ACS Catalysis
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robustness of CiVCPO under operational conditions. The
Supporting material is available free of charge via the Inter-
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tunover number for CiVCPO in this experiment exceeded
one million, which should be seen as a minimal value and
not as a total turnover number as the reaction proceeded
almost linear to full conversion (Figure 5 ꢀ). In contrast, the
accumulation of 2d (oxo-Achmatowicz reaction) was
somewhat slower and yielded less product. It is also worth
mentioning that after approximately 3h product
accumulation ceased and formation of a (yet undefined) side
product was observed with HPLC (please see SI X for further
information). Table 1 summarizes the semi-preparative
conversions of starting materials 1a-d.
net at http://pubs.acs.org. These contain control experiments
detailed experimental information including full characteri-
zation of the products.
AUTHOR INFORMATION
Corresponding Authors
f.rutjes@science.ru.nl; f.hollmann@tudelft.nl
Notes
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The authors declare no competing financial interests.
ACKNOWLEDGMENT
Table 1. Summary of semi-preparative scale reac-
a
This work was financially supported by the European Union
tions.
(
KBBE- 2013-7-613549, ‘INDOX’).
REFERENCES
(
1)
Achmatowicz Jr. O; Bukowski, P.; Szechner, B.;
Zwierzchowska Z; Zamojski, A. Tetrahedron 1971, 27, 1973-
1996.
Product
Con-
Isolated
d.r.
a
version product
b
(2)
(3)
Ciufolini, M. A.; Hermann, C. Y. W.; Dong, Q.; Shimizu,
T.; Swaminathan, S.; Xi, N. Synlett 1998, 1998, 105-114.
Merino, P.; Tejero, T.; Delso, J. I.; Matute, R. Curr. Org.
Chem. 2007, 11, 1076-1091.
[
%]
2a
100
100
100
100
228 mg (69%)
160 mg (56%)
175 mg (50%)
195 mg (82%)
-
2
2
2
b
65:35
80:20
75:25
(
(
(
(
(
4)
5)
6)
7)
8)
van der Pijl, F.; van Delft, F. L.; Rutjes, F. P. J. T. Eur. J.
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Ransborg, L. K.; Lykke, L.; Hammer, N.; Naesborg, L.;
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2041.
c
d
a: Please see SI for further details on the reaction
conditions and product isolation and –purification, b:
determined via HPLC.
The aza-Achmatowicz reactions prodeeded smoothly to full
conversion of the starting materials into the target products
with only trace amounts of by-products formed (see SI for
further details), which were removed by a single flash
chormmatograpy step. Hence, the moderate isolated yields
shown in Table 1 can be assigned to a sub-optimal reaction
workup and product isolation, which will be further
optimized in our laboratories. It should also be mentioned
that so far we have no indication about racemization of the
chiral center (‘furanylic C-H bond’) in the course of the
(9)
10)
Thiel, D.; Doknić, D.; Deska, J. Nat. Commun. 2014, 5,
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(
Ni, Y.; Fernández-Fueyo, E.; Baraibar, A. G.; Ullrich, R.;
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Getrey, L.; Krieg, T.; Hollmann, F.; Schrader, J.; Holtmann,
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(11)
12)
(
9
reaction. Deska et al. found no racemization under
(13)
Perez, D. I.; Mifsud Grau, M.; Arends, I. W. C. E.;
Hollmann, F. Chem. Commun. 2009, 44, 6848-6850.
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comparable conditions.
(
(
14)
15)
Summarizing, we have presented
alternative to the established stoichiometric (aza-
Achmatowicz protocols. CiVCPO is an efficient catalyst to in
a
chemoenzymatic
)
situ generate hypohalogenites under mild reaction
conditions from catalytic amounts of halogenides. Thanks to
its high robustness and catalytic activity excellent turnover
numbers and -frequencies have been observed making it a
promising catalyst. Next to broadening the scope of the
proposed chemoenzymatic protocol a particular focus will lie
on mechanistic studies and investigation of the
stereochemical outcome.
(16)
Renirie, R.; Pierlot, C.; Aubry, J.-M.; Hartog, A. F.;
Schoemaker, H. E.; Alsters, P. L.; Wever, R. Adv. Synth.
Catal. 2003, 345, 849-858.
(
17)
ten Brink, H. B.; Dekker, H. L.; Schoemaker, H. E.; Wever,
R. J. Inorg. Biochem. 2000, 80, 91-98.
(18)
Hemrika, W.; Renirie, R.; Macedo-Ribeiro, S.;
Messerschmidt, A.; Wever, R. J. Biol. Chem. 1999, 274,
23820-23827.
(
19)
ten Brink, H. B.; Tuynman, A.; Dekker, H. L.; Hemrika, W.;
Izumi, Y.; Oshiro, T.; Schoemaker, H. E.; Wever, R. Inorg.
Chem. 1998, 37, 6780-6784.
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