Sequential platinum-catalyzed cycloisomerization and cope rearrangement of dienynes

Article abstract of DOI:10.1002/anie.200905361

Enyne-enyne-o: Tandem cycloisomerization of dienynes catalyzed by platinum dichloride and subsequent Cope rearrangement affords bicyclic rings (see scheme; Z=NTs, O, CH₂). such as bicyclo[3.2.2]nonadienes 1 or tetrahydrocyclohepta[c]pyrans and

Full text of DOI:10.1002/anie.200905361

Angewandte
Chemie
DOI: 10.1002/anie.200905361
Tandem Reactions
Sequential Platinum-Catalyzed Cycloisomerization and Cope
Rearrangement of Dienynes**
Sun Young Kim, Youjung Park, and Young Keun Chung*
Transition-metal-catalyzed carbocyclization reactions of
unsaturated hydrocarbons are known to be powerful methods
for the construction of complex polycyclic systems.[1] Among
them, transition-metal-catalyzed cycloisomerizations have
recently received a great deal of attention owing to their
ability to furnish a variety of structures from a single substrate
by changing the catalyst and reaction conditions.[2] Interest-
ingly, most of the reported transition-metal-catalyzed cyclo-
isomerizations have focused on enyne substrates,[2,3] with
comparatively little attention devoted to the cycloisomeriza-
tion of dienynes,[4] perhaps because the [4+2] cycloaddition
reaction is prevalent for dienynes.[5]
The synthetic potential of ring systems such as bicyclo-
[4.1.0]heptenes a, which are easily obtainable from the
transition-metal-catalyzed cycloisomerization of enynes, has
not yet been thoroughly examined.[6] We envisioned that if a
dienyne bearing a divinylcyclopropane group was used as a
substrate, such as 7-vinylbicyclo[4.1.0]hept-4-ene a, subse-
quent rearrangement might lead to the formation of bicyclic
rings such as b and d.[7] (Scheme 1). Herein, we present a
facile method for the stereoselective construction of bicyclo-
Scheme 1. The possible stereoselective construction of bicyclic rings
by sequential metal-catalyzed cycloisomerization and Cope rearrange-
ment.
[3.2.2]nonadienes,
1,6,7,9a-tetrahydrocyclohepta[c]pyrans,
iridium catalyst afforded the [4+2] cycloaddition product in
21% yield; a relatively higher yield of 1b (81%) was
observed with a PtCl2 catalyst.
and 1,6,7,9a-tetrahydrocyclohepta[c]pyridines, from dienyne
substrates using a PtCl2-catalyzed cycloisomerization and
subsequent Cope rearrangement.
Initially, we tested a series of catalysts for the cyclo-
isomerization reaction of dienyne 1 [Eq. (1)], under standard
reaction conditions, which were adopted from previous
studies (see the Supporting Information).[8] Despite expecting
the formation of large amounts of [4+2] cycloaddition
product, no such product was observed in the presence of
gold or platinum catalysts. Compared with the previously
reported gold-catalyzed [4+2] cycloaddition, this observed
difference in reactivity [5f] may relate to the substrate used. An
We then investigated the scope of the reaction for various
substrates (Table 1). Methyl-substituted dienyne 2 success-
fully afforded bicyclo[3.2.2]nona-2,8-diene 2b as the sole
cycloadduct in good yield (61%). Dienyne 3, which contained
a terminal alkyne and was known to decompose in the
presence of a gold catalyst,[5f] afforded a modest yield of 3b
(34%) with the concomitant formation of a [4+2] cyclo-
addition product (44% yield). It has been reported that the
Cope rearrangement of compounds containing an aryl sub-
stituent at the C3 position of 1,5-hexadiene proceeds faster
than their unsubstituted analogues.[9] Thus, we focused our
attention on dienynes which contained a phenyl-substituted
alkyne (1 and 4–12). When an oxygen- or nitrogen-tethered
dienyne containing a mono-substituted E-alkene was used as
the substrate (4–6), the corresponding nonadienes 4b–6b
[*] S. Y. Kim, Y. Park, Prof. Y. K. Chung
Intelligent Textile System Research Center, and Department of
Chemistry, College of Natural Sciences, Seoul National University
Seoul 151-747 (Korea)
Fax: (+82)-2-889-0310
E-mail: ykchung@snu.ac.kr
[**] This work was supported by the Korean Government (MOEHRD)
(KRF-2008-341-C00022) and the Korea Science and Engineering
Foundation (KOSEF) grant funded by the Korea Government
(MEST) (R11-2005-065). We thank S. Y. Choi and I. S. Lee for X-ray
crystallographic analysis. S.Y.K. thanks the Brain Korea (BK) 21
fellowship and the Seoul Science Fellowship and Y.P. thanks the BK
21 fellowship.
Supporting information for this article, including experimental
procedures, is available on the WWW under http://dx.doi.org/10.
