Efficient synthesis of phenalenone derivatives by rhodium(II)-catalyzed reactions

Article abstract of DOI:10.1016/S0040-4039(00)00716-4

An efficient synthesis of phenalenone derivatives is achieved by rhodium(II)-catalyzed reactions of 2-diazo-1H-1,3-phenalenedione with a variety of substrates in moderate yields. This method also provides a rapid route to biologically interesting polycycles and heterocycles. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)00716-4

Tetrahedron Letters 41 (2000) 4795±4799
Ecient synthesis of phenalenone derivatives by
rhodium(II)-catalyzed reactions
Yong Rok Lee* and Jung Yup Suk
School of Chemical Engineering and Technology, College of Engineering, Yeungnam University,
Kyongsan 712-749, South Korea
Received 14 February 2000; revised 10 April 2000; accepted 28 April 2000
Abstract
An ecient synthesis of phenalenone derivatives is achieved by rhodium(II)-catalyzed reactions of
2-diazo-1H-1,3-phenalenedione with a variety of substrates in moderate yields. This method also provides
a rapid route to biologically interesting polycycles and heterocycles. # 2000 Elsevier Science Ltd. All rights
reserved.
Phenalenone derivatives are widely distributed in nature.1 They are produced de novo by some
plant organs when provoked by biotic, physical, and chemical agents.2 They are also reported to
have various important biological activities such as antibiotic, antimicrobial, and phytoalexin.3
This wide range of biological properties has stimulated the development of new methods for the
synthesis of phenalenone derivatives. The strategy for the synthesis of phenalenone derivatives
begins with the reaction of 2-diazo-1H-1,3-phenalenedione (2) with a number of substrates under
the rhodium catalysis.
The rhodium-catalyzed decomposition of diazocarbonyl compounds has become an important
method in organic synthesis.4 However, the rhodium-catalyzed reaction of 2-diazo-1H-1,3-
phenalenedione to substrates has not been investigated. Recently, we have been interested in
rhodium(II)-catalyzed reactions of diazodicarbonyl compounds to a number of substrates.5 We
report here an ecient synthesis of phenalenone derivatives utilizing the rhodium(II)-catalyzed
reaction of 2-diazo-1H-1,3-phenalenedione with several unsaturated substrates.
Diazodicarbonyl compound 2 was readily prepared by the diazotransfer reaction of 3-hydroxy-
1H-phenalen-1-one (1) with mesyl azide according to Taber's method in 82% yield (Eq. (1)).6 It is
* Corresponding author.
0040-4039/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00716-4

4796
stable at room temperature and it can be stored in the refrigerator for a long time without
any decomposition.
ꢀ1†
Reactions of 2 with several types of substrates containing heteroatoms such as nitriles, iso-
cyanates, and ketones were ®rst examined to synthesize phenalenone derivatives with ®ve-membered
heterocycles. When acetonitrile was used at 60ꢁC for 5 h as a solvent and a reactant in the presence
of 2 mol% Rh2(OAc)4, oxazole 3 was obtained in 57% yield (Eq. (2)). The structure of oxazole 3
is easily established spectroscopically. Similarly, with other nitriles containing electron-donating
and -withdrawing groups, the expected oxazoles 4±7 were also produced in 57±85% yields.
ꢀ2†
Next, when propyl isocyanate was used at 60ꢁC for 5 h, oxazolone 8 was obtained in 53% yield
(Eq. (3)). The structure of oxazolone 8 is easily identi®ed by observation of IR absorption at
ꢂ1776 cm^l associated with a carbonyl group of the oxazolone ring. In this case, only a single
product was seen and no regioisomers were found. Similarly, under the same conditions, other
oxazolones 9 and 10 were also obtained in 35 and 30% yields, respectively.
ꢀ3†
Rhodium-catalyzed reactions of diazocarbonyl compounds to ketones have not been studied.
In related work, Alonso has demonstrated that copper(II)-mediated cycloaddition of methyl 2-diazo-
3-oxobutyrate to ketones delivers the 1,3-dioxazole in moderate yield.7 Treatment of 2 with acetone
at re¯ux for 3 h gave the 1,3-dioxole 11 in 62% yield (Eq. (4)). The formation of 11 is supported
by the observation of a peak in the IR spectum at ꢂ1631 cm^1 (enone CˆO) and a singlet in the
1H NMR spectrum at ꢀ 1.81 (geminal dimethyl groups). Reactions of 2 with 3-methyl-2-butanone
and cyclohexanone also gave 1,3-dioxole 12 and 13 in 65 and 42% yields, respectively.

