F
Y. Hayashi, S. Toda
Letter
Synlett
In conclusion, we have developed an efficient method
for the synthesis of chiral 1,3-dimethyl units through a dou-
ble Michael reaction of an aldehyde and nitroalkane cata-
lyzed by a diphenylprolinol silyl ether. There are several
noteworthy features of this reaction. Either 1,3-syn- or 1,3-
anti-dimethyl units can be selectively synthesized depend-
ing on the appropriate choice of enantiomer of the diphen-
ylprolinol silyl ether catalyst. The excellent optical purity of
the double Michael product was much higher than that of
the first Michael reaction because of the ‘meso-trick’. In ad-
dition to the 1,3-dimethyl unit, both 1,3-methyl alkyl and
1,3-methyl aryl units can be prepared. Finally, the side
chain of pneumocandin B0 was enantioselectively synthe-
sized by using the present method as a key step.
(6) (a) Oppolzer, W.; Moretti, R.; Bernardinelli, G. Tetrahedron Lett.
1986, 27, 4713. (b) Hanessian, S.; Chahal, N.; Giroux, S. J. Org.
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Eur. J. 2010, 116, 11726.
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Funding Information
(10) (a) Hayashi, Y.; Gotoh, H.; Hayashi, T.; Shoji, M. Angew. Chem.
Int. Ed. 2005, 44, 4212. (b) Marigo, M.; Wabnitz, T. C.;
Fielenbach, D.; Jørgensen, K. A. Angew. Chem. Int. Ed. 2005, 44,
794.
(11) (a) Gotoh, H.; Ishikawa, H.; Hayashi, Y. Org. Lett. 2007, 9, 5307.
(b) Hayashi, Y.; Kawamoto, Y.; Honda, M.; Okamura, D.;
Umemiya, S.; Noguchi, Y.; Mukaiyama, T.; Sato, I. Chem. Eur. J.
2014, 20, 12072.
JSPS KAKENHI grant number JP18H04641: Hybrid Catalysis for En-
abling Molecular Synthesis on Demand, and The Uehara Memorial
Foundation.
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Supporting Information
(12) (a) Seebach, D.; Grosĕlj, U.; Badine, D. M.; Schweizer, W. B.;
Beck, A. K. Helv. Chim. Acta 2008, 91, 1999. (b) Hayashi, Y.;
Okamura, D.; Yamazaki, T.; Ameda, Y.; Gotoh, H.; Tsuzuki, S.;
Uchimaru, T.; Seebach, D. Chem. Eur. J. 2014, 20, 17077.
(13) Umemiya, S.; Sakamoto, D.; Kawauchi, G.; Hayashi, Y. Org. Lett.
2017, 19, 1112.
Supporting information for this article is available online at
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References and Notes
(14) Xu, F.; Zacuto, M.; Yoshikawa, N.; Desmond, R.; Hoermer, S.;
Itoh, T.; Journet, M.; Humphrey, G. R.; Cowden, C.; Strotman, N.;
Devine, P. J. Org. Chem. 2010, 75, 7829.
(15) Zu, L.; Xie, H.; Li, H.; Wang, J.; Wang, W. Adv. Synth. Catal. 2007,
349, 2660.
(16) In the reactions of entries 2–8 in Table 1, nitroalkane 2 was
recovered in good yield (>90%).
(17) The diastereoselectivity and enantioselectivity of 3 (Table 1,
entry 9) were not determined. The dr after denitration is 2.2:1,
see Scheme 4.
(1) Norte, M.; Fernández, J. J.; Padilla, A. Tetrahedron Lett. 1994, 35,
3413.
(2) Liu, C.-M.; Hermann, T. E. J. Biol. Chem. 1978, 253, 5892.
(3) (a) Nara, F.; Tanaka, M.; Masuda-Inoue, S.; Yamasato, Y.; Doi-
Yoshioka, H.; Suzuki-Konagai, K.; Kumakura, S.; Ogita, T. J. Anti-
biot. 1999, 52, 531. (b) Nara, F.; Tanaka, M.; Hosoya, T.; Suzuki-
Konagai, K.; Ogita, T. J. Antibiot. 1999, 52, 525.
(4) (a) Berger, J.; Jampolsky, L. M.; Goldberg, M. W. Arch. Biochem.
1949, 22, 476. (b) Trader, D. J.; Carlson, E. E. Bioorg. Med. Chem.
Lett. 2015, 25, 4767.
(18) (a) Ono, N.; Miyake, H.; Tamura, R.; Kaji, A. Tetrahedron Lett.
1981, 22, 1705. (b) Tanner, D. D.; Blackburn, E. V.; Diaz, G. E.
J. Am. Chem. Soc. 1981, 103, 1557.
(5) For a review, see: Schmid, F.; Varo, A.; Laschat, S. Synthesis 2017,
49, 237.
(19) The enantioselectivity of compound 5 is determined according
to the scheme below.
NaClO2
NaH2PO4⋅2H2O
2-methyl-2-butene
O
O
MNBA
DMAP
MeO
MeO
TsOH⋅H2O
O
O
+
OH
CH2Cl2, r.t.
THF-H2O, r.t.
t-BuOH/H2O, r.t.
dr = 2.2:1
72% over 3 steps, dr = 2.2:1
O
O
BzCl, Et3N
DMAP
O
NaOMe
BzO
OMe
OMe
MeOH, r.t.
CH2Cl2, r.t.
96% ee
O
O
O
BzCl, Et3N
DMAP
NaOMe
BzO
MeOH, r.t.
CH2Cl2, r.t.
77% ee
Scheme 8
Georg Thieme Verlag Stuttgart · New York — Synlett 2019, 30, A–G