Platinum(II)-catalyzed 1,6-diene cycloisomerizations: Turnover in the absence of β-hydride elimination

Article abstract of DOI:10.1021/ol048780u

(Equation Presented) Electrophilic pincer-ligated Pt(II)-dications are efficient catalysts for the cycloisomerization of 1,6-dienes, initiated by alkene activation. The tridentate ligands inhibit β-hydride elimination and thus enable cationic mechanisms that turnover by Pt(II) extrusion. PPP ligands lead to cyclopropane products, while PNP ligands provide cyclohexene products; mechanistic issues are also discussed.

Full text of DOI:10.1021/ol048780u

ORGANIC
LETTERS
2004
Vol. 6, No. 17
3013-3015
Platinum(II)-Catalyzed 1,6-Diene
Cycloisomerizations: Turnover in the
Absence of â-Hydride Elimination
William D. Kerber, Jeong Hwan Koh, and Michel R. Gagne´*
Department of Chemistry, UniVersity of North Carolina at Chapel Hill,
Chapel Hill, North Carolina 27599-3290
mgagne@unc.edu
Received June 26, 2004
ABSTRACT
Electrophilic pincer-ligated Pt(II)-dications are efficient catalysts for the cycloisomerization of 1,6-dienes, initiated by alkene activation. The
tridentate ligands inhibit â-hydride elimination and thus enable cationic mechanisms that turnover by Pt(II) extrusion. PPP ligands lead to
cyclopropane products, while PNP ligands provide cyclohexene products; mechanistic issues are also discussed.
The cationic cyclization of polyolefins is an important
biosynthetic process that has been extensively studied in the
past 50 years.1 Because large increases in molecular com-
plexity can be obtained in a single step, synthetic chemists
have developed analogous nonenzymatic processes that
employ electrophilic reagents to activate polyolefins.2 A wide
range of Brønsted and Lewis acids have been examined;3
the intermediate carbocations often have low barriers to
rearrangement/cyclization, the reactions are extremely sensi-
tive to reaction conditions, and both kinetic and thermody-
namic control is possible.4
alkyl.5 In contrast, Vitagliano has recently reported that 1b
dimerizes olefins and that the tridentate ligand inhibits
â-hydride elimination, which promotes cationic intermediates
and turnover by extrusion of Pt(II) from a â-cation-containing
Pt-alkyl.6
We have investigated the use of catalysts 1a and 1b for
the cyclization of 6-methyl-1,6-dienes, which may be
considered intramolecular analogues of the Vitagliano alkene
dimerization reaction. Unexpectedly, however, 10 mol %
catalyst 1a rearranges diene 2a, with good selectivity (95:5
dr), to the fully saturated trans-[4.1.0] bicyclic product 3a
(eq 1), a common terpene-like fragment with a stereogenic
quaternary center.7
Group 10 metals are well-known to activate olefins toward
nucleophilic addition; however, turnover in these systems
often hinges on â-hydride elimination of the resulting metal-
A mechanistic proposal for the formation of 3 is shown
in Scheme 1.8 6-Exo-endo addition9 to the activated terminal
(1) (a) Wendt, K. U.; Schulz, G. E.; Corey, E. J.; Liu, D. R. Angew.
Chem., Int. Ed. 2000, 39, 2812. (b) Abe, I.; Rohmer, M.; Prestwich, G. D.
Chem. ReV. 1993, 93, 2189. (c) Richards, J. H.; Hendrickson, J. B. In The
Biosynthesis of Steroids, Terpenes, and Acetogenins; Breslow, R., Karplus,
M., Eds.; W. A. Benjamin, Inc.: New York, 1964.
(2) (a) Bartlet, P. A. In Asymmetric Synthesis; Morrison, J. D., Ed.;
Academic Press: Orlando, 1984; Vol. 3, p 342. (b) Sutherland, J. K. In
ComprehensiVe Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon
Press: Oxford, England, 1991; Vol. 3, p 341.
(3) See ref 2 and also: (a) Johnson, W. S.; Bartlett, W. R.; Czeskis, B.
