Manganese(II)-Catalyzed Esterification of N-β-Hydroxyethylamides

Article abstract of DOI:10.1055/s-0034-1380428

A catalyst system of manganese with 2,2-bipyridine for amide alcoholysis of N-β-hydroxyethylamides is described. This protocol enabled selective cleavage of the amide bond through a mechanism involving sequential N,O-acyl rearrangement and transesterification.

Full text of DOI:10.1055/s-0034-1380428

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© Georg Thieme Verlag Stuttgart · New York
2015, 26, 1831–1834
letter
1831
Y. Nishii et al.
Letter
Synlett
Manganese(II)-Catalyzed Esterification of N-β-Hydroxyethyl-
amides
Yuji Nishii
Mn(acac)2
Shoko Akiyama
Yusuke Kita
2,2'-bipyridine
O
O
diethyl carbonate
OH
R1
N
H
R1 OR2
up to >99% yield
Kazushi Mashima*
R2OH
Department of Chemistry, Graduate School of Engineering Science,
Osaka University, Toyonaka, Osaka 560-8531, Japan
mashima@chem.es.osaka-u.ac.jp
O
NH2
R1
O
transesterification
N,O-acyl rearrangement
Received: 29.04.2015
Accepted after revision: 18.05.2015
Published online: 26.06.2015
with 2,2′-bipyridine. Herein, we report the efficiency of a
new catalyst system of Mn(acac)2 and 2,2′-bipyridine for
the esterification of N-β-hydroxyethylamides (Scheme 1,B).
DOI: 10.1055/s-0034-1380428; Art ID: st-2015-u0326-l
Abstract A catalyst system of manganese with 2,2-bipyridine for am-
ide alcoholysis of N-β-hydroxyethylamides is described. This protocol
enabled selective cleavage of the amide bond through a mechanism in-
volving sequential N,O-acyl rearrangement and transesterification.
Zn(OTf)2
A.
(5.0 mol%)
diethyl carbonate
(2.0 equiv)
O
O
OH
Ph
On-Bu
Ph
N
H
n-BuOH, reflux
85% yield (45 h)
Key words amides, esterification, manganese, selective reaction, acyl
rearrangement
O
O
Amides are ubiquitous in nature and are vital motifs in
various important synthetic molecules. In synthetic chem-
istry, amides are stable functional groups that have attract-
ed much interest over the last few decades as versatile di-
recting groups for transition-metal-catalyzed C–H bond
functionalization1 and lithium/magnesium-mediated C–H
functionalization.2 Due to the inert nature of amides, cleav-
age of amide bonds requires harsh conditions using strong
acids or bases under high reaction temperatures, which
hinders their frequent use as protecting or directing groups
in organic synthesis. Accordingly, catalytic conversion of
amides into other functional groups under mild conditions
is therefore highly desirable. In this context, we have fo-
cused our interests on amide alcoholysis3–6 because the re-
sulting esters are easily converted into various functional
groups.
We previously reported that zinc triflate catalyzes se-
lective esterification of N-β-hydroxyethylamides via N,O-
acyl rearrangement (Scheme 1,A), and a peptide bond at
serine residues is selectively cleaved, although a longer re-
action time is essential for achieving a high yield.7 Further,
dinuclear cobalt(II) carboxylate complexes supported by
2,2′-bipyridine act as O-selective acylation catalysts over N-
amidation.8 These findings prompted us to screen catalyst
systems of transition-metal complexes upon combination
NH2
Ph
Mn(acac)2
(5.0 mol%)
2,2'-bipyridine
(5.0 mol%)
diethyl carbonate
(2.0 equiv)
B.
O
O
OH
n-BuOH, reflux
Ph
N
H
Ph
On-Bu
>99% yield (6 h)
Scheme 1 Catalytic esterification N-β-hydroxyethylamides via N,O-
acyl rearrangement
We began with catalyst screening for the esterification
of N-(2-hydroxyethyl)-3-phenylpropionamide (1a) with n-
butanol in the presence of various metal salts (5.0 mol%)
and 2,2′-bipyridine (5.0 mol%) to afford butyl 3-phenylpro-
pionate (2a, Table 1).
Among acetate salts of first-row transition metals, such
as Zn(OAc)2, Cu(OAc)2, Ni(OAc)2·4H2O, Co(OAc)2, Fe(OAc)2,
and Mn(OAc)2, we found that Mn(OAc)2 afforded the highest
yield of 2a (Table 1, entries 1–6). Hydrated manganese salt
Mn(OAc)2·2H2O exhibited comparable reactivity to the an-
hydrous Mn(OAc)2 (Table 1, entry 6 vs. 7). Because not only
zinc and cobalt clusters,9 but also lanthanum10 and tin11
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1831–1834

