Gold(I) as an artificial cyclase: Short stereodivergent syntheses of (-)-epiglobulol and (-)-4β,7α- and (-)-4α,7α- aromadendranediols

Article abstract of DOI:10.1002/anie.201402044

Three natural aromadendrane sesquiterpenes, (-)-epiglobulol, (-)-4β,7α-aromadendranediol, and (-)-4α,7α- aromadendranediol, have been synthesized in only seven steps in 12, 15, and 17% overall yields, respectively, from (E,E)-farnesol by a stereodivergent gold(I)-catalyzed cascade reaction which forms the tricyclic aromadendrane core in a single step. These are the shortest total syntheses of these natural compounds.

Full text of DOI:10.1002/anie.201402044

Angewandte
Chemie
DOI: 10.1002/anie.201402044
Natural Product Synthesis
Gold(I) as an Artificial Cyclase: Short Stereodivergent Syntheses of
(À)-Epiglobulol and (À)-4b,7a- and (À)-4a,7a-Aromadendranediols**
Javier Carreras, Madeleine Livendahl, Paul R. McGonigal, and Antonio M. Echavarren*
Abstract: Three natural aromadendrane sesquiterpenes, (À)-
epiglobulol, (À)-4b,7a-aromadendranediol, and (À)-4a,7a-
aromadendranediol, have been synthesized in only seven steps
in 12, 15, and 17% overall yields, respectively, from (E,E)-
farnesol by a stereodivergent gold(I)-catalyzed cascade reac-
tion which forms the tricyclic aromadendrane core in a single
step. These are the shortest total syntheses of these natural
compounds.
have been isolated from corals.[7] Aromadendranes with
amino, isonitrile, isothiocyano, and urea functionalities at
C4 have been found in sponges.[8] Diterpenoids with an
aromadendrane structure are also natural products.[9]
The synthesis of members of this family of tricyclic
sesquiterpenes has attracted significant interest.[10] (À)-Epi-
globulol (3), isolated in hop[11] and many essential oils,[12] was
prepared from 1 or the corresponding ketone (apoaromaden-
drone).[13] A first total synthesis of 3 from the chiral pool was
accomplished in eight steps (4% overall yield).[14] A recent
synthesis of (Æ)-epiglobulol in 18 steps used a rhodium(I)-
catalyzed hydroacylation/cycloisomerization as the key
step.[15]
(À)-4a,7a-Aromadendranediol (4) was isolated from
a marine coral Sinularia may[7] and the leaves of the
Amazonian tree Xylopia brasiliensis.[2] A semisynthesis of 4
from (+)-spathulenol[7] and one total synthesis have been
reported.[16] This total synthesis involved a three-reaction
sequence in a three-component reaction to generate four
stereogenic centers in one step and required ten steps to
produce 4 in 23% overall yield. (À)-4b,7a-Aromadendrane-
diol (5) has been isolated from the leaves of Chloranthus
glaber.[17] A semisynthesis of 5 from (+)-spathulenol has been
reported.[7]
Aromadendranes are a family of hydroazulenes named after
(+)-aromadendrene (1, Figure 1), the main component in the
essential oil from Eucaliptus trees. The related sesquiterpe-
noids (À)-globulol (2), (À)-epiglobulol (3), (À)-4a,7a-aro-
madendranediol (4), and (À)-4b,7a-aromadendranediol (5)
are widespread in plant species[1] and display antifungal,[2]
antibacterial,[3] antiviral,[4] cytotoxic,[5] and other activities.[6]
Interestingly, the antipodes of 1 and other aromadendrenes
We developed a gold(I)-catalyzed cascade cyclization of
the dienyne 6, a cascade consisting of a cyclization, 1,5-
migration of the propargylic OR group, and intramolecular
cyclopropanation, thus leading to tricyclic structures closely
related to the aromadendrene sesquiterpenes (Scheme 1).[18]
This reaction is stereospecific since (E)-6 gave the tricyclic
product 7 having the relative configuration of 3 and 5,
whereas the geometrical isomer of 6 led to 8, the C4 epimer of
7, having the configuration of 2 and 4. We recently applied
a strategy based on a gold(I)-catalyzed cyclization/1,5-OR
migration/intermolecular cyclopropanation for the first total
synthesis of (+)-schisanwilsonene A. As part of our program
Figure 1. Naturally occurring aromadendranes.
