Ruthenium-catalyzed nucleophilic ring-opening reactions of 7-oxabenzonorbornadienes with methanol

Article abstract of DOI:10.1080/00397911.2011.626140

Ruthenium-catalyzed nucleophilic ring-opening reaction of 7-oxabenzonorbornadienes with methanol was investigated. Among various ruthenium catalysts tested, Cp*Ru (COD)Cl gave the greatest yields in the ring-opening reaction. The reactions were found to b

Full text of DOI:10.1080/00397911.2011.626140

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Ruthenium-Catalyzed Nucleophilic
Ring-Opening Reactions of 7-
Oxabenzonorbornadienes with Methanol
Kelsey Jack a , Elisabeth Fatila a , Colleen Hillis a & William Tam a
a Department of Chemistry, Guelph-Waterloo Centre for Graduate
Work in Chemistry and Biochemistry, University of Guelph, Guelph,
Ontario, Canada
Accepted author version posted online: 14 Mar 2012.Version of
record first published: 21 Feb 2013.
To cite this article: Kelsey Jack , Elisabeth Fatila , Colleen Hillis & William Tam (2013): Ruthenium-
Catalyzed Nucleophilic Ring-Opening Reactions of 7-Oxabenzonorbornadienes with Methanol,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic
Chemistry, 43:8, 1181-1187
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Synthetic Communications1, 43: 1181–1187, 2013
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2011.626140
RUTHENIUM-CATALYZED NUCLEOPHILIC
RING-OPENING REACTIONS OF
7-OXABENZONORBORNADIENES WITH METHANOL
Kelsey Jack, Elisabeth Fatila, Colleen Hillis, and William Tam
Department of Chemistry, Guelph-Waterloo Centre for Graduate Work in
Chemistry and Biochemistry, University of Guelph, Guelph, Ontario, Canada
GRAPHICAL ABSTRACT
Abstract Ruthenium-catalyzed nucleophilic ring-opening reaction of 7-oxabenzonorborna-
dienes with methanol was investigated. Among various ruthenium catalysts tested, CpꢀRu
(COD)Cl gave the greatest yields in the ring-opening reaction. The reactions were found
to be highly stereoselective, giving only the anti-ring-opening products in moderate yields.
Both symmetrical and unsymmetrical 7-oxabenzonorbornadienes were employed in the
study, and moderate to excellent regioselectivities were observed.
Supplemental materials are available for this article. Go to the publisher’s online edition
of Synthetic Communications1 to view the free supplemental file.
Keywords Bicyclic alkenes; catalysis; 7-oxanorbornadienes; ring-opening reactions;
ruthenium
INTRODUCTION
Oxabicyclic alkenes are valuable synthetic intermediates as they can serve as
a general template to create highly substituted ring systems.[1] For instance, metal-
catalyzed ring opening of these alkenes allows for the formation of several stereocen-
ters in a single step.[2,3] We have recently investigated different modes of transition
metal–catalyzed reactions of oxabenzonorbornadiene 1a and found that depending
on the reaction conditions, several products (2–6) could be obtained (Scheme 1).
For example, when oxabenzonorbornadiene 1a was treated with an alkyne in the
presence of the ruthenium catalyst, CpꢀRu(COD)Cl (Cpꢀ ¼ 1,2,3,4,5-pentamethylcy-
clopentadienyl, COD ¼ cyclooctadienyl), a [2 þ 2] cycloaddition was observed and
Received September 1, 2011.
Address correspondence to William Tam, Guelph-Waterloo Centre for Graduate Work in
Chemistry and Biochemistry, Department of Chemistry, University of Guelph, Guelph, Ontario, N1G
2W1, Canada. E-mail: wtam@uoguelph.ca
1181