A.; Gautier, A.; Lee, C. H.; Lemoine, R.; Leopold, E. J.; Luedtke, G. R.;
Bancroft, K. J. J. Org. Chem. 1999, 64, 9587 and references therein. (b)
Ishihara, K.; Ishibashi, H.; Yamamoto, H. J. Am. Chem. Soc. 2002, 124,
3647. (c) Nishizawa, M.; Takenaka, H.; Hayashi, Y. J. Org. Chem. 1986,
51, 806. (d) Corey, E. J.; Wood, H. B. J. Am. Chem. Soc. 1996, 118, 11982
and references therein.
(4) See, for example, Bright, S. T.; Coxon, J. M.; Steel, P. J. J. Org.
Chem. 1990, 55, 1338.
10.1021/ol048780u CCC: $27.50 © 2004 American Chemical Society
Published on Web 07/23/2004

consistent with this mechanism. Since each step in Scheme
1 is stereospecific, the initial C-C bond formation (A) sets
all three stereocenters in the product. In situ 31P NMR
analysis indicates that the catalyst rests at the coordinated
alkene stage.
Scheme 1. Proposed Cyclopropanation Mechanism
A brief examination of the scope of the cyclopropanation
indicated a tolerance for ortho- and para-OMe donors, but
not a meta-OMe or an unsubstituted ring (Table 1). In the
Table 1. Cycloisomerizations Catalyzed by Pt(II) Pincer
Complexes
a
Ar
diene
[Pt2+
]
t (h)
product
yieldd
olefin in A generates the cyclic Pt-alkyl cation B. This
intermediate undergoes a 1,2-hydride shift to place the
carbocation γ to the metal center, where capture by the Pt-C
bond generates the cyclopropane and extrudes Pt(II) (see
inset, Scheme 1).
The trans stereochemistry of the product requires that the
activated terminal alkene adopt a pseudoaxial orientation in
A. The accessibility of this conformer was previously noted
(in a minor product) in the stoichiometric cyclization of 1,6-
dienylphenols by 1a and 1b.10,11 Although the observed
cyclopropanation was unexpected, stannyl and ferrous γ-car-
bocations will lose M+ to form cyclopropanes,7,12,13 a direct
parallel to the postulated loss of Pt2+. Moreover, the
stereoelectronic preference for double inversion in the Sn
and Fe reactions (W configuration) is accommodated in the
putative intermediate C. The reactivity of 2a derivatives
labeled with deuterium at C-1, C-2, and C-8 (Scheme 1) was
1
2
3
4
5
6
2a
2c
2a
2b
2c
2d
o-MeOC6H4
p-MeOC6H4
o-MeOC6H4
m-MeOC6H4
p-MeOC6H4
C6H5
1a
1a
1b
1b
1b
1b
16
96
12
12
12
12
3a (95:5)b
3c (95:5)b
5a (2:1)c
5b (2:1)c
5c (2:1)c
5d (2:1)c
83%
65%
68%
70%
64%
68%
a 1a was generated in situ from (PPP)PtI2 and AgSbF6. 1b was isolated.
b Dr determined by 1H NMR. c Ratio of 3- to 2-cyclohexene determined
by GC. d Isolated.
latter cases, Brønsted background reactions initiate and cis-
and trans-4 result.4 This Brønsted mechanism could be
suppressed by the addition of excess Ph2NMe, but at the
expense of catalyst turnover. In the case of 2b and 2d,
unknown catalyst decomposition products were detected by
31P NMR14 that apparently led to HSbF6 generation. The
general requirement for an electron-rich aromatic ring (but
one not activated for addition) suggests a possible role for
bridging phenonium ions in intermediates such as C.15
(5) (a) Hegedus, L. S. In Transition Metals in the Synthesis of Complex
Organic Molecules; University Science Books: Mill Valley, CA, 1994; p
199. (b) Hegedus, L. S. In ComprehensiVe Organic Synthesis; Trost, B.
M., Ed.; Pergamon Press: 1991; Vol. 4, p 571.
(6) Hahn, C.; Cucciolito, M. E.; Vitagliano, A. J. Am. Chem. Soc. 2002,
124, 9038.
