with
either Monophos or phenyl-Binepine based catalysts Keywords: chiral phosphines; enantioselective de-
(ees=82–96%), although phenyl-Binepine outper- symmetrization; enyne cycloisomerization; N-hetero-
forms Monophos in these reactions. The absolute cyclic carbenes; platinacycles
Introduction
chiral catalysts. Altough high enantioselectivity is reg-
ularly attained, the restricted substrate scope and
Enyne cycloisomerizations under transition metal cat- overall moderate efficiency fully motivate the search
alysis have attracted considerable attention in recent for new and efficient catalytic systems. In this context,
years since they represent powerful synthetic tools for we have disclosed recently Pt(II) complexes of the
the construction of cyclic and heterocyclic moieties.[1] general formulae I[10] and II[11] as the first promising
Except for palladium- or rhodium-promoted Alder- platinum-based chiral pre-catalysts for the cycloiso-
ene-type cyclizations,[2] asymmetric variants of these merization of 1,6-enynes bearing N-containing tethers
reactions are, however, comparatively underdevel- (Figure 1).
oped.[3] This is the case also for the cycloisomeriza-
tions of 1,6-enynes into bicyclo
Following on from our preliminary communication,
AHCTUNGERTG[NNUN 4.1.0]heptenes which we report here a more detailed account of the design
are specifically targeted in this paper. They have been and structural tuning of the platinacyclic complexes
shown to proceed in the presence of various Pt(II),[4] II, as well as a comparison of the catalytic properties
Ir(I),[5] Rh(II)[6] and Au(I)[7] achiral pre-catalysts, of Binepine and Monophos containing pre-catalysts
while a very restricted range of enantioselective pro- II. Finally, an extension of the cycloisomerization re-
cesses have been reported to date. Enantioselective actions to nitrogen-tethered dienynes is disclosed.
variants make use of Ir/TolBinap,[5a] Au/MeO-
BIPHEP[8] and Rh/chiral diene[9] complexes as the
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where the “bidentate phosphine/monodentate NHC”
ligand pair of complexes I would be replaced by a
“bidentate NHC/monodentate phosphine” pair. At
this point, the specific design of the metallacyclic
structures II was inspired by the synthetic approach
used to access complexes I, that is a two-step se-
quence which involves oxidative addition of I2 to a
Pt(0)-NHC complex as the key step (Figure 2).[10]
We reasoned that the same oxidative addition/
ligand exchange sequence might be easily adapted to
the synthesis of platinacyclic derivatives by taking ad-
vantage of an intramolecular oxidative addition step.
The metallacyclic unit will be combined then with a
monodentate phosphorus ligand to complete the coor-
dination sphere of platinum. With this in mind, we
targeted Pt(0) complexes bearing N-2-iodobenzylimi-
dazolylidene ligands (e.g., 2a in Scheme 1) as suitable
intermediates, prone to intramolecular oxidative addi-
tion through their aryl iodide function. In Scheme 1
hereafter, the preparation of complexes 3–5 typifies
our synthetic strategy.
Figure 1. Platinum pre-catalysts for the enantioselective cy-
cloisomerizations of N-tethered 1,6-enynes.
Results and Discussion
Catalysts Design and Optimization
Our design of the platinacyclic complexes I and II as
Complex 2a has been prepared by reacting the N-
potential pre-catalysts was based initially on a simple (2-iodobenzyl)imidazolium salt 1a[14] with a xylene so-
mechanistical hypothesis and a few literature data lution of the so-called Karstedtꢄs catalyst, Pt2ACTHNUTRGNEN(UG dvtms)3
showing that platinum catalysts can operate as simple (dvtms=divinyltetramethyldisiloxane), in the pres-
Lewis acids in some cycloisomerization proces- ence of t-BuOK as the deprotonating agent.[15] The
ACHTUNGTRENNUNG
ses.[1a,4c,12] It was anticipated, therefore, that 16-elec- Pt(0) complex 2a was isolated in 68% yield after
tron, tricoordinated platinum(II) complexes with a chromatography. The intramolecular oxidative addi-
single free coordination site will promote cycloisome- tion reaction and the ligand exchange processes have
rization reactions of this class. The concept has been been performed then in a single step by heating 2a in
demonstrated initially by Gagnꢀ who carried out the presence of the well known chiral monodentate
diene cycloisomerizations by means of cationic plati- phosphines (R)-MOP, (S)-Ph-Binepine[16] and (R)-
num complexes containing either a tridentate phos- Monophos.
phorus ligand or a bidentate phosphine/monodentate
These experiments led to isolation of the desired
metallacyclic compounds 3–5 in moderate to good
phosphine pair.[13]
Shortly after, our group disclosed that the Pt(II) yields after purification by column chromatography.
complexes I displaying a bidentate phosphine and an Crystals suitable for X-ray diffraction studies could be
NHC ligand (NHC=N-heterocyclic carbene), togeth- obtained for 4a and 5a by crystallization from toluene
er with a labile iodide ligand, afford suitable pre-cata- solutions. X-ray data for the Ph-Binepine complex 5a
lysts for the cycloisomerization of nitrogen-tethered have been reported in our previous communication,
1,6-enynes (Figure 1).[10] Enantioselective processes showing that the phosphorus ligand lies trans to the
could be established by using (S,S)-Chiraphos as the NHC unit. The solid state structure of the MonoPhos
chiral bidentate ligand, giving ees up to 74% in a complex 4a is shown in Figure 3 hereafter. Overall, it
model cycloisomerization reaction.
displays the same geometric features as 5a: a square
These encouraging results led us to consider then planar coordination of platinum, with the phosphorus
an analogous series of tricoordinated Pt(II) complexes ligand trans to the carbene moiety. The planar NHC
Figure 2. Synthetic approach to the ꢅfirst generationꢄ 1,6-enynes cycloisomerization pre-catalysts, I.
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Cyclometalated N-Heterocyclic Carbene-Platinum Catalysts for the Enantioselective Cycloisomerization
Figure 3. X-ray crystal structure for the (R)-MonoPhos com-
À
plex (R,Sa)-4a. Selected bond distances (ꢇ): Pt I=2.695(1),
À
À
À
Pt P=2.261(2),
Pt C(1)=2.012(8),
Pt C(8)=2.00(1),
À
À
C(8) N(1)=1.35(1), C(8) N(2)=1.38(2). Selected bond
À À
À À
angles (deg): C(1) Pt C(8)=84.0(4), C(8) Pt I=92.8(3),
À À
À À
À
À
I Pt P=91.89(6), P Pt C(1)=91.2(2), N1 C(8) N(2)=
104.3(9).
According to our initial target, complexes 3–5 have
been evaluated as pre-catalysts for the cycloisomeri-
zation of the N-allyl-N-3-phenylprop-2-ynylsulfona-
mide 6a (Scheme 2). The reaction had been intro-
duced by Fꢆrstner et al. who demonstrated that the
bicyclic sulfonamide 7a is produced under PtCl2 cata-
lysis.[4b,c]
Starting from complexes 3–5, the catalytically
active species are formed by addition of AgBF4 as the
iodide trapping agent. Abstraction of the iodide
ligand generates formally three-coordinated com-
plexes which might adopt either a T-shaped[20] or a Y-
shaped[21] arrangement. These three-coordinated com-
plexes are anticipated to be either achiral (Y-shaped)
or configurationally unstable (T-shaped) with respect
Scheme 1. Synthesis and 31P NMR data for the platinacyclic
complexes 3–5.
ligand forms a dihedral angle of 29.28 with the coordi- to the above-mentioned axial chirality.[10b] Therefore,
nation plane of platinum. the diastereomeric mixtures of complexes 3–5 can be
The boat-shaped platinacyclic moiety differentiates used as pre-catalysts, without foreseeable drawbacks
the upper and bottom faces of the square planar com- in terms of chiral induction.
plex which displays therefore a chiral core struc-
In standard conditions, complexes 3–5 displayed
ture.[17,18] Axially chiral square planar NHC complexes moderate to good catalytic activity, leading to the ex-
have been shown to be usually configurationally pected bicyclic sulfonamide 7a in 40–93% isolated
stable.[19] Thus, complexes 3–5 which combine axial yields.
chirality and a chiral phosphorus ligand, are expected
From this initial screening, the (S)-Ph-Binepine
to form diastereomeric pairs. Complexes 3–5 were complex 5a has emerged as the most efficient catalyst
indeed obtained as mixtures of two isomers (isomers
ratios: 3, 55:45; 4a, 75:25; 5a, 80:20). The minor iso-
mers have not been unambiguously characterized,
nevertheless 31P NMR data strongly support a trans
relative coordination of the phosphorus and NHC li-
gands, since chemical shifts and P-Pt coupling con-
stants are of the same order of magnitude as for the
major isomer. Therefore the two observed isomers
have been tentatively assigned as diastereomeric com-
plexes with opposite axial configurations.
Scheme 2. Screening of complexes 3–5 as pre-catalysts for a
model cycloisomerization reaction.
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Table 1. Platinum-promoted enantioselective cycloisomerizations of nitrogen-tethered 1,6-enynes.
Entry
Substrate
ArSO2
Prod.
G
Yield [%]
ee[b] [%]
A
Yield [%]
ee[b] [%]
R
R1
1
2
3
4
5
6
7
8
6a
6a
6b
6c
6d
6e
6f
6g
Ts
H
H
H
H
H
Me
H
Ph
Ph
7a
7a
7b
7c
7d
7e
7f
7g
5a
5c
5a
5b
5c
5c
5c
5a
88
90
95
77
51
98
98
71
93[a]
96[a]
90[a]
91[a]
97[a]
88[a]
94
4a
4a
93
88
75
84
Ts
Ts
Ts
Ts
Ts
Ns
Ts
3,5-(Me2)C6H3
4-MeO-C6H4
4-NO2-C6H4
Ph
Ph
Me
4a
77
25
Me
19
[a]
From ref.[11]
[b]
Enantiomeric excesses have been measured by chiral HPLC.
giving a good conversion rate and high enantioselec- reactions promoted by the (R)-MonoPHOS based cat-
tivity level (93% enantiomeric excess). The MOP alyst 4a are also mentioned in this table.
complex 3 gave a racemic product, while the Mono-
Complexes 5a–c efficiently promote the enantiose-
phos complex 4a gave a significant, 75% enantiomeric lective cycloisomerization of allyl propargyl tosyla-
excess and a higher conversion rate than the Binepine mides, with various aryl groups on the alkyne moiety,
complex 5a.