1182
K. JACK ET AL.
Scheme 1. Our previous studies on transition metal–catalyzed reactions of oxabenzonorbornadiene 1a.
cyclobutene cycloadduct 2 was formed.[4] When oxabenzonorbornadiene 1a was
treated with the secondary propargylic alcohol 7 in the presence of the neutral Ru
catalyst, CpꢀRu(COD)Cl, in MeOH, or using a cationic Ru catalyst (e.g., [CpRu
(CH3CN)3]PF6), isochromene 3 was formed.[5] On the other hand, if the same reac-
tion between oxabenzonorbornadiene 1a and the secondary propargylic alcohol 7
was carried out with CpꢀRu(COD)Cl in tetrahydrofuran (THF), cyclopropane 4
was produced.[6] We have also observed that in the absence of an alkyne, CpꢀRu
(COD)Cl catalyzed the isomerization of oxabenzonorbornadiene 1a to the corre-
sponding naphthalene oxide 5 when neutral alumina was used in the workup.[7]
We have also reported that asymmetric cationic rhodium(I)-catalyzed cyclodimeriza-
tion of oxabenzonorbornadiene 1a to produce dimers 6 in excellent enantioselectivity
(up to 99% ee).[8]
Metal-catalyzed nucleophilic ring-opening reactions of 7-oxabenzonorborna-
dienes have been studied in the presence of nickel, titanium, zirconium, iron, copper,
palladium, and rhodium.[1b] However, to the best of our knowledge, no ruthenium-
catalyzed nucleophilic ring-opening reactions of 7-oxabenzonorbornadienes have
been reported in the literature. In this article, we report our investigation on the
ruthenium-catalyzed nucleophilic ring-opening reactions of 7-oxabenzonorborna-
dienes with methanol as the nucleophile.
RESULTS AND DISCUSSION
To begin our investigations, we screened a variety of ruthenium catalysts and
different reaction conditions, and the results are shown in Table 1. Cationic
ruthenium catalysts (entries 1 and 2) showed little reactivity, giving the ring-opening
product 8a in poor yields (7–12%) together with a small amount of 1-naphthol 9a
resulting from the isomerization of 1a.[7,9] Among various neutral ruthenium catalysts

NUCLEOPHILIC RING-OPENING REACTIONS
1183
Table 1. Optimization for Ru-catalyzed ring-opening reactions of 7-oxabenzonorbornadiene 1a with
methanol
Yielda (%)
Entry
Ru catalyst
T (ꢁC)
Solvent
8a
9a
1
2
[CpRu(CH3CN)]PF6
[CpꢀRu(CH3CN)]PF6
Ru(PPh3)3Cl2
65
65
65
65
65
65
65
65
65
65
65
65
40
25
65
65
65
65
65
65
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
THFb
7c
12c
5c
3
5
3
3
4
[Ru(COD)Cl2]x
[RuCl2(CO)3]2
0c
0
5
0c
0c
45
0
6
CpRu(PPh3)2Cl
CpRu(COD)I
7
11c
6c
5
8
CpRu(COD)Br
CpRu(COD)Cl
CpꢀRu(COD)I
CpꢀRu(COD)Br
CpꢀRu(COD)Cl
CpꢀRu(COD)Cl
CpꢀRu(COD)Cl
CpꢀRu(COD)Cl
CpꢀRu(COD)Cl
CpꢀRu(COD)Cl
CpꢀRu(COD)Cl
CpꢀRu(COD)Cl
CpꢀRu(COD)Cl
6
9
8c
5
10
11
12
13
14
15
16
17
18
19
20
10c
57
66
62d
68e
8c
11
17
5
3
2
38
47
36
48
42
44
DCEb
5c
13c
7
Tolueneb
Acetoneb
Dioxaneb
Hexanesb
6
0
aIsolated yield after column chromatography.
b20 equivalent of MeOH was used.
c7-Oxabenzonorbornadiene 1a was recovered (22–91%).
dThe reaction mixture was stirred for 4 h.
eThe reaction mixture was stirred for 6 h.
tested (entries 3–12), CpꢀRu(COD)X (where X ¼ Cl and Br, entries 11 and 12), which
were found to be useful catalysts in many of our previous studies of metal-catalyzed
reactions of 7-oxabenzonorbornadienes (Scheme 1), gave the ring-opening product 8a
in the greatest yields of 57–66%. Decreasing the reaction temperature from 65 ꢁC to
40 ꢁC and 25 ꢁC also afforded 8a in comparable yields but longer reaction times were
required (entries 12–14). However, when MeOH was only used in 20 equivalents and
another solvent [such as THF, dichloroethane (DCE), toluene, acetone, dioxane, and
hexanes] was used, the yields decreased dramatically (entries 15–20). Similar to
rhodium-catalyzed nucleophilic ring-opening reactions of 7-oxabenzonorbornadiene
1a, these ruthenium-catalyzed nucleophilic ring-opening reactions were found to be
highly stereoselective,[10] giving the anti-product as the only stereoisomer. The stereo-
chemistry of the product 8a was confirmed by comparing NMR data with literature
values.[10,11]

