Platinum- and gold-catalyzed cycloisomerization reactions of hydroxylated enynes

Article abstract of DOI:10.1021/ja048094q

Exposure of enynes containing a hydroxyl group at one of the propargylic positions to catalytic amounts of either PtCl₂ or (PPh₃)AuCl/AgSbF₆ results in a selective rearrangement with formation of bicyclo[3.1.0]hexan-3-one

Full text of DOI:10.1021/ja048094q

Published on Web 06/25/2004
Platinum- and Gold-Catalyzed Cycloisomerization Reactions of Hydroxylated
Enynes
Victor Mamane, Tobias Gress, Helga Krause, and Alois Fu¨rstner*
Max-Planck-Institut fu¨r Kohlenforschung, D-45470 Mu¨lheim/Ruhr, Germany
Received April 2, 2004; E-mail: fuerstner@mpi-muelheim.mpg.de
Scheme 1
Complexation of enynes to PtCl2 engenders a host of selective
cycloisomerization reactions that likely involve cyclopropyl plati-
num carbenes as reactive intermediates (Scheme 1).1-3 Such species
are best viewed as latent cyclopropyl methyl cations that can evolve
along different pathways.4 The overall transformations are inherently
atom economical, result in a substantial increase in structural
complexity, and are simple, safe, and convenient to perform and
therefore meet many of the stringent criteria imposed upon
contemporary organic synthesis.1
Scheme 2
In pursuit of previous investigations in this field,4,5 we envisaged
that enynes bearing an -OH group at the propargylic position might
undergo an as yet unknown transformation. The evolving platinum
carbene is expected to trigger an irreversible 1,2-hydrogen shift6
with formation of a bicyclo[3.1.0]hexanone skeleton as shown in
Scheme 2. Since this structural motif is present in a large number
of terpenes,9 a concise entry into this important class of natural
products might ensue.
Scheme 3
To probe this concept, alcohol 2-D1 was prepared from the
deuterated aldehyde 1-D1 and allylmagnesium bromide (Scheme
3). Treatment of this enyne with PtCl2 in toluene at 60 °C furnished
the bicyclic ketone 3-D1 in 75% yield. In line with the proposed
mechanism, the deuterium label in the product appears exclusively
at the C-atom R to the newly formed carbonyl group.
Next, it was attempted to integrate the allylation and the cyclo-
isomerization into a “one-pot” transformation. This seemed possible
since previous investigations from this laboratory had shown that
aldehydes react with allyl chlorosilane 4 in the presence of PtCl2
to afford the corresponding homoallylic alcohols via “halophilic
activation” of the donor.7 In fact, treatment of alkynal 1 with 4
and PtCl2 catalyst in MeCN at 80 °C engendered a reaction cascade
comprising an allylation followed by in situ rearrangement of the
resulting enyne and delivered the bicyclic product 3 in 55% yield
(Scheme 3). This outcome compares well to the two-step protocol
(60% overall) and shows that PtCl2 can act as dual-specific catalyst.
Table 1 illustrates the generality of this novel skeletal reorganiza-
tion reaction of hydroxylated enynes. It is noteworthy that the
propargylic alcohol unit in the substrates can also be remote from
the alkene as exemplified by the conversion of 13 (R ) Me, Ph)
into the bicyclic products 14 bearing the newly formed ketone in
the lateral chain. Moreover, it was found that PtCl2 can be replaced
by (PPh3)AuCl/AgSbF6 as the catalyst;8 the resulting cationic gold
complex is particularly reactive and induces the isomerization even
at ambient temperature (entry 1, footnote b).
Scheme 4
fere with the skeletal reorganization of the hex-1-en-5-yn-4-ol back-
bone. Reduction of 18 with NaBH4/CeCl3 afforded cis- and trans-
sabinol 19 as a 1:1 mixture, which was separated by preparative GC.
To extend the scope of the method further, alcohol 2 was
converted into the corresponding acetate 20. As suggested by
previous findings,11 the ester might be able to participate in the
rearrangement process by attacking the polarized metal-alkyne
complex initially formed. Interception of the emerging carbene by
the terminal double bond results in the formation of compound 21
in which the acetate has migrated, masking a ketone group at C-2
as the corresponding enol ester (Scheme 5). This simple method
allows functionalization of this otherwise inaccessible position on
the bicyclic skeleton and therefore complements the hydride shift
process outlined above.
The favorable profile of this rearrangement became apparent from
a concise approach to sabinone 18 and the two isomeric sabinols 19
(Scheme 4), characteristic terpenes found in various Artemisia,
Juniperus, and Thuja species.9 Lewis acid-catalyzed addition of
the allenyl silane 16 to aldehyde 15 afforded the labile 1,3-buta-
dienyl derivative 17,10 which delivered sabinone 18 on exposure to
catalytic amounts of PtCl2 in benzene in good yield. This example
shows that an additional double bond in the substrate does not inter-
9
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J. AM. CHEM. SOC. 2004, 126, 8654-8655
10.1021/ja048094q CCC: $27.50 © 2004 American Chemical Society