into the corresponding bicycloACTHUNGETRNNU[G 4.1.0]heptenes. Enan-
To the best of our knowledge, these are the first tiomeric excesses in the range 91–96% are obtained
known Pt-based catalysts for the enantioselective cy- for the reactions in entries 1–5. As shown in entry 6,
cloisomerization of 1,6-enynes. Moreover, only a very the presence of a methyl substituent on the allylic
few examples have been reported so far of analogous function is tolerated, since the cycloisomerization of
cycloisomerizations of N-tethered enynes by using 7e (R=Me, R1 =Ph) takes place with high yield and
other transition metal catalyts. These reactions have an enantiomeric excess of 88%. A dramatic decrease
been carried out notably by means of Ir-TolBinap of the enantioselectivity was observed, however, in
complexes, giving enantiomeric excesses in the range the cycloisomerization of substrate 6g where the
35–78%.[5a] More recently, chiral gold-diphosphine[8] alkyne aryl group has been replaced by a methyl
and rhodium-diene[9] complexes have been applied group (entry 8). The nitrogen tosyl substituent can be
succesfully to these cycloisomerizations, on a rather suitably replaced by a nosyl group (entry 7) while re-
restricted range of substrates (1 example, 98% ee and taining high levels of chiral induction (94% ee,
7 examples, 68–95% ee, respectively).
entry 7). Noteworthy, we have also ascertained that
The encouraging results obtained with 5a the nosyl group can be removed from the final bicy-
(Scheme 2) led us to expand the family of Ph-Bine- clic product. The nitrogen-deprotection procedure,
pine-based catalysts to the platinacyclic complexes 5b which involves reaction of the N-nosyl substituted bi-
and 5c which display an ethyl and a benzyl substituent cyclic derivative with PhSH/K2CO3 in MeCN,[22, 23] sig-
on the carbene nitrogen atom, respectively. The nificantly expands the synthetic utility of the enantio-
nature of the nitrogen substituent was indeed expect- selective cycloisomerizations mentioned above.
ed to modulate the enantioselectivity levels by steric
In addition to the high efficiency of the Ph-Bine-
effects. With these three catalysts in hand, the scope pine complexes 5, the preliminary experiments in
of the enantioselective cycloisomerization reaction Table 1 (right columns) also highlight MonoPhos as a
was established by considering various enyne sub- promising chiral ligand for cycloisomerization reac-
strates, as reported in our previous communication.[11] tions of this class. The Monophos complex 4a indeed
Selected results are recalled in Table 1. For compari- combines significant enantioselectivity levels (ees of
son purposes, a few examples of cycloisomerization 75% and 84% in the cycloisomerizations of the prop-
argyl allyl amides 6a and 6b in entries 1 and 3, respec-
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Cyclometalated N-Heterocyclic Carbene-Platinum Catalysts for the Enantioselective Cycloisomerization
tively) and high catalytic activity. Moreover, the easy
availability of the chiral auxiliary also represents a
major practical advantage. This led us to investigate
in more detail possible strategies for the optimization
of the chiral induction from MonoPhos-based cata-
lysts: (i) optimization of the reaction conditions; (ii)
modulation of the carbene N and aryl substituents;
(iii) addition of a stereogenic centre in the metallacy-
clic scaffold. The main results are reported hereafter.
Firstly, the high catalytic efficiency of the Mono-
phos complex 4a allowed us to perform the cycloiso-
merization reaction of entry 1 (Table 1, right columns)
in milder conditions. The reaction temperature was
lowered, with respect to the initially applied 608C:
conversion rates >95% and of ~50% were observed
after 18 h at 408C and room temperature, respective-
ly. Unexpectedly, however, lowering of the reaction
temperature did not result in increased enantioselec-
tivity. A slight decrease of the ee was observed for re-
actions run at room temperature (64% ee), while the
ee is roughly constant at 75% for reaction tempera-
tures between 508C and 908C. In this respect, the be-
Scheme 3. Synthesis of the platinacyclic (R)-Monophos com-
plexes 4b–e.
haviour of the Pt-MonoPhos catalyst 4a markedly
contrasts with that of the Binepine complex 5a which
gives higher enantiomeric excesses at lower reaction
temperature (82% ee at 908C vs. 93% ee at 608C).
Secondly, we thought that a major drawback of
complex 4a, when used in enantioselective catalysis,
might be the unhindered rotation of the monodentate
À
chiral phosphine around the Pt P bond. We therefore
considered the use of Monophos-platinacyclic com-
plexes with increased steric constraints and conse-
quently reduced conformational flexibility. Bulkier
substituents have been introduced either on the car-
bene nitrogen atom (complexes 4b–d) or on the aryl
moiety of the platinacyclic unit (complex 4e).
Complexes 4b–d bearing ethyl, benzyl and tert-
butyl substituents on the nitrogen atom have been
prepared as shown in Eq. (4) (Scheme 3) from the
corresponding Pt(0)-NHC complexes 2b–d.
The N-Et, N-benzyl and N-tert-butyl substituted
complexes 4b–d were formed as 75:25, 80:20 and
77:23 mixtures of diastereomers, respectively. Crystals
suitable for X-ray diffraction studies have been ob-
tained for 4d. An ORTEP drawing, selected bond
angles and distances are given in Figure 4. The isolat-
ed crystalline complex 4d displays an opposite axial
configuration of the platinum core, with respect to
complex 4a above.[24]
Figure 4. ORTEP drawing for the MonoPhos complex
(R,Sa)-4d. Selected bond distances (ꢇ): Pt I=2.7043(7), Pt
À
À
À
À
À
P=2.233(2), Pt C(1)=2.002(8), Pt C(8)=2.047(7), C(8)
N(2)=1.329(9), C(8) N(2)=1.368(9). Selected bond angles
À
À À
À À
À À
(deg): C(1) Pt C(8)=83.7(3), C(8) Pt I=91.8(2), I Pt
À À
À
À
P=88.81(5), P Pt C(1)=95.2(2), N1 C(8) N(2)=105.1(6).
As shown in Scheme 3 above, we have prepared
also the Monophos complex 4e, which displays an in-
creased steric hindrance of the platinacyclic aryl heating of a 1:1 mixture of 2e and (R)-Monophos in
À
moiety, due to the t-Bu group, meta to the Pt C bond. THF at 608C converts the Pt(0) complex 2e into the
The synthesis of 4e starts from the 4-tert-butyl-2-iodo- platinacyclic derivative 4e which was isolated as a
benzylimidazolium salt 1e and involves generation of >95:5 mixture of isomers (Scheme 3).
the N-heterocyclic carbene in the presence of Pt2
It should be mentioned here that the attempted
ACHTUNGTRENNUNG
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From these experiments it appears that complexes
4 with nitrogen substituents of moderate steric hin-
drance afford significant levels of enantioselectivity,
with ees peaking at 78% for 4c (R2 =CH2Ph). The
pre-catalyst 4d (R2 =t-Bu), which displays high steric
hindrance at the imidazole nitrogen, retains a high
level of catalytic activity, it induces however a dra-
matic decrease of the enantiomeric excess (10% ee vs.
75% ee for 4a, R2 =Me). On the other hand, complex
4e, which displays a t-Bu substituted aryl moiety,
gives both a good yield (97%) and a slightly improved
enantiomeric excess (78% ee), with respect to the ref-
erence catalyst 4a. Although only moderate improve-
ments of the enantioselectivity levels have been ob-
tained so far, the above results demonstrate that mod-
ulation of both the aryl moiety and the nitrogen sub-
stituent have an effect on the catalytic properties of
these Monophos complexes.
Scheme 4. Screening of the (R)-MonoPhos based cataysts 4
in the enantioselective cycloisomerization of the model allyl-
propargylic amine 6a (Scheme 2).
Thirdly and finally we envisioned the synthesis of
the platinum complexes 4f and 4g (Scheme 5) display-
ing an additional stereogenic centre, with defined ste-
reochemistry, at the platinacyclic units. Our aim was
from
platinum(0)
to the excessive steric hindrance which prevents the with appropriate relative configurations.
a
(3-methyl-2-iodobenzyl imidazolylidene)- to highlight a cooperative effect between the chiral
ACHTUNGTRENNUNG
oxidative addition reaction to take place.
The Pt(0) complex (S)-2f was prepared from the
The new Monophos complexes 4 have been evalu- corresponding chiral imidazolium salt (S)-1f and
ated in the model cycloisomerization of enyne 6a, in Pt2ACHTUNRTGNEUNG(dvtms)3, according to the general procedure. It
standard conditions (4 mol% pre-catalyst, excess was reacted then with Monophos ligands of opposite
AgBF4, in toluene at 608C). Results are reported in absolute configurations in the usual conditions
Scheme 4.
(Scheme 5).
Scheme 5. Synthesis of the Monophos complexes 4f and 4g displaying a stereogenic carbon centre in the platinacyclic unit.
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Cyclometalated N-Heterocyclic Carbene-Platinum Catalysts for the Enantioselective Cycloisomerization
The (R)-Monophos complex (R,SC)-4f was isolated points out some simple structural units that can be
as
a
92:8 mixture of diastereomers [31P NMR modulated to improve the catalytic properties of the
(CDCl3): broad signal at d=131 (JP,Pt =4536 Hz) for Monophos platinacyclic complexes. Therefore, we
the major isomer], while a 7:3 mixture of the diaste- consider Monophos complexes as undoubtedly prom-
reomeric complexes (S,SC)-4g was obtained from (S)- ising catalysts and their use in the cycloisomerization
Monophos [Major isomer: 31P NMR (CDCl3): d=129 of other enynes is currently being investigated.
(JP,.Pt =4600 Hz); minor isomer: 31P NMR (CDCl3):
d=131, broad signal]. Complexes 4f and 4g have
been evaluated as catalysts in the model cycloisomeri- Assignment of the Absolute Configuration of the
zation reaction of Eq. (3).
Cycloisomerization Products
To the best of our knowledge, the absolute configura-
tion of the bicyclic N-tosylamines 7 is unknown so far.
Therefore, in order to establish the sense of chiral in-
duction from the chiral platinacyclic catalysts, we
have considered using X-ray diffraction studies and
vibrational circular dichroism (VCD) for their config-
Scheme 6. Catalytic cycloisomerizations promoted by com-
plexes 4f and 4g.
urational assignment. The 6-azabicycloACTHNUGRTENUNG[4.1.0]heptene
7h, which contains a 1-phenylethoxy unit of known S-
configuration, has been prepared by cycloisomeriza-
Both catalysts gave high conversion rates, 95% and tion of (S)-6h in the presence of the platinum catalyst
98% yields being obtained with 4f and 4g, respective- 5c (Scheme 7).
ly. The (R,SC)-complex 4f gave the same enantiomeric
The reaction takes place with good yields and dia-
excess as the ꢅparentꢄ complex 4a (75% ee), while stereoselectivity (90:10 isomers ratio) affording 7h as
complex (S,SC)-4g enabled the enantiomeric excess to a crystalline compound. The ORTEP drawing for the
be increased to 82%. The (SC)-platinacycle/(S)-Mono- major diastereoisomer is depicted in Figure 5. Com-
phos pair thus represents the matching pair for this pound 7h displays a (1R,6S) configuration of the bicy-
cycloisomerization process. It provides so far the most clic moiety.
efficient Monophos-based catalyst for the enantiose-
lective cycloisomerization reaction of Eq. (3) tion from complexes 5, the absolute configuration of
(Scheme 6) (98% yield, 82% ee). the major enantiomer of 7a (96% ee, from entry 2 in
As a further evidence for the sense of chiral induc-
On the whole, the Monophos-based platinum cata- Table 1) has also been assigned by X-ray crystal stud-
lysts 4a–g do not attain so far the very high enantiose- ies and supported by VCD studies (see Supporting In-
lectivity levels afforded by the Binepine-platinum formation). These studies consistently demonstrate
complexes 5, nevertheless they often display higher that (S)-Ph-Binepine complexes afford a (1R,6S) con-
catalytic activity and a proper design allows accepta- figured bicycloheptene units.
ble enantiomeric excesses, up to 82%, to be obtained.