[*] Dr. J. Carreras, M. Livendahl, Dr. P. R. McGonigal,
Prof. A. M. Echavarren
Institute of Chemical Research of Catalonia (ICIQ)
Av. Paꢀsos Catalans 16, 43007 Tarragona (Spain)
Prof. A. M. Echavarren
Departament de Quꢁmica Analꢁtica i Quꢁmica Orgꢂnica
Universitat Rovira i Virgili, C/Marcel·li Domingo s/n
43007 Tarragona (Spain)
E-mail: aechavarren@iciq.es
[**] We thank the European Research Council (Advanced Grant No.
321066), the MINECO (CTQ2010-16088/BQU), and the ICIQ
Foundation for financial support. We thank Elina Buitrago (visiting
student from the University Stockholm) for experiments on the
synthesis of (Æ)-3, and the ICIQ X-Ray Diffraction and Chroma-
tograpy units.
Scheme 1. Gold-catalyzed formation of tricyclic cores of the aromaden-
dranes by cyclization/1,5-OR migration/intramolecular cyclopropana-
tion.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201402044.
Angew. Chem. Int. Ed. 2014, 53, 1 – 5
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1
These are not the final page numbers!

.
Angewandte
Communications
on the synthesis of terpenoids by using new gold-catalyzed
cyclization cascades,[19] we decided to target 3, 4, and 5, each
of which present six stereogenic centers in a tricyclic skeleton.
In principle, 3 and 5 could be synthesized from the dienyne
(S,E)-6 (Scheme 1), whereas 4 would be prepared from
geometric isomer (S,Z)-6. However, although enantioen-
riched (E)-6 could be readily prepared from (E,E)-farnesol
(9), the starting material, (E,Z)-farnesol, required for the
synthesis of (Z)-6 is not commercially available.[20]
Herein we report a simple solution to this problem and it
allows general access to this class of sesquiterpenes from
(S,E)-6 as a common precursor by means of a stereodivergent
gold(I)-catalyzed cascade process. The reaction can take
place intramolecularly by 1,5-migration of OR in A and in the
presence of an external nucleophile (via B), thus leading to 7
and 8, respectively, having opposite configurations at C4
(Scheme 1). Starting from (R,E)-6, enantiomeric aromaden-
dranes can be similarly obtained. This proposal is based on
our initial mechanistic study in the Z series, in which we found
that the cyclopropyl gold(I) carbene intermediate could be
trapped with methanol to form an epimeric compound as
a minor product.[18] In these transformations, gold(I) acts as an
artificial cyclase,[21] thus mimicking the action of terpene
cyclases forming polycyclic skeletons by the selective activa-
tion of the alkyne terminus of a dienyne, to readily build
a tricyclic skeleton with exquisite stereocontrol.[22,23]
Scheme 3. Reagents and conditions: a) [(JohnPhos)Au(MeCN)]SbF6
(13; 2 mol%), 238C, 5 min (60%); b) H2, Pd(OH)2/C, 1:1 MeOH/
THF, 238C, 4 h (79%); c) [Ir(cod)(PCy3)py]BArF (15 mol%), H2
(80 atm), CH2Cl2, 408C, 4 days (40%); d) oxone, NaHCO3, 18-crown-6,
1:1:2 acetone/CH2Cl2/H2O, 238C, 1 h (51%); e) Li, EDA, 508C, 1 h
(78%); f) allyl alcohol (20 equiv), 13 (2 mol%), À308C, 15 min (56%
+ 21% 7); g) [Pd(PPh3)4] (5 mol%), K2CO3, MeOH, reflux 72 h (72%);
h) mCPBA, CH2Cl2, 0 to 238C (83%); i) Li, EDA, 508C, 1.5 h (62%).
BArF =3,5-bis(trifluoromethyl)phenylborate, cod=1,5-cyclooctadiene,
EDA=ethylenediamine, JohnPhos=(2-biphenyl)-di-tert-butylphos-
phine; mCPBA=m-chloroperbenzoic acid.
The dienyne (S,E)-6 (R = Bn) was prepared in four steps
and 62% overall yield by using a route similar to that used in
the transformation of the lower homologue geraniol.[19a,24] the
transformation involved the known Sharpless asymmetric
epoxidation of (E,E)-farnesol (9) to give the epoxide (S,S)-10
(88% yield, 91:9 e.r.)[25,26] (Scheme 2). Substitution of the
diffraction.[28,29] Debenzylation of 7 with H2 (1 atm) and
Pd(OH)2/C gave the alcohol 14 (79% yield), which was
hydrogenated with [Ir(cod)(PCy3)py]BArF catalyst[30] under
high pressure of H2 to give 3 in 40% yield (95:5 e.r.). The
synthesis 3 from 9 required seven steps and proceeded in 12%
overall yield.
