6006
W. Tang, S. Fang / Tetrahedron Letters 49 (2008) 6003–6006
workup and ion-exchange column chromatography.13 To prepare
compound 13, Wang’s group used the expensive 9-BBN to cover
one of the two amino groups of the starting diamine and the reac-
tion had to be performed under carefully controlled anhydrous
conditions.5 Compound 18 appeared in many literatures; recently
it was prepared in 95% yield by slow addition of Boc2O in CHCl3
(1 equiv, 0.5 M) to 5 (in CHCl3, 5 equiv, 0.25 M) over 2 h by Dardon-
ville et al.14 Other compounds including 1914,15 and 207,16 were
also prepared under high dilution and slow addition conditions
using excess diamines. We believe that the method described in
this Letter will be preferred for preparing these and related com-
pounds in the future.
Jerry L. Lutz (NMR), Mr. Shane Crist (computation), and Mr. Dean
W. Seppala (electronics); and an NSF equipment grant (CHE-
9512445) are all gratefully acknowledged.
Supplementary data
Supplementary data associated with this article can be found, in
References and notes
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diamine at the reaction temperature.
Different methods have been used in the literature for isolation
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few exceptions; after cooling the reaction mixture to rt under inert
atmosphere, it was dissolved in a suitable amount (roughly three
times the volume of the reaction mixture) of the solvent mixture
of the non-polar component Et2O and the polar component
MeOH/MeCN/Et3N (2:2:1). The ratio of the two components was
determined by TLC (SiO2) so that the Rf value of the mono-acylated
product fell between 0.2 and 0.4; under these conditions, on TLC
plate the unreacted diamine normally remained at the origin and
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tion mixture in these solvents was loaded directly on a silica gel
column and pure mono-acylated product was collected by eluting
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drin solution briefly followed by heating with a heat gun. In a
few cases, the side product PhOH was not completely removed
by column chromatography; a partition between CH2Cl2 and 10%
NaOH was needed.
In conclusion, we have developed a new method for mono-acyl-
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method can be used to make compounds such as 1, 8, and 16 in
one pot, which otherwise need multiple steps to synthesize. The
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techniques, and employs equal equiv of diamine and acylating
agent; the acylating agents are simple, stable, and are commer-
cially available; and only the environmentally benign water is used
as the reaction medium. We expect that the method will find wide
applications for linking different functionalities together in areas
such as solid-phase synthesis and bioconjugate chemistry.
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Acknowledgments
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Financial supports from US NSF (CHE-0647129), MTU Chemis-
try Department, Research Excellence Fund and Summer Under-
graduate Research Fellowship (W. Tang); the assistance from Mr.
20. Zaragozadorwald,
917–918.
F.;
Vonkiedrowski,
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Synthesis-Stuttgart
1988,