Bicyclic derivatives with the opposite (1S,6R) con-
Moreover, the optimization study above highlights figurations are obtained by using (R)-Monophos as
some trends in the structure-activity relationship and the chiral auxiliary.
Scheme 7. Synthesis of the 3-azabicycloACTHNUGRTENUNG[4.1.0]heptene 7h from enantiomerically enriched (S)-1-iodo-4-(1-phenylethoxy)ben-
zene.
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Dienynes 9 have been subjected to catalytic cycloi-
somerization in the presence of either platinum(II)
chloride or the chiral (S)-Ph-Binepine complex 5a
(Table 2). The expected bicyclic products 10 were ob-
tained as >95:5 diastereomeric mixtures,[29] irrespec-
tive of the catalyst used. This suggests that a highly
diastereoselective, substrate controlled reaction path-
way operates here.
In the cycloisomerizations of dienynes 9, the chiral
pre-catalyst 5a displays a moderate catalytic activity,
compared to that previously observed in the cycloiso-
merizations of the simple 1,6-enynes 6 (Table 1). This
is likely due to the increased steric hindrance of the
additional vinyl substituent. Gratifyingly, however cat-
alyst 5a affords very high diastereoselectivity, as well
as high levels of enantioselectivity, with enantiomeric
excesses of between 80% and 95% (entries 2–5 in
Table 2).
Figure 5. Crystal structure of (1R,6S,S)-7h allowing assign-
ment of the absolute configuration of the bicyclic unit.
Enantioselective Cycloisomerizations of 1,6-Enynes
with Enantiotopic Vinyl Moieties
The isolated yields given in Table 2, correspond to
reactions run in standard conditions (608C, 24 h).
As a further step in the development of enantioselec- Higher conversion rates can be attained at higher re-
tive enyne cycloisomerizations, we next considered action temperatures, which induce however a signifi-
the dienyne derivatives 9 as potential new substrates. cant decrease of the enantioselectivity levels (ee=
Substrates 9 display the same 1,6-enyne moiety as 6, 64% at 908C vs. 87% at 608C, for the cycloisomeriza-
they have however two enantiotopic vinyl moieties. If tion reaction in entry 2).
the cycloisomerization reaction takes place according
Crystals suitable for X-ray diffraction studies have
to the usual pathway, then the bicyclic scaffold 10 will been obtained from a CH2Cl2/heptane solution of 10d
be generated which contains an additional, vinyl-sub- (92% ee, from entry 5). The solid state structure of
stituted stereogenic centre in position 2.[25] Our aim 10d (Figure 6) displays a relatively flat tetrahydropyri-
À
was to investigate these cyclization reactions and to dine ring with a dihedral angle of 368 between the N
À
À
À
evaluate the ability of chiral catalysts to induce both C12 C11 plane and the N C8 C9 plane. The vinyl
diastereo- and enantioselective tranformations of substituent is opposite to the cyclopropane unit, that
these substrates. As far as we know, the cycloisomeri- is, syn to the aryl substituent. X-ray data display a tor-
À
À
À
zation of dienynes 9 has never been investigated sion angle of 69.68 for the H C8 C9 H moiety,
before, while prochiral dienynes of this class have which is overall consistent with the small J coupling
3
been used as substrates for enantioselective ring-clos-
ing enyne metathesis reactions,[26] as well as for asym-
Table 2. Catalytic cycloisomerization of dienynes 9 in the
metric Pauson–Khand type reactions.[27]
presence of Pt(II) catalysts.
The preferred synthetic approach to dienynes 9 in-
volves addition of vinylmagnesium bromide to ethyl
N-tosylformimidate[28] to produce the 1-vinylallyla-
mide 8,[27] and subsequent alkylation of the nitrogen
atom with a propargylic bromide (Scheme 8).
Entry Substrate
Ar
[Pt]
Product Yield[a] ee
[%]
[%]
1
2
3
4
5
6
9a Ph
9a Ph
9b 3,5-(Me2)C6H3 5a
9c 4-MeO-C6H4
9d 3-MeO-C6H4
9e 4-NO2-C6H4
PtCl2 10a
45[b]
46
66
55
28
0
–
5a
10a
10b
10c
10d
–
87
80
95
92
–
5a
5a
5a
[a]
Isolated yields. The isolated samples may contain some
residual starting material. The yields of 10 are calculated
1
then from H NMR spectra.
Reaction performed at 908C.
[b]
Scheme 8. Synthesis of the dienyne substrates 9.
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Adv. Synth. Catal. 2011, 353, 1109 – 1124

Cyclometalated N-Heterocyclic Carbene-Platinum Catalysts for the Enantioselective Cycloisomerization
Figure 7. Geometrical features of the (S)-Ph-Binepine com-
plex 5a from X-ray crystal data (ref.[11]). Sterically hindered
quadrants are displayed.
Figure 6. ORTEP drawing for the cycloisomerization prod-
uct (1R,2S,6S)-10d.
constant (<1 Hz) observed between the two adjacent
1
CH groups in the H NMR spectrum. The observed
diastereomer was anticipated to be the most stable
isomer, as far as it minimizes steric interactions be-
tween the vinyl substituent and the contiguous cyclo-
propane ring.
The major enantiomer of compound 10d displays
1R,2S,6S configurations of the three stereogenic cen-
tres. Thus, cycloisomerizations of dienynes 9 take
place with the same sense of chiral induction as ob-
served for the simple enynes 6. It can be reasonably
assumed that, in both cases, the cyclopropane unit is
Figure 8. A plausible stereochemical pathway for the enan-
tioselective cycloisomerizations promoted by 5a.
Anyhow, such foreseeable steric constraints and
constructed on the Si-face of the olefin (1R-config- simplified models alone cannot afford a clear rational
ured products) under catalyst control. The configura- for the stereochemical control. Detailed mechanistic
tion of the additional stereogenic centre in 10 might studies are still required.
be dictated by the relative stabilities of the diastereo-
meric products, if the reaction involves a late, prod- prochiral dienynes 9 are suitable substrates in enan-
uct-like transition state. tioselective cycloisomerizations. The platinum-pro-
Altogether, these experiments demonstrate that the
To date, building of simple models accounting for moted rearrangements produce the bicyclic, function-
the observed stereochemical control is rather chal- alized scaffolds 10 containing three stereogenic cen-
lenging, due to significant conformational freedom of tres, with total control of their relative stereochemis-
both the Pt complex and the reaction intermediates. try and high enantiomeric excess. The exocyclic vinyl
The chiral PtACHTUNGTRENNUNG(NHC)(phosphine) complexes them- groups of 10 open the way to further functionaliza-
selves indeed display unlocked geometries, mainly tions for synthetic purposes.
due to free rotation of the chiral phosphorus ligand
À
around the Pt P bond. If we assume however that the
active catalyst retains the solid state geometry of the Conclusions
corresponding pre-catalyst,[11] we can considered that
the key Pt(II) complex shields three space quadrants, In conclusion, this work highlights the (S)-Ph-Bine-
as shown in Figure 7.
pine-containing platinacycles 5 as excellent catalysts
Based on this hypothesis, the approach of the for the enantioselective cycloisomerization of nitro-
alkene moiety to the p-complexed alkyne might take gen-tethered 1,6-enynes into the corresponding 3-
place as shown in Figure 8 above. This model postu- azabicycloACTHNUGRTENUNG[4.1.0]heptenes. The scope of the reaction
lates that the highest steric constraints result from the has been successfully extended to the cycloisomeriza-
alkyne aryl substituent, cis to the metal centre in the tion of prochiral dienynes. As far as we know, these
rigid transition state. This aryl group is expected reactions represent the first examples of enantioselec-
therefore to occupy the less hindered quadrant, i.e., tive desymmetrizations performed via cycloisomeriza-
the bottom left quadrant in Figure 5. Obviously other tion reactions. This work also demonstrates that the
hypothesis are plausible as well, which involve mini- Monophos-containing platinacycles 4 are promising
mization of the steric interactions between the N-Ts alternative chiral catalysts for enyne cycloisomeriza-
group and the chiral complex.[9]
tions. Therefore, both Binepine and Monophos are
Adv. Synth. Catal. 2011, 353, 1109 – 1124
ꢃ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1117

Hꢀlꢁne Jullien et al.
FULL PAPERS
2.2 mmol) and 4-tert-butyl-2-iodobenzyl methanesulfonate
(810 mg, 2.2 mmol, obtained from the corresponding alco-
hol,[31] mesyl chloride and Et3N) in DMF (6 mL) at room
temperature. The reaction mixture was stirred overnight at
room temperature, diluted with water and extracted with di-
chloromethane. The N-substituted imidazole was purified by
column chromatography with a CH2Cl2-MeOH 98:2 mixture
as the eluent; yield: 330 mg (65%). 1H NMR (300 MHz,
being considered as potentially suitable chiral ligands
in our ongoing studies on various platinum promoted
cycloisomerizations.
Experimental Section
3
The experimental procedures and spectral data given herein
complement those reported in our preliminary communica-
tion.[11] X-ray data for compounds 4a, 4d, 7h, 7a and 10d
have been deposited at the Cambidge Data base, registry
numbers CCDC 800935, CCDC 8000936, CCDC 8000937,
CCDC 800938 and CCDC 800939. These data can be ob-
tained free of charge from The Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
CDCl3): d=1.30 (s, 9H, CMe3), 5.14 (s, CH2), 6.82 (d, J=
8.0 Hz, 1H, Ar), 6.95 (s, 1H, NCH), 7.12 (s, 1H, NCH), 7.34
3
3
(dd, J=8.0 Hz, J=2.1 Hz, 1H, Ar), 7.59 (s, 1H, NCHN),
3
7.87 (d, J=2.1 Hz, 1H, Ar).