Epoxidation of 7 with dimethyldioxirane yielded 15
stereoselectivily. Epoxide opening and ether cleavage with
Li in ethylenediamine[31] yielded 5 in 78% (96:4 e.r.), which
gave enantiopure material after crystallization. The synthesis
of 5 from 9 was accomplished in seven steps with 15% overall
yield.
Scheme 2. a) l-(+)-DIPT, Ti(OiPr)4, tBuOOH, 4 ꢃ M.S., CH2Cl2,
À488C, 88%, 82% ee;[25] b) PPh3, NaHCO3, CCl4, reflux, 6 h, 94%;
c) nBuLi, THF, À408C, 2 h, 82%; d) BnBr, NaH, Bu4NI, THF, 238C
12 h, 91%. DIPT=diisopropyl tartrate, M.S.=molecular sieves,
THF=tetrahydrofuran.
When the gold-catalyzed reaction of dienyne (S,E)-6 was
performed in the presence of allyl alcohol as an external
nucleophile, the allyl ether 8 was obtained with the opposite
configuration at C4 compared to that of 7 (Table 1). While
lowering the reaction temperature to À308C led to a 1:1
mixture of 7 and 8 (Table 1, entry 3), increasing the concen-
tration of allyl alcohol to 20 equivalents favored the inter-
molecular pathway (Table 1, entry 5). Similar results were
obtained with using only 1 mol% gold(I) catalyst (Table 1,
entry 5). Under the optimized reaction conditions, 8 was
obtained in 56% yield, along with 7 (21% yield; Scheme 3).
Removal of the allylic ether with [Pd(PPh3)4] in MeOH gave
the alcohol 16, whose structure was confirmed by X-ray
primary alcohol by chloride with CCl4 and PPh3 gave 11,
which was treated with nBuLi to yield the propargylic alcohol
12. Finally, benzylation under standard reaction conditions
gave (S,E)-6.
Exposing (S,E)-6 to the cationic gold(I) complex
[(JohnPhos)Au(MeCN)]SbF6 (13) for 5 minutes at room
temperature gave 7 in 60% yield (Scheme 3). Other gold(I)
catalysts were also screened for this reaction, but the best
results were obtained using complex 13.[27] The relative
configuration of 7 (racemic series) was confirmed by X-ray
2
www.angewandte.org
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2014, 53, 1 – 5
These are not the final page numbers!

Angewandte
Chemie
Table 1: Gold(I)-catalyzed addition of allyl alcohol to (S,E)-6.[a]
cursor by a stereodivergent gold-catalyzed reaction which
establishes four new stereogenic centers from a single one.
The three natural sesquiterpenes (À)-epiglobulol (3), (À)-
4a,7a-aromadendranediol (4), and (À)-4b,7a-aromadendra-
nediol (5) have been synthesized in seven steps in 12, 17, and
15% overall yields, respectively, from commercially available
(E,E)-farnesol (9), and constitutes the shortest total syntheses
of these natural compounds. This route could be extended for
the enantioselective synthesis of any enantiomer of other
aromadendranes and non-natural analogues.
Entry
AllylOH (equiv)
T [8C]
t [min]
7/8[b]
1
2
3
10
10
10
20
20
23
0
À30
À30
À30
5
10
15
20
30
75:25
55:45
50:50
27:73
33:67
4
Received: February 3, 2014
Published online: && &&, &&&&
5[c]
[a] 0.05m. [b] Determined by GC-MS. [c] 1 mol% 13.
Keywords: cyclization · gold · natural products · terpenoids ·
.
total synthesis
crystal diffraction[29] in the racemic series (Figure 2).[26]
Although 4 could be synthesized from 16, a more direct
synthesis was completed from 8 by selective epoxidation with
mCPBA from the convex face (83% yield), followed by
opening of the epoxide and allyl cleavage with Li in ethyl-
[1] H. J. M. Gijsen, J. B. Wijnberg, A. de Groot, Prog. Chem. Org.
Nat. Prod. 1995, 64, 149 – 193.
[2] I. C. Moreira, J. H. G. Lago, N. C. M. Young, N. F. Roque, J.
Braz. Chem. Soc. 2003, 14, 828 – 831.
[3] a) C. Gaspar-Marques, M. F. Simꢀes, B. Rodrꢁguez, J. Nat. Prod.
