Tetrahedron Letters
Iridium-catalyzed enantioselective synthesis of (À)- and
(
+)-aurantioclavine
Ting Lei a,b,c, Hongbin Zhang a, , Yu-Rong Yang b,
⇑
⇑
a
Key Laboratory of Medicinal Chemistry for Natural Resources (Yunnan University), Ministry of Education, School of Chemical Science and Technology, Yunnan University,
Kunming 650091, China
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China
b
c
University of Chinese Academy of Sciences, Beijing 100049, China
a r t i c l e i n f o
a b s t r a c t
Article history:
A new protocol for generating indoleazepine 9 via an Ir-catalyzed intramolecularly asymmetric
Received 26 August 2015
Revised 11 September 2015
Accepted 14 September 2015
Available online 14 September 2015
3
amination of secondary allylic alcohol 5 in the presence of Carreira ligand (10) and Sc(OTf) is described.
This methodology has been exploited in the facile synthesis of natural (À)-aurantioclavine (1), a
biosynthetical precursor of communesins, and its unnatural enantiomer (+)-aurantioclavine (ent-1).
Ó 2015 Elsevier Ltd. All rights reserved.
Keywords:
Iridium-catalyzed
Asymmetric amination
Aurantioclavine
The communesin family of natural products has received con-
Stoltz.6 Although several racemic and enantiomeric syntheses of
(À)-aurantioclavine have been achieved to date, to our surprise,
1
6,7
siderable attention from synthetic community recently. These
alkaloids are popular with synthetic chemists,2 no doubt, mainly
for their challenging structures which featured in the complex hep-
tacyclic skeleton incorporating two aminal linkages and vicinal
quaternary centers. Despite several elegant total syntheses out-
in which there is only one through the catalytic asymmetric
synthesis reported by Takemoto group until 2014.7g The Pd-
catalyzed intramolecular asymmetric allylic amination using
tosylamide as nucleophile and linear allylic carbonate as
electrophile is the key step of Takemoto’s synthesis (Scheme 1).
The transition metal-catalyzed intramolecular asymmetric
amination of allylic alcohol derivative with nucleophilic N sources
is a powerful method for the construction of N-containing hetero-
cycles. In this regard, transition metals such as Pd, Ir, Ru, Au and
lined in the literature2
a–f
after the inaugural Qin synthesis of
2a
racemic communesin F, asymmetric catalytic synthesis for these
alkaloids largely remains a formidable obstacle. In 2003, Stoltz
proposed that the communesin core might be biosynthetically
produced through a dimerization of (À)-aurantioclavine and
2
g,3
8
tryptamine.
Very recently, Tang and Garg confirmed that the
Cu can serve this aim. Among these metals, Ir displays similar gen-
biosynthetic pathway involves aurantioclavine as
a
building
erality as Pd with respect to the scope of allylic substrates and
nucleophiles. Interestingly, we noticed that in Takemoto’s synthe-
9
block through genetic-inactivation studies (Fig. 1), which also led
to isolation of three new communesin analogues.4 Inspired by
these results, we initiated a synthetic program aiming at the cat-
alytic asymmetric approach to the communesins through a bio-in-
spired convergent strategy. In this context, catalytic asymmetric
synthesis of (À)-aurantioclavine is our first step on the road of con-
quering the communesin alkaloids.
sis of (À)-aurantioclavine, Pd rather than Ir was judiciously selected
as the catalyst probably due to the uncertainties of Ir-catalysis.7g
Given the rapid advance in iridium-catalyzed allylic substitution
in recent years, in particular, the branched, racemic allylic
alcohols directly used as the electrophilic allylic partner,
1
0
contributions mainly from the Carreira laboratory, we hypothe-
sized Ir-catalysis could be employed in the asymmetric amination
en route to aurantioclavine. As shown in Scheme 1, we envisioned
that an intramolecular amination of 3,4-disubstituted indole 5
would furnish the desired indoleazepine skeleton of aurantio-
clavine. In our case, much easily prepared secondary allylic alcohol
was utilized as electrophile, not linear allylic carbonate. The alcohol
could be arisen from the corresponding 4-bromo-tryptamine
(
À)-Aurantioclavine was isolated5 from Penicillium auran-
tiovirens in 1981. Structurally, this ergot alkaloid has the signatures
of indoleazepine with a chiral center of R configuration assigned by
⇑
(
Y.-R. Yang).
040-4039/Ó 2015 Elsevier Ltd. All rights reserved.
0