Secondly, the imidazolium salt 1e was prepared as fol-
lows:
N-(4-tert-butyl-2-iodophenyl)methyl)imidazole
(210 mg, 0.62 mmol) has been reacted with MeI (46 mL,
0.74 mmol) in refluxing acetonitrile (3 mL) for 6 h in a
sealed tube. After evaporation of the volatiles, the crude
imidazolium salt 1e was isolated and used in the next step
without further purification. 1H NMR (300 MHz, CDCl3):
d=1.28 (s, 9H, CMe3), 3.89 (s, 3H, NMe), 5.42 (s, CH2),
7.20 (d, 3J=8.0 Hz, 1H, Ar), 7.51 (dd, 3J=8.0 Hz, 3J=
2.0 Hz, 1H, Ar), 7.77 (s, 1H, NCH), 7.78 (s, 1H, NCH), 7.92
Synthesis of the (NHC)Pt(0)ACTHNUGTRNEUNG(dvtms) Complexes 2a–e
The synthesis of complexes 2a–c has been described in our
previous report.
3
(d, J=2.0 Hz, 1H, Ar), 9.13 (s, 1H, NCHN).
Synthesis of the (NHC)Pt(0)ACHTUNTRGNEUNG(dvtms) Complex 2d
Thirdly, 2e was synthesized as follows: an excess of t-
BuOK (47 mg, 0.39 mmol) was added at 08C to a suspension
of the imidazolium iodide 1e (125 mg, 0.26 mmol) and Kar-
stedtꢄs catalyst [Pt2(1,3-divinyl-1,1,3,3-tetramethyldisilox-
ane)3, 0.1M in xylene, 2.6 mL] in a dichloromethane (1 mL)/
toluene (3 mL) mixture. The reaction mixture was stirred
overnight at room temperature and evaporated to dryness.
The crude product was purified by column chromatography
on silica gel with a heptane/ethyl acetate 9:1 mixture. Com-
plex 2e (Rf =0.3) was obtained as a white solid; yield:
Firstly, 1-tert-butylimidazole has been prepared in 33% yield
from tert-butylamine, glyoxal and paraformaldehyde, accord-
ing to the literature.[30]
Secondly, the imidazolium salt 1d was prepared as fol-
lows: 2-iodobenzyl methanesulfonate (312 mg, 1.8 mmol)
was added to a solution of 1-tert-butylimidazole (152 mg,
1.2 mmol) in CH3CN (1.8 mL). The mixture was stirred
overnight at 808C. After concentration, the crude product
was diluted in a minimun amount of DCM. Heptane was
added until the solution became cloudy. After 2 h at À208C,
the supernatant was removed and 1-(tert-butyl)-3-(2-iodo-
benzyl)imidazolium was obtained as an oil; yield: 485 mg
1
132 mg (69%). H NMR (300 MHz, CDCl3): d=À0.39 (br,
6H, SiMe), 0.30 (s, 6H, SiMe), 1.27 (s, 9H, CMe3), 1.8–1.9
(m, 4H), 2.1–2.2 (m, 2H), 3.58 (s, 3H, NMe), 5.12 (s, 2H,
1
3
4
(90%). H NMR (300 MHz, CDCl3): d=1.74 (s, 9H, CH3),
NCH2), 6.97 (d, J=2.1 Hz, JH,Pt =11 Hz, 1H, NCH=), 7.04
(d, 3J=2.1 Hz, 4JH,Pt =12 Hz, 1H, NCH=), 7.26 (br, 1H),
7.29 (d, J=2.1 Hz, 1H), 7.79 (d, J=2.1 Hz, 1H); 13C NMR
(CDCl3, 125 MHz): d=À1.9 (Me), 0.4 (Me), 1.5 (Me), 31.1
(CMe3), 34.4 (CH2=CHSi), 34.7 (=CHSi), 37.0 (NMe), 40.4
(1JC,Pt =157 Hz, =CH2), 57.6 (NCH2), 120.7 (3JC,Pt =37 Hz,
NCH=), 122.3 (3JC,Pt =36 Hz, NCH=), 125.5 (CH), 136.5
(CH).
2.85 (s, 3H, CH3), 5.78 (s, 2H, CH2), 7.12 (m, 1H), 7.25 (m,
1H), 7.47 (m, 2H), 7.81 (dd, J=6.9 Hz, J=0.6 Hz, 1H), 7.92
(dd, J=7.8 Hz, J=1.2 Hz, 2H), 10.13 (s, 1H, NCHN)
Thirdly, 2d was ynthesized as follows: An excess t-BuOK
(96 mg, 0.86 mmol) was added at 08C to a suspension of the
imidazolium salt 1d (250 mg, 0.57 mmol) and Karstedtꢄs cat-
alyst [Pt2(1,3-divinyl-1,1,3,3-tetramethyldisiloxane)3, 0.1M in
xylene, 5.7 mL] in
a dichloromethane (2.5 mL)/toluene
(9.5 mL) mixture. The reaction mixture was stirred over-
night at room temperature and evaporated to dryness. The
crude product was purified by column chromatography on
silica gel with a heptane/ethyl acetate 9:1 mixture. Complex
2d (Rf =0.3) was obtained as an oil; yield: 231 mg (56%)
Synthesis of the Cyclometalated
(NHC)IPt(II)(phosphine) Complexes 3–5
Complexes 5a–c have been described in our previous
report.[11] The synthesis of the (R)-Monophos-Pt(II) complex
4a is described hereafter as a representative procedure.
(two rotamers in
a
59/41 ratio). 1H NMR (300 MHz,
CDCl3): d= À0.55 (s, 6H, SiMe, major), À0.35 (s, 6H,
SiMe, minor), 0.21 (s, 6H, SiMe, major), 0.25 (s, 6H, SiMe,
minor), 1.56 (s, 9H, CMe3, major), 1.59 (s, 9H, CMe3,
minor),1.8–1.9 (m, 4H), 2.1–2.2 (m, 2H), 5.12 (s, 2H, NCH2,
minor), 5.20 (s, 2H, NCH2, major), 6.60 (d, J=7.2 Hz, 1H,
major), 6.8–7.3 (m, 5H), 7.74 (d, J=7.8 Hz, 1H) ppm.
Typical Procedure: Synthesis of the (R)-Monophos-
Pt(II) Complex 4a
A THF solution (5 mL) containing the Pt(0) complex 2a
(140 mg, 0.2 mmol) and (R)-Monophos (72 mg, 0.2 mmol)
was heated at 608C for 5 h. After evaporation of the solvent,
the final product was purified by column chromatography
with a heptane/ethyl acetate gradient (from 8:2 to 7:3) as
the eluent (Rf =0.2 in heptane-ethyl acetate 7:3). Complex
4a was obtained as a 75:25 mixture of isomers; yield:
Synthesis of the (NHC)Pt(0)ACHTUNTRGNEUNG(dvtms) Complex 2e
Firstly, N-(4-tert-butyl-2-iodophenyl)methyl)imidazole has
been prepared by reacting imidazole (102 mg, 1.5 mmol)
with, successively, NaH (90 mg, 60% in mineral oil,
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Adv. Synth. Catal. 2011, 353, 1109 – 1124

Cyclometalated N-Heterocyclic Carbene-Platinum Catalysts for the Enantioselective Cycloisomerization
110 mg (65%). 31P NMR (121 MHz, CDCl3): d=130.6
(broad, 1JP,Pt =4510 Hz) (major), 130.2 (1JP,Pt =4543 Hz)
(minor); 1H NMR (500 MHz, CDCl3; major isomer): d=
(br d, 2Jꢀ13 Hz, 1H, NCH2), 5.55 (d, 2J=14.8 Hz, 1H,
NCH2), 6.00 (d, 2J=14.8 Hz, 1H, NCH2), 6.64 (s, 1H,
NCH=), 6.8–8.3 (NCH, aryls); 13C NMR (CDCl3, 125 MHz;
3
2.91 (d, JH,P =10.0 Hz, 6H, PNMe2), 4.01 (s, 3H, NMe), 4.44
major isomer): d=38.4 (d, JC,P =10.1 Hz, NMe2), 55.5
(d, 2J=13.5 Hz, 1H, NCH2), 5.08 (d, 2J=13.5 Hz, 1H,
NCH2), 6.74 (s, 1H), 6.94 (s, 1H), 7.0–8.0 (aryls); (minor
isomer): d=2.85 (d, 3JH,P =10.5 Hz, 6H, PNMe2), 3.98 (s,
(NCH2Ph), 58.8 (3JC,Pt =104 Hz, NCH2); HR-MS (ESI):
m/z=950.0914, calcd. for C39H33IN3O2P194PtNa: 950.0880;
[a]D: À16 (c 0.5, CHCl3).
2
2
3H, NMe), 4.23 (d, J=13.5 Hz, 1H, NCH2), 4.90 (d, J=
13.5 Hz, 1H, NCH2); 13C NMR (CDCl3, 125 MHz, major
isomer): d=38.5 (d, 2JC,P =10.9 Hz, PNMe2), 40.3 (NMe),
58.65 (NCH2); HRMS (ESI): m/z=875.0690, calcd. for
C33H30N3IO2P194PtNa: 875.0645.
(R)-MonoPhos-Pt(II) Complex 4d
Complex 4d was obtained from 2d (166 mg, 0.23 mmol) and
(R)-Monophos (83 mg, 0.23 mmol) as a 77:23 mixture of iso-
mers; yield: 96 mg (47%). 31P NMR (121 MHz, CDCl3): d=
127.1 (major), 125.9 (minor); 1H NMR (500 MHz, CDCl3;
major isomer): d=1.88 (s, 9H, CMe3), 2.87 (br, 6H,
PNMe2), 4.42 (d, 2J=13.5 Hz, 1H, NCH2), 5.32 (br, 1H,
NCH2), 6.73 (br, 1H, NCH=), 6.9–8.3 (aryls); (minor
isomer): d=1.89 (s, 9H, CMe3), 2.8 (br, 6H, PNMe2), 4.19
(br d, 2J=11 Hz, 1H, NCH2), 5.05 (br d, 2J=11 Hz, 1H,
NCH2); 13C NMR (CDCl3, 125 MHz): d=32.0 (CMe3), 38.1
(d, 2JC,P =8,6 Hz, PNMe2), 59.2 (NCH2); HR-MS (ESI):
m/z=768.2 (MÀI), calcd. for C36H36IN3O2P195Pt: 909.1394.
(R)-MOP-Pt(II) Complex 3
Complex 3 was obtained from 2a and (R)-MOP as a 55:45
mixture of isomers; yield: 38 mg (20%). 31P NMR
(121 MHz, CDCl3): d=28.3 (1JP,Pt =2836 Hz) (major), 27.3
(1JP,Pt =2834 Hz) (minor); 1H NMR (500 MHz, CDCl3;
major isomer): d=3.36 (s, 3H, OMe), 3.96 (s, NMe), 4.28
(d, 2J=13.5 Hz, 1H, NCH2), 5.05 (d, 2J=13.5 Hz, 1H,
NCH2), 6.15 (t, J=6.5 Hz, 1H), 6.4–7.9 (aryls); (minor
2
isomer): d=3.66 (s, 3H, OMe), 3.94 (s, NMe), 4.41 (d, J=
2
13.5 Hz, 1H, NCH2), 5.35 (d, J=13.5 Hz, 1H, NCH2), 6.09
(R)-MonoPhos-Pt(II) Complex 4e
(t, J=6.5 Hz, 1H), 6.4–7.9 (aryls); 13C NMR (CDCl3,
125 MHz; major isomer): d=40.3 (NMe), 54.9 (OMe), 58.80
(NCH2), 111.6 (CH); 13C NMR (CDCl3, 125 MHz; minor
isomer): d=40.1 (NMe), 55.3 (OMe), 58.9 (NCH2), 112.1
(CH); HR-MS (ESI): m/z=834.2254, calcd. for
C44H37N2OP194Pt: 834.2270.