2004, 67, 614 – 621; b) Y. Yamakoshi, M. Murata, A. Shimizu, S.
Homma, Biosci. Biotechnol. Biochem. 1992, 56, 1570 – 1576;
c) J. M. Jacyno, N. Montemurro, A. D. Bates, H. G. Cutler, J.
Agric. Food Chem. 1991, 39, 1166 – 1168; d) M. Murata, Y.
Yamakoshi, S. Homma, K. Aida, K. Hori, Y. Ohashi, Agric. Biol.
Chem. 1990, 54, 3221 – 3226.
[4] a) M. Nishizawa, M. Emura, Y. Kan, H. Yamada, K. Ogawa, N.
Hamanaka, Tetrahedron Lett. 1992, 21, 2983 – 2986; b) N.
De Tommasi, C. Pizza, C. Conti, N. Orsi, M. L. Stein, J. Nat.
Prod. 1990, 53, 830 – 835.
[5] a) Z.-S. Su, S. Yin, Z.-W. Zhou, Y. Wu, J. Diang, J.-M. Yue, J. Nat.
Prod. 2008, 71, 1410 – 1413; b) H. Tada, F. Yasuda, Chem.
Pharm. Bull. 1985, 33, 1941 – 1945.
Figure 2. X-ray structures for (Æ)-16 and 4. Thermal ellipsoids are
[6] a) A. Matsuo, K. Atsumi, M. Nakayama, S. Hayashi, J. Chem.
Soc. Perkin Trans. 1 1981, 2816 – 2824; b) T. D. Hubert, D. F.
Wiemer, Phytochemistry 1985, 24, 1197 – 1198; c) Y. Asakawa,
M. Toyota, T. Takemoto, I. Kubo, K. Nakanishi, Phytochemistry
1980, 19, 2147 – 2154; d) N. Pꢂrez-Hernꢃndez, H. Ponce-Monter,
M. I. Ortiz, R. CariÇo-Cortꢂs, P. Joseph-Nathan, Z. Naturforsch.
C 2009, 64, 840 – 846; e) T. S. Wu, Y. Chan, Y. Leu, Chem.
Pharm. Bull. 2000, 3, 357 – 361.
shown at 50% probability.
enediamine to give 4 in 62% yield (87:13 e.r.), yielding
enantiopure 4 after crystallization. Spectral data and optical
rotation of synthetic 4a,7a-aromadendranediol matched
those reported for the natural compound. The relative and
absolute configuration of 4 were confirmed by X-ray diffrac-
tion (Figure 2).[29] The synthesis of (+)-4a,7a-aromadendra-
nediol was similarly carried out from (R,R)-10.[27]
The stereochemical divergent synthesis of 3 and 4 from
(S,E)-6 confirms the proposal that this cascade cyclization
process proceeds by intra- or intermolecular reactions of
cyclopropyl gold(I) carbene-like intermediates such as A or
B.[18,32] The enantioselectivity is fully preserved in the
formation of 3 and 5 via 7 by an intramolecular gold(I)-
catalyzed 1,5-migration of a propargylic group. The intermo-
lecular reaction of (S,E)-6 with allyl alcohol occurs with high
enantioselectivity (ca. 96%). In this case, the slight racemi-
zation is due to the competitive formation of a propargyl
carbocation, presumably facilitated by the higher polarity of
the reaction medium.
[7] a) C. M. Beechan, C. Djerassi, H. Eggert, Tetrahedron 1978, 34,
2503 – 2508.
[8] a) E. Fattorusso, S. Magno, L. Mayol, C. Santacroce, D. Sica,
Tetrahedron Lett. 1975, 31, 269 – 270; b) C. C. da Silva, V.
Almagro, J. Zukerman-Schpector, E. E. Castellano, A. J. Mar-
saioli, J. Org. Chem. 1994, 59, 2880 – 2881; c) S. Kozawa, H.
Ishiyama, J. Fromont, J. Kobayashi, J. Nat. Prod. 2008, 71, 445 –
447; d) H. Ishiyama, S. Kozawa, K. Aoyama, Y. Mikami, J.
Fromont, J. Kobayashi, J. Nat. Prod. 2008, 71, 1301 – 1303.
[9] A. S. R. Anjaneyulu, M. V. R. Krishnamurthy, G. V. Rao, Tetra-
hedron 1997, 53, 9301 – 9312.
