Ruthenium-catalyzed isomerization of oxa/azabicyclic alkenes: An expedient route for the synthesis of 1,2-naphthalene oxides and imines

Article abstract of DOI:10.1021/ja058621l

1,2-Naphthalene oxides and imines can be rapidly accessed through a ruthenium-catalyzed isomerization of readily available 7-oxa/azabenzonorbornadienes. These mild reaction conditions were found to be tolerant to various functional groups and the isomerization is highly regioselective. Copyright

Full text of DOI:10.1021/ja058621l

Published on Web 02/25/2006
Ruthenium-Catalyzed Isomerization of Oxa/Azabicyclic Alkenes: an
Expedient Route for the Synthesis of 1,2-Naphthalene Oxides and Imines
Karine Villeneuve and William Tam*
Guelph-Waterloo Centre for Graduate Work in Chemistry and Biochemistry, Department of Chemistry,
UniVersity of Guelph, Guelph, Ontario, Canada, N1G 2W1
Received December 30, 2005; E-mail: wtam@uoguelph.ca
Scheme 1
Brønsted acid-catalyzed isomerization of 7-oxabenzonorborna-
dienes into 1-naphthols is a well-known procedure and a valuable
method for incorporating a naphthol fragment in more complex
molecules.1 Similar isomerization has been previously observed as
an unwanted side pathway in the rhodium2- or nickel3-catalyzed
nucleophilic ring opening of oxabenzonorbornadienes. However,
metal-catalyzed isomerization of 7-oxabicyclic alkenes to naph-
thalene oxides has not been explored thus far. 1,2-Naphthalene
oxides are known to be important intermediates in the metabolism
of aromatic hydrocarbons4 and can be useful synthetic intermedi-
ates.5 The synthesis of these epoxides usually requires several steps.6
Herein we report an expedient method to form 1,2-naphthalene
oxides 3 in mild conditions from readily available 7-oxabenzonor-
bornadienes 1, utilizing Cp*Ru(cod)Cl (Cp* ) pentamethylcyclo-
pentadienyl; cod ) 1,5-cyclooctadiene). This unprecedented ex-
ample of a nonmetathesis ruthenium-catalyzed ring opening of oxa-
bicyclic alkenes was also extended to the isomerization of 7-aza-
benzonorbornadienes to the corresponding 1,2-naphthalene imines.
Since 1,2-naphthalene oxides are known to easily isomerize to
the related naphthols in the presence of weak acid or mild heat,7
our initial efforts were concentrated on the elaboration of optimal
conditions for the isomerization of 1a into 1-naphthol 2a using the
ruthenium catalyst Cp*Ru(cod)Cl. We observed that performing
the reaction at 60 °C in either THF, nitromethane, or acetone
resulted in slow and incomplete reaction. Using toluene, the reaction
was found to be complete in 1 h, giving 2a in 83% yield. To our
delight, employing DMF or 1,2-DCE improved the yield to
respectively 90% and 91%. In both cases, a complete conversion
of 1a to 2a was obtained in 15 min.
Table 1. Isomerization of Different 7-Oxabenzonorbornadienes
Using 1,2-DCE as the solvent,8 we explored the effect of the
temperature. Lowering the temperature from 60 to 45 °C did not
affect the yield (90%), although 1 h was required for complete
conversion. Further decrease of the temperature to 25 °C resulted
in no reaction. Other catalysts were also investigated but Cp*Ru-
(cod)Cl was the most effective one. No reaction occurred when
CpRu(cod)Cl, [Cp*Ru(CH3CN)3]PF6, [CpRu(CH3CN)3]PF6, or
CpRu(PPh3)2Cl were used, and longer reaction time was required
with Cp*Ru(cod)Br and Cp*Ru(cod)I.9
Most importantly, the conversion of 1a to 1-naphthol could also
be “interrupted” at the 1,2-naphthalene oxide intermediate when
the manipulations were carefully operated (Scheme 1). We found
that performing the isomerization at 60 °C for 15 min followed by
cooling the reaction mixture to 0 °C, filtering over neutral alumina,
and evaporating the solvent under reduced pressure at low tem-
perature yielded 3a (containing less than 5% of 2a) in 86% isolated
yield.
To study the generality of this isomerization reaction, several
7-oxabenzonorbornadienes were synthesized, as depicted in Table
1. As previously observed in our ruthenium-catalyzed [2 + 2]
cycloaddition reactions,10 different functional groups are tolerated
in the presence of the catalyst. These groups also play a major role
a Cp*Ru(cod)Cl (5 mol %), 1,2-DCE (0.7M), 60 °C. b A second portion
of Cp*Ru(cod)Cl (5 mol %) was added after 1 h. c Isolated yield.
in the stability of the epoxide toward further aromatization to the
corresponding naphthol. The presence of an electron-withdrawing
group such as an ester (entries 5-7) stabilizes the naphthalene oxide
product. The stability of these epoxides (3e, 3f, 3f′, and 3g) is indeed
reflected in the fact that they can tolerate “for a short period of
time” the presence of a weak acid such as silica gel during the
purification step. In contrast, electron-donating groups favor the
formation of the naphthol product, which occurs in situ in the case
of 2h. When unsymmetrical alkenes were subjected to the reaction
conditions, the regioselectivity was significantly affected by the
9
3514
J. AM. CHEM. SOC. 2006, 128, 3514-3515
10.1021/ja058621l CCC: $33.50 © 2006 American Chemical Society