Complex 4e was obtained from 2e (147 mg, 0.2 mmol) and
(R)-Monophos as a >95:5 mixture of isomers; yield: 87 mg
(48%). 31P NMR (121 MHz, CDCl3): d=130 (broad signal,
1JP, Pt =2765 Hz); 1H NMR (500 MHz, CDCl3): d=1.2 (br,
9H, CMe3), 2.92 (br, 6H, PNMe2), 4.02 (s, 3H, NMe), 4.43
2
(d, J=13.0 Hz, 1H, NCH2), 5.05 (br, 1H, NCH2), 6.73 (s,
1H, NCH=), 6.92 (s, 1H, NCH=), 7.0–8.0 (aryls); 13C NMR
(CDCl3, 125 MHz): d=31.3 (CMe3), 34.1 (CMe3), 38.3 (d,
2JC,P =10 Hz, PNMe2), 40.4 (NMe), 58.1 (3JC„Pt =97 Hz,
NCH2), 171.4 (d, 2JC,P =210 Hz, C=Pt); [a]D: À3 (c 0.3,
CHCl3); HR-MS (ESI): m/z=909.1351, calcd. for
C37H38IN3O2P195Pt: 909.1394.
(R)-MonoPhos-Pt(II) Complex 4b (Scheme 3)
Complex 4b was obtained from 2b as a 75:25 mixture of iso-
mers; yield: 87 mg (50%); 31P NMR (121 MHz, CDCl3): d=
130.5 (major), 129.9 (1JP,Pt =4550 Hz) (minor); 1H NMR
(500 MHz, CDCl3; major isomer): d=1.45 (t, 3J=7.5 Hz,
3
2
3H, Me), 2.90 (d, JH,P =10.0 Hz, 6H, PNMe2), 4.43 (d, J=
13.5 Hz, 1H, NCH2), 4.48 (m, 1H, NCH2CH3), 4.63 (m, 1H,
Synthesis of the (NHC)Pt(0)ACHTUNTRGNEUNG(dvtms) Complex 2f
2
NCH2CH3), 5.08 (d, J=13.5 Hz, 1H, NCH2), 6.80 (s, 1H,
Firstly, (S)-N-[1-(2-iodophenyl)ethyl]imidazole was prepared
from (S)-1-(2-iodophenyl)ethanamine,[32] glyoxal, parafomal-
dehyde and ammonium chloride according to the known
procedure;[33] yield: 44%.1H NMR (500 MHz, CDCl3): d=
1.85 (d, 3J=7.0 Hz, 3H, Me), 5.63 (q, 3J=7.0 Hz, 1H, N-
NCH=), 6.94 (s, 1H, NHC=), 7.0–8.0 (aryls); (minor
3
isomer): d=1.47 (t, 3J=7.5 Hz, 3H, Me), 2.84 (d, JH,P
=
2
10.5 Hz, 6H, PNMe2), 4.23 (d, J=13.0 Hz, 1H, NCH2), 4.48
(m, 2H, NCH2CH3), 4.89 (d, 2J=13.0 Hz, 1H, NCH2);
13C NMR (CDCl3, 125 MHz, major isomer): d=15.9 (Me),
3
38.4 (d,
J
C,P =10.1 Hz, NMe2), 46.8 (3JC,Pt =26 Hz,
CHMe), 6.96 (s, 1H, NCH=), 6.98 (d, J=8.0 Hz, 1H), 7.02
3
3
NCH2CH3), 58.7 (NCH2), 119.4 (d, 4JC,P =7.2 Hz, CH=),
120.2 (d, 4JC,P =5.4 Hz, CH=); MS (ESI): 890 (M+Na,
19%), 771 (MÀC5H7N2, 100%), 740 (MÀI, 100%); [a]D:
À22 (c0.2, CHCl3).
(t, J=8.0 Hz, 1H), 7.11 (s, 1H, NCH=), 7.33 (t, J=8.0 Hz,
3
1H), 7.65 (s, 1H, N=CH-N), 7.89 (d, J=8.0 Hz, 1H); [a]D:
+55 (c 1, CHCl3).
Secondly, (S)-N-Me-N-[1-(2-iodophenyl)ethyl]imidazoli-
um iodide (S)-1f was obtained by alkylation of (S)-N-[1-(2-
iodophenyl)ethyl]imidazole with MeI (1.2 equiv.) in reflux-
ing acetonitrile (5 h); yield: 95%. 1H NMR (300 MHz,
CDCl3): d=2.09 (d, 3J=7.0 Hz, 3H, Me), 4.17 (s, 3H,
NMe), 5.88 (q, 3J=7.0 Hz, 1H, N-CHMe), 7.08 (t, 3J=
(R)-MonoPhos-Pt(II) Complex 4c (Scheme 3)
Complex 4c was obtained from 2c (157 mg, 0.2 mmol) and
(R)-Monophos as a 80:20 mixture of isomers; yield: 110 mg
(59%). 31P NMR (121 MHz, CDCl3): d=131 (br, major),
3
8.0 Hz, 1H), 7.14 (s, 1H, NCH=), 7.45 (t, J=8.0 Hz, 1H),
1
3
129.5 (1JP,Pt =4552 Hz, minor); H NMR (500 MHz, CDCl3;
7.47 (s, 1H, NCH=), 7.53 (d, J=8.0 Hz, 1H), 7.88 (d, J=
3
major isomer): d=2.86 (d, JH,P =10.5 Hz, 6H, PNMe2), 4.48
8.0 Hz, 1H),10.20 (s, 1H, N=CH-N); [a]D: +43 (c 1,
CHCl3).
Thirdly, an excess t-BuOK (40 mg, 0.35 mmol) was added
at 08C to a suspension of the imidazolium iodide (S)-1f
(100 mg, 0.23 mmol) and Karstedtꢄs catalyst [Pt2(1,3-divinyl-
1,1,3,3-tetramethyldisiloxane)3, 0.1M in xylene, 2.3 mL] in a
(d, 2J=13.5 Hz, 1H, NCH2), 5.18 (br d, 2J ꢀ 13 Hz, 1H,
NCH2), 5.44 (d, 2J=14.8 Hz, 1H, NCH2), 6.20 (d, 2J=
14.8 Hz, 1H, NCH2), 6.61 (s, 1H, NCH=), 6.94 (s, 1H,
3
NHC=), 7.0–8.0 (aryls); (minor isomer): d=2.77 (d, JH,P
=
2
10.5 Hz, 6H, PNMe2), 4.30 (d, J=12.5 Hz, 1H, NCH2), 5.02
Adv. Synth. Catal. 2011, 353, 1109 – 1124
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1119

Hꢀlꢁne Jullien et al.
FULL PAPERS
dichloromethane (1 mL)/toluene (3 mL) mixture. The reac-
tion mixture was stirred overnight at room temperature and
evaporated to dryness. The crude product was purified by
column chromatography on silica gel with a heptane/ethyl
acetate gradient (from 9:1 to 8:2 mixture). Complex 2f was
obtained as a white solid; yield: 121 mg (76%). 1H NMR
(500 MHz, CDCl3): d=À0.34 (s, 3H, SiMe), À0.28 (s, 3H,
SiMe), 0.27 (s, 3H, SiMe), 0.34 (s, 3H, SiMe), 0.78 (br, 1H,
traction with CH2Cl2 and evaporation of the solvent, the
crude N-nosylallylamine was isolated and used for the next
1
step; yield: 1.81 g (94%). H NMR (300 MHz, CDCl3): d=
3.70 (tt, 3J=6 Hz, 4J=1.5 Hz, 2H, NCH2), 5.00 (br t, 3J=
6.0 Hz, 1H, NH), 5.1–5.2 (2H, CH2=), 5.71 (m, 1H, 3J=
3
3
17.1 Hz, J=10.2 Hz, J=5.7 Hz, CH=), 8.07 (2H, Ar), 8.37
(2H, Ar); 13C NMR (CDCl3, 125 MHz): d=45.8 (NCH2),
118.3 (CH2=), 124.4 (Ns), 128.4 (Ns), 132.4 (CH), 146.1 (C),
150.1 (C).
3
CH2=CHSi), 1.49 (br, 2H, CH2=CHSi), 1.69 (d, J=7.0 Hz,
3H, CHMe), 1.88 (br, 2H, CH2=CHSi), 2.30 (br, 1H, CH2=
CHSi), 3.53 (s, 3H, NMe), 5.71 (br, 1H, NCHMe), 6.90
(2H), 7.13 (s, 1H, NCH), 7.25 (1H), 7.38 (s,1H, NCH), 7.70
(d, J=8.0 Hz,1H); 13C NMR (CDCl3, 125 MHz): d= À2.0
Secondly, a solution of N-allyl-p-nitrobenzenesulfonACHTUNGTRENNUNGamide
(0.50 g, 2.0 mmol), 3-phenylpropargyl bromide (0.48 g,
2.4 mmol) and potassium carbonate (0.60 g, 4.3 mmol) in
MeCN (5 mL) was heated at 608C overnight.The reaction
mixture was filtered, the solid washed with CH2Cl2 and the
(Me), À2.1 (Me), 1.5 (Me), 20.7 (NCHMe), 34.4 (1JC,Pt
=
116 Hz, CH2 =CHSi), 36.9 (3JC,Pt =54 Hz, NMe), 39.6 (CH2= solvents removed under vacuum. Enyne 6f was purified by
CHSi), 39.9 (CH2=CHSi), 62.8 (NCHMe), 118.5 (NCH=),
121.3 (3JC,Pt =37 Hz, NCH=), 126.0, 128.4, 128.9, 139.5, 143.7
(C).
column chromatography with heptane-ethyl acetate 8:2 as
the eluent and obtained as a yellow solid; yield: 0.63 g
1
3
(89%). H NMR (500 MHz, CDCl3): d=3.95 (d, J=6.5 Hz,
2H, NCH2), 4.37 (s, 2H, NCH2), 5.33 (d, J=10.0 Hz, 1H, =
CH2), 5.39 (d, J=17.0 Hz, 1H, =CH2), 5.84 (m, 1H, =CH),
7.0–7.2 (5H, Ph), 8.01 (2H, Ns), 8.28 (2H, Ns); 13C NMR
(CDCl3, 125 MHz): d=36.9 (NCH2), 49.6 (NCH2), 80.9 (C),
83.7 (C), 120.7 (CH2=), 122.3 (C), 124.0, 128.4, 128.9, 129.0,
131.2, 144.8 (C), 150.1 (C); MS (ESI): m/z=379 (M+Na,
100).
