Transition-metal-based synthesis of dendralenes

Article abstract of DOI:10.1055/s-2007-966069

The consecutive ring-closing enyne metathesis of allylsilyl propargyl ethers with Grubbs' ruthenium-alkylidene catalyst, followed by rhenium oxide mediated 1,4-elimination of the Si-O moiety from the siloxenes, provides [3]- and [4]dendralenes in good yie

Full text of DOI:10.1055/s-2007-966069

PAPER
2313
Transition-Metal-Based Synthesis of Dendralenes
T
ransition-M
e
a
tal-Base
d
S
n
ynthesis of
D
g
endralene
s
ho Park, Daesung Lee*
Department of Chemistry, University of Wisconsin, Madison, WI 53706, USA
Fax +1(608)2654534; E-mail: dlee@chem.wisc.edu
Received 20 March 2007
This paper is dedicated to Professor Paul Wender on the occasion of his 60th birthday.
Abstract: The consecutive ring-closing enyne metathesis of allyl-
silyl propargyl ethers with Grubbs’ ruthenium–alkylidene catalyst,
followed by rhenium oxide mediated 1,4-elimination of the Si–O
moiety from the siloxenes, provides [3]- and [4]dendralenes in good
yields.
450 °C
– SO2
(1)
S
O
O
OH
dehydration
Key words: dendralenes, enynes, ring-closing metathesis, 1,4-
eliminations, rhenium oxide
R
(2)
(3)
R
catalyst
M
Br
R
Dendralenes make up a novel class of cross-conjugated
acyclic polyenes, and are represented by the two lowest
homologues [3]dendralene (3-methylenepenta-1,4-diene)
and [4]dendralene (3,4-bismethylenehexa-1,5-diene)
(Figure 1).1 Compared to other unsaturated hydrocarbon
compounds, such as linear conjugated polyenes, annu-
lenes, cumulenes, fulvenes, and radialenes, the den-
dralene class of compounds is the least explored.
Although the first dendralene derivatives were prepared
more than half a century ago, general synthetic methods
for the efficient preparation of dendralenes and their ap-
plication have been limited.2 However, dendralenes have
started attracting interest recently in the context of trans-
missive Diels–Alder reactions.3
Br
Scheme 1
transmissive Diels–Alder reaction would be an ideal strat-
egy to achieve molecular diversity and complexity.6 To
serve this goal, the development of a mild and efficient
synthesis protocol to generate dendralenes with various
substituent patterns is crucial. In this regard, we envi-
sioned that the ring-closing metathesis (RCM) of 1 cata-
lyzed by the Grubbs ruthenium complex 4,7 followed by
1,4-elimination of siloxane 2 catalyzed by rhenium(VII)
oxide would be an effective method to deliver various
dendralenes 3 (Scheme 2). Although the acid-8 and fluo-
ride-promoted9 1,4-elimination reaction of a siloxene re-
lated to 2 has been reported, the corresponding transition-
metal-catalyzed 1,4-elimination is unprecedented.10
[4]dendralene
[3]dendralene
Si
Si
Figure 1
O
O
4
R1
R1
Dendralenes have generally been prepared by thermal
isomerization or elimination from rather elaborate precur-
sors. Two recent representative examples by Sherburn and
Fallis include the extrusion of sulfur dioxide from sul-
folene derivatives at high temperatures (Scheme 1, reac-
tion 1) and the removal of water from the adduct between
the divinylmethyl anion and an aldehyde (Scheme 1, reac-
tion 2).4 Alternatively, bis-Negishi coupling of 1,1-dibro-
moalkenes with vinylmetal species has been employed by
Sherburn (Scheme 1, reaction 3).5
R2
R2
1
2
Re2O7
N
N
Mes
Mes
Cl
Cl
Ru
R1
Ph
PCy3
R2
3
4
Scheme 2
From the perspective of expanding the utility of den-
dralenes in the area of diversity-oriented synthesis, the
We surmised that the easy formation of silyl ether 1 from
various propargylic alcohols and allylsilyl chloride or tri-
flate, followed by the well-established ring-closing enyne
metathesis11 would render 2 an ideal substrate for testing
the rhenium oxide catalyzed 1,4-elimination reaction.
SYNTHESIS 2007, No. 15, pp 2313–2316
Advanced online publication: 11.05.2007
DOI: 10.1055/s-2007-966069; Art ID: C01707SS
© Georg Thieme Verlag Stuttgart · New York
x
x.
x
x
.
2
0
0
7

