5
Scheme 2. Total synthesis of (+)-safingol and D-threo-clavaminol H
3
4
5
Morales, A.; Fernandez-Checa, J. C. Mini-Rev. Med. Chem. 2007, 7,
71.
Dickson, M. A.; Carvajal, R. D.; Merrill, A. H. J.; Gonen, M.; Cane,
L. M.; Schwartz, G. K. Clin. Cancer Res. 2011, 17, 2484.
For reviews, see: (a) Howell, A. R.; So, R. S.; Richardson, S. K.
Tetrahedron 2004, 60, 11327. (b) Howell, A. R.; Ndakala, A. J. Curr.
Org. Chem. 2002, 6, 365.
For some selected examples, see: (a) Siciliano, C.; Barattucci, A.;
Bonaccorsi, P.; Di Gioia, M. L.; Leggio, A.; Minuti, L.; Romio, E.;
Temperini A. J. Org. Chem. 2004, 79, 5320; (b) So, R. C.; Ndonye,
R.; Izmirian, D. P.; Richardson, S. K.; Guerrera, R. L.; Howell, A. R.
J. Org. Chem. 2004, 69, 3233; (c) Ndonye, R. M.; Izmirian, D. P.;
Dunn, M. F.; Yu, K. O. A.; Porcelli, S. A.; Khurana, A.; Kronenberg,
M.; Richardson, S. K.; Howell, A. R. J. Org. Chem. 2005, 70, 10260.
For some selected recent examples, see: (a) Ko, J.; Molinski, T. F. J.
Org. Chem. 2013, 78, 498. (b) Dere, R. T.; Zhu, X. Org. Lett. 2008,
provided the corresponding alcohols 1j (42% isolated yield, 99%
ee) and 1k (45% isolated yield, 99% ee), respectively. Then the
deprotection of 1j and 1k afforded the target sphingoid bases.
Several reductive conditions including hydrogenation with
Pd(OH) /C, Pd/C and PtO have been investigated, and
2 2
corresponding 2-amino-1,3-diols 6j and 6k (i.e. (+)-safingol)
3
6
were obtained through concomitant cleavage of the N-N and N-O
bonds via hydrogenation with Pd(OH)
hydrogenation with Pd/C and PtO couldn’t give 6j and 6k.
Then the amine group of compound 6j was acetylated to give 7j
i.e. D-threo-clavaminol H) in 75% yield. The absolute
2
/C in MeOH,while
[18]
2
(
configuration of these products were determined by comparison
7
8
of the optical rotation of (+)-safingol 6k with previously reported
[19]
in literature.
1
0, 4641.
In summary, we have developed a one-pot sequential oxa-
Michael/α-amination reaction through combining iminium and
enamine activation of α,β-unsaturated aldehydes. The
enantioenriched syn-β,γ-functional alcohols were obtained in
good to excellent diastereo- and enantioselectivities. Those
alcohols could be facilely transformed to syn-2-amino-1,3-diols
via hydrogenation. Moreover, this method has been successfully
applied to highly efficient syntheses of (+)-safingol and D-threo-
clavaminol H with excellent stereoselectivities.
For some selected recent examples, see: (a) He, L.; Byun, H. S.;
Bittman, R. J. Org. Chem. 2000, 65, 7618. (b) Olofsson, B.; Somfai,
P. J. Org. Chem. 2003, 68, 2514. (c) Righi, G.; Ciambrone, S.;
D’Achille, C.; Leonelli, A.; Bonini, C. Tetrahedron 2006, 62, 11821.
(
d) Yoon, H. J.; Kim, Y.-W. ; Lee, B. K.; Lee, W. K.; Kim, Y.; Ha,
H.-J. Chem. Commun. 2007, 79.
9
(a) Qin, D.-D.; Yu, W.; Zhou, J.-D.; Zhang, Y.-C.; Ruan, Y.-P.; Zhou,
Z.-H.; Chen, H.-B. Chem. Eur. J. 2013, 19, 16541. (b) Sasai, H.;
Tokunaga, T.; Watanabe, S.; Suzuki, T.; Itoh, N.; Shibasaki, M. J.
Org. Chem. 1995, 60, 7388.
1
1
0
1
(a) Cai, Y.; Ling, C.-C.; Bundle, D. R. Org. Biomol. Chem. 2006, 4,
1
140. (b) Kobayashi, J.; Nakamura, M.; Mori, Y.; Yamashita, Y.;
Acknowledgments
Kobayashi, S. J. Am. Chem. Soc. 2004, 126, 9192.
(a) Ait-Youcef, R.; Moreau, X.; Greck, C. J. Org. Chem. 2010, 75,
5312. (b) Enders, D.; Palecek, J.; Grondal, C. Chem. Commun. 2006,
655. (c) Pandey, M.; Chowdhury, P. S.; Dutta, P. Kumar, A. K.; Pal,
S. RSC Adv. 2013, 3, 15442.
For reviews on organocatalytic domino reactions, see: (a) Pellissier,
H. Domino Reactions (Edited by L. F. Tietze) 2014, 325. (b) Volla,
C. M. R.; Atodiresei, I.; Rueping, M. Chem. Rev. 2014, 114, 2390. (c)
Pellissier, H. Adv. Synth. Catal. 2012, 354, 237. (d) Grondal, C.;
Jeanty, M.; Enders, D. Nat. Chem. 2010, 2, 167.
(a) Weng, J.; Wang, S.; Huang, L.-J.; Luo, Z.-Y.; Lu, G. Chem.
Commun. 2015, 10170. (b) Weng, J.; Li, Y.-B.; Wang, R.-B.; Lu, G.
ChemCatChem 2012, 4, 1007. (c) Weng, J.; Li, J.-M.; Li, F.-Q.; Xie,
Z.-S.; Lu, G. Adv. Synth. Catal. 2012, 354, 1961.
For selected organocatalytic oxa-Michael reactions of oximes, see: (a)
Bertelsen, S.; Diner, P.; Johansen, R. L.; Jørgensen, K. A. J. Am.
Chem. Soc. 2007, 129, 1536; (b) Andersen, N. R.; Hansen, S. G.;
Bertelsen, S.; Joergensen, K. A. Adv Synth. Catal. 2009, 351, 3193;
The authors thank the National Natural Science Foundation of
China (No. 21502240), the National High-tech R&D Program of
China (No. 2013AA092903), and Guangdong Natural Science
Foundation (Nos. S2013040012409 and 2015A030313130).
1
2
Supplementary Material
Supplementary data (typical experimental procedures,
1
1
3
4
1
13
physical data of new compounds, copies of H and C NMR, and
HPLC spectra) associated with this article can be found, in the
online version, at http://dx.doi.org/xxxxx.
References and notes
1
For examples, see: (a) Morita, M.; Motaki, K.; Akimoto, K.; Natori,
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For selected organocatalytic α-amination reactions of aldehydes, see:
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5
(a) List, B. J. Am. Chem. Soc. 2002, 124, 5656; (b) Bogevig, A.; Juhl,
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2