Synthesis of the Cyclometalated
(NHC)IPt(II)ACHTUNGTRENNUNG(Monophos) Complexes 4f and 4g
The cyclometalated complexes 4f and g were prepared ac-
cording to the general procedure above.
Complex 4f was obtained from the Pt(0) complex 2f
(145 mg, 0.2 mmol) and (R)-MonoPhos (72 mg, 0.2 mmol).
Purification by column chromatography with heptane/ethyl
acetate 7:3 mixture (Rf =0.2) gave 4f in an isomer ratio of
92:8; yield: 68 mg (0.08 mmol, 39%). 31P NMR (121 MHz,
N-(2-Methylallyl)-N-(2-butynyl)-p-nitrophenylsulfonamACHTUNGTRENNUNGide
(6g) was prepared as follows: Firstly, a solution of p-toluene-
sulfonyl chloride (1.9 g, 10.2 mmol) in CH2Cl2 (10 mL) was
added dropwise to a solution of 2-methylallylamine hydro-
chloride (1.0 g, 9.3 mmol) and Et3N (1.4 mL, 10.2 mmol) in
CH2Cl2 (3 mL) at 08C. The mixture was stirred at room tem-
perature overnight and hydrolyzed then with a saturated so-
lution of NH4Cl. After extraction with CH2Cl2, drying over
MgSO4 and evaporation of the solvent, the final product
was purified by chromatography with a heptane/ethyl ace-
tate gradient (from 9:1 to 1:1) to afford N-2-methylallyl-p-
toluenesulfonamide;[34] yield: 1.1 g (51%). 1H NMR
(300 MHz, CDCl3): d=1.67 (s, 3H, Me), 2.42 (s, 3H, Me),
3.47 (d, J=6.6 Hz, 2H, NCH2), 4.69 (br, 1H, NH), 4.81 (s,
1H, CH=), 4.85 (s, 1H, CH=), 7.30 (d, J=8.4 Hz, 2H, Ts),
7.75 (d, J=8.4 Hz, 2H, Ts).
Secondly, a solution of N-2-methylallyl-p-toluenesulfona-
mide (0.61 g, 2.7 mmol), 1-bromo-2-butyne (260 mL,
3.0 mmol) and potassium carbonate (0.42 g, 3.0 mmol) in
MeCN (5 mL) was heated at 608C overnight.The reaction
mixture was filtered, the solid washed with CH2Cl2 and the
solvents removed under vacuum. Enyne 6g[35] was purified
by column chromatography with heptane-ethyl acetate 9:1
as the eluent: yield: 0.63 g (2.27 mmol, 84%). 1H NMR
(300 MHz, CDCl3): d=1.49 (t, J=2.3 Hz, 3H, Me), 1.75 (s,
3H, Me), 2.42 (s, 3H, Me), 3.69 (s, 2H, NCH2), 3.97 (q, J=
2.3 Hz, 2H, NCH2), 4.94 (2H, =CH2), 7.28 (2H, Ts), 7.74
(2H, Ts); 13C NMR (CDCl3, 75 MHz): d=3.2 (Me), 19.7
(Me), 21.5 (Me), 36.0 (NCH2), 52.4 (NCH2), 71.5 (C), 81.5
(C), 115.1 (=CH2), 127.9 (CH, Ts), 129.2 (CH, Ts), 136.2
(C), 139.5 (C), 143.1 (C).
CDCl3):
d=131
(broad,
1JP,Pt ~4530 Hz);
1H NMR
(300 MHz, CDCl3): d=1.91 (br, 3H, Me), 2.94 (d, 6H,
3JH,P =10.5 Hz, PNMe2), 4.05 (s, 3H, NMe), 5.00 (q, J=
6.5 Hz, 1H, NCH), 6.77 (s, 1H, NCH=), 6.98 (s, 1H, NCH=
), 7.5–8.0 (aryls); 13C NMR (CDCl3, 125 MHz)ꢄ: d=26.7
2
(CHMe), 38.5 (d, JC,P =10.0 Hz, PNMe2), 40.9 (NMe), 66.8
(3JC,Pt =73 Hz, NCHMe), 119.9 (d, J=6 Hz, NCH=), 121.3
(d, J=6 Hz, NCH=), 121.6–132 (Ar), 140.1 (d, J=13 Hz,
CH), 143.6, 147.9, 149.5 (d, J=13 Hz, C), 171.5 (d, J=
63 Hz, C); [a]D: À33 (c 0.4, CHCl3); HR-MS (ESI): m/z=
866.0886, calcd. for C34H32N3IO2P194Pt: 866.0904.
Complex 4g was obtained as a 6:4 mixture of isomers,
from the Pt(0) complex 2f (145 mg, 0.2 mmol) and (S)-
MonoPhos (72 mg, 0.2 mmol); yield: 109 mg, (0.13 mmol,
63%). 31P NMR (121 MHz, CDCl3): d=129.1 (1JP,Pt
=
4604 Hz); 1H NMR (300 MHz, CDCl3; major isomer): d=
3
3
1.58 (d, J=7.0 Hz, 3H, CHMe), 2.89 (d, JH,P =10.5 Hz, 6H,
3
PNMe2), 4.03 (s, NMe),4.76 (q, J=7.0 Hz, CHMe), 6.7–8.4
3
(aryls); (minor isomer): d=1.94 (d, J=7.0 Hz, 3H, CHMe),
3
2.93 (d, JH,P =10.0 Hz, 6H, PNMe2), 4.02 (s, NMe), 5.50 (br,
CHMe), 6.7–8.0 (aryls); HR-MS (ESI): m/z=866.0946,
calcd. for C34H32N3IO2P194Pt: 866.0904.
Preparation of 1,6-Enynes 6 (Table 1)
Enynes 6a–e have been prepared according to the reported
procedures (see ref.[11] and references therein).
N-Allyl-N-(3-phenyl-2-propynyl)-p-nitrophenylsulfonam-
ACHTUNGTRENNUNGide (6f) was prepared in two steps, as follows: Firstly, a solu-
tion of p-nitrobenzenesulfonyl chloride (2.0 g, 9.0 mmol) in
CH2Cl2 (8 mL) was added to a solution of allylamine
(0.60 mL, 8.0 mmol) and Et3N (1.3 mL, 9 mmol) in CH2Cl2
(2 mL) at 08C. The mixture was stirred at room temperature
for 1 h and hydrolyzed then with aqueous NH4Cl. After ex-
Synthesis of Dienynes 9 (Table 2)
Dienyne 9a was prepared as described.[26] 1H NMR
(500 MHz, CDCl3): d=2.36 (s, 3H, Me), 4.31 (s, 2H,
NCH2), 5.08 (m, 1H, NCH), 5.25 (d, 3J=17.0 Hz, 2H, =
1120
asc.wiley-vch.de
ꢃ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2011, 353, 1109 – 1124

Cyclometalated N-Heterocyclic Carbene-Platinum Catalysts for the Enantioselective Cycloisomerization
CH2), 5.27 (d, 3J=10.5 Hz, 2H, =CH2), 5.98 (ddd, 3J=
17.0 Hz, 3J=10.5 Hz, 3J=6.0 Hz, H, CH=), 7.1–7.3 (7H,
Ar), 7.81 (d, J=8.5 Hz, 2H, Ts).
Synthesis (3-Penta-1,4-dien-3-yl)tosylamide 8: Amide 8
was obtained by addition of vinylmagnesium bromide to
ethyl N-tosylformimidate according to the reported
method.[26] 1H NMR (300 MHz, CDCl3): d=2.43 (s, 3H,
Me), 4.39 (m, 1H, CH), 4.60 (br, 1H, NH), 5.1–5.2 (4H,
Ar), 7.82 (2H, Ts), 8.16 (2H, Ar); 13C NMR (CDCl3,
125 MHz): d=21.5 (Me), 34.2 (NCH2), 62.0 (NCH), 82.7
(C ), 90.8 (C ), 119.2 (CH2=), 123.4, 127.7, 129.3, 132.1,
134.3, 137.7 (C), 143.4 (C), 147.1 (C); HR-MS (ESI): m/z=
397.1236, calcd. for C21H21N2O4S: 397.1222.
3
ꢁ
ꢁ
General procedure for the Pt(II)-Promoted
CH2=), 5.69 (ddd, J=16.2 Hz, J=10.2 Hz, J=5.7 Hz, 2H, Cycloisomerizations
CH=), 7.3 ( d, 2H, J=8.1 Hz, Ts), 7.76 (d, 2H, J=8.4 Hz,
Ts).
Dienynes 9 were prepared from (3-penta-1,4-dien-3-yl)to-
To a solution of the Pt(II) complex 5 (6.4·10À3 mmol,
4 mol%) in toluene (0.5 mL) under argon AgBF4 (4 mg,
0.02 mmol) and the enyne substrate 6 (or 9) (0.16 mmol, in
4.5 mL toluene) were added sequentially. The mixture was
stirred at 608C for 18–24 h. The reaction was monitored by
NMR. The solvent was removed under reduced pressure
and the final product was purified by column chromatogra-
phy. Enantiomeric excesses have been measured by chiral
HPLC. Samples of racemic compounds have been obtained
via PtCl2 promoted cycloisomerizations.
sylamide 8 according to methods A or B.
Method A: Diisopropyl azodicarboxylate (DIAD)
(375 mg, 1.9 mmol) was added dropwise at 08C to a THF so-
lution (13 mL) containing (3-penta-1,4-dien-3-yl)tosylamide
8 (0.29 g, 1.2 mmol) and the desired 3-arylpropargyl alcohol
(1.9 mmol). The mixture was stirred at room temperature
for 2 h. After removal of the solvent, the final product was
purified by column chromatography.
Method B: Potassium carbonate (320 mg, 2.2 mmol) was
added to a solution containing (3-penta-1,4-dien-3-yl)tosyl-
ACHTUNGTRENNUNGamide 8 (0.27 g, 1.1 mmol) and 3-arylpropargyl bromide
(1.4 mmol) in MeCN (4 mL). The mixture was heated over-
night at 608C. After removal of the solvent, the final prod-
uct was purified by column chromatography.
Enyne 9b: Prepared in 83% yield according to method B.
