Enantioselective cycloisomerization of 1,5-enynes promoted by cyclometalated NHC-PtII-Monophos catalysts

Article abstract of DOI:10.1002/ejic.201100818

The enantioselective cycloisomerizations of 1,5-enynes bearing non-migrating oxygen functions at the propargylic carbon atom have been carried out by using Monophos-Pt^II and Binepine-Pt^II complexes as chiral precatalysts. They afforded the corresponding bicyclo[3.1.0]hexan-3-one in up to 63 % enantiomeric excess. The stereochemical outcome of these reactions has been investigated in order to highlight possible matching-mismatching effects between the chiral catalyst and chiral substrates with opposite configurations at the stereogenic carbon. A substantial effect of the stereogenic carbon has been evidenced. Copyright

Full text of DOI:10.1002/ejic.201100818

SHORT COMMUNICATION
DOI: 10.1002/ejic.201100818
Enantioselective Cycloisomerization of 1,5-Enynes Promoted by
Cyclometalated NHC–PtII–Monophos Catalysts
Hélène Jullien,[a] Delphine Brissy,[a] Pascal Retailleau,[a] and Angela Marinetti*[a]
Keywords: Platinum / Isomerization / Enantioselectivity
The enantioselective cycloisomerizations of 1,5-enynes bear- reactions has been investigated in order to highlight possible
ing non-migrating oxygen functions at the propargylic car-
bon atom have been carried out by using Monophos–PtII and
Binepine–PtII complexes as chiral precatalysts. They afforded
the corresponding bicyclo[3.1.0]hexan-3-one in up to 63%
enantiomeric excess. The stereochemical outcome of these
matching–mismatching effects between the chiral catalyst
and chiral substrates with opposite configurations at the ste-
reogenic carbon. A substantial effect of the stereogenic car-
bon has been evidenced.
cycloisomerizations of N-tethered enynes into the corre-
sponding aza-bicyclo[4.1.0]heptenes.[8c,8d] The Ph-Binepine
complexes 2 afforded very high levels of enantioselectivity
(ees of up to 97%), while the Monophos complexes 1 dis-
played higher catalytic activity but somewhat lower stereo-
control in these reactions (ees of up to 84%).
Introduction
Extensive synthetic and mechanistic studies have been
carried out on the transition-metal promoted cycloisomer-
izations of enynes, since these are key reactions that allow
the easy preparation of synthetically important building
blocks.[1] Notably, 1,5-enynes bearing an oxygenated func-
tion at the propargylic position have been widely used as
suitable precursors for the bicyclic and polycyclic scaffolds
of terpenoid derivatives. Relevant examples are the synthe-
ses of sabinol,[2] sabina ketone,[3] cubebol,[4] carenes,[4b,5]
cedrene,[6] and others,[7] by gold- or platinum-catalyzed re-
arrangements of enynes of this class. The highly desirable
access to these and analogous bicyclic scaffolds in enantio-
merically enriched form has been envisioned so far by either
diastereoselective cyclizations or chirality transfer from en-
antiomerically enriched substrates.[2,4] Here, we disclose the
first studies on the enantioselective cycloisomerizations of
1,5-enynes of this class, in the frame of our ongoing work
on enantioselective platinum-promoted cycloisomeriza-
tions.[8] Especially, the preliminary studies reported here are
intended to evidence the effects of the stereogenic carbon
of the substrates on the stereochemical course of these reac-
tions.
Scheme 1. Platinacyclic catalysts for the enantioselective cyclo-
isomerizations of [1,n]-enynes.
These previous studies demonstrated that precatalysts 1
and 2 are especially suited for reactions in which platinum
behaves as a Lewis acid, i.e. for reactions involving an elec-
trophilic activation of the alkyne moiety.[9] Therefore, as a
logical extension of this work, we next considered the cyclo-
isomerization of 3-hydroxylated 1,5-enynes[10] and their O-
substituted analogues, typified by 3a–e in Scheme 2.
Results and Discussion
Our previous work highlighted cyclometalated N-hetero-
cyclic carbene complexes 1 and 2 (Scheme 1) as the first
platinum-based catalysts allowing highly enantioselective
[a] Institut de Chimie des Substances Naturelles, CNRS UPR 2301
1, av. de la Terrasse, 91198 Gif-sur-Yvette, France
Fax: +33-1-69077247
E-mail: angela.marinetti@icsn.cnrs-gif.fr
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejic.201100818.