C O M M U N I C A T I O N S
Scheme 5
Scheme 6
Table 1. Metal-Catalyzed Cycloisomerizations of Hydroxylated
Enynesa
Merck Research Council is gratefully acknowledged. We thank
Umicore AG & Co KG, Hanau, for a gift of noble metal salts.
Supporting Information Available: Experimental part including
spectroscopic data of all new compounds. This material is available
free of charge via the Internet at http://pubs.acs.org.
References
(1) 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,
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a All reactions were performed in toluene at 60-80 °C with PtCl2 (5
mol %) unless stated otherwise. b Using (PPh3)AuCl/AgSbF6 (2 mol %) in
CH2Cl2 at 20 °C. c After workup with aq HCl. d dr ) 3:1.
(3) Mechanistic investigation: Martin-Matute, B.; Nevado, C.; Ca´rdenas, D.
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Finally, the stereochemical implications of the novel rearrange-
ment have been investigated (Scheme 6). Brown crotylation12 of 1
afforded the homoallylic alcohols 23 in high optical purity, which
were isomerized with PtCl2 catalyst in toluene at 60 °C. In full
accordance with the mechanistic proposal, the diastereomeric
substrates syn-23 and anti-23 furnished the enantiomeric products
24/25 and ent-24/ent-25, respectively. The significantly higher dr
in the syn series is likely explained by the fact that only carbene A
is devoid of eclipsing interactions between the methyl branch, the
adjacent alcohol, and the incipient cyclopropyl ring and should
therefore be more favored over B than the diastereomeric inter-
mediate D is favored over C.13 Further studies to probe this and
related aspects of the novel cycloisomerization are underway and
will be reported in due course.
(5) (a) Fu¨rstner, A.; Mamane, V. J. Org. Chem. 2002, 67, 6264. (b) Fu¨rstner,
A.; Mamane, V. Chem. Commun. 2003, 2112.
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D. J.; Echavarren, A. M. Angew. Chem., Int. Ed. 2004, 43, 2402.
(9) Breitmeier, E. Terpene; Teuber: Leipzig, 1999.
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Lett. 1991, 32, 4509. The moderate yield in this reaction is mainly due to
the high volatility of compounds 15 and 17.
(11) (a) Mainetti, E.; Mourie`s, V.; Fensterbank, L.; Malacria, M.; Marco-
Contelles, J. Angew. Chem., Int. Ed. 2002, 41, 2132. (b) Rautenstrauch,
V. J. Org. Chem. 1984, 49, 950. (c) See also: Miki, K.; Ohe, K.; Uemura,
S. J. Org. Chem. 2003, 68, 8505.
(12) Brown, H. C.; Bhat, K. S. J. Am. Chem. Soc. 1986, 108, 5919.
(13) This interpretation assumes that the steric interactions in the carbene region
are similar for A/B and C/D as suggested by molecular modeling.
Acknowledgment. Generous financial support by the DFG
(Leibniz award), the Fonds der Chemischen Industrie, and the
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