1H NMR (300 MHz, CDCl3): d=2.18 (s, 6H, Me), 2.28 (s,
3H, Me), 4.99 (br t, 1H, NCH), 5.15 (d, J ~17 Hz, 2H,
CH2), 5.17 (d, J ~11 Hz, 2H, CH2), 5.88 (ddd, J=16.8 Hz,
J=10.8 Hz, J=6.0 Hz, 2H, CH=), 6.71 (s, 2H), 6.85 (s, 1H),
7.14 (2H, ts), 7.75 (2H, Ts); 13C NMR (CDCl3, 125 MHz)
d=21.1 (Me), 21.5 (Me), 34.4 (NCH2), 62.2 (NCH), 84.3
NMR data for the bicyclic cycloisomerization products
7a–e have been reported previously.[11]
6-Phenyl-3-(p-nitrophenysulfonyl)-3-azabicycloACTHNUGTRNEUNG[4.1.0]-
1
hept-4-ene (7f): H NMR (300 MHz, CDCl3): d=0.75 (t, J=
5.3 Hz, 1H, CH2), 1.42 (dd, J=8.5 Hz, J=5.3 Hz, 1H, CH2),
1.79 (m, 1H, CH), 3.29 (dd, 2J=12.0 Hz, J=2.5 Hz, 1H,
NCH2), 4.07 (d, 2J=12.0 Hz, 1H, NCH2), 5.65 (d, 3J=
3
8.0 Hz, 1H, =CH), 6.46 (d, J=8.0 Hz, 1H, NCH=), 7.1–7.3
(5H, Ph), 8.01 (2H, Ns), 8.42 (2H, Ns); 13C NMR (CDCl3,
125 MHz): d=21.0 (CH2), 21.8 (C), 28.4 (CH), 41.1 (NCH2),
117.1 (CH=), 119.9 (CH=), 124.5, 126.5, 126.9, 128.2, 128.5,
142.9 (C), 143.3 (C), 150.1 (C); HR-MS (ESI): m/z=
378.1139, calcd. for C20H21NO3SNa: 378.1140; HPLC {[Chir-
alpak IA column; eluent heptane/2-propanol (98:2),
1 mLminÀ1]: retention times 17.3 and 19.9 min (major).
ꢁ
ꢁ
(C ), 84.9 (C ), 118.8 (CH2=), 122.3 (C), 127.8, 129.1, 129.3,
130.2, 134.7, 137.7 (C), 137.9 (C), 143.1 (C).
1,6-Dimethyl-3-(p-nitrophenysulfonyl)-3-azabicycloACHTUNGTRENNUNG[4.1.0]-
hept-4-ene (7g): 1H NMR (500 MHz, CDCl3): d=0.33 (d,
J=4.0 Hz, 1H, CH2), 0.74 (d, J=4.0 Hz, 1H, CH2), 1.12 (s,
Enyne 9c: Prepared in 32% yield according to method A.
1H NMR (300 MHz, CDCl3): d=2.36 (s, 3H, Me), 3.82 (s,
3H, OMe), 4.28 (s, 2H, CH2), 5.07 (br t, 1H, NCH), 5.23
(dm, J=16 Hz, 2H, CH2), 5.25 (dm, J=10 Hz, 2H, CH2),
5.97 (ddd, J=16.5 Hz, J=10.5 Hz, J=5.7 Hz, 2H, CH=),
6.80 (2H, Ar), 7.12 (2H, Ar), 7.21 (2H, Ts), 7.83 (2H, Ts);
13C NMR (CDCl3, 125 MHz): d=21.4 (Me), 34.4 (NCH2),
2
3H, Me), 1.13 (s, 3H, Me), 2.44 (s, 3H, Me), 2.68 (d, J=
2
11.5 Hz, 1H, NCH2), 3.79 (d, J=11.5 Hz, 1H, NCH2), 5.19
2
2
(d, J=7.5 Hz, 1H, =CH), 6.26 (d, J=7.5 Hz, 1H, NCH=),
7.33 (2H, Ts), 7.66 (2H, Ts); 13C NMR (CDCl3, 125 MHz):
d=17.5 (Me), 17.6 (C), 18.7 (Me), 21.5 (Me), 26.2 (CH2),
29.4 (C), 46.6 (NCH2), 118.2 (CH=), 120.0 (CH=), 127.0,
129.7, 135.0 (C), 143.6 (C); HR-MS (ESI): m/z=300.1028,
calcd. for C15H19NO2S.Na: 300.1034; HPLC [Chiralpak AD-
H column; eluent heptane/2-propanol (99:1), 1 mLminÀ1]:
retention times 11.0 and 12.0 min.
ꢁ
ꢁ
55.3 (OMe), 62.1 (NCH), 83.6 (C ), 84.5 (C ), 113.8 (CH),
114.7 (C), 118.7 (CH2=), 127.8, 129.2, 132.8, 134.7, 137.8 (C),
143.1 (C), 159.6 (C).
Enyne 9d: Prepared in 40% yield according to method A.
1H NMR (300 MHz, CDCl3): d=2.37 (s, 3H, Me), 3.80 (s,
3H, OMe), 4.30 (s, 2H, CH2), 5.08 (br t, 1H, NCH), 5.24
(dm, J=16 Hz, 2H, CH2), 5.26 (dm, J=10 Hz, 2H, CH2),
5.97 (ddd, J=16.8 Hz, J=10.5 Hz, J=6.0 Hz, 2H, CH=),
6.71 (m, 1H, Ar), 6.78 (d, J=7.5 Hz, 1H, Ar), 6.87 (ddd, J=
8.4 Hz, J=2.7 Hz, J=1.0 Hz, 1H, Ar), 7.19 (t, 2H, Ar), 7.23
(2H, Ts), 7.84 (2H, Ts); 13C NMR (CDCl3, 125 MHz): d=
6-Phenyl-3-(p-toluenesulfonyl)-2-vinyl-3-azabicycloACHTUNGTRENNUNG[4.1.0]-
hept-4-ene (10a): 1H NMR (500 MHz, CDCl3): d=0.41 (t,
J=4.8 Hz, 1H, CH2), 1.30 (dd, J=9.0 Hz, J=5.0 Hz, 1H,
CH2), 1.78 (br t, Jꢀ8 Hz, 1H, CH), 2.46 (s, 3H, Me), 4.81
3
3
(d, J=6.0 Hz, 1H, NCH), 5.16 (d, J=10.5 Hz, 1H, =CH2),
3
3
5.30 (d, J=17.5 Hz, 1H, =CH2), 5.61 (d, J=8.0 Hz, 1H, =
CH), 5.91 (ddd, 3J=17.5 Hz, 3J=10.5 Hz, 3J=6.0 Hz, H,
CH=), 6.31 (d, 3J=8.0 Hz, 1H, NCH=), 7.1–7.4 (7H, ar),
7.72 (d, 3J=8.0 Hz, 2H, Ts); 13C NMR (CDCl3, 75 MHz):
d=21.0 (CH2), 21.6 (CH3), 22.5 (C), 35.8 (CH), 52.7 (NCH),
116.4 (=CH2), 117.7 (CH=), 118.5 (CH=), 126.3, 126.9, 127.2,
128.5, 129.7, 136.0, 136.4 (C); HR-MS (ESI): m/z=352.1382,
calcd. for C21H22NO2S: 352.1371; HPLC [Chiralpak IC
column; eluent heptane/ethanol (99:1), 1 mLminÀ1]: reten-
tion times 29 and 32 min (major).
ꢁ
21.4 (Me), 34.3 (NCH2), 55.2 (OMe), 62.1 (NCH), 84.5 (C
ꢁ
), 84.9 (C ), 114.4 (CH), 116.6 (CH), 118.8 (CH2=), 123.6
(C), 123.9, 129.7, 134.6, 137.8 (C), 143.2 (C), 159.2 (C); HR-
MS (ESI): m/z=382.1494, calcd. for C22H24NO3S: 382.1477.
Enyne 9e: Prepared in 16% yield according to method A.
1H NMR (300 MHz, CDCl3): d=2.38 (s, 3H, Me), 4.32 (s,
2H, CH2), 5.10 (br, 1H, NCH), 5.26 (dm, J=17 Hz, 2H,
CH2), 5.29 (dm, J=10 Hz, 2H, CH2), 5.93 (ddd, J=16.5 Hz,
J=10.2 Hz, J=5.7 Hz, 2H, CH=), 7.24 (2H, Ar), 7.31 (2H,
Adv. Synth. Catal. 2011, 353, 1109 – 1124
ꢃ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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1121

Hꢀlꢁne Jullien et al.
FULL PAPERS
6-(3,5-Dimethylphenyl)-3-(p-toluenesulfonyl)-2-vinyl-3-
phenylethanol (1 mL, 8.2 mmol), 4-iodophenol (1.8 g,
8.2 mmol) and triphenylphosphine (2.1 g, 8.2 mmol) in THF
(30 mL) at 08C. After stirring overnight at room tempera-
ture, the solvents were removed under high vacuum. The
crude mixture was taken up in hexane, filtered and the fil-
trate was evaporated. The residue was purified by flash
chromatography with heptane/EtOAc (99:1) as eluent to
give the desired product as a pale yellow solid; yield: 1.6 g
azabicycloACHTUNGTRENNUNG
[4.1.0]hept-4-ene (10b): 1H NMR (300 MHz,
CDCl3): d=0.37 (t, J=4.8 Hz, 1H, CH2), 1.27 (dd, J=
9.0 Hz, J=4.8 Hz, 1H, CH2), 1.77 (br t, 1H, CH), 2.28 (s,
3
6H, Me), 2.46 (s, 3H, Me), 4.81 (d, J=6.3 Hz, 1H, NCH),
3
3
5.18 (d, J=10.5 Hz, 1H, =CH2), 5.31 (d, J=17.1 Hz, 1H, =
3
3
CH2), 5.61 (d, J=8.0 Hz, 1H, =CH), 5.92 (ddd, J=17.1 Hz,
3J=10.5 Hz, J=6.3 Hz, H, CH=), 6.30 (d, J=8.0 Hz, 1H,
3
3
3
1
NCH=), 6.81 (s, 2H), 6.86 (s, 1H), 7.35 (d, J=8.1 Hz, 2H,
(60%). H NMR (300 MHz, CDCl3): d=1.62 (d, J=6.0 Hz,
Ts), 7.72 (d, 3J=8.1 Hz, 2H, Ts); 13C NMR (CDCl3,
125 MHz): d=21.0 (CH2), 21.3 (Me), 21.6 (Me), 22.3 (C),
35.7 (CH), 52.8 (NCH), 116.4 (CH2=), 118.1 (CH=), 118.3
(CH=), 125.0, 127.0, 128.0, 129.7, 136.1 (CH=), 136.4 (C),
138.0 (C), 143.5(C), 143.6 (C); HR-MS (ESI): m/z=
402.1520, calcd. for C23H25NO2S.Na: 402.1504; HPLC [Chir-
alpak IC column; eluent heptane/ethanol (99:1),
1 mLminÀ1]: retention times 28 and 30 min (major).