[10] a) G. Bꢄchi, W. Hofheinz, J. V. Paukstelis, J. Am. Chem. Soc.
1966, 88, 4113 – 4114; b) G. Buechi, W. Hofheinz, J. V. Paukstelis,
J. Am. Chem. Soc. 1969, 91, 6473 – 6478; c) J. A. Marshall, J. A.
Ruth, J. Org. Chem. 1974, 39, 1971 – 1973; d) H. J. M. Gijsen,
J. B. P. A. Wijnberg, G. A. Stork, A. de Groot, Tetrahedron 1991,
47, 4409 – 4416; e) H. J. M. Gijsen, J. B. P. A. Wijnberg, G. A.
Stork, A. de Groot, M. A. de Waard, J. G. M. van Nistelrooy,
Tetrahedron 1992, 48, 2465 – 2476; f) H. J. M. Gijsen, J. B. P. A.
Wijnberg, C. van Ravenswaay, A. de Groot, Tetrahedron 1994,
50, 4733 – 4744; g) H. J. M. Gijsen, J. B. P. A. Wijnberg, A.
In summary, we have completed highly concise syntheses
of three representative aromadendranes from a single pre-
Angew. Chem. Int. Ed. 2014, 53, 1 – 5
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
3
These are not the final page numbers!

.
Angewandte
Communications
de Groot, Tetrahedron 1994, 50, 4745 – 4754; h) S. L. Gwalt-
ney II, K. J. Shea, Tetrahedron Lett. 1996, 37, 949 – 952; i) R.
Guillermo, J. R. Hanson, A. Truneh, J. Chem. Res. Synop. 1997,
28 – 29; j) F. J. Moreno-Dorado, Y. M. A. W. Lamers, G. Miro-
nov, J. B. P. A. Wijnberg, A. de Groot, Tetrahedron 2003, 59,
7743 – 7750; k) Y. M. A. W. Lamers, G. Rusu, J. B. P. A. Wijn-
berg, A. de Groot, Tetrahedron 2003, 59, 9361 – 9369.
[11] R. Tressl, K.-H. Engel, M. Kossa, H. Koppler, J. Agric. Food
Chem. 1983, 31, 892 – 897.
[12] a) A. Elaissia, H. Medinia, M. L. Khoujab, M. Simmonds, F.
Lynend, F. Farhat, R. Chemli, F. Harzallah-Skhiri, Chem.
Biodiversity 2011, 8, 352 – 361; b) M. Z. ꢅzel, F. Gçgꢄs, A. C.
Lewis, J. Chromatogr. Sci. 2008, 46, 157 – 161; c) H. Nazemiyeh,
S. M. Razavi, R. Hajiboland, A. Delazar, S. Esna-asharii, R.
Bamdad, L. Nahar, S. D. Sarker, Chem. Nat. Compd. 2007, 43,
736 – 737; d) M. E. A. Stefanello, A. C. R. F. Pascoal, M. J.
Salvador, Chem. Biodiversity 2011, 8, 73 – 94.
[13] H. J. M. Gijsen, K. Kanai, G. A. Stork, J. B. P. A. Wijnberg,
R. V. A. Orru, C. G. J. M. Seelen, S. M. van der Kerk, A. de G-
root, Tetrahedron 1990, 46, 7237 – 7246.
[14] D. Caine, J. T. Gupton III, J. Org. Chem. 1975, 40, 809 – 810.
[15] Y. Oonishi, A. Taniuchi, M. Mori, Y. Sato, Tetrahedron Lett.
2006, 47, 5617 – 5621.
[16] B. Simmons, A. M. Walji, D. W. C. MacMillan, Angew. Chem.
2009, 121, 4413 – 4417; Angew. Chem. Int. Ed. 2009, 48, 4349 –
4353.
[17] Y. Takeda, H. Yamashita, T. Matsumoto, H. Terao, Phytochem-
istry 1993, 33, 713 – 715.
[20] A mixture of isomers is also available. (Z,Z)- or (E,Z)-farnesol
are just available as analytical standards. Although (E,Z)-
farnesol can be prepared in two steps from nerylacetone (10:1
E,Z/E,E mixture, 55% yield): J. S. Yu, T. S. Kleckley, D. F.
Wiemer, Org. Lett. 2005, 7, 4803 – 4806), pure nerylacetone is
commercially available only in milligram amounts.
[21] M. Willot, M. Christmann, Nat. Chem. 2010, 2, 519 – 520.
[22] Selected examples of gold(I)-catalyzed polycyclizations: a) A.
