Cyclobutenes by platinum-catalyzed cycloisomerization reactions of enynes

Article abstract of DOI:10.1021/ja050845g

1,6-Enynes bearing (electron-rich) aryl substituents on their alkyne moiety rearrange to cyclobutene derivatives in the presence of catalytic amounts of PtCl₂ in toluene. The reaction is significantly accelerated when performed under an atmosph

Full text of DOI:10.1021/ja050845g

Published on Web 05/18/2005
Cyclobutenes by Platinum-Catalyzed Cycloisomerization Reactions of Enynes
Alois Fu¨rstner,* Paul W. Davies, and Tobias Gress
Max-Planck-Institut fu¨r Kohlenforschung, D-45470 Mu¨lheim/Ruhr, Germany
Received February 9, 2005; E-mail: fuerstner@mpi-muelheim.mpg.de
Scheme 1
Although the ability of PtCl2 to induce a host of selective
rearrangements of polyunsaturated compounds was recognized only
recently,1 this branch of catalysis research is now rapidly expanding.
Driven by the high affinity of Pt(+2) or other noble metal cations
to the π-systems of the substrates, such transformations engender
a significant increase in molecular complexity, while being
operationally simple, safe, and convenient to perform.2,3
It is generally accepted that nonstabilized platinum carbenes
constitute the actual intermediates in these reactions.2,4 Because such
species are best viewed as latent “non-classical” cations A that
evolve along different pathways,5 the diversity of product structures
accessible by this methodology is easy to explain (Scheme 1).
Specifically, the canonical form B representing a complexed cyclo-
propyl methyl cation leads to vinylcyclopropanes which are well
documented reaction products, especially for substrates with hetero-
atoms in the tether (X ) NTs, O);6 another conceivable cyclopropyl
Scheme 2
methyl cation form E (5-exo cyclization mode) has also been ex-
perimentally verified.7 The corresponding representation of the re-
active intermediate as “homoallylic cation” C visualizes the enyne
metathesis pathway to 1,3-diene products, which has been studied
in great detail.2 In contrast to these established “outlets”, the re-
maining canonical form D representing the putative cyclobutenyl
cation has been repeatedly invoked but hardly confirmed experi-
mentally.8,9 This paper shows how simple structural modifications
in the substrates allow one to substantiate this immanent reactive in-
termediate and thereby give access to polycyclic skeletons that are
difficult to obtain otherwise. Moreover, a convenient way to accel-
erate these novel Pt(+2)-catalyzed skeletal rearrangements is outlined.
For the canonical form D to gain weight in the equilibrium shown
in Scheme 1, it may suffice to substitute the color-coded position
with an appropriate cation-stabilizing group. The most expedient
way to do so uses enynes with aromatic residues on their alkyne
unit (Scheme 2).
Scheme 3
In fact, small amounts of cyclobutene 2a were obtained in addi-
tion to the regular “metathesis product” 3a1 when compound 1a
was exposed to catalytic amounts of PtCl2 in toluene at 80 °C.
Gratifyingly, substrate 1b, bearing a p-methoxyphenyl ring able to
stabilize a putative benzylic cation of type D more effectively, clearly
favors 2b over 3b. The reaction, however, was fairly slow and re-
quired >16 h to go to completion. In an attempt to accelerate this
transformation, the mixture was stirred under an atmosphere of CO.
By virtue of its strongly π-acidic character, this ligand should in-
crease the electrophilicity of the metal center and, hence, the cationic
character of the reactive intermediate while being sufficiently labile
on the Pt(+2) template not to block the necessary coordination sites
for the reaction to proceed.10 In line with this rationale, only 2 h
reaction time was necessary to effect the rearrangement of 1b when
performed under CO (1 atm), providing the desired cyclobutene
2b in 58% yield.11 The diagnostic pink color of the mixture fades
away when the conversion is complete, thus allowing one to
conveniently monitor the course of this reaction.12
Supporting Information). Although a detailed mechanistic picture
requires further studies, the site of unsaturation in 2 suggests that
the cation of type D favors loss of a proton over simple elimination
of PtCl2 to avoid positioning the alkene in the highly unfavorable
bridgehead position of the “anti-Bredt” isomer 2′ (Scheme 3).13-16
The formally resulting allylplatinum hydride species F then
undergoes reductive elimination to give the observed product 2.
No indications whatsoever are available that 2 is derived from the
isomeric compound 2′ by shift of the double bond. Therefore, it is
also unlikely that the PtCl2-catalyzed reactions described herein
proceed via metallacyclopentenes,17 as such intermediates would
necessarily lead to 2′ rather than 2 as the primary product.
As shown by the examples compiled in Scheme 4, the PtCl2-
catalyzed cyclobutene formation is fairly general for carbocyclic
skeletons. It is interesting to note that substrate 4 bearing the ether
substituent in the ortho- rather than the para-position of the phenyl
ring affords product 5 in 84% isolated yield, with virtually no
metathesis product being detected in the crude mixture. Likewise,
Extensive NMR studies provide unambiguous proof for the
constitution of 2 (and all other cyclobutenes described below; cf.
9
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J. AM. CHEM. SOC. 2005, 127, 8244-8245
10.1021/ja050845g CCC: $30.25 © 2005 American Chemical Society