4797
ꢀ4†
To synthesize a variety of phenalenone derivatives, additional reactions with ole®ns were
examined (Fig. 1). Reaction with 1-hexene as a reactant and a solvent (re¯ux, 5 h, 2 mol%
Rh2(OA)4) gave dihydrofuran 14 in 40% yield. The dihydrofuran 14 is con®rmed by analysis of
the expected chemical shifts of methine and methylene protons associated with the dihydrofuran
ring. The formation of 14 is very surprising in comparison to the reported results by Shechter that
the rhodium(II)-catalyzed reaction of 2-diazo-1,3-indandione with 1-octene gave exclusively a
cyclopropanation product.8
Figure 1.
Reaction of 2 with 2,3-dimethyl-1,3-butadiene at 60ꢁC for 5 h gave dihydrofuran 15 and dihydro-
oxepine 16 as a separable mixture in 44 and 36% yields, respectively. The formation of dihydro-
furan 15 is de®ned by the chemical shifts and geminal coupling constants associated with the
methylene group of the dihydrofuran ring, whereas the dihydrooxepine 16 is identi®ed by two
methylene peaks of the seven-membered ring. However, reaction with cis,cis-1,3-cyclooctadiene
as a cyclic 1,3-butadiene a€orded cycloadduct 17 (32%) as a single compound.
As electron-rich ole®ns, reaction with an excess amount of vinyl acetate at 60ꢁC for 5 h a€orded
the dihydrofuran 18 in 67% yield. Under the same conditions, reaction with isopropenyl acetate
gave the dihydrofuran 19 (39%) and unexpected rearranged product 20 (30%) as a mixture of
isomers. The methylene protons of 20 are observed at ꢀ 3.67 as a singlet, and two methyl signals
of the ester and the ketone are shown at ꢀ 2.46 and ꢀ 2.21, also as singlets. Further support for the
structural assignment of 20 is also accomplished from its IR spectrum, which clearly shows the
expected three CˆO absorptions at 1763, 1713, and 1640 cm^1 due to one ester and two ketones.
With isobutyl vinyl ether and ethyl 1-propenyl ether, dihydrofuran 21 and 22 were produced in 91
and 86% yields, respectively. The dihydrofuran 22 was isolated as a cis-compound despite the use

4798
of a 3:1 mixture of cis- and trans-isomers. Other electron-rich ole®ns, such as dihydrofuran and
dihydropyran, gave the fused acetals 23 and 24 in 60 and 80% yields, respectively. The structures
of 23 and 24 are also clearly assigned as cis-compounds by analysis of the vicinal coupling
constant of the two methine protons and by the analogy of the earlier reported data.9 The
methine proton of 23 appeared as a doublet (J=5.8 Hz) at ꢀ 6.56 and that of 24 as a doublet
(J=7.6 Hz) at ꢀ 6.23.
Extension of the rhodium(II)-catalyzed reaction of other electron-de®cient ole®ns was also
successful (Eq. (5)). Treatment with an excess of ethyl acrylate as a solvent and a reactant in the
presence of 2 mol% Rh2(OAc)4 at 60ꢁC for 5 h gave dihydrofuran 25 in 26% yield. Similarly,
reaction with methyl methacrylate gave the expected dihydrofuran 26 in 30% yield. As another
electron-de®cient ole®n, reaction with acrylonitrile at 60ꢁC for 5 h gave oxazole 27 (57%) as a
single compound without any trace of the expected dihydrofuran adduct. However, on heating of
2 with methacrylonitrile, oxazole 28 and dihydrofuran 29 were obtained in 31 and 38% yield
as an inseparable mixture. The ratio of yield is calculated from the data of 1H NMR spectrum. In
view of our results, it may be expected that the formation of phenalenone derivatives is facilitated
by both electron-rich and -de®cient ole®ns. However, reactions with electron-rich ole®ns proceed
in higher yields than electron-de®cient ole®ns.
ꢀ5†
As other electron-de®cient ole®ns, several allylic halides were next investigated (Eq. (6)). The
metal-catalyzed reactions of acyclic diazo compounds with allyl halides have been shown by
Doyle.10 Reaction of 2 with allyl chloride at room temperature for 5 h gave the [2,3]-sigmatropic
rearrangement product 30 (74%) as a major component in competition with the dihydrofuran
product 31 (21%). Similarly, reactions with allyl bromide also a€orded the [2,3]-sigmatropic
rearrangement product 32 (60%) and cycloaddition product 33 (26%). However, reaction with
allyl iodide gave the cycloaddition product 34 as a single compound in an 81% yield without any
trace of the expected rearrangement product. These results are in clear contrast to those of Doyle,
who reported that the rhodium(II)-catalyzed reactions of ethyl diazoacetate with allyl iodide
a€orded the [2,3]-rearranged product as a single compound, whereas the cyclopropanation
adduct occurred almost exclusively with allyl chloride and bromide.
ꢀ6†

4799
In order to extend the utility of these reactions as the synthesis of phenalenone derivatives, two
types of alkynes were ®nally examined (Eq. (7)). Reaction with 1-hexyne at 60ꢁC for 5 h resulted
1
in furan 35 (44%) as a single compound. In the H NMR spectrum of 35, the vinyl proton of
furan ring was found at ꢀ 6.64. Similarly, reaction with phenyl acetylene gave the expected furan
36 in 30% yield.
ꢀ7†
In conclusion, rhodium(II)-catalyzed reactions of 2 with several unsaturated substrates are
described. These reactions provide a rapid entry to the synthesis of phenalenone derivatives found
in nature. Further mechanistic studies and applications of these rhodium(II)-catalyzed reactions
are in progress in our laboratory.
Acknowledgements
This work was supported by the Korea Research Foundation Grant (KRF-99-041-D00306).
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