Fꢄrstner, L. Morency, Angew. Chem. 2008, 120, 5108 – 5111;
Angew. Chem. Int. Ed. 2008, 47, 5030 – 5033; b) P. Y. Toullec, T.
Blarre, V. Michelet, Org. Lett. 2009, 11, 2888 – 2891; c) S. G.
Sethofer, T. Mayer, F. D. Toste, J. Am. Chem. Soc. 2010, 132,
8276 – 8277.
[23] For lead references on late transition metal catalyzed polycyc-
lizations of polyenes: a) M. A. Schafroth, D. Sarlah, S. Kraut-
wald, E. M. Carreira, J. Am. Chem. Soc. 2012, 134, 20276 –
20278; b) O. F. Jeker, A. G. Kravina, E. M. Carreira, Angew.
Chem. 2013, 125, 12388 – 12391; Angew. Chem. Int. Ed. 2013, 52,
12166 – 12169; c) M. J. Geier, M. R. Gagnꢂ, J. Am. Chem. Soc.
2014, 136, 3032 – 3035.
[24] D. K. Mohapatra, C. Pramanik, M. S. Chorghade, M. K. Gurjar,
Eur. J. Org. Chem. 2007, 5059 – 5063.
[25] J. Tanuwidjaja, S.-S. Ng, T. F. Jamison, J. Am. Chem. Soc. 2009,
131, 12084 – 12085.
[26] The syntheses of (Æ)-epiglobulol and (Æ)-4a,7a-aromadendra-
nediol was also carried out from a 1.2:1 mixture of geranyl- and
nerylacetone. See the Supporting Information for details.
[27] See the Supporting Information for additional details.
[28] Racemic 7 was prepared in four steps from a 1.2:1 mixture of
geranyl- and nerylacetone.[27]
[29] CCDC 983695 (4), 983696 [(Æ)-7)], 983697 [(Æ)-16)] contain the
supplementary crystallographic data for this paper. These data
can be obtained free of charge from The Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
[30] B. Wꢄstenberg, A. Pfaltz, Adv. Synth. Catal. 2008, 350, 174 – 178.
[31] H. C. Brown, S. Ikegami, J. H. Kawakami, J. Org. Chem. 1970,
35, 3243 – 3245.
[18] E. Jimꢂnez-NuÇez, M. Raducan, T. Lauterbach, K. Molawi,
C. R. Solorio, A. M. Echavarren, Angew. Chem. 2009, 121,
6268 – 6271; Angew. Chem. Int. Ed. 2009, 48, 6152 – 6155.
[19] a) E. Jimꢂnez-NfflÇez, K. Molawi, A. M. Echavarren, Chem.
Commun. 2009, 7327 – 7329; b) K. Molawi, N. Delpont, A. M.
Echavarren, Angew. Chem. 2010, 122, 3595 – 3597; Angew.
Chem. Int. Ed. 2010, 49, 3517 – 3519; c) M. Gaydou, R. E.
Miller, N. Delpont, J. Ceccon, A. M. Echavarren, Angew. Chem.
2013, 125, 6524 – 6527; Angew. Chem. Int. Ed. 2013, 52, 6396 –
6399; d) A. Pitaval, D. Leboeuf, J. Ceccon, A. M. Echavarren,
Org. Lett. 2013, 15, 4580 – 4583.
[32] a) E. Jimꢂnez-NfflÇez, A. M. Echavarren, Chem. Rev. 2008, 108,
3326 – 3350; b) C. Obradors, A. M. Echavarren, Acc. Chem. Res.
2014, 47, 902 – 912.
4
www.angewandte.org
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2014, 53, 1 – 5
These are not the final page numbers!

Angewandte
Chemie
Communications
Natural Product Synthesis
J. Carreras, M. Livendahl,
P. R. McGonigal,
A. M. Echavarren*
&&&& — &&&&
Gold(I) as an Artificial Cyclase: Short
Stereodivergent Syntheses of
Aromasynthesis: Aromadendrane ses-
quiterpenes (À)-epiglobulol, (À)-4a,7a-
aromadendranediol, and (À)-4b,7a-aro-
madendranediol are synthesized in only
seven steps from (E,E)-farnesol by a ster-
eodivergent gold(I)-catalyzed cascade
reaction.
(À)-Epiglobulol and (À)-4b,7a- and
(À)-4a,7a-Aromadendranediols
Angew. Chem. Int. Ed. 2014, 53, 1 – 5
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5
These are not the final page numbers!