PtCl2-catalyzed cycloisomerizations of 5-en-1-yn-3-ol systems.

Full text of DOI:10.1021/ja0474695

Published on Web 06/25/2004
PtCl2-Catalyzed Cycloisomerizations of 5-En-1-yn-3-ol Systems
Youssef Harrak, Christophe Blaszykowski, Matthieu Bernard, Kevin Cariou, Emily Mainetti,
Virginie Mourie`s, Anne-Lise Dhimane,* Louis Fensterbank,* and Max Malacria*
UniVersite´ Pierre et Marie Curie, Laboratoire de Chimie Organique, UMR CNRS 7611, Tour 44-54, case 229,
4, place Jussieu, 75252 Paris Cedex 05, France
Received April 30, 2004; E-mail: adhimane@ccr.jussieu.fr; fensterb@ccr.jussieu.fr; malacria@ccr.jussieu.fr
Scheme 1
Because of the compatibility and the utilization of very diverse
precursors, the PtCl2-catalyzed cycloisomerization of enyne systems
has recently witnessed synthetically versatile developments, includ-
ing notably applications in the total synthesis of natural products.1
However, these reactions have appeared as highly substrate-
dependent, so that further insight into the mechanism of these
transformations is desirable.2 Thus, the reactivity of novel unsatur-
ated systems constitutes an important opportunity in terms of
synthetic applications as well as mechanistic findings. We have
recently shown that these cycloisomerization processes can be
extended to a variety of partners such as enynol derivatives 1,3
allenynes,4 and ene-tosylynamides.5 Moreover, in the case of
substrates 1 (R * H), the nature of the hydroxy protecting group
at the propargylic position is a very practical handle for controlling
the outcome of the reaction.3 When this function is free, or appears
as a silyl or a methoxy ether, the presumed cyclopropyl platina-
carbene intermediate 21 leads to metathesis-type6 and polycyclic
derivatives, while bicyclic [4.1.0] derivatives are isolated when an
O-acyl group is present. In the latter case, the electrophilic activation
of the alkyne would trigger a 1,2-migration of the O-acyl group,
which generates the platinacarbene intermediate 3 (Scheme 1).7,8
While delineating the scope of this process, an interesting
observation emerged from the fact that secondary analogues of 1
(R ) H) provided contrasting results (Scheme 2). Precursor 6a
furnished the expected metathesis-type product 8a.9 However, for
ester precursors, O-acyl migration process is significantly retarded
compared to this metathesis-type pathway. No bicyclic [4.1.0]
derivative was observed in the case of 4,10 while the introduction
of a gem-dimethyl group on the tether as in precursors 6b and 6c
would slow the formation of intermediate 2 and restore the
migration process. It is also worthy of note that both 6b and 6c
yielded to the same ratio of products 7 and 8. Although consistent
with Uemura’s results,8 but still in need of being fully rationalized,11
the difficulty of the O-acyl migration on these secondary substrates
led us to study the analogue enyne precursors shortened by one
carbon atom. Indeed, because of a putative highly strained
intermediate, the competitive metathesis-type pathway should be
now disfavored and only the migration process would remain
possible. Herein, we report on the wealth of the reactivity of the
previously unexplored secondary 5-en-1-yn-3-ol systems.
Scheme 2 a
a Reaction was run in refluxing toluene.
yield and as a single diastereomer whose stereochemistry was
deduced from NOE studies. Finally, a carbonate substrate could
be successfully engaged in these reactions, as demonstrated by the
transformation of 15 into 16. Enol ester 12a and carbonate 16 were
then hydrolyzed to give the same known ketone 17,12 thus
establishing the regiochemical assignment of these products.
We next turned our attention to the possibility of promoting a
1,2-hydride shift13 on these subtrates as suggested in Scheme 4,
which would imply the existence of a nonparticipating OX group
at the propargylic position.14 This could be easily demonstrated by
using OTBS precursors 18 and eVen more gratifyingly with free
hydroxy substrates 20 and styryl 22!
It should be noted that ketone 21 is regioisomeric with respect
to 17, thus demonstrating that access to both products is straight-
forward by simple tuning of the OX group. In the case of styryl
precursors, stereochemical information of the precursor double bond
was retained, furnishing high yields of bicyclic derivatives 23 and
24 as single distinct diastereomers whose relative stereochemistries
were established by NOE.
We initially focused on the simplest term (precursor 9) and were
pleased to confirm that our assumption was correct since bicyclic
[3.1.0] 10 was smoothly obtained in 85% yield (see Scheme 3).
Similarly, methallyl precursor 11a could undergo the transformation
(80% of 12a). The catalyst loading could even be reduced to 2
mol % with no alteration of the yield. Substitution of the alkyne is
possible since introduction of an ester still gave a valuable
transformation (50% yield of 12b), albeit under harsher conditions.
A styryl moiety proved to be a good partner for the intermediate
carbene. Indeed, cyclopropyl derivative 14 was obtained in good
Finally, this chemistry can be useful for the synthesis of important
molecules in the aroma and fragrance industry. This is illustrated
9
8656
J. AM. CHEM. SOC. 2004, 126, 8656-8657
10.1021/ja0474695 CCC: $27.50 © 2004 American Chemical Society

