10.1002/anie.201713106
Angewandte Chemie International Edition
COMMUNICATION
OMe
OMe
OMe
Cambridge, U.K., 1990; c) D. A. Whiting, Nat. Prod. Rep. 1985, 2, 191;
d) D. A. Whiting, Nat. Prod. Rep. 1987, 4, 499.
MeO
MeO
MeO
MeO
CO2Me
[2]
[3]
[4]
Y. Ikeya, H. Taguchi, H. Mitsuhashi, S. Takeda, Y. Kase, M. Aburada,
Phytochemistry 1988, 27, 569.
a
b
CO2Me
TIPS
MeO
CHO TIPS
MeO
CHO
94%
o
68%
o
o'
o'
o
o'
S. M. Kupchan, R. W. Britton, M. F. Zeigler, C. J. Gilmore, R. J. Restivo,
R. F. Bryan, J. Am. Chem. Soc. 1973, 95, 1335.
O
O
O
O
O
a) Y. Liu, J. Chang, J. Xie, Chin. J. Org. Chem. 2012, 32, 2040; b) G.
Bringmann, T. Gulder, T. A. M. Gulder, M. Breuning, Chem. Rev. 2011,
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2009, 38, 3193; d) L. Xie, L. H. Chen, J. X. Xie, Chin. J. Org. Chem. 1991,
11, 371.
O
14
15
16
, 98% ee, o:o' = 5.9 :1
3.40 g
, o:o' = 5.7:1
3.89 g
OMe
OMe
MeO
MeO
MeO
CO2Me
CO2Me
CO2Me
Br
g
c,d,e
91%
f
[5]
[6]
For stereoselective synthesis of (+)-isoschizandrin, see: a) A. M.
Warshawsky, A. I. Meyers, J. Am. Chem. Soc. 1990, 112, 8090; b) M.
Tanaka, H. Itoh, H. Mitsuhashi, M. Maruno, T. Wakamatsu, Tetrahedron:
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e) W.-W. Chen, Q. Zhao, M.-H. Xu, G.-Q. Lin, Org. Lett. 2010, 12, 1072.
For stereoselective synthesis of (-)-steganone, see: a) J. P. Robin, O.
Gringore, E. Brown, Tetrahedron Lett. 1980, 21, 2709; b) K. Tomioka, T.
Ishiguro, Y. Iitaka, K. Koga, Tetrahedron 1984, 40, 1303; c) A. I. Meyers,
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MeO
o'
CO2Me
Br
O
o
o
90%
61%
o'
O
O
O
O
19
18
, 97% ee, o:o' 8.9:1
2.30 g
, 95% ee
1.45 g
OMe
OMe
MeO
MeO
MeO
O
CO2Me
CO2Me
ref 6c
MeO
O
O
O
O
O
O
O
(+)-steganone
20, 96% ee, 1.11 g
[]20D = +69.2(c 1.0, CHCl3)
Lit: []D = -62.4 (c 2.6, THF)
7 steps, 32% total yield
20
Scheme 3. Formal synthesis of (+)-steganone. (a) Pd(OAc)2, L1, AgTFA,
KH2PO4, 2a, HOAc, 55 oC, 48 h, N2, 68%; (b) L-Proline, DMM, DMSO, Et3N, rt,
94%; (c) Raney-Ni, H2, THF, rt, 100%; (d) TBAF, THF 0 oC; (e) AgNO3, NBS,
acetone, 0 oC 91% for 3 steps; (f) Hg(OTf)2, AgSbF6, CH3OH, DCM, H2O, rt,
61%; (g) DBU, THF, rt, 90%. DMM
dichloromethane, DMSO = dimethyl sulfoxide, NBS = N-bromosuccinimide,
[7]
For recent reviews on the synthesis of axially chiral biaryls, see: a) O.
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Yang, W. Tang, Tetrahedron 2016, 72, 6143.
= dimethyl malonate, DCM =
DBU = 1,8-Diazabicyclo[5.4.0]undec-7-ene.
In conclusion, we have demonstrated the remarkable synthetic
potential of a Pd-catalyzed atroposelective C‒H alkynylation
strategy in natural product syntheses. tert-Leucine was used as a
key catalytic transient chiral auxiliary.
A broad range of
[8]
For representative reviews on asymmetric C-H activation, see: a) R. Giri,
B.-F. Shi, K. M. Engle, N. Maugel, J.-Q. Yu, Chem. Soc. Rev. 2009, 38,
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C. Zheng, S.-L. You, Acc. Chem. Res. 2017, 50, 351.
enantioenriched biaryls were obtained in good yields (up to 99%)
with excellent enantioselectivities (up to > 99% ee). The gram-
scale, stereocontrolled formal syntheses of (+)-isoschizandrin
and (+)-steganone were achieved based on this method. These
syntheses compare very favorably with previous syntheses in
terms of step-economy, overall yields and stereocontrol. Further
applications of this method in the synthesis of other
dibenzocyclooctadiene lignan analogues and axially chiral biaryls
are in progress.
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F. Kakiuchi, P. L. Gendre, A. Yamada, H. Ohtaki, S. Murai, Tetrahedron:
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Acknowledgements
[12] a) T. Wesch, F. R. Leroux, F. Colobert, Adv. Synth. Catal. 2013, 355,
2139; b) C. K. Hazra, Q. Dherbassy, J. Wencel-Delord, F. Colobert,
Angew. Chem. Int. Ed. 2014, 53, 13871; c) Q. Dherbassy, G. Schwertz,
M. Chessé, C. K, Hazra, J. Wencel-Delord, F. Colobert, Chem. Eur. J.
2016, 22, 1735;
Financial support from the NSFC (21772170, 21422206,
21572201), the National Basic Research Program of China
(2015CB856600), the Fundamental Research Funds for the
Central
Universities
and
Zhejiang
Provincial
NSFC
[13] a) Y.-N. Ma, H.-Y. Zhang, S.-D. Yang, Org. Lett. 2015, 17, 2034; b) S.-X.
Li, Y.-N. Ma, S.-D. Yang, Org. Lett. 2017, 19, 1842; c) C. He, M. Hou, Z.
Zhu, Z. Gu, ACS Catal. 2017, 7, 5316.
(LR17B020001) is gratefully acknowledged.
Keywords: atroposelective • C‒H alkynylation • formal synthesis
[14] F.-L. Zhang, K. Hong, T.-J. Li, H. Park, J.-Q. Yu, Science 2016, 351, 252.
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56, 6617.
• (+)-isoschizandrin • steganone
[16] Suitable crystals were selected for measurement on an Oxford Diffraction
Gemini A Ultra diffractometer with Cu Kα radiation (λ = 1.54178 Å).
Crystallographic data have been deposited with the Cambridge
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For selected reviews, see: a) J. Chang, J. Reiner, J. Xie, Chem. Rev.
2005, 105, 4581; b) D. D. Ayres, J. D. Loike, Lignans: Chemical,
Biological and Clinical Properties; Cambridge University Press:
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