C O M M U N I C A T I O N S
Scheme 4
Scheme 5
gained to various target structures of significant complexity from
readily available starting materials.
Acknowledgment. Financial support by the MPG and the Fonds
der Chemischen Industrie is gratefully acknowledged. We thank
Umicore AG, Hanau, for a gift of noble metal salts.
Supporting Information Available: Experimental part including
spectroscopic data for all new compounds. This material is available
free of charge via the Internet at http://pubs.acs.org.
References
(1) Pioneering study on PtCl2-catalyzed metathesis reactions: Chatani, N.;
Furukawa, N.; Sakurai, H.; Murai, S. Organometallics 1996, 15, 901.
(2) Reviews: (a) Aubert, C.; Buisine, O.; Malacria, M. Chem. ReV. 2002,
102, 813. (b) Me´ndez, M.; Echavarren, A. M. Eur. J. Org. Chem. 2002,
15. (c) Lloyd-Jones, G. C. Org. Biomol. Chem. 2003, 1, 215. (d) Me´ndez,
M.; Mamane, V.; Fu¨rstner, A. Chemtracts 2003, 16, 397.
(3) (a) Mamane, V.; Gress, T.; Krause, H.; Fu¨rstner, A. J. Am. Chem. Soc.
2004, 126, 8654. (b) Fu¨rstner, A.; Hannen, P. Chem. Commun. 2004, 2546.
(c) Mamane, V.; Hannen, P.; Fu¨rstner, A. Chem.sEur. J. 2004, 10, 4556.
(d) Fu¨rstner, A.; Mamane, V. J. Org. Chem. 2002, 67, 6264. (e) Fu¨rstner,
A.; Mamane, V. Chem. Commun. 2003, 2112.
(4) (a) Echavarren, A. M.; Nevado, C. Chem. Soc. ReV. 2004, 33, 431. (b)
Soriano, E.; Ballesteros, P.; Marco-Contelles, J. J. Org. Chem. 2004, 69,
8018.
(5) Fu¨rstner, A.; Szillat, H.; Gabor, B.; Mynott, R. J. Am. Chem. Soc. 1998,
120, 8305.
enynes of type 6 and 8 perform remarkably well despite the high
stain of the resulting tricyclic skeletons. As expected, variations of
the substituent on the phenyl ring affect the product distribution,
most likely by modulating the stability of the presumed benzylic
cation D. Thus, substrates 8a,b provide the cyclobutenes 9a,b in
high yields; likewise, 8c gives compound 9c in 76% yield together
with 11% of 10 derived from direct attack of its phenolic -OH
group onto the initial alkyne-Pt(+2) π-complex. In contrast,
compound 8d (Ar ) p-F3CC6H4) affords a mixture of cyclobutene
9d and the metathesis product 11 (1.5:1, 84%). Replacement of
the electron-deficient arene by the electron-rich benzofuran in 8e
re-establishes the formation of the cyclobutene product. It should
be emphasized that all examples depicted in Scheme 4 show a
particularly pronounced effect of CO on the reaction rates.11 Only
very poor conversions are reached under argon, even if the mixtures
are stirred for several days at 80 °C, whereas all rearrangements
proceed smoothly when performed under CO (1 atm) as described.
As mentioned above, enynes with heteroelements in the tether
tend to form vinylcyclopropanes as products supposedly via the
canonical form B, which is stabilized by orbital overlap between
the metal carbene moiety and the adjacent C-X (X ) O, NTs)
bond. To see whether substrates of this type might be forced to
deviate from this preferred pathway, enyne 12 was reacted with
