5658
J . Org. Chem. 1997, 62, 5658-5659
Communications
A New P h otoa n n u la tion Rea ction of
2-Ar yl-3-a lk oxy-1,4-n a p h th qu in on es.
Syn th esis of Dim eth yln a p h th ger a n in e E
Sch em e 1
Thomas J . Onofrey, Dario Gomez,
Michael Winters, and Harold W. Moore*
Department of Chemistry, University of California at Irvine,
Irvine, California 92697
Received February 28, 1997
Reported here is the synthesis of the pyranonaphtho-
quinone 5b, a dimethyl analog of naphthgeranine E (5c),
a member of a family of bioactive naturally occurring
naphthoquinones found in Streptococcus violaceous.1 Key
to this synthesis are the utility of the thermally induced
ring expansion of 4-arylcyclobutenones for the regiospe-
cific synthesis of 2-aryl-3-isopropoxy-1,4-naphthoquino-
nes and a new photoannulation reaction of quinones of
this structural type for the construction of the pyranon-
aphthoquinone nucleus.2,3
Cyclobutenedione 2 (87%) was prepared in a “one-pot”
reaction sequence involving 1,2-addition of 5-lithio-2-
(triisopropylsiloxy)benzyl triisopropylsilyl ether to diiso-
propyl squarate (1) followed by trifluoroacetic anhydride
(TFAA) and aqueous workup (Scheme 1).4 Regiospecific
addition of 4-lithio-1,3-dimethoxybenzene to the more
reactive carbonyl group in 2 gave cyclobutenone 3 in 76%
yield. Thermolysis of 3 (p-xylene, 138 °C) followed by
oxidation (Ag2O) provided naphthoquinone 4 (53%). Pho-
tolysis (2 × 40 W fluorescent lamps) of a benzene solution
of 4 at ambient temperature in the presence of a 5-fold
excess of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ)
gave 5a and its regioisomer 6 in 82% yield as a 1:1
mixture. Finally, desilylation of 5a (TBAF) provided 5b
(76%).5
tion provides hydroquinone 11. Subsequent DDQ oxida-
tion of 11 provides quinone 12.7
The above photoannulation reaction is noteworthy
since it appears to have little precedence in the litera-
ture.3 A proposed mechanism is presented in Scheme 2
as it applies to the conversion of 3-isopropoxy-2-phenyl-
1,4-naphthoquinone6 (7) to the pyranonaphthoquinone 12
in 87% yield. Visible light excitation of 7 is envisaged to
lead to zwitterionic (or diradical) intermediate 8. Proton
transfer from the methine carbon of the isopropoxy group
to the adjacent carbonyl with concomitant aromatization
would then give 9. Intramolecular ring closure to the
proposed o-quinone methide 10 followed by tautomeriza-
The presence of excess DDQ (5 equiv) is required in
order to maximize the yield of 12. Indeed, if this high
potential quinone is absent, not only do the yields of the
pyranoquinone suffer, but a significant amount of the
hydroquinone of 7 is realized. A reasonable pathway to
account for this would involve oxidation of 11 by the
starting quinone 7. Thus, DDQ converts 11 to 12 during
the course of the photolysis, thereby preventing the
consumption of 7 by the nonphotolytic oxidation/reduc-
tion pathway suggested above.
The scope of the photoannulation was further probed
and found to have useful generality. Specifically, alkox-
yquinone analogs6 13a , 13b, 7, and 15 give the respective
annulated quinones 14a (27%), 14b (38%), 12 (83%), and
16 (80%) when subjected to the above reaction conditions
(Scheme 3). The lower yields observed for 14a ,b as
compared to 12 and 16 point to the possible importance
of radical (or carbocation) stabilization of the intermedi-
ate (e.g. 9) to the efficiency of the reaction.
(1) .Zeeck, A.; Wessels, P.; Gohrt, A.; Drautz, H.; Zahner, H. J .
Antibiot. 1991, 44, 1013.
(2) For a review on the ring expansions of cyclobutenones see:
Moore, H. W.; Yerxa, B. R. Synthetic Utility of Cyclobutenones:
Advances in Strain in Organic Chemistry; J AI Press Inc.: Grenwich,
CT, 1995; Volume 4.
(3) For a review on the photolysis of quinones see: Maruyama, K.;
Osuka, A. Chemistry of the Quinonoid Compounds; Patai, S., Ed.,
Wiley: New York, 1988; Vol. II.
In conclusion, we wish to make the following significant
points: (1) For the first time, a direct analog of a member
(4) Gayo, L. M.; Winters, M. P.; Moore, H. W. J . Org. Chem. 1992,
57, 6896.
(5) The structures of the new compounds reported here are in strict
agreement with their spectral and analytical properties.
(6) In direct analogy to the preparation of 4, quinones 7, 12a , 12b,
and 14 were prepared from the corresponding dialkyl cyclobutenedi-
ones. Consult the Supporting Information for experimental details on
7, 12a , 12b, and 14 and all intermediates.
(7) Radical-radical (or ion-ion) combination is apparently more
favorable than the stereoelectronically less favorable endo-trig ring
closure between the carbenium ion center and the adjacent phenolic
hydroxyl group.
S0022-3263(97)00385-X CCC: $14.00 © 1997 American Chemical Society
Onofrey