C O M M U N I C A T I O N S
Scheme 2
7-Azabenzonorbornadienes could also be subjected to the same
conditions. In this case, the choice of the functional group attached
on the nitrogen is rather important. No reaction was found to occur
t
when R ) CO2Me or CO2 Bu. Alternatively, when utilizing the
azabicyclic alkene 6 (R ) Ts), the reaction occurred smoothly, and
86% of the aziridine 715 was isolated.
Scheme 3
In conclusion, we have demonstrated the first examples of
ruthenium-catalyzed isomerization of 7-oxa/azabenzonorbornadienes
to their corresponding vinyl epoxides or aziridines. This method
presents a mild, simple, and efficient experimental procedure for
the preparation of 1,2-naphthalene oxides and imines. Further
investigations of the scope of the reaction and the development of
a chiral catalyst are currently in progress in our laboratory.
Acknowledgment. This work was supported by NSERC
(Canada). K.V. thanks NSERC for providing a CGS-D2 scholarship.
Scheme 4
Supporting Information Available: Detailed procedures and full
characterization of new compounds. This material is available free of
charge via the Internet at http://pubs.acs.org.
References
(1) (a) Kaelin, D. E.; Lopez, O.; Martin, S. F. J. Am. Chem. Soc. 2001, 123,
6937. (b) Apsel, B.; Bender, J. A.; Escobar, M.; Kaelin, D. E.; Lopez, O.
D.; Martin, S. F. Tetrahedron Lett. 2003, 44, 1075. (c) Kaelin, D. E.;
Sparks, S. M.; Plake, H. R.; Martin, S. F. J. Am. Chem. Soc. 2003, 125,
12994. (d) Biland-Thommen, A. S.; Raju, G. S.; Blagg, J.; White, A. J.
F.; Barrett, A. G. M. Tetrahedron Lett. 2004, 45, 3181.
(2) Lautens, M.; Fagnou, K.; Taylor, M.; Rovis, T. J. Organomet. Chem.
2001, 624, 259.
(3) Feng, C.-C.; Nandi, M.; Sambaiah, T.; Cheng, C.-H. J. Org. Chem. 1999,
64, 3538.
(4) (a) Jerina, D. M.; Daly, J. W.; Witkop, B. J. Am. Chem. Soc. 1968, 90,
6525. (b) Jerina, D. M.; Daly, J. W.; Witkop, P.; Zaltzman-Nirenberg, P.;
Udenfriend, S. Biochemistry 1970, 9, 147. (c) Kaubisch, N.; Daly, J. W.;
Jerina, D. M. Biochemistry 1972, 11, 3080. (d) Harvey, R. G.; Geacintov,
N. E. Acc. Chem. Res. 1988, 21, 66.
position and the nature of the functional group. In the presence of
groups located at the oxabicyclic ring junction (entries 5, 7, and
8), single regioisomers were formed, whereas a poor regioisomeric
ratio was observed in the case of a remote ester substituent (entry
6). It is also noteworthy that alkenes 1g and 1h, bearing respectively
an electron-withdrawing and an electron-donating group at the ring
junction, give opposite regioselectivity.
(5) (a) Jeffrey A. M.; Yeh H. J. C.; Jerina D. M.; DeMarinis R. M.; Foster C.
H.; Piccolo D. E.; Berchtold G. A. J. Am. Chem. Soc. 1974, 96, 6929. (b)
Tsang W.-S.; Griffin, G. W.; Horming, M. G.; Stillwell, W. G. J. Org.
Chem. 1982, 47, 5339. (c) Agarwal, R.; Boyd, D. R.; McMordie, R. A.
S.; O’Kane, G. A.; Porter, P.; Sharma, N. D.; Dalton, H.; Gray, D. J. J.
Chem. Soc., Chem. Commun. 1990, 1711.
(6) (a) Vogel, E.; Kla¨rner, F.-G. Angew. Chem., Int. Ed. Engl. 1968, 7, 374.
(b) Boyd, D. R.; Jerina, D. M.; Daly, J. W. J. Org. Chem. 1970, 35, 3170.
(c) Yagi, H.; Jerina, D. M. J. Am. Chem. Soc. 1975, 97, 3185. (d) Akhtar,
M. N.; Boyd, D. R.; Hamilton, J. G. J. Chem. Soc., Perkin Trans. 1 1979,
