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©
Georg Thieme Verlag Stuttgart · New York
2015, 26, 331–334
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cluster
Synlett
L. R. Jefferies et al.
Cluster
Iron-Catalyzed C–N Bond Formation via the Beckmann Rearrange-
ment
cat.
FeCl3/AgSbF6
Latisha R. Jefferies
Savannah R. Weber
Silas P. Cook*
OH
H
N
R2
N
• functional-group tolerant
reactions can be run in air
R1
•
R1
R2
DCE, 80 °C, 24 h
O
Department of Chemistry, Indiana University, 800 East Kirkwood Avenue,
Bloomington, IN 47405-7102, USA
Received: 20.09.2014
Accepted after revision: 21.10.2014
Published online: 20.11.2014
rangement variants represent the most active line of inqui-
6
ry. Typical catalysts used for this transformation include
7
8
9
DOI: 10.1055/s-0034-1379540; Art ID: st-2014-r0784-c
various Lewis acids such as AlCl , BF ·OEt , In(OTf) , and
3 3 2 3
several lanthanide-containing catalysts such as Ce(III),
La(III), and Sm(III). More recently, propylphosphonic an-
Abstract A simple, iron-based catalytic system allows for facile Beck-
mann rearrangement of various oximes. The mild conditions avoid the
use of harsh or expensive acids, and the reactions do not require an
inert atmosphere. Additionally, a range of amides can be accessed
through this transformation.
10
hydride has been shown to be an effective catalyst for Beck-
mann rearrangement.11 Although these advancements al-
low the Beckmann rearrangement to proceed in good
yields, they suffer from the use of either exceptionally
strong or rare Lewis acids or require an inert atmosphere.
Mild, naturally abundant, and environmentally friendly
iron(III) salts have been reported to be effective Lewis acid
catalysts for the Beckmann rearrangement.12 Unfortunately,
the solvent-free procedure is super-stoichiometric in iron
and is limited to aliphatic oximes. We recently reported on
the superior Lewis acidity of FeCl /AgSbF in a formal
Key words iron, amides, Beckmann rearrangement, oximes, Lewis
acid
The Beckmann rearrangement employs ketoximes or al-
doximes to make the corresponding amides/lactams. This
reaction is most valuable for the commercial production of
caprolactam (Figure 1) en route to nylon-6 and nylon-12.1
Moreover, the Beckmann rearrangement has enabled the
total synthesis of several natural products such as (+)-co-
3
6
13
Friedel–Crafts alkylation reaction, the Ritter reaction, and
alcohol addition to alkynes.14 In an effort to further demon-
strate the utility of this catalytic system, we investigated
this new system in the Beckmann rearrangement. Here we
report mild conditions for the Beckmann rearrangement of
functionalized oximes that can be run without the need for
an inert atmosphere.
2
3
4
deine, (–)-ibogamine, and (+)-sparteine (Figure 1).
NH
O
NH
MeO
H
O
To compare known Lewis acids in the Beckmann rear-
H
rangement, 1a was used as a model substrate (Table 1). In
caprolactam
OH
12
line with previous reports, FeCl provided desired product
3
(
+)-codeine
2a in 23% yield (entry 1). Although other iron sources
proved competent in the Beckmann rearrangement, none
N
provided yields higher than 23% (entries 2–4). Even AlCl , a
3
N
H
N
powerful Lewis acid, only provided 17% yield of 2a
(entry 5). When 1a was subjected to our previously de-
scribed conditions,13 we were pleased to see that product
N
H
H
(–)-ibogamine
(+)-sparteine
2a was produced in quantitative yield (entry 7). Moreover,
Figure 1 Molecules that have been synthesized via Beckmann rear-
the addition of silver hexafluoroantimonate to FeCl2 also
led to pronounced enhancement in reactivity over FeCl2
alone (compare entries 2 and 10). Although silver hexafluo-
roantimonate in combination with FeCl or FeCl dramati-
rangement
The classic Beckmann rearrangement requires strong
acid and relatively high reaction temperatures, thereby
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2
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cally improved the yield (entries 7 and 10), the reaction
generating a large amount of waste and poor E-factors. Cur-
rent work in the area aims to develop milder reaction con-
ditions that also generate significantly less waste. To
achieve this goal, catalytic solution-phase Beckmann rear-
does not proceed in the presence of AgSbF alone (entry 6).
6
Moreover other silver salts, such as silver hexafluorophos-
phate and hexafluoroarsenic, in combination with FeCl3,
produced low to moderate yields (entries 8 and 9). Tradi-
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 331–334