C O M M U N I C A T I O N S
Scheme 3
Scheme 5
activation of the alkyne moiety triggers at wish a hydride or an
O-acyl migration yielding at the end to regioisomeric keto deriva-
tives. The efficient preparation of an important monoterpene
precursor has been worked out. Further applications of this process
in complex natural product synthesis as well as asymmetric catalysis
are being pursued.
Acknowledgment. M.M. is a member of the Institut Univer-
sitaire de France, and the authors thank IUF for generous financial
support of this work, as well as the Ministe`re de la Recherche for
a postdoctoral grant to Y.H., and Ph.D. grants to C.B. and E.M.
We thank Prof. P. A. Wender (Stanford University) for helpful
discussions.
Supporting Information Available: Experimental procedures and
spectral data for all new compounds. This material is available free of
charge via the Internet at http://pubs.acs.org.
References
(1) For recent contributions, see: (a) Chatani, N.; Kataoka, K.; Murai, S.;
Furukawa, N.; Seki, Y. J. Am. Chem. Soc. 1998, 120, 9104-9105. (b)
Trost, B. M.; Doherty, G. A. J. Am. Chem. Soc. 2000, 122, 3801-3810.
(c) Me´ndez, M.; Mun˜oz, M. P.; Nevado, C.; Ca´rdenas, D. J.; Echavarren,
A. M. J. Am. Chem. Soc. 2001, 123, 10511-10520. (d) Mart´ın-Matute,
B.; Nevado, C.; Ca´rdenas, D. J.; Echavarren, A. M. J. Am. Chem. Soc.
2003, 125, 5757-5768. (e) Fu¨rstner, A.; Stelzer, F.; Szillat, H. J. Am.
Chem. Soc. 2001, 123, 11863-11869. (f) Fu¨rstner, A.; Szillat, H.; Gabor,
B.; Mynott, R. J. Am. Chem. Soc. 1998, 120, 8305-8314. (g) Charruault,
L.; Michelet, V.; Taras, R.; Gladiali, S.; Geneˆt, J.-P. Chem. Commun.
2004, 850-851.
Scheme 4
(2) (a) Aubert, C.; Buisine, O.; Malacria, M. Chem. ReV. 2002, 102, 813-
834. (b) Me´ndez, M.; Mamane, V.; Fu¨rstner, A. ChemtractssOrg. Chem.
2003, 16, 397-425. (c) Lloyd-Jones, G. C. Org. Biomol. Chem. 2003, 1,
215-236. (d) Nevado, C.; Ca´rdenas, D. J.; Echavarren, A. M. Chem. Eur.
J. 2003, 9, 2627-2635.
(3) Mainetti, E.; Mourie`s, V.; Fensterbank, L.; Malacria, M.; Marco-Contelles,
J. Angew. Chem., Int. Ed. 2002, 41, 2132-2135.
(4) Cadran, N.; Cariou, K.; Herve´, G.; Aubert, C.; Fensterbank, L.; Malacria,
M.; Marco-Contelles, J. J. Am. Chem. Soc. 2004, 126, 3408-3409.
(5) Marion, F.; Coulomb, J.; Courillon, C.; Fensterbank, L.; Malacria, M.
Org. Lett. 2004, 6, 1509-1511.
(6) Formation of metathesis-type products from intermediates of type 2 has
been proposed: (a) Trost, B. M.; Tanoury, G. H. J. Am. Chem. Soc. 1988,
110, 1636-1638. (b) Oi, S.; Tsukamoto, I.; Miyano, S.; Inoue, Y.
Organometallics 2001, 20, 3704-3709.
(7) For a pioneering report, see: Rautenstrauch, V. J. Org. Chem. 1984, 49,
950-952.
(8) For a recent intermolecular version: Miki, K.; Ohe, K.; Uemura, S. J.
Org. Chem. 2003, 68, 8505-8513.
(9) This moderate yield of 6a is presumably attributable to the volatility of
this material.
(10) Other dienic isomers (15%) contaminated product 5.
(11) One hypothesis is that due to orbital stereocontrol, the 1,2-migration is
not a concerted process, so that a certain degree of positive charge
(carbocation) stabilization is required at the propargylic position. This
would take place in the case of tertiary substrates.
(12) Kirschberg, T.; Mattay, J. J. Org. Chem. 1996, 61, 8885-8896.
herein by the expeditive synthesis of the sabina ketone from
precursor 25 (see Scheme 5). Sabina ketone is a natural product
that is a key intermediate for the synthesis of important monoter-
penes such as sabinene and sabinene hydrates.15
(13) For previous reports of similar 1,2-hydride shifts with heteroprecursors,
see refs 1c and 1e.
(14) An alternative mechanism for this process would involve a 1,2-hydride
shift taking place on a bicyclic platinum carbene formed by a 5-endo-dig
process. We thank one referee for this suggestion.
In conclusion, we have shown that 5-en-1-yn-3-ol substrates
bearing a free hydroxyl group or an acyl group are highly versatile
partners for PtCl2-catalyzed cycloisomerizations. Electrophilic
(15) (a) Barberis, M.; Pe´rez-Prieto, J. Tetrahedron Lett. 2003, 44, 6683-6685.
(b) Galopin, C. C. Tetrahedron Lett. 2001, 42, 5589-5591.
JA0474695
9
J. AM. CHEM. SOC. VOL. 126, NO. 28, 2004 8657