3H, Me), 5.25 (q, J=6.0 Hz, 1H, CH), 6.63 (2H, Ar), 7.2–
7.3 (m, 5H, Ph), 7.45 (2H, Ar); 13C NMR (CDCl3,
À
125 MHz): d=24.4 (Me), 76.2 (CH), 82.7 (C I), 118.3,
À
125.5, 127.6, 128.7, 138.1, 142.7 (C), 157.8 (O C); MS (ESI):
m/z=324.0 [M], 219.0, 105.0; [a]D: À25 (c 0.9, CHCl3; ee
97% by HPLC).
(ii) A solution of (S)-1-iodo-4-(1-phenylethoxy)benzene
(0.35 g, 1.1 mmol), propargyl alcohol (67 mL, 1.14 mmol) in
toluene (1.1 mL), bis(triphenylphosphine)palladium chloride
(23 mg, 0.033 mmol, 3 mol%), copper iodide (12.5 mg,
0.066 mmol, 6 mol%) and piperidine (0.2 mL, 2.2 mmol) was
heated at 358C for 4 h. The mixture was filtered and the sol-
vents were removed under vacuum. The residue was puri-
fied by flash chromatography with DCM as eluent to give
6-(4-Methoxyphenyl)-3-(p-toluenesulfonyl)-2-vinyl-3-aza-
1
bicyclo
N
d=0.37 (dd, J=6.0 Hz, J=4.8 Hz, 1H, CH2), 1.22 (dd, J=
9.0 Hz, J=4.8 Hz, 1H, CH2), 1.74 (br t, 1H, CH), 2.46 (s,
3H, Me), 3.78 (s, 3H, OMe), 4.80 (d, 3J=6.3 Hz, 1H,
NCH), 5.17 (d, 3J=10.5 Hz, 1H, =CH2), 5.31 (dd, 3J=
3
17.1 Hz, J=1.2 Hz, 1H, =CH2), 5.56 (d, J=8.1 Hz, 1H, =
(S)-3-[4-(1-phenylethoxy)phenyl]-prop-2-yn-1-ol
as
an
CH), 5.92 (ddd, 3J=17.1 Hz, 3J=10.5 Hz, 3J=6.3 Hz, H,
1
orange oil; yield: 0.23 g (82%). H NMR (300 MHz, CDCl3):
d 1.65 (d, J=6.0 Hz, 3H, Me), 1.8 (br, 1H, OH), 4.46 (d, J=
3.0 Hz, 2H, CH2OH), 5.32 (q, J=6.0 Hz, 1H, CH), 6.80
(2H, Ar), 7.20 (2H, Ar), 7.2–7.3 (5H, Ph); 13C NMR
(CDCl3, 125 MHz): d 24.4 (Me), 51.7 (CH2OH) 76.1 (CH),
3
CH=), 6.29 (dd, J=8.1 Hz, J=1.0 Hz, 1H, NCH=), 6.82 (d,
3
3J=8.7 Hz, 2H, Ar), 7.11 (d, J=8.7 Hz, 2H, Ar), 7.35 (d,
3
3J=8.1 Hz, 2H, Ts), 7.72 (d, J=8.1 Hz, 2H, Ts); 13C NMR
(CDCl3, 125 MHz): d=21.0 (CH2), 21.6 (Me), 22.0 (C), 35.6
(CH), 52.8 (NCH), 55.3 (OMe), 113.9 (CH), 116.3 (CH2=),
118.3 (CH=), 118.3 (CH=), 127.0, 128.5, 129.7, 135.8 (C),
136.2 (CH=), 136.4 (C), 143.6 (C), 158.2 (C); HR-MS (ESI):
m/z=382.1473, calcd. for C22H24NO3S: 382.1477; HPLC
[Chiralpak IC column; eluent heptane/ethanol (98:2),
1 mLminÀ1]: retention times 33 and 36 min. A sample of
enantiomerically pure 10c has been obtained by crystalliza-
tion.
ꢁ
ꢁ
85.7 (C ), 85.8 (C ), 114.5 (C), 115.9, 125.5, 127.6, 128.7,
133.0, 142.7 (C), 158.2 (C); MS (ESI): m/z=251.1 [MÀH];
[a]: À28 (c 0.9, CHCl3).
(ii) Di-tert-butyl azodicarboxylate (0.38 g, 1.6 mmol) was
added to a solution of (S)-3-(4-(1-phenylethoxy)phenyl)-
prop-2-yn-1-ol (0.41 g, 1.6 mmol), N-allyl-p-nitrobenzene-
sulfonamide (0.40 mg, 1.6 mmol) and triphenylphosphine
(0.43 mg, 1.6 mmol) in THF (10 mL) at 08C. After stirring
overnight at room temperature, solvents were removed
under vacuum. The residue was purified by flash chromatog-
raphy with a heptane/EtOAc gradient, from 95:5 to 90:10,
as the eluent to give (S)-N-allyl-4-methyl-N-{3-[4-(1-phenyl-
ethoxy)phenyl]prop-2-ynyl}-p-nitrophenylsulfonamide 6h as
a yellow oil; yield: 0.40 g (51%); ee 97% by HPLC.
1H NMR (300 MHz, CDCl3): d=1.65 (d, J=6.0 Hz, 3H,
Me), 3.92 (d, J=7.0 Hz, 2H, NCH2), 4.34 (s, 2H, NCH2),
5.3–5.4 (3H, =CH2 + OCH), 5.78 (m, 1H, CH=), 6.73 (d,
J=9.0 Hz, 2H, Ar), 6.91 (d, J=9.0 Hz, 2H, Ar), 7.2–7.4
(5H, Ph), 8.06 (d, J=9.0 Hz, 2H, Ns), 8.70 (d, J=9.0 Hz,
2H, Ns); 13C NMR (75 MHz, CDCl3): d=24.4 (Me), 37.0
6-(3-Methoxyphenyl)-3-(p-toluenesulfonyl)-2-vinyl-3-aza-
1
bicyclo
N
d=0.41 (dd, J=6.0 Hz, J=4.8 Hz, 1H, CH2), 1.29 (dd, J=
9.0 Hz, J=4.8 Hz, 1H, CH2), 1.78 (br t, 1H, CH), 2.46 (s,
3H, Me), 3.79 (s, 3H, OMe), 4.80 (br d, 3J=6.4 Hz, 1H,
NCH), 5.16 (d, 3J=10.3 Hz, 1H, =CH2), 5.29 (d, 3J=
3
17.0 Hz, 1H, =CH2), 5.60 (dd, J=8.0 Hz, J=0.6 Hz, 1H, =
CH), 5.89 (ddd, 3J=17.0 Hz, 3J=10.3 Hz, 3J=6.3 Hz, 1H,
CH=), 6.31 (dd, 3J=8.0 Hz, J=1.1 Hz, 1H, NCH=), 6.76
3
(3H, Ar), 7.20 (m, 1H, Ar), 7.34 (d, J=8.3 Hz, 2H, Ts),
3
7.72 (d, J=8.3 Hz, 2H, Ts); 13C NMR (CDCl3, 125 MHz):
d=21.2 (CH2), 21.6 (Me), 22.5 (C), 35.9 (CH), 52.7 (CH),
55.2 (OMe), 111.4 (CH), 113.4 (CH), 116.4 (CH2=), 117.5
(CH),118,6 (CH), 119.5, 127.0 (Ts), 129.7 (Ts), 136.0 (CH),
136.3 (C), 143.6 (C), 145.2 (C), 159.7 (C); HR-MS (ESI):
m/z=382.1462, calcd. for C22H24NO3S: 382.1477; HPLC
[Chiralpak IC column; eluent heptane/2-propanol (98:2),
1 mLminÀ1]: retention times 28 and 30 min.
ꢁ
ꢁ
(NCH2), 49.5 (NCH2), 76.2 (OCHMe), 79.5 (C ), 86.4 (C ),
113.4 (C), 115.9, 120.5 (CH2=), 124.0, 125.5, 127.6, 128.7,
129.0, 131.4, 132.7, 142.6 (C), 144.9 (C), 150.0 (C), 158.4 (C);
MS (ESI): m/z=499 [M+Na]; HPLC [Chiralpak IA
column, heptane/2-propanol (90:10), 1 mLminÀ1]: retention
times 14.8 (major) and 17.8 min; ee 97%.
6-{4-[(S)-1-Phenylethoxy]phenyl}-3-(p-nitrobenzenesulfo-
namide)-3-azabicycloACTHNUGRTENUNG[4.1.0]hept-4-ene (7h) (Scheme 7):
(S)-N-Allyl-4-methyl-N-{3-[4-(1-phenylethoxy)-
phenyl]-prop-2-yn-1-yl}-p-nitrophenylsulfon-
amide (6h) (Scheme 7)
1H NMR (300 MHz, CDCl3): d=0.63 (t, J=6.0 Hz, 1H,
CH2), 1.26 (t, J=6.0 Hz, 1H, CH2), 1.60 (d, J=7.0 Hz, 3H,
Me), 1.65 (m, 1H, CH), 3.21 (d, J=12.0 Hz, 1H, NCH2),
4.00 (d, J=12.0 Hz, 1H, NCH2), 5.24 (q, J=7.0 Hz, 1H,
OCHMe), 5.53 (d, J=8.0 Hz, 1H, CH=), 6.37 (d, J=8.0 Hz,
Amide 6h was prepared in three steps: (i) Diethyl azodicar-
boxylate (1.2 mL, 8.2 mmol) was added to a solution of (R)-
1122
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Adv. Synth. Catal. 2011, 353, 1109 – 1124

Cyclometalated N-Heterocyclic Carbene-Platinum Catalysts for the Enantioselective Cycloisomerization
1H, CH=), 6.74 (d, J=9.0 Hz, 2H, Ar), 6.96 (d, J=9.0 Hz,
2H, Ar), 7.2–7.3 (m, 5H, Ph), 7.97 (d, J=9.0 Hz, 2H, Ns),
8.39 (d, J=9.0 Hz, 2H, Ns); 13C NMR (75 MHz, CDCl3):
d=20.9 (CH2), 21.2 (C), 24.5 (CHMe), 28.0 (CH), 41.1
(NCH2), 76.0 (OCHMe), 115.8, 117.7 (CH=), 119.5 (CH=),
124.5, 125.5, 127.4, 128.0, 128.2, 128.6; MS (ESI): m/z=499
[M+Na]; HPLC [Chiralpak IA column, eluent heptane-2-
propanol (90:10), 1 mLminÀ1]: retention times 24.6 (major)
and 29.6 min.
Xia, W-B. Liu, T-M. Wang, S-L. You, Chem. Eur. J.
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Acknowledgements
We are grateful to ICSN for financial support. This work has
been done within the PhoSciNet COST action.
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1123

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[22] 6-Phenyl-3-(p-nitrophenylsulfonyl)-3-azabicycloACTHUNTGRNEUNG[4.1.0]-
hept-4-ene 7f (50 mg, 0.14 mmol) has been reacted
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at 508C for 1 h, in the presence of K2CO3 (77 mg,
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amine has been converted into the known N-tosyl-pro-
1124
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Adv. Synth. Catal. 2011, 353, 1109 – 1124