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ChemComm
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DOI: 10.1039/C5CC10093C
ARTICLE
Encouraged by the excellent compatibility of the
Journal Name
Funded by the Priority Academic Program Development of
Jiangsu Higher Education Institutions).
organocatalytic oxidation reaction, we further targeted a
homologous strategy to construct polyene architectures.
According to the strategy described in Figure 1b, the polyene
framework can be dissected into several butanol C4 templates
(Figure 5). For example, a physarigin A framework that
contains six contiguous E double bonds can be divided into
cinnamaldehyde and two copies of butanol fragments.
Meanwhile, heteranthin that bears six contiguous methyl
substituted olefinic bonds can be split into a hexenoate and an
isopentanol fragment. The amine-catalyzed IBX-oxidation can
Notes and references
1
P. I. Dalko, Comprehensive Enantioselective Organocatalysis:
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(a) S. L. Zhang, H. X. Xie, J. Zhu, H. Li, X. S. Zhang and W.
2
3
4
5
be applied directly to alcohols for the formation of α,β
-
unsaturated aldehydes, and C4 fragments can be conveniently
assembled to the terminal aldehyde group by using Julia or
Wittig reagent for chain elongation. Thus, the iterative process
of organocatalytic oxidation and C4 elongation could provide a
simple, efficient and modular way for synthesizing polyene
architectures.
Wang, Nat. Commun. 2011, 2, 211; (b) Y. Hayashi, T. Itoh and
H. Ishikawa, Angew. Chem. Int. Ed. 2011, 50, 3920; (c) S.
Zhang, H. Xie, A. Song, D. Wu, J. Zhu, S. Zhao, J. Li, X. Yu and
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6
7
H. Xie, S. Zhang, H. Li, X. Zhang, S. Zhao, Z. Xu, X. Song, X. Yu
and W. Wang, Chem. Eur. J. 2012, 18, 2230.
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and A. Whiting, J. Chem. Soc. Perkin Trans I, 2002, 999; (c) A.
L. K. Shi Shun and R. R. Tykwinski, Angew. Chem. Int. Ed.
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G. Britton and T. W. Goodwin, Carotenoid Chemistry and
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M. Bates, B. Huang, G. T. Dempsey and X. Zhang, Science,
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After the preparation of Julia reagent 13, elongation of
cinnamaldehyde 6a under cryogenic conditions followed by
TBS deprotection offered propanol alcohol precursor 9 with
good E stereoselectivity (Scheme 2). Precursor was then
9
subjected to an organocatalytic oxidative reaction to generate
triene aldehyde 10 in 71% yield with exclusive E configuration.
The iterative process of elongation and oxidation was
performed to homologously assemble another C4 fragment to
8
9
prepare physarigin
A framework 12 by repeating the
sequential Julia-Kocienski18 and amine-catalyzed IBX-oxidation
reactions. For the methyl substituted polyene framework,
hexenoate 14 was first oxidized to dienal 15 using
organocatalytic oxidation (Scheme 3). Elongation of the
aldehyde with Wittig reagent19 19 afforded triene 16 with an
E/Z ratio of 57:43. The E stereomer 17E was isolated by
preparative HPLC after tetrahydropyran deprotection. Iterative
10 E. M. Woerly, J. Roy and M. D. Burke, Nat. Chem. 2014, 6,
484.
11 K. C. Nicolaou, P. G. Bulger and D. Sarlah, Angew. Chem. Int.
Ed. 2005, 44, 4442.
12 For reviews on combining organocatalysis with transition
metal catalysis: (a) Z. Shao and H. Zhang, Chem. Soc. Rev.
2009, 38, 2745; (b) C. C. J. Loh and D. Enders, Chem. Eur. J.
2012, 18, 10212; (c) Z.-T. Du and Z.-H. Shao, Chem. Soc. Rev.
2013, 42, 1337.
