J. Am. Chem. Soc. 1998, 120, 3801-3802
3801
Scheme 1
New Metathesis Methodololgy Leading to
Angularly-Fused Polycyclic Quinones and Related
Compounds
Matthew J. Heileman, Ralf Tiedemann, and
Harold W. Moore*
Department of Chemistry, UniVersity of California
IrVine, California 92697-2025
ReceiVed January 5, 1998
Reported here is a new method for the regiospecific synthesis
of phenanthraquinones and related angularly fused polycyclic
compounds from squaric acid derived cyclobutenones.1 The
method rests on dual annulation reactions. One inVolVes the well-
known electrocyclic ring opening of appropriately substituted
cyclobutenones to Vinylketenes and their subsequent reactions with
proximally placed ketenophiles.2 The other constitutes a new
metathesis sequence leading to aromatic rings which arise from
a photofragmentation of cyclobutyl-substituted quinones as the
ultimate step.3
The salient details are outlined in Scheme 1. Cyclobutenone
1 undergoes ring closure to the tetracyclic cyclobutenone 3 (85%)
upon mild thermolysis (benzene, 70 °C), a transformation
envisaged to involve an 8π electrocyclization to cyclooctatriene
intermediate 2, followed by a 6π electrocyclic ring closure to
the observed product 3.4 Treatment of 3 with phenylcerium(III)
chloride5 followed by acid hydrolysis (concentrated HCl) gave
cyclobutenone 4, which was immediately thermolyzed (benzene,
80 °C).2 The resulting ring expanded hydroquinone was not
isolated but directly oxidized (Ag2O) to quinone 5 in >90%
overall yield from 3.
When the red-colored benzene solution of 5 was exposed to
fluorescent laboratory light it underwent an efficient photofrag-
mentation reaction to yield yellow benzo[a]anthracene-7,12-dione
(8)6 (87%), a compound representing the basic framework of the
angucycline group of antibiotics.7-9 The mechanism of this
unusual photofragmentation is envisaged to involve the excited-
state diradical 6 whose strain energy is relieved upon cleavage
of the cyclobutane ring to give 7. Subsequent expulsion of
isobutylene provides 8.
109 (71%), and 11 (75%) by using respectively 1-hexynylcerium-
(III) chloride, 2-anisoylcerium(III) chloride, and 2-lithiofuran. For
comparison, 12 (obtained from 22 in 91% yield) gave the
regioisomers 13 (73%), 1410 (83%), and 15 (75%).
The following data suggest this method to be a general,
regiospecific route to angularly fused polycyclic aromatic com-
pounds (Scheme 2). For example, 3 was converted to 9 (89%),
A particularly interesting example is the conversion of cy-
clobutenone 16 to 6-(4-pentenyl)benzo[a]anthracene-7,12-dione
(19) (Scheme 3). Here, 16 gave 17 in 89% yield upon mild
thermolysis at 80 °C. Ring expansion of 17, using phenylcerium-
(III) chloride, gave the quinone 18 in 93% yield. Photofragmen-
tation of 18 then gave 19 in 81% yield (75% from 17).
(1) For a listing of naturally occurring phenanthraquinones see: Thomson,
R. H. Naturally Occurring Quinones; Chapman and Hall: New York, 1987;
Vol. III.
(2) For a recent review on the ring expansion of cyclobutenones see:
Moore, H. W.; Yerxa B. R. AdV. Strain Org. Chem. 1995, 4, 81-162.
(3) For a review of olefin metathesis in organic chemistry see: Schuster,
M.; Blechert, S. Angew. Chem., Int. Ed. Engl. 1997, 36, 2036.
(4) For an elegant application of this electrocyclic cascade in natural
products synthesis see: Nicolaou, K. C.; Petasis, N. A.; Zipin, R. E.; Uenishi,
J. J. Am. Chem. Soc. 1982, 104, 5555.
(5) Imamoto, T.; Sugiora, Y.; Takiyama, N. Tetrahedron Lett. 1984, 25,
4233.
(6) Elbs, K. Ber. 1886, 19, 2209. Badger, G. M. J. Chem. Soc. 1939, 802.
(7) The photolysis is carried out by exposing a benzene solution of the
quinone to two 40 W fluorescent lights for a few hours.
Syntheses of the requisite cyclobutenones 1, 22, and 16 were
accomplished as outlined in Scheme 4.11 Specifically, treatment
of dimethyl squarate12 (20) with 2-lithiostyrene followed by
methanolysis (TFAA, MeOH) of the resulting â-hydroxyenol ether
gave cyclobutenone 21 in 86% yield. This was converted to 1
(88%) upon treatment with 1-lithio-2-methylpropene. Similarly,
20 gave 22 (64% overall) by changing the addition order of the
organometallic reagents, i.e., 1-lithio-2-methylpropene preceded
(8) For a recent review on these compounds see: Rohr, J.; Thiericke, R.
Nat. Prod. Rep. 1992, 103. Also see: (a) Krohn, K.; Ballwanz, F.; Baltus, W.
Liebigs Ann. Chem. 1993, 911. (b) Larsen, D. S.; O’Shea, M. D. Tetrahedron
Lett. 1993, 34, 1373. (c) Krohn, K.; Khanbabaee, K. Angew. Chem., Int. Ed.
Engl. 1994, 33, 99. (d) Larsen, D. S.; O’Shea, M. D. J. Chem. Soc., Perkin
Trans. 1 1995, 1019. (e) Kim, K.; Sulikowski, G. A. Angew. Chem., Int. Ed.
Engl. 1995, 34, 2397. (f) Matsuo, G.; Miki, Y.; Nakata, M.; Matsumura, S.;
Toshima, K. Chem. Commun. 1996, 225. (g) Carreno, M. C.; Urbano, A.;
Fischer, J. Angew. Chem., Int. Engl. Engl. 1997, 36, 1621. (h) Larsen, D. S.;
O’Shea, M. D.; Brooker, S. Chem. Commun. 1996, 203.
(10) Manning, W. B.; Muschik, G. M.; Tomaszewski, J. E. J. Org. Chem.
1979, 44, 699.
(11) For examples of analogous synthetic methodology see: Gayo, L.;
Moore, H. W. J. Org. Chem. 1992, 57, 6896. Santora, V. J.; Moore, H. W. J.
Am. Chem. Soc. 1995, 117, 8486.
(9) The structure assignments of all new compounds reported here are based
upon characteristic spectral and analytical data (see Supporting Information).
(12) Liu, H.; Tomooka, C. S.; Moore, H. W. Synth. Commun. 1997, 27,
2177.
S0002-7863(98)00039-0 CCC: $15.00 © 1998 American Chemical Society
Published on Web 04/02/1998
Heileman