Scheme 2. Cycloisomerization of 1,5-enynes with non-migrating
oxygen functions at the propargylic position.
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H. Jullien, D. Brissy, P. Retailleau, A. Marinetti
SHORT COMMUNICATION
The starting materials 3 display a stereogenic center at the O–Bn and O–Me substituted enynes 3b and 3c, respec-
the propargylic position, which might affect the stereo- tively, afforded the corresponding ketones in Ͻ30% ee (En-
chemical course of the reaction. A priori, the presence of tries 3 and 4), while the bulky silyl ethers 3d and 3e allowed
this stereogenic center does not rule out the possibility of enantiomeric excesses of 63–65% to be obtained. The
setting enantioselective, catalyst-controlled reactions; never- enantioselectivity levels could be slightly modulated by
theless, the role of the stereogenic center should be estab- changing the N-substituent in the carbene moiety of the
lished before entering into extensive studies on enantioselec- platinum catalysts 1 (Entries 5–7) – the bulky tBu group
tive variants of these processes.
gives the highest enantioselectivity.
For initial studies, 5-methyl-1-phenylhex-5-en-1-yn-3-ol
These preliminary results demonstrate the feasibility of
(3a) served as the model substrate, then the corresponding the enantioselective cycloisomerization of 1,5-enynes with
ethers 3b,c and the O-silylated derivatives 3d,e were consid- non-migrating oxygen functions at the propargylic position,
ered. On the basis of extensive literature reports,[2,3,11] these into bicyclic [3.1.0] scaffolds. An interesting issue that re-
1,5-enynes, which display non-migrating oxygen functions mains to be solved is the role of the stereogenic carbon
at the propargylic position, were anticipated to lead to the center of the substrate in the stereochemical control of these
bicyclo[3.1.0]hexan-3-one 4 or to the corresponding enol cycloisomerization processes.
ethers 5 as the cycloisomerization products (Scheme 2). The
Literature data provide strong evidence for a degree of
cycloisomerization experiments were carried out under chirality transfer from chiral propargylic substrates to the
standard conditions, by activating the platinum complexes final products in analogous reactions. Studies on this topic
1 and 2 by addition of AgBF4.[12] The main results are sum- involve, however, either enyne substrates with migrating
marized in Table 1. Both the Monophos and Binepine com- oxygen groups (OAc, OPiv)[4,16] at their propargylic posi-
plexes 1 and 2 proved to be suitable precatalysts for these tions or propargylic alcohols with additional stereogenic
reactions, which led to the expected bicyclic derivatives 4 or centers.[2] Therefore, the results of these studies cannot con-
5 in moderate to good yields. The silyl enol ethers 5d,e were sistently be extrapolated to substrates 3 in Scheme 2. It is
suitably converted into 4 by reaction with tetrabutylammo- reasonably expected that the stereogenic center of 3 will
nium fluoride (TBAF), and the enantiomeric excesses were modulate the enantioselectivity levels, although the degree
measured on samples of 4[13] by HPLC.
of stereochemical control afforded by the stereogenic center
and the chiral catalyst can hardly be anticipated. The fol-
lowing experiments allowed us to get reliable information
on this crucial point.
Table 1. Enantioselective cycloisomerizations of 1,5-enynes pro-
moted by the PtII complexes 1 and 2.
At first, the reaction sequence in Scheme 3 provided us
with samples of the enantiomerically enriched, silylated en-
ynes 3d with opposite carbon configurations. The procedure
involves resolution of alcohol 3a by SFC separation of the
diastereomeric camphanic esters 6 and conversion of the
enantiomerically enriched alcohols to the corresponding
TBS ethers (R)- and (S)-3d.
[a] Conditions: 4 mol-% catalyst, 12 mol-% AgBF4, toluene, 60 °C,
18 h. [b] Isolated yield of 4 + 5. [c] The 4/5 ratios are given for
reactions run in reagent grade, non-dried solvents. Ratios may vary
with the amount of water in the reaction mixture. [d] By chiral
HPLC.
