1982
L. M. Blair, J. Sperry / Tetrahedron Letters 54 (2013) 1980–1982
i. DMF-DMA
pyrrolidine
DMF
ii. H2 (40 psi)
10% Pd/C
THF
66%
(2 steps)
Br
K2CO3
iPrO
iPrO
Me
NO2
Me
HO
DMF
N
H
96%
NO2
11
12
13
i. (COCl)2
ether
ii. LiAlH4
67%
(2 steps)
i. TBDMSCl
imidazole
DMF
THF
ii. KHMDS
THF
OH
R
then TsCl
iii. TBAF
AcOH-THF
R = OH
10
MeSO2Cl
Et3N
iPrO
iPrO
CH2Cl2
R = OH
R = OMs
N
H
N
10
93%
, 61%
7
Ts
(3 steps)
14
Scheme 4. Synthesis of mesylate 7.
structure 16. As the deprotection of 16 was not successful, alterna-
tive routes to 5 are currently being pursued.
OH
iPrO
Acknowledgment
N
Ts
The University of Auckland is acknowledged for financial
assistance.
10
DBAD, 0%
DIAD, 78%
(crude)
PPh3
THF
Supplementary data
Supplementary data (experimental procedures, 1H and 13C NMR
spectra for all new compounds) associated with this article can be
O
N
iPrO
H
N
OiPr
O
iPrO
References and notes
15
N
1. LaRue, T. A. Lloydia 1977, 40, 307.
Ts
2. Hydrazidomycins, A.-C.; Ueberschaar, N.; Ndejouong, B. L. S. T.; Ding, L.; Maier,
A.; Fiebig, H. H.; Hertweck, C. Bioorg. Med. Chem. Lett. 2011, 21, 5839.
3. Elaiomycins B and C: (a) Helaly, S. E.; Pesic, A.; Fiedler, H. P.; Sussmuth, R. D.
Org. Lett. 2011, 13, 1052; (b) Kim, B. Y.; Willbold, S.; Kulik, A.; Helaly, S. E.;
Zinecker, H.; Wiese, J.; Imhoff, J. F.; Goodfellow, M.; Sussmuth, R. D.; Fiedler, H.
P. J. Antibiot. 2011, 64, 595; Dinohydrazides A and B: (C) Maru, N.; Ohno, O.;
Yamada, K.; Uemura, D. Chem. Lett. 2012, 29, 596.
7
KOH
37%
DMSO
Ts
N
4. Geralcins A and B: Le Goff, G.; Martin, M. T.; Servy, C.; Cortial, S.; Lopes, P.;
Bialecki, A.; Smadja, J.; Ouazzani, J. J. Nat. Prod. 2012, 75, 915.
5. Isolation of a macrocyclic diacyl hydrazide: (a) Xu, S. H.; Cen, Y. Z.; Li, Y. L.; Xu,
S. Y. Chin. Chem. Lett. 1999, 10, 401; A 2-butenoylhydrazide: (b) Bordoli, M.;
Kotoky, R.; Mahanta, J. J.; Sarma, T. C.; Kanjilal, P. B. Eur. J. Med. Chem. 2009, 44,
2754.
6. Shoeb, M.; MacManus, S. M.; Jaspars, M.; Trevidu, J.; Nahar, L.; Kong-Thoo-Lin,
P.; Sarker, S. D. Tetrahedron 2006, 62, 11172.
OiPr
O
iPrO
N
N
N
OiPr
O
iPrO
16
8. Bredikhin, A.; Maeorg, U. Tetrahedron 2008, 64, 6788.
Ts
9. (a) Dow, R. L.; Kelly, R. C.; Schletter, I.; Wierenga, W. Synth. Commun. 1981, 11,
43; (b) Di Grandi, M. J.; Tilley, J. W. Tetrahedron Lett. 1996, 37, 4327; For an
application of this reaction in the synthesis of 3-methylene-1,2-diazetidines,
see: (c) Brown, M. J.; Clarkson, G. J.; Inglis, G. G.; Shipman, M. Org. Lett. 2011, 13,
1686.
10. La Regina, G.; Edler, M. C.; Brancale, A.; Kandil, S.; Coluccia, A.; Piscitelli, F.;
Hamel, E.; De Martino, G.; Matesanz, R.; Diaz, J. F.; Scovassi, A. I.; Prosperi, E.;
Lavecchia, A.; Novellino, E.; Artico, M.; Silvestri, R. J. Med. Chem. 2007, 50, 2865.
11. For a discussion of E/Z isomerism in N,N0-diacylhydrazides, see: Le Grel, P.;
Salaun, A.; Mocquet, C.; Le Grel, B.; Roisnel, T.; Potel, M. J. Org. Chem. 2011, 76,
8756.
Scheme 5. A variant of the Mitsunobu reaction in the synthesis of 16.
In conclusion, we have achieved the synthesis of a protected
1,2-bis(indolyl)ethylhydrazine bearing the substitution pattern
present in the unusual dimeric alkaloid montamine. The synthesis
relied on a variant of the Mitsunobu reaction to incorporate di-
rectly the reduced azodicarboxylate into the tryptophol side chain.
The resulting carbazate 15 underwent alkylation to give the core