2314
S. Park, D. Lee
PAPER
Especially a one-pot sequence of RCM followed by the lyl(chloro)dimethylsilane were subjected to typical RCM
metal-catalyzed 1,4-elimination without isolation of conditions in dichloromethane at 40 °C in the presence of
RCM product 2 would provide a significant advantage second-generation Grubbs’ catalyst 4 to provide RCM
over the corresponding two-step sequence, because of the products 2a–e (Table 1, entries 1–5). Upon completion of
operational simplicity. Herein, we report our preliminary RCM, the reaction mixture was cooled to room tempera-
results for the efficient synthesis of mono- and disubstitut- ture and was treated with a catalytic amount of rheni-
ed [3]- and [4]dendralenes by the RCM of 1 to 2, followed um(VII) oxide (5 mol%) for four hours; this, to our
by 1,4-elimination of 2 with rhenium oxide (Scheme 2).12 delight, delivered the desired [3]dendralenes 3a–d
(Table 1, entries 1–4) in good yields after simple flash
column chromatography on silica gel. The elimination of
2e, derived from dihydrolinalool, gave cyclic dendralene
First, various allyldimethylsilyl ethers 1 derived from
simple monosubstituted propargyl alcohols 5a–e and al-
Table 1 One-Pot Synthesis of Dendralenes
Entry
Alcohol 5
RCM product 2
[3]Dendralene 3
Yield of 3a (%)
Si
O
OH
R
1
78%
R
R
5a, R = CH2CH2Ph
3a
3b
2a
2b
2
3
5b, R = CH2CH2OTHP
5c, R =
63%
66%
2c
3c
5d, R =
OMe
4
5
2d
3d
71%
OMe
Si
O
OH
5e, R =
–
3e
2e
Si
O
OH
6
7
72%
OBn
OBn
OBn
5f
3f
2f
Ph
Si
Ph
OH
Ph
O
81% (57%)b
OMe
OMe
OMe
5g
3g
2g
OH
Si
O
Ar
Ar
8
78%
O
OH
Si
3h
5h
2h
a Overall yield of 3 over three steps (silylation of 5, RCM of 1, elimination of 2 by method B), as determined by 1H NMR spectroscopy of the
unpurified reaction mixture against an external standard.
b Overall yield of 3g over three steps in one pot (by method A).
Synthesis 2007, No. 15, 2313–2316 © Thieme Stuttgart · New York