(7) (a) Taylor, R. E.; Engelhardt, F. C.; Schmitt, M. J. Tetrahedron 2003,
59, 5623. (b) Wessjohann, L. A.; Brandt, W.; Thiemann, T. Chem. ReV.
2003, 103, 1625.
(8) Diene cycloisomerization processes do not typically give cyclopro-
panes; see: (a) Lloyd-Jones, G. C. Org. Biomol. Chem. 2003, 1, 215. (b)
Widenhoefer, R. A. Acc. Chem. Res. 2002, 35, 905. Ene-ynes, on the other
hand, do typically give cyclopropanes: (c) Diver, S. T.; Giessert, A. J.
Chem. ReV. 2004, 104, 1317. For a recent Au(I) catalyst, see: (d) Nieto-
Oberhuber, C.; Mun˜oz, M. P.; Bun˜uel, E.; Nevado, C.; Ca´rdenas, D. J.;
Echavarren, A. M. Angew. Chem., Int. Ed. 2004, 43, 2402.
(9) This nomenclature first refers to the bond being activated and then
the nucleophilic bond.
(10) Koh, J. H., Gagne´, M. R. Angew. Chem., Int. Ed. 2004, 43, 3459.
(11) Cation-olefin cyclizations with oxonium initiators also proceed
selectively via this conformer; see ref 2a and: (a) Seiders, J. R., II; Wang,
L.; Floreancig, P. E. J. Am. Chem. Soc. 2003, 125, 2406. (b) Johnson, W.
S.; van der Gen, A.; Swoboda, J. J. J. Am. Chem. Soc. 1967, 89, 170.
(12) (a) Davis, D. D.; Johnson, H. T. J. Am. Chem. Soc. 1974, 96, 7576.
(b) Fleming, I.; Urch, C. J. Tetrahedron Lett. 1983, 24, 4591. (c) McWilliam,
D. C.; Balasubramanian, T. R.; Kuivila, H. G. J. Am. Chem. Soc. 1978,
100, 6407. (d) Lambert, J. B.; Salvador, L. A.; So, J. H. Organometallics
1993, 12, 697.
In contrast to the [4.1.0] bicyclic products formed from
1a, 10 mol % Pt(II) dication 1b converted the 1,6-dienes
2a-d to a mixture of geminal disubstituted cyclohexenes
5a-d (eq 2 and Table 1, entries 3-6). In each case, the
3-substituted regioisomer was the major product by a 2:1
ratio. The rate of this reaction was somewhat variable,
apparently because of small amounts of impurities in the
solvent.
(13) (a) Casey, C. P.; Smith, L. J. Organometallics 1989, 8, 2288. (b)
Casey, C. P.; Smith Vosejpka, L. J. Organometallics 1992, 11, 738. (c)
Brookhart, M.; Liu, Y.; Goldman, E. W.; Timmers, D. A.; Williams, G. D.
J. Am. Chem. Soc. 1991, 113, 927. (d) Brookhart, M.; Liu, Y. J. Am. Chem.
Soc. 1991, 939. Ti is also known, see: (e) Casey, C. P.; Strotman, N. A. J.
Am. Chem. Soc. 2004, 126, 1699.