1184
K. JACK ET AL.
Table 2. Ru-catalyzed ring-opening reactions of 7-oxabenzonorbornadienes 1a–1k with methanol
7-Oxabenzo-
norbornadienes 1
Nucleophilic ring-opened
product 8
Time
(h)
Yielda (%)
Entry
1
of 8 (9)b
1
1
66 (5)b
2
3
59
1
40c
4
5
1
2
56 (17)b
81 (19)b
6
1d
26c
7
1
30c
(Continued )

NUCLEOPHILIC RING-OPENING REACTIONS
1185
Table 2. Continued
7-Oxabenzo-
norbornadienes 1
Nucleophilic ring-opened
product 8
Time
(h)
Yielda (%)
of 8 (9)b
Entry
8
2d
42
9
—
72
72
0e
10
20 (70)b
11
—
48
0 (35)b
aIsolated yield after column chromatography.
bYields in brackets are the amount of the corresponding naphthol isomerization product isolated.
cSome 7-oxabenzonorbornadiene was recovered.
dThe reaction was run at 80 ꢁC.
eDecomposition of 7-oxabenzonorbornadiene 1i was observed.
To investigate the scope of the reactions with different 7-oxabenzonorborna-
dienes, 7-oxabenzonorbornadienes 1b–1k were prepared[9] and subjected to the
optimized ruthenium-catalyzed nucleophilic ring-opening reaction conditions, and
the results are shown in Table 2. Similar to 1a, substitution on the benzo ring of
7-oxabenzonorbornadiene led to moderate to good yields of the nucleophilic ring-
opening products 8b–8e (Table 2, entries 2–5). With electron-donating groups
(Me and OMe, entries 2 and 3), no naphthol isomerization products were detected.
However, with electron-withdrawing groups (Br and F, entries 4 and 5), significant
amount of the corresponding 1-naphthol isomerization products were isolated.
7-Oxabenzonorbornadiene 1f required a higher reaction temperature of 80 ꢁC to
afford a 26% yield of the nucleophilic ring-opening products 8f (Table 2, entry 6).