PtCl2 catalyst in toluene under CO atmosphere (Scheme 5). The
only product isolated, however, was cyclopropane 13, thus showing
that the resonance stabilization in B is more effective than the
stabilization of the benzylic cation in D by the attached electron-
rich arene ring.
(6) (a) Fu¨rstner, A.; Szillat, H.; Stelzer, F. J. Am. Chem. Soc. 2000, 122,
6785. (b) Fu¨rstner, A.; Stelzer, F.; Szillat, H. J. Am. Chem. Soc. 2001,
123, 11863.
(7) (a) Me´ndez, M.; Mun˜oz, M. P.; Nevado, C.; Ca´rdenas, D. J.; Echavarren,
A. M. J. Am. Chem. Soc. 2001, 123, 10511. (b) Chatani, N.; Kataoka, K.;
Murai, S.; Furukawa, N.; Seki, Y. J. Am. Chem. Soc. 1998, 120, 9104.
(8) Bicyclic cyclobutenes with the double bond between the bridgehead atoms
were obtained from ene-ynamides: Marion, F.; Coulomb, J.; Courillon,
C.; Fensterbank, L.; Malacria, M. Org. Lett. 2004, 6, 1509.
(9) Single examples of cyclobutenes were reported in ref 6b and the
following: Bajracharya, G. B.; Nakamura, I.; Yamamoto, Y. J. Org. Chem.
2005, 70, 892. In both cases, the position of the double bond differs from
that in compound 2 and its analogues.
(10) Lutton, J. M.; Parry, R. W. J. Am. Chem. Soc. 1954, 76, 4271.
(11) Kinetic experiments show that in our case the presence of CO decelerates
the “enyne metathesis” pathway but accelerates cyclobutene formation.
This result contrasts a report of Murai et al. in which enyne metathesis
catalyzed by [RuCl2(CO)3]2 is accelerated when performed under a CO
atmosphere: Chatani, N.; Morimoto, T.; Muto, T.; Murai, S. J. Am. Chem.
Soc. 1994, 116, 6049.
(12) Only enynes with ether substituents on their phenyl rings show this
characteristic coloration of the reaction mixture.
(13) In addition, coordination of Pt(+2) in intermediate F to CO reduces its
electron density and, hence, its ability to eliminate directly, thus rendering
proton loss a competitive process.
(14) A similar argument pertains to products 7 and 9, which are significantly
more stable than their positional isomers.
(15) Cyclobutenes with the double bond in the same location are extremely
scarce; two examples are described as products of palladol-catalyzed
processes: (a) Trost, B. M.; Tanoury, G. J. J. Am. Chem. Soc. 1988, 110,
1636. (b) Trost, B. M.; Trost, M. K. Tetrahedron Lett. 1991, 32, 3647.
(16) While this paper was under review, Echavarren et al. reported two related
examples using gold complexes as catalysts: Nieto-Oberhuber, C.; Lo´pez,
S.; Echavarren, A. M. J. Am. Chem. Soc. 2005, 127, 6178.
(17) Metallacyclopentenes were proposed as intermediates in cycloisomeriza-
tions of electron-poor enynes mediated by palladacycle catalysts: (a) Trost,
B. M.; Trost, M. K. J. Am. Chem. Soc. 1991, 113, 1850. (b) Trost, B. M.;
Yanai, M.; Hoogsteen, K. J. Am. Chem. Soc. 1993, 115, 5294.
In summary, evidence is provided for an essential component
of the cationic manifold by which the diverse array of rearrangement
reactions catalyzed by PtCl2 is explained. Furthermore, access is
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