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Y. Nishii et al.
Letter
Synlett
clusters, are reported to be superior catalysts for the corre-
sponding mononuclear compounds in the transformation of
esters, we tested the catalytic performance of a trinuclear
manganese complex, Mn3(OAc)6(bpy)2,12 which was used as
a catalyst in the present reaction, but produced less yield
(Table 1, entry 8). The mixture of 2,2′-bipyridine and anhy-
drous or hydrated MnCl2 resulted in an off-white suspen-
sion without catalytic activity (Table 1, entries 9 and 10).
Although triflate salt is a strong Lewis acid, Mn(OTf)2 was
not effective (Table 1, entry 11). The combination of
Mn(acac)2 with 2,2′-bipyridine was the best catalyst, con-
verting 1a into 2a quantitatively (Table 1, entry 12), while
Mn(acac)2 without 2,2′-bipyridine significantly decreased
the yield (Table 1, entry 13).
Table 1 Catalyst Screeninga
catalyst
(5.0 mol% on metal)
2,2'-bipyridine
(5.0 mol%)
diethyl carbonate
(2.0 equiv)
O
O
OH
Ph
N
Ph
On-Bu
n-BuOH, reflux, 6 h
H
1a
2a
Yield (%)b
Entry
Catalyst
1
2
Zn(OAc)2
Cu(OAc)2
29
trace
trace
29
3
Ni(OAc)2·4H2O
Co(OAc)2
4
With the best catalyst of Mn(acac)2 and 2,2′-bipyridine
in hand, we evaluated the scope and limitations of the pres-
ent reaction with both aliphatic and aromatic amides (Table
2).13
5
Fe(OAc)2
trace
58
6
Mn(OAc)2
7
Mn(OAc)2·2H2O
Mn3(OAc)6(bpy)2
MnCl2
64
A limitation was encountered with amides having a ste-
rically congested group such as pivalamide (1c) and ortho-
substituted benzamides 1i and 1j (Table 2, entries 2, 8, and
9). Electron-rich compounds 1e retarded the reaction (Table
2, entry 4). Manganese(II) catalyst converted 1b and 1i into
the corresponding esters in higher yield even in shorter re-
action time compared to our previous Zn(OTf)2-catalyzed
reaction7 which afforded 2b in 71% (45 h) and 2i in 32% (45
h), respectively. Heteroaromatic substrates 1k and 1l were
also applicable, and the corresponding esters were isolated
in 57% and 51% yields (Table 2, entries 10 and 11). Interest-
ingly, an N-methylated tertiary amide 3 successfully under-
went esterification to give 2a (Table 2, entry 12). This result
ruled out the formation of N-acyloxazolidone, which was
considered an activated amide, from the direct reaction of
diethyl carbonate with N-β-hydroxyethylamides.14 As con-
trol experiments, amide cleavage of N-hexylamide 4 and O-
protected amide 5 did not occur (Table 2, entries 13 and
14), suggesting that this reaction proceeded through an
N,O-acyl rearrangement,15 but not through coordination of
the oxygen atom to assist complexation of reactive metal
species by carbonyl oxygen.4
8c
9
38
n.d.e
n.d.e
19
10
11
12
13c
MnCl2·H2O
Mn(OTf)2
Mn(acac)2
Mn(acac)2
>99 (91d)
22
a Reaction conditions: A mixture of amide (0.5 mmol), catalyst (5.0 mol%
on metal), 2,2′-bipyridine (5.0 mol%), and diethyl carbonate (1.0 mmol) in
n-BuOH (0.5 mL) was refluxed.
b Determined by GC analysis.
c Run without 2,2′-bipyridine.
d Isolated yield (1.0 mmol scale).
e n.d. = not detected.
To exclude the possibility of reverse amidation from the
produced ester, a 1:1 mixture of 1d and 4 was treated with
n-butanol under the optimized reaction conditions and, as
expected, no crossover product was afforded; butyl benzo-
ate 2d was obtained as a sole product with the remaining 4
intact, as outlined in Scheme 2.16
In conclusion, we developed a new efficient catalyst sys-
tem of Mn(acac)2 with 2,2′-bipyridine that functioned as a
superior catalyst for amide alcoholysis of N-β-hydroxyeth-
ylamides to give the corresponding esters in up to 99% yield
O
O
Ph
N
Ph
N
H
H
Mn(acac)2 (5.0 mol%)
2,2'-bipyridine (5.0 mol%)
4
4 <5% conv.
+
+
n-BuOH (2.0 mL)
reflux, 18 h
O
O
OH
Ph
N
Ph
O
H
1d
2d 68% yield
Scheme 2 A crossover experiment
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1831–1834