1186
K. JACK ET AL.
With unsymmetrical 7-oxabenzonorbornadienes 1 g and 1 h, both provided the
corresponding nucleophilic ring-opening products in moderate yields as 1:1 mixture
of regioisomers (entries 7 and 8). C1-substituted 7-oxabenzonorbornadiene 1i, with
an ester group attached to C1, led only to decomposition of 7-oxabenzonorborna-
diene 1i, and only a trace amount of the nucleophilic ring-opening product was
1
detected by H NMR of the crude reaction mixture. With C1-methyl substituted
7-oxabenzonorbornadiene 1j, a much longer reaction time was required to produce
20% of the nucleophilic ring-opening product 8j, together with 70% of the corre-
sponding 1-naphthol isomerization product 9j. 1,4-Dimethyl-7-oxabenzonorborna-
diene 1k failed to product any nucleophilic ring-opening product, and only the
corresponding 2-naphthol isomerization product 9k was isolated in 35% yield.
CONCLUSION
In conclusion we have investigated the ruthenium-catalyzed nucleophilic ring-
opening reactions of 7-oxabenzonorbornadienes with methanol as the nucleophile.
This represents the first examples of using ruthenium complexes to catalyze this type
of nucleophilic ring-opening reactions of 7-oxabenzonorbornadienes. Further inves-
tigation to expand the scope of the reactions as well as the study of asymmetric
ring-opening reactions will continue in our laboratory.
EXPERIMENTAL
1
All reactions were carried out in an atmosphere of dry nitrogen or argon. H
and 13C NMR spectra were recorded on a 400-MHz spectrometer. 7-Oxabenzonor-
bornadienes 1a–1k were prepared according to literature procedures.[9] 1H NMR
and 13C NMR spectra were recorded at 300=400 and 75=100 MHz, respectively.
Chemical shifts are reported in parts per million (d) using internal solvent signals
as references and coupling constants are reported in hertz (Hz). A typical procedure
for the ruthenium-catalyzed ring-opening reactions of 7-oxabenzonorbornadienes is
given. Full experimental detail, with spectroscopic and characterization data and
1H and 13C NMR spectra, are provided in supplementary information.
Typical Procedure for Ruthenium-Catalyzed Ring-Opening Reactions
of 7-Oxabenzonorbornadienes: (1Rꢀ,2Rꢀ)-2-Methoxy-1,2-
dihydronaphtalen-1-ol 8a
Inside an inert atmosphere glove box, a solution of 7-oxabenzonorbornadiene 1a
(47.5 mg, 0.329 mmol) and degassed methanol (0.8 mL) in an oven-dried vial was
added to an oven-dried screw-cap vial containing CpꢀRu(COD)Cl (7.7 mg,
0.021 mmol). The reaction mixture was stirred outside the glove box at 65 ꢁC for
1 h. The crude product was purified by column chromatography (EtOAc–hexanes ¼
1:9) to give 8a (38.1 mg, 0.226 mmol, 66%) as a white solid (mp. 49–51 ꢁC). Rf 0.22
1
(EtOAc–hexanes ¼ 1:4); H NMR (CDCl3, 400 MHz) d 7.58 (d, 1H, J ¼ 6.8 Hz),
7.24–7.27 (m, 2H), 7.08–7.10 (m, 1H), 6.48 (dd, 1H, J ¼ 9.9, 2.0 Hz), 6.06 (dd, 1H,
J ¼ 9.9, 2.3 Hz), 4.91 (d, 1H, J ¼ 10.2 Hz), 4.11 (app dt, 1H, J ¼ 10.3, 2.2 Hz), 3.51
(s, 3H), 2.64 (br s, 1H); 13C NMR (APT, CDCl3, 100 MHz) d 135.8, 131.9, 128.3,