1002/anie.200905361.
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Table 1: Tandem platinum(II)-catalyzed cycloisomerization of dienynes
and subsequent Cope rearrangement.[a]
When 7 was heated in xylene at 1308C, 7b was obtained in
77% yield after only 30 minutes.
Substrate
Conditions
Product (Yield [%][b])
(R1=Ph)
1
808C, 9 h
1b (81)
(R1=Me)
(R1=H)
2[c] 808C, 24 h
2b (61)
3
1008C,
3b (34)[d]
Encouraged by this observation, substrates 8–11 were
heated in xylene at 1308C. However, in the case of 8, a
mixture of 8b and [4+2] cycloadduct 8c was obtained, which
suggested that a lower reaction temperature was required.
When 8 was heated at 708C for 48 h, 8b was isolated as the
sole product in 66% yield. Interestingly, the E/Z ratio of 8
(1:2.3) changed slightly to 1:1.8 in the product 8b, presumably
owing to the sterically unfavorable cyclic transition state of
the Z-form during the rearrangement. Compound 9b was
isolated in 68% yield from dienyne 9 with the concomitant
formation of 9c in 8% yield. Compounds 10b and 11b were
obtained in respectable yields from their starting dienynes
(45% and 72%, respectively). The structure of 11b was
confirmed by X-ray diffraction analysis (Figure 1).[10] Non-
24 h
(X=O)
(X=NTs)
4
5
808C, 4 h
808C, 2 h
4b (91)
5b (86)
6
7
608C, 9 h
6b (68)
7b (77)
1308C,
0.5 h
(E:Z=1:2.3)
8, 8’ 708C, 48 h
708C,
8b/8b’ (24/42)
9b (68)[e]
7.5 h!
1308C,
1.5 h
9
708C,
5 h!
1308C,
2.5 h
Figure 1. ORTEP structure of 11b. Ellipsoids are set at 30% proba-
bility.
10
10b (45)
adiene 12b was obtained in 79% yield from 12 without
further ring-expansion products. In all cases, apart from
terminal alkyne 3, a [4+2] cycloadduct was not obtained or
was obtained in less than 10% yield. Moreover, because the
bicyclo[4.1.0]heptene frame restricted the rotation of the
divinylcyclopropane moiety, only a single diastereoisomer of
nonadiene product was observed for each substrate
(Scheme 1).
758C,
5 h!
1308C,
1.5 h
11
12
11b (72)
12b (79)
608C, 7 h
Next, we investigated the cyclization of enynes with a
carbon tether [Eq. (3)]. It has been reported that the
platinum-catalyzed cycloisomerization of hept-1,6-enynes
yields the conventional Alder-ene type products.[11] Recently,
there has been extensive research on the reactivity of
propargyl esters, preferably acetates, because of their intrigu-
ing reactivity, especially regarding their high propensity to
undergo 1,2- and 1,3-acyl migrations.[12] Thus, nonadiene 13b
was successfully isolated from dienyne 13 in 53% yield.
[a] 5 mol% PtCl2; toluene was used for reactions under 1108C, xylene was
used above 1108C. [b] Yield of isolated product. [c] 10 mol% PtCl2.
[d] [4+2] cycloaddition product 3c was isolated in 44% yield. [e] [4+2]
cycloaddition product 9c was isolated in 8% yield.
were obtained in good yields (68–91%). The reaction time
became more prolonged when additional substituents were
introduced onto the diene (7–11). The reaction of 2,5-
disubstituted diene 7 gave a mixture of 7a and 7b after 48 h
in 7% and 52% yields, respectively. A pure sample of 7a was
used to examine whether the second step was a completely
thermal process. When 7a was heated in toluene at 808C, 7b
was obtained as the sole product in 68% yield [Eq. (2)].
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Next, we investigated the use of vinyl-substituted dien-
ynes as substrates (Table 2). We expected that the intermedi-
ate divinyl cyclopropanes would undergo facile rearrange-
ment to d-type bicycles, rather than b-type nonadienes,
Experimental Section
General procedure: PtCl2 and toluene (2 mL) were added to a
Schlenk flask equipped with a stirring bar and capped with a rubber
septum. The substrate (0.3 mmol) and toluene (4 mL) were then
added to the flask. The resulting mixture was stirred until the
substrate was completely consumed (reaction monitored by TLC).
The product was purified by flash chromatography on a silica gel
column by eluting with n-hexane/ethyl acetate.
Table 2: Tandem platinum(II)-catalyzed cycloisomerization of vinyl-sub-
stituted dienynes and subsequent Cope rearrangement.[a]
Received: September 24, 2009
Published online: November 30, 2009
Keywords: alkynes · cyclization · dienes · isomerization ·
.
platinum
Entry
Substrate
R1
Product (Yield [%][b])
X
R2
R3
14[c]
15[c]
16
17
18
O
O
O
O
O
H
Me
Ph
Ph
Ph
Ph
H
H
H
H
Me
H
H
H
H
Me
Me
H
14d (34)[d]
15d (36)
16d (55)
17d (83)
18d (59)
19d (80)
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