13 (a) S. Bertelsen, M. Marigo, S. Brandes, P. Dinér and K. A.
Jørgensen, J. Am. Chem. Soc. 2006, 128, 12973; (b) G.
Bencivenni, P. Galzerano, A. Mazzanti, G. Baroli and P.
Melchiorre, PNAS, 2010, 107, 20642; (c) B. Zhu, W. Zhang, R.
Lee, Z. Han, W. Yang, D. Tan, K.-W. Huang and Z. Jiang,
Angew. Chem. Int. Ed. 2013, 52, 6666.
amine-catalyzed
homologous tetraene 18
IBX-oxidation
,
eventually
a heteranthin framework with
provided
exclusive E configuration, which was confirmed by 2D NMR
spectra. Finally, considering the potent and practical role of
the aldehyde precursors generated by organocatalytic
oxidation, application of this homologous strategy with diverse
butanol building blocks could result in a large range of natural
polyenes and natural polyene-like derivatives that could be
used for the total synthesis of natural products and screening
of bioactive compounds20 as drug candidates in medicinal
chemistry.
14 K. C. Nicolaou, T. Montagnon and P. S. Baran, Angew. Chem.
Int. Ed. 2002, 41, 993.
15 (a) H. Kakeya, S. Kageyama, L. Nie, R. Onose, G. Okada, T.
Beppu, C. J. Norbury and H. Osada, J. Antibiot. 2001, 54, 850;
(b) K. D. Eom, J. V. Raman, H. Kim and J. K. Cha, J. Am. Chem.
Soc. 2003, 125, 5415; (c) D. A. Evans and B. T. Connell, J. Am.
Chem. Soc. 2003, 125, 10899; (d) S. Manaviazar and K. J.
Hale, Angew. Chem. Int. Ed. 2011, 50, 8786.
16 Y. Misono, A. Ito, J. Matsumoto, S. Sakamoto, K. Yamaguchi
and M. Ishibashi, Tetrahedron Lett. 2003, 44, 4479.
17 M. D. Méndez-Robles, H. H. Permady, M. E. Jaramillo-Flores,
E. C. Lugo-Cervantes, A. Cardador-Martínez, A. A. Canales-
Aguirre, F. Lopez-Dellamary, C. M. Cerda-García-Rojas and J.
Tamariz, J. Nat. Prod. 2006, 69, 1140.
In conclusion, we have developed an amine-catalyzed IBX-
oxidation strategy through the unprecedented oxidative
conversion of enamine to iminium. This smooth synthetic
method features: 1) the selective and efficient conversion of
simple saturated propanols and propionaldehydes to poly-
unsaturated aldehydes; 2) a high tolerance for substrates,
including various
γ
-SP2 functionalities; and 3) an
unprecedented oxidative process with high yields and
exclusive geometric E selectivities. Furthermore, we also
developed a homologous strategy using an iterative process of
elongation and oxidation that enables the syntheses of various
natural polyene frameworks, thus setting the stage for
potential access to natural polyenes and their derivatives.
This work was supported by National Natural Science
Foundation of China (Grant No.21202112) and PAPD (A Project
18 (a) M. Julia and J.-M. Paris, Tetrahedron Lett. 1973, 73, 4833;
(b) G. Bauduin, D. Bondon, Y. Pietrasanta and B. Pucci,
Tetrahedron 1978, 34, 3269; (c) P. R. Blakemore, J. Chem.
Soc., Perkin Trans. 1 2002, 2563.
19 (a) A. Marinier and P. Deslongchamps, Can. J. Chem. 1992, 70
2350; (b) M. F. Chellat, N. Proust, M. G. Lauer, J. P. Sambuli,
2011, 13, 3246.
,
20 H. Huang, G. Wang, Q. Shen, X. Liu, S. Lu, L. Geng, Z. Huang
and J. Zhang, Bioinformatics 2015, 31, 2598.
4 | J. Name., 2012, 00, 1-3
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