NUCLEOPHILIC RING-OPENING REACTIONS
1187
127.9, 127.8, 126.7, 126.3, 125.0, 82.2, 72.4, 56.8. IR (CH2Cl2) 3420, 3037, 2979, 2929,
2825, 1455 cmꢂ1. HRMS (EI) calcd. for C11H12O2 (Mþ) 176.0837; found: 176.0840.
Spectral data obtained matched with those reported in the literature.[10a,11]
ACKNOWLEDGMENTS
This work was supported by Merck Frosst Centre for Therapeutic Research
and Natural Sciences and Engineering Research Council of Canada (NSERC).
K. J. thanks NSERC for a postgraduate scholarship (CGS M). Karine Villeneuve
and Avila De Sousa are thanked for preliminary experiments.
REFERENCES
1. For reviews, see (a) Rayabarapu, D. K.; Cheng, C.-H. Acc. Chem. Res. 2007, 40, 971–983;
(b) Lautens, M.; Fagnou, K.; Heibert, S. Acc. Chem. Res. 2003, 36, 48–58.
2. For selected examples of ring-opening reactions of 7-oxabicyclo[2.2.1]heptenes, see (a)
Padwa, A.; Wang, Q. J. Org. Chem. 2006, 71, 7391–7402; (b) Cho, Y.; Zunic, V.; Senboku,
H.; Olsen, M.; Lautens, M. J. Am. Chem. Soc. 2006, 128, 6837–6846; (c) Chen, C. L.;
Martin, S. F. J. Org. Chem. 2006, 71, 4810–4818; (d) Wu, M.-S.; Jeganmohan, M.; Cheng,
C.-H. J. Org. Chem. 2005, 70, 9545–9550; (e) Lautens, M.; Hiebert, S. J. Am. Chem. Soc.
2004, 126, 1437–1447; (f) Leong, P.; Lautens, M. J. Org. Chem. 2004, 69, 2194–2196; (g)
Zhang, T.-K.; Yuan, K.; Hou, X.-L. J. Organomet. Chem. 2007, 692, 1912–1919.
3. For selected examples of ring-opening reactions of 7-oxabicyclo[3.2.1]octenes, see (a)
Lautens, M.; Colucci, J. T.; Hiebert, S.; Smith, N. D.; Bouchain, G. Org. Lett. 2002, 4,
1879–1882; (b) Lautens, M.; Rovis, T. J. Am. Chem. Soc. 1997, 119, 11090–11091; (c)
Lautens, M.; Ma, S.; Chiu, P. J. Am. Chem. Soc. 1997, 119, 6478–6487; (d) Lautens,
M.; Chiu, P.; Ma, S.; Rovis, T. J. Am. Chem. Soc. 1995, 117, 532–533; (e) Lautens, M.;
Abd-El-Aziz, A. S.; Lough, A. J. Org. Chem. 1990, 55, 5305–5306.
4. For selected examples of our recent studies of Ru-catalyzed [2 þ 2] cycloadditions of bicyc-
lic alkenes and alkynes, see (a) Villeneuve, K.; Tam, W. Angew. Chem. Int. Ed. 2004, 43,
610–613; (b) Burton, R. R.; Tam, W. Tetrahedron Lett. 2006, 47, 7185–7189; (c) Burton,
R. R.; Tam, W. J. Org. Chem. 2007, 72, 7333–7336; (d) Allen, A.; Villeneuve, K.;
Cockburn, N.; Fatila, E.; Riddell, N.; Tam, W. Eur. J. Org. Chem. 2008, 4178–4192.
5. (a) Villeneuve, K.; Tam, W. Eur. J. Org. Chem. 2006, 5499–5435; (b) Villeneuve, K.; Tam,
W. Organometallics 2007, 26, 6082–6090.
6. Villeneuve, K.; Tam, W. Organometallics 2006, 25, 843–848.
7. Villeneuve, K.; Tam, W. J. Am. Chem. Soc. 2006, 128, 3514–3515.
8. Allen, A.; Le Marquand, P.; Burton, R.; Villeneuve, K.; Tam, W. J. Org. Chem. 2007, 72,
7849–7857.
9. Ballantine, M.; Menard, P.; Tam, W. J. Org. Chem. 2009, 74, 7570–7573.
10. (a) Lautens, M.; Fagnou, K.; Rovis, T. J. Am. Chem. Soc. 2000, 122, 5650–5651; (b)
Lautens, M.; Fagnou, K.; Taylor, M.; Rovis, T. J. Organomet. Chem. 2001, 624, 259–270.
11. Kende, A. S.; Belletire, J.; Bentley, J.; Hume, E.; Airey, J. J. Am. Chem. Soc. 1975, 97,
4427–4428.