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Y. Nishii et al.
Letter
Synlett
Table 2 Substrate Scopea
under mild conditions. Control experiments revealed that
this reaction proceeded through subsequent N,O-acyl rear-
rangement and transesterification.
Mn(acac)2 (5.0 mol%)
2,2'-bipyridine (5.0 mol%)
diethyl carbonate (2.0 equiv)
O
O
OR3
R1
N
R1
On-Bu
n-BuOH, reflux, 6 h
Acknowledgment
R2
1–5
2
This work is financially supported by a Grant-in-Aid for Young Scien-
tists (B) (No. 25810062) from MEXT, Japan. Y.N. expresses his special
thanks for the financial support provided by the JSPS Research Fel-
lowship for Young Scientists.
Entry Amide
Yield (%)b
O
OH
1
1b
80c (18 h)
N
H
Supporting Information
Supporting information for this article is available online at
O
http://dx.doi.org/10.1055/s-0034-1380428.
S
u
p
p
o
nrtIo
g
f
rmoaitn
S
u
p
p
ortiInfogrmoaitn
2
3
1c
4c (18 h)
OH
N
H
References and Notes
O
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OH
1d R = H
90
N
H
R
4
5
6
7
1e R = OMe
1f R = CF3
1g R = Br
52
75
81
81
1h R = CN
R
O
OH
OH
8
1i R = OMe
1j R = CF3
1k
36 (18 h)
41c (18 h)
57 (18 h)
N
H
9
O
10
N
H
N
O
OH
O
11
12
1l
3
51 (18 h)
N
H
O
OH
98
Ph
N
Me
O
13
14
4
5
traced
traced
Ph
Ph
N
H
O
OMe
N
H
(6) For examples on the catalytic esterification, see: (a) Fisher, L. E.;
Caroon, J. M.; Stabler, S. R.; Lundberg, S.; Zaidi, S.; Sorensen, C.
M.; Sparacino, M. L.; Muchows, J. M. Can. J. Chem. 1994, 72, 142.
(b) Kita, Y.; Nishii, Y.; Onoue, A.; Mashima, K. Adv. Synth. Catal.
a Reaction conditions: A mixture of amide (1.0 mmol), Mn(acac)2 (5.0 mol%),
2,2′-bipyridine (5.0 mol%), and diethyl carbonate (2.0 mmol) in n-BuOH (1.0
mL) was refluxed.
b Isolated yield.
c Determined by 1H NMR analysis.
d Determined by GC analysis.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1831–1834

