Concise syntheses of (±)-dichroanone, (±)-dichroanal B, (±)-taiwaniaquinol B, and (±)-taiwaniaquinone D

Article abstract of DOI:10.1016/j.tetlet.2009.02.074

The total syntheses of dichroanone and dichroanal B, as well as the formal syntheses of taiwaniaquinol B and taiwaniaquinone D, are reported.

Full text of DOI:10.1016/j.tetlet.2009.02.074

Tetrahedron Letters 50 (2009) 3311–3313
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Concise syntheses of ( )-dichroanone, ( )-dichroanal B, ( )-taiwaniaquinol
B, and ( )-taiwaniaquinone D
*
George Majetich , Joel M. Shimkus
Department of Chemistry, University of Georgia, Athens, GA 30602, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
The total syntheses of dichroanone and dichroanal B, as well as the formal syntheses of taiwaniaquinol B
and taiwaniaquinone D, are reported.
Received 7 February 2009
Accepted 10 February 2009
Available online 14 February 2009
Ó 2009 Elsevier Ltd. All rights reserved.
In 1995, Cheng and co-workers isolated a new class of diterpe-
noids having a fused [6,5,6]-tricyclic skeleton from the Taiwanese
evergreen Taiwania cryptomerioides.1 Over the next decade, this
species, along with Salvia dichroantha and Thuja standishii, pro-
vided numerous examples of this class of rearranged abietanes,
which have been named according to their source of origin and or-
der of isolation (Figure 1).2–4 These natural products have been col-
lectively called taiwaniaquinoids which, although convenient, may
be incorrect from the standpoint of their phytochemical origin.5
In 2003, Banerjee and co-workers reported the total syntheses
of dichroanone (1) and dichroanal B (2) using a Pd(0)-catalyzed
reductive cyclization to create the [6,5,6]-skeleton.6a Since then
taiwaniaquinoids 3, 4, 5, 6, and 7 have been synthesized through
various ring forming strategies as summarized in Scheme 1. For
example, Fillion and Fishlock appended Meldrum’s acid to an
appropriately substituted C-ring precursor to effect a novel domino
bis-cyclization route to taiwaniaquinol B.6b Node and co-workers
featured a Heck reaction in their streamlined synthesis of dichro-
anal B.6c In 2005, Banerjee and co-workers utilized their reductive
cyclization approach to synthesize taiwaniaquinol B and taiwani-
aquinones D and H.6d Stoltz and McFadden used an enantioselec-
tive Tsuji allylation in their A ? AB ? ABC construction of
ent-dichroanone.6e In 2006, Trauner et al. showcased a triflic
anhydride-promoted Nazarov cyclization in their syntheses of
dichroanone, taiwaniaquinols B and D, and taiwaniaquinone H.6f
Chiu and Li attempted a domino bis-cyclization route to taiwan-
iaquinol B through the geranoyl system, but were forced into
two sequential cyclizations to build the tricyclic ring system.6g
She’s synthesis of dichroanone6h and taiwaniaquinol B exploited
a domino Friedel–Crafts acylation/alkylation strategy, which was
first reported by Bhar and Ramana,6i,j to achieve tricycle formation.
Recently, Alvarez-Mansaneda and co-workers featured a thermal
sized racemic dichroanone in 2006,7 but deemed it necessary to
prepare other taiwaniaquinoids before reporting this work. Herein,
we detail the total syntheses of dichroanone, dichroanal B, and the
formal syntheses of taiwaniaquinol B and taiwaniaquinone D.
We decided to prepare the carbocyclic skeleton of dichroanone
using an A + C ? ABC strategy (Scheme 2). Vinyl iodide 88,9 was
smoothly lithiated in THF and coupled with aldehyde 910 to form
allylic alcohol 10 in 80% yield. The anticipated intramolecular Fri-
edel–Crafts alkylation was effected by treating 10 with BF3–Et2O
in DCM at 0 °C to yield tricyclic alkene 11 in quantitative yield.
Heating 11 in DCM with excess BBr3 gave ( )-dichroanone in 81%
yield, with spectral data identical to those reported.3
6p cyclization to introduce the six-membered C-ring onto a chiral
[6,5]-system in their synthesis of taiwaniaquinone G.6k We synthe-
* Corresponding author. Tel.: +1 706 542 1966; fax: +1 706 542 9454.
E-mail address: majetich@chem.uga.edu (G. Majetich).
Figure 1.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.02.074

3312
G. Majetich, J. M. Shimkus / Tetrahedron Letters 50 (2009) 3311–3313
Scheme 2.
also found that the Nazarov reaction failed on a similar system, but
effected ring closure when nitromethane was used as the reaction
solvent.6f Ketone 16 can be converted into taiwaniaquinol B, using
known transformations.6f
Scheme 1.
Scheme 3.
We were confident that oxidation of alcohol 10, followed by
cyanohydrin formation, would yield Friedel–Crafts precursor 14,
in which the C(7) nitrile serves as a latent formyl group (Scheme
3). Unfortunately, all attempts to oxidize alcohol 10 using standard
methods instead resulted in the formation of diene 13; exposure of
this diene to BF3–Et2O in DCM produced alkene 11 in quantitative
yield.
Enone 12 was prepared in 70% yield by adding a solution of the
vinyl anion (i) to acid chloride 15 (Scheme 4). Unfortunately, all ef-
forts to form cyanohydrin 14, including using TMSCN,11 failed.
Moreover, all attempts to first assemble the taiwaniaquinoid nu-
cleus via a Nazarov cyclization of enone 12 failed under standard
conditions despite the examination of several Lewis acids and
commonly used mineral acid catalysts. We found that gently
warming 12 in neat methanesulfonic acid produced ketone 16 in
73% yield. We were gratified to learn that Trauner and co-workers
Scheme 4.

G. Majetich, J. M. Shimkus / Tetrahedron Letters 50 (2009) 3311–3313
3313
ence of the C(5),C(7)-double bond was achieved in 62% yield using
ruthenium chloride and NaIO4.12 Treatment of 20 with a catalytic
amount of thiophenolate anion13 yielded dichroanal B in 75%
yield.3
Scheme 6 details our formal synthesis of taiwaniaquinone D.
Treatment of tertiary alcohol 17 with 6 equiv of methanesulfonyl
chloride in refluxing DCM furnished diene 21 in 84% yield. The oxi-
dative cleavage of the vinyl moiety was accomplished using ruthe-
nium chloride and NaIO4 to furnish aldehyde 22, an intermediate
in Banerjee’s synthesis6d of taiwaniaquinone D.
Acknowledgment
We thank the National Science Foundation for support of this re-
search (CHE-05064846).
References and notes
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Scheme 5.
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nucleus, the mechanism of its formation is not necessarily the same. For
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regarded as 5(6 ? 7)–abeoabietane diterpenoids or 6-nor-5(6 ? 7)–
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is a 6(7 ? 11)abeoabietane. The position of the formyl group in the natural
products isolated from Salvia dichroantha is not accounted for by either
mechanism; if dichroanone and dichroanal are formed by the same process,
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Scheme 6.
We believed that more nucleophilic reagents, such as vinylmag-
nesium bromide, would add to the C(7) carbonyl (Scheme 5). If so,
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contrast, adding the Grignard reagent to ketone 16 in toluene at
0 °C gave a 1:4 ratio of adducts 17:18, respectively, in 75% yield.
The reduction of ketone 18 with LAH, followed by dehydration
using trifluoroacetic acid, produced diene 19 in 78% yield over
two steps. The selective cleavage of the vinyl moiety in the pres-
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