In contrast to the cycloisomerizations of the N-tethered
enynes,[8c,8d] here the Monophos-PtII complexes 1 proved to
be better catalysts than the Binepine complexes 2, in terms
of both catalytic activity and enantioselectivity. Thus, for
instance, the propargylic alcohol 3a was converted into the
bicyclo[3.1.0]hexan-3-one derivative 4 in 53% ee when using
the (R)-Monophos complex 1a as the precatalyst, while the
(S)-Ph-Binepine complex 2a afforded 4 in Ͻ10% ee (Entry
1 vs. 2). The same trend was observed for the O-silylated
substrate 3d (Entries 5–7 vs. 8,9).
Scheme 3. Synthesis of (R)- and (S)-3d.
From experiments on different substrates, it appears that
The configuration of the propargylic carbons of the dia-
simple modifications of the oxygen substituent are crucial stereomeric esters 6 has been assigned by an X-ray diffrac-
with respect to the stereochemical outcome of the reaction: tion study of (S)-6b (see Supporting Information).[15]
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Enantioselective Cycloisomerization of 1,5-Enynes
(6.4ϫ10–3 mmol, 4 mol-%) in toluene (0.5 mL) under argon. The
mixture was stirred at 60 °C for 18 h. The solvent was removed
under reduced pressure, the crude mixture was monitored by NMR
spectroscopy, and the final product, 4, was purified by column
chromatography with heptane/EtOAc (90:10) as the eluent. 1H
NMR (300 MHz, CDCl3): δ = 0.64 (d, 2J = 6.0 Hz, 1 H, CH2),
The enantiomerically enriched substrates 3d were sub-
jected to cycloisomerization in the presence of either PtCl2
or the (R)-Monophos complex (R)-1. The results are re-
ported in Scheme 4. From these experiments, it appears
that: (a) a substantial but partial transfer of chirality from
enantiomerically enriched 3d (Ͼ95% ee) takes place when
using PtCl2 as the catalyst, which leads to the final product
4 in 54% enantiomeric excess (Entry 2); (b) when using the
platinacyclic catalyst 1a, the stereochemical control from
2
1.06 (s, 3 H, Me), 1.24 (m, 1 H, CH2), 2.48 (d, J = 19.0 Hz, 1 H,
2
2
4
CH2), 2.63 (d, J = 19.0 Hz, 1 H, CH2), 2.67 (dq, J = 19.0, J =
2.0 Hz, 1 H, CH2), 2.92 (dq, J = 19.0, J = 2.0 Hz, 1 H, CH2), 7.25–
7.4 (5 H, Ph) ppm. 13C NMR (75 MHz, CDCl3): δ = 18.6 (Me),
the chiral catalyst overcomes the effect of the chiral sub- 23.8 (CH2), 26.1 (C), 33.5 (C), 48.3 (CH2), 50.3 (CH2), 126.6, 128.5,
129.2, 140.1 (C), 216.4 (CO) ppm. ESI-MS: m/z = 187 [M + H]+.
Enantiomeric excesses were measured by chiral HPLC: Chiracel
AD-H, heptane/2-propanol 99:1, 1 mL/min, retention times 4.4 and
strate (Entries 2 and 3); (c) the (R)-configured substrate
(R)-3d constitutes a matching pair with the (R)-Monophos
complex (R)-1a, which allows the desired cycloisomeriza-
tion product 4 to be obtained in 92% enantiomeric excess.
The same catalyst converts the (S)-configured substrate into
4 with 35% ee (Entries 3 and 4). These results are fully
consistent with the 63% ee obtained in the cycloisomeriza-
tion of racemic 3d.
5.3 min. Racemic
isomerization.
4 was obtained by PtCl2-promoted cyclo-
Supporting Information (see footnote on the first page of this arti-
cle): Further experimental procedures and characterization details
of the compounds and an ORTEP diagram of the S-configuration
of the propargylic carbon of (SCH)-6b are presented.
Acknowledgments
We would like to thank the COST action (CM0802) “PhoSciNet”
for support.
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Eur. J. Inorg. Chem. 2011, 5083–5086
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H. Jullien, D. Brissy, P. Retailleau, A. Marinetti
SHORT COMMUNICATION
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Received: August 2, 2011
Published Online: October 21, 2011
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