2437. (e) Jennings, W. B.; Rutherford, M. Tetrahedron Lett. 1988, 44,
7551. (f) Agarwal, S. K.; Boyd, D. R.; Jennings, W. B.; McGuckin, R.
M.; O’Kane, G. A. Tetrahedron Lett. 1989, 30, 123. (g) Oh, S. S.; Butler,
W. M.; Koreeda, M. J. Org. Chem. 1989, 54, 4499.
(7) (a) See ref 6. (b) Rao, S. N.; More O’Ferrall, R. A.; Kelly, S. C.; Boyd,
D. R.; Agarwal, R. J. Am. Chem. Soc. 1993, 115, 5458. (c) Brandt, P.;
Jia, Z. S.; Thibblin, A. J. Org. Chem. 2002, 67, 7676.
(8) DCE was chosen for the rest of the study because of its ease of removal.
(9) For the synthesis of Cp*Ru(cod)Br and Cp*Ru(cod)I, see: Villeneuve,
K.; Tam, W. Organometallics 2006, 25, 843.
(10) (a) Jordan, R. W.; Tam, W. Org. Lett. 2001, 3, 2367. (b) Villeneuve, K.;
Riddell, N. G.; Jordan, R. W.; Tsui, G.; Tam, W. Org. Lett. 2004, 6,
4543. (c) Riddell, N.; Villeneuve, K.; Tam, W. Org. Lett. 2005, 7, 3681.
(11) C-O insertion has been previously reported with the exact same catalyst,
see: Yamamoto, Y.; Nakagai, Y.; Itoh, K. Chem. Eur. J. 2004, 10, 231
and references therein.
(12) A similar argument was proposed in the investigation of the rhodium-
catalyzed ring-opening reaction, see: Lautens, M.; Fagnou, K. Proc. Natl.
Acad. Sci. U.S.A. 2004, 101, 5455.
(13) Equey, O.; Vrancken, E.; Alexakis, A. Eur. J. Org. Chem. 2004, 2151.
(14) (a) Tueting, D. R.; Echavarren, A. M.; Stille, J. K. Tetrahedron 1989, 45,
979. (b) Castan˜o, A. M.; Me´ndez, M.; Ruano, M.; Echavarren, A. M. J.
Org. Chem. 2001, 66, 589.
(15) Related aziridines have been prepared via a multistep route similar to the
one used for naphthalene oxides, see: Blum, C. J.; Ittah, Y.; Shahak, I.
Tetrahedron Lett. 1975, 51, 4607.
On the basis of the results presented above, a mechanistic
pathway divided in two segments accounting for the formation of
1,2-naphthalene oxide and 1-naphthol is proposed in Scheme 2.
After dissociation of the cod ligand, the ruthenium catalyst can be
chelated by 1a, which would allow strain release through an
oxidative insertion of ruthenium into the C-O bond.11 Since no
nucleophile is present, which precludes nucleophilic ring-opening
processes,2 a reductive elimination closes the epoxide ring and
regenerates the catalyst. Finally, the corresponding naphthol 2a
would arise from 3a as previously described.7
One piece of evidence for the insertion into the C-O bond
pathway is the fact that opposite regioisomers are formed in the
case of 1g and 1h. The exclusive formation of 4-methyl-1-naphthol
2h when 1h was treated with Cp*Ru(cod)Cl, suggests that oxidative
insertion occurs in the most electron-rich C-O bond a (Scheme
3).12 On the other hand, opposite selectivity was observed with
alkene 1g. In this case, oxidative insertion occurs in C-O bond b,
away from electron-withdrawing methyl ester group.
The instability of arene oxide 3a could be circumvented by
transforming them in situ into more stable products (Scheme 4).
On the basis of previous work,5 we performed a nucleophilic 1,2-
13
addition of LiAlMe4 on 3a, yielding 4 in 41% (unoptimized).
Additionally, cis-1,4-disubstituted dihydronaphthalenol 5 was syn-
thesized (40% unoptimized yield) by taking advantage of the vinyl
epoxide to achieve a palladium-catalyzed allylic substitution with
diethylmalonate.14
JA058621L
9
J. AM. CHEM. SOC. VOL. 128, NO. 11, 2006 3515