1834
Y. Nishii et al.
Letter
Synlett
2013, 355, 3391. (c) Siddiki, S. M. A. H.; Touchy, A. S.; Tamura,
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δ = 0.91 (t, J = 7.4 Hz, 3 H, CH3), 1.12–1.66 (m, 10 H, methylene),
1.70–1.80 (m, 2 H, methylene), 1.80–1.90 (m, 2 H, methylene),
2.27 (tt, J = 3.7, 11.2 Hz, 1 H, COCH), 4.04 (t, J = 6.6 Hz, 2 H,
OCH2). 13C NMR (100 MHz, CDCl3, 30 °C): δ = 13.6, 19.1, 25.4,
25.8, 29.0, 30.7, 43.3, 63.9, 176.1.
(7) Kita, Y.; Nishii, Y.; Higuchi, T.; Mashima, K. Angew. Chem. Int. Ed.
2012, 51, 5723.
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Mashima, K. J. Am. Chem. Soc. 2013, 135, 6192.
Butyl 2-(Trifluoromethyl)benzoate (2j)
Purified by flash column chromatography (silica gel, hexane–
EtOAc = 20:1); colorless oil. IR (neat NaCl): ν = 2964 (m), 2876
(9) (a) Iwasaki, T.; Maegawa, Y.; Hayashi, Y.; Ohshima, T.; Mashima,
K. J. Am. Chem. Soc. 2008, 130, 2944. (b) Iwasaki, T.; Maegawa,
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Mashima, K. Synlett 2009, 1659. (d) Iwasaki, T.; Agura, K.;
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2010, 16, 11567. (e) Maegawa, Y.; Ohshima, T.; Hayashi, Y.;
Agura, K.; Iwassaki, T.; Mashima, K. ACS Catal. 2011, 1, 1178.
(f) Maegawa, Y.; Agura, K.; Hayashi, Y.; Ohshima, T.; Mashima,
K. Synlett 2012, 23, 137.
(w), 1736 (s), 1316 (s), 1292 (s), 1264 (s), 1168 (s), 1144 (s) cm–1
.
1H NMR (400 MHz, CDCl3, 30 °C): δ = 0.96 (t, J = 7.5 Hz, 3 H,
CH3), 1.40–1.50 (m, 2 H, CH2CH3), 1.70–1.80 (m, 2 H, OCH2CH2),
4.34 (t, J = 6.7 Hz, 2 H, OCH2), 7.50–7.60 (m, 2 H, Ar), 7.70–7.80
(m, 2 H, Ar). 13C NMR (100 MHz, CDCl3, 30 °C): δ = 13.6, 19.0,
30.4, 65.9, 123.4 (q, JC–F = 272 Hz), 126.6 (q, JC–F = 5 Hz), 128.7 (q,
JC–F = 32 Hz), 130.1, 130.9, 131.6, 131.7, 167.0. 19F NMR (376
MHz, CDCl3, 30 °C): δ = –58.1. MS–FAB+: m/z (relative intensity)
= 247 (20) [M + H]+, 173 (40), 57 (100). HRMS–FAB+: m/z calcd
for C10H11F3NO2: 247.0948 [M + H]+; found: 247.0946.
(10) Hatano, M.; Furuya, Y.; Shimmura, T.; Moriyama, K.; Kamiya, S.;
Maki, T.; Ishihara, K. Org. Lett. 2011, 13, 426.
For other compounds, see Supporting Information.
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(13) General Procedure for the Mn-Catalyzed Esterification
(Table 2)
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(a) Gothelf, K. V.; Hazell, R. G.; Jørgensen, K. A. J. Org. Chem.
1996, 61, 346. (b) Evans, D. A.; Coleman, P. J.; Dias, L. C. Angew.
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An oven-dried Schlenk tube was equipped with Mn(acac)2 (0.05
mmol), amide (1.0 mmol), 2,2′-bipyridine (0.05 mmol), diethyl
carbonate (2.0 mmol), and n-BuOH (1.0 mL) and the resulting
mixture was refluxed for periodic time under an argon atmo-
sphere. After cooling to r.t., yields were determined by the fol-
lowing procedures:
(15) Yashiro, M.; Sonobe, Y.; Yamamura, A.; Takarada, T.; Komiyama,
M.; Fujii, Y. Org. Biomol. Chem. 2003, 1, 629.
1. Isolated yield; after removal of solvents in vacuo, the product
was then isolated with column chromatography.
2. NMR yield; metal salts were removed by filtration through
silica gel eluting with EtOAc, and solvents were removed in
vacuo. Yield was determined by 1H NMR analysis using phenan-
threne as an internal standard.
3. GC yield; metal salts were removed by filtration through
silica gel eluting with EtOAc, and yield was determined by GC
analysis using dodecane as an internal standard.
(16) Procedure of a Crossover Experiment (Scheme 2)
An oven-dried Schlenk tube was equipped with Mn(acac)2 (0.05
mmol), N-(2-hydroxyethyl)benzamide (1d) (1.0 mmol), N-
hexyl-3-phenylpropionamide (4, 1.0 mmol), 2,2′-bipyridine
(0.05 mmol), diethyl carbonate (2.0 mmol), and n-BuOH (1.0
mL), and the resulting mixture was refluxed for 18 h under an
argon atmosphere. After cooling to r.t., metal salts were
removed by filtration through silica gel eluting with EtOAc, and
solvents were removed in vacuo. Yield and conversion were
determined by 1H NMR analysis using phenanthrene as an
internal standard.
Butyl Cyclohexanecarboxylate (2b)
Purified by flash column chromatography (silica gel, hexane–
EtOAc = 20:1); colorless oil. 1H NMR (400 MHz, CDCl3, 30 °C):
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1831–1834