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Transition-Metal-Based Synthesis of Dendralenes
2315
3e, which was too unstable to be isolated without poly- surmise that Lewis acid mediated and sigmatropic-rear-
merization (Table 1, entry 5). Propargylic alcohols with rangement-mediated pathways12b–e compete at multiple
internal alkynes 5f and 5g provided RCM products 2f and stages along the catalytic cycle. That Lewis acid mediated
2g, which subsequently underwent 1,4-elimination to give elimination takes place was further supported by the for-
mono- and disubstituted [3]dendralenes 3f and 3g in re- mation of 2a from 1a in the presence of other Lewis acids,
spectable yields (Table 1, entries 6 and 7). The stereo- such as SnCl4 (75%), HfOTf (92%), AgSbF6 (88%),
chemistry of 3g was unambiguously assigned on the basis BF3·OEt2 (84%), and Ph3PAuCl (<20%).
of NOE experiments. Similarly, symmetrical propargylic
diol 3h was silylated, ring-closed, and 1,4-eliminated to
give bis-[3]dendralene 3h in good yield (Table 1, entry 8).
In conclusion, we have developed a one-pot method for
the synthesis of [3]- and [4]dendralenes under mild condi-
tions via two consecutive transition-metal-catalyzed reac-
Next, we also briefly examined the synthesis of [4]den- tions. This method should constitute a more general
dralenes. The tandem RCM of silicon-tethered dienynes alternative for the synthesis of a variety of substituted
6a and 6b, derived from the corresponding diols, provided dendralenes compared to the existing methods.1,2c
bis-siloxenes 7a and 7b at an elevated temperature
(110 °C in toluene) (Scheme 3). Double 1,4-elimination
All reagents and solvents were purchased from Sigma-Aldrich and
of 7a and 7b afforded mono- and disubstituted [4]den-
dralenes 8a and 8b, respectively, in good yields
(Scheme 3).13
used as received. NMR spectra were recorded on a Bruker AC-300
spectrometer. Chemical shifts are relative to TMS as an internal
standard. Siloxy-tethered enyne precursors 1a–h for RCM and
RCM products were prepared according to a literature procedure.15
Si
Si
5-[3-(Benzyloxy)prop-1-en-2-yl]-2,2-dimethyl-3,6-dihydro-2H-
1,2-oxasiline (2f); Typical Procedure
O
O
Re2O7
R1
4
To a soln of 5f (0.176 g, 1.0 mmol) in anhyd CH2Cl2 (5 mL) were
added AllylSiMe2Cl (0.114 g, 1.05 mmol) and imidazole (0.071 g,
1.05 mmol) at 0 °C. The mixture was stirred at 0 °C for 10 min and
at r.t. for an additional 3 h. The solvent was removed under reduced
pressure, and the residue was diluted with anhyd Et2O (10 mL) and
filtered through a Celite plug. After removal of the Et2O, the siloxy-
tethered enyne 1f was redissolved in anhyd CH2Cl2 (20 mL) and
treated with the Grubbs catalyst 4 (0.042 g, 5 mol%) under heating
at reflux for 5 h under N2. Conversion was monitored by TLC anal-
ysis.
Ph
Ph
R1
toluene
(110 °C)
O
6a, 6b
7a, 7b
Si
O
Si
Ph
Ph
8a (64%)
8b (62%)
[(2,3-Dimethylenepent-4-enyloxy)methyl]benzene (3f); Typical
Procedures
Scheme 3
Method A. One-pot procedure: To the crude reaction mixture con-
taining 2f in CH2Cl2 (see above) was added Re2O7 (0.024 g, 5
mol%), and the soln was stirred at r.t. for 4 h and then concentrated
under reduced pressure. The residue was purified by column chro-
matography (silica gel, Et2O–pentane, 1:10); this provided 3f as a
colorless oil.
Although the exact mechanism of this rhenium oxide cat-
alyzed 1,4-elimination is yet to be elucidated, our current
working hypothesis is depicted in Scheme 4. On the basis
of the known Lewis acidity of rhenium(VII) oxide,14 we
Yield: 0.106 g (53%).
Method B. Stepwise procedure: The solvent from the crude reaction
mixture containing 2f in CH2Cl2 (see above) was removed under re-
duced pressure, and the residue was filtered through a Celite pad
with Et2O. After addition of Re2O7 (0.024 g, 5 mol%) to the Et2O
soln, the mixture was stirred at r.t. for 3 h and purified as in method
A above.
O
Re
O
O
Re
O
O
O
O
Si
O
O
O
Si
Si
O
Re
O
O
O
O
Si
O
O
O
O
O
Re
Yield: 0.144 g (72%).
1H NMR (300 MHz, CDCl3): d = 7.257.36 (m, 5 H), 6.44 (dd,
J = 17.4, 10.7 Hz, 1 H), 5.135.38 (m, 6 H), 4.54 (s, 2 H), 4.16 (s, 2
O
O
O
O
Si
Re
Si
Re
R1
O
O
O
R2
R1
1
H).
R2
13C NMR (75 MHz, CDCl3): d = 146.04, 143.70, 138.52, 137.28,
128.58, 127.92, 127.78, 116.52, 115.71, 115.19, 72.32, 71.96.
HRMS (ESI): m/z [M + Na]+ calcd for C14H16ONa: 223.1099;
found: 223.1106.
R1
O
O
O
O
O
O
O
O
O
O
Re
Si
Re
Re
Re
R2
2
O
O
O
O
O
O
Si
R1
R1
Acknowledgment
R2
R2
We thank the NSF (CHE-0410783) and the Sloan Foundation for fi-
nancial support of this work as well as the NSF and NIH for NMR
and MS instrumentation.
Scheme 4 Putative reaction mechanism for 1,4-elimination
Synthesis 2007, No. 15, 2313–2316 © Thieme Stuttgart · New York

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S. Park, D. Lee
PAPER
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Synthesis 2007, No. 15, 2313–2316 © Thieme Stuttgart · New York