Although no data has yet been mechanistically definitive,
the loss of one degree of unsaturation in 5 suggests a
cycloisomerization that turns over by eliminating Pt(II) from
3014
Org. Lett., Vol. 6, No. 17, 2004

a â-metalated carbocation (Vitagliano-like),6 e.g., Scheme
2. This mechanism invokes a 6-endo-exo addition to the Pt-
analogue of 1b converted 2a into a 3:1 mixture of cyclo-
propane and cyclohexene (the Pd analogue of 1a was
unreactive). This departure from Pt reactivity clearly indicates
that the competing turnover mechanisms are not only
sensitive to metal and ligand but also have sufficiently similar
rates to be affected by subtle catalyst changes.19
Scheme 2. Possible Mechanism for Cyclohexene Formation
The mechanisms proposed vide supra involve generation
of cationic intermediates in dichloromethane, and not sur-
prisingly, ion pairing with the catalyst counteranion proved
energetically important. When catalyst 1a was prepared with
-
the more-strongly coordinating BF4 anion, rates of cyclo-
propanation were significantly retarded. When catalyst 1b
-
was prepared with the more weakly coordinating SbF6
anion, rates of substrate consumption were increased;
however, significant decomposition occurred.20
Despite mechanistic ambiguities (for cyclohexene forma-
tion), these reactions are clean, under catalyst control, and
generate chiral quaternary centers from achiral alkene
substrates. Mechanistic observations suggest cycloisomer-
ization processes that proceed via intermediate carbocations,
each made possible by the inhibition of â-hydride elimina-
tion. Our working hypothesis places the platinum alkyl cation
intermediates on a relatively flat, multistructural potential
energy surface, with product output occurring under catalyst
control by the relative energetics of Pt(II) dication extrusion.
Encouraging for future development are observations that
despite the flat potential energy surface of the intermediate
carbocations and their inherent high reactivity, highly selec-
tive and diverse transformations are possible through catalyst
variations.
activated terminal olefin (D), followed by an uncommon 1,3-
hydride transfer16 to move the 2° cation into the ring.17
Extrusion of Pt2+ leads to the minor alkene isomer,6 which
can be subsequently isomerized to the major isomer.18
Unfortunately, efforts to test this hypothesis (and others) with
D-labeled 2a isotopomers were compromised by in situ
isotopic scrambling (intermolecular).
Crossover experiments were also performed to determine
if 5a resulted from isomerization of cyclopropane 3a. In the
event, 3a was unchanged in the presence of 10 mol % 1b,
eliminating this possible mechanism. Similarly, 5a was not
converted to 3a with catalyst 1a.
Acknowledgment. We gratefully acknowledge the NIGMS
(GM60578) for funding. W.D.K thanks Glaxo-Smith-Kline
for a graduate fellowship. M.R.G. is a Camille-Dreyfus
Teacher-Scholar.
In addition to being sensitive to ligand, the product
outcome was also sensitive to metal, as 10 mol % of the Pd
(14) Friedel-Craft-type cyclization on the activated ortho positions is
intuitively reasonable, though we have no proof at this time.
(15) For recent examples, see: (a) Nagumo, S.; Ono, M.; Kakimoto,
Y.; Furukawa, T.; Hisano, T.; Mizukami, M.; Kawahara, N.; Akita, H. J.
Org. Chem. 2002, 67, 6618. (b) Nagumo, S.; Ishii, Y.; Kakimoto, Y.;
Kawahara, N. Tetrahedron Lett. 2002, 43, 5333.
(16) (a) Schmidt, C. O.; Bouwmeester, H. J.; Franke, S.; Ko¨nig, W. A.
Chirality 1999, 11, 353. (b) Arigoni, D. Pure Appl. Chem. 1975, 41, 219.
(17) Alternative 1,4- or 1,5-transfers from the ring are also possible. (a)
Saunders: M.; Jimenez-Vazquez, H. A. Chem. ReV. 1991, 91, 375. (b) Watt,
C. I. F. In AdVances in Physical Organic Chemistry; Bethell, D., Ed.;
Academic Press: New York, 1988; Vol. 24, p 57.
Supporting Information Available: Experimental pro-
cedures, deuterium labeling experiments, and structural
determination of 3 and 5. This material is available free of
charge via the Internet at http://pubs.acs.org.
OL048780U
(19) Pt catalysts 1a and 1b are completely selective for 3 and 5,
respectively. No traces of cyclohexenes were detected (GC) in the crude
cyclopropane reaction mixtures, and vice versa.
(18) Control experiments showed that 1b catalyzes the isomerization of
4,4-dimethylcyclohexene to 3,3-dimethylcyclohexene.
(20) Evans, D. A.; Murry, J. A.; von Matt, P.; Norcross, R. D.; Miller,
S. J. Angew. Chem., Int. Ed. Engl. 1995, 34, 798.
Org. Lett., Vol. 6, No. 17, 2004
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