Iron chloride-catalyzed three-component domino sequences: Syntheses of functionalized α-Oxy-N-acylhemiaminals and α-Oxyimides

Article abstract of DOI:10.1002/adsc.201300847

The iron(III) chloride-multicatalyzed dioxygenation of enamides with TEMPO in the presence of alcohols has been developed. This multicomponent domino process affords efficient new strategies for the synthesis of α-oxy-N-acylhemiaminals or α-oxyimides in g

Full text of DOI:10.1002/adsc.201300847

COMMUNICATIONS
DOI: 10.1002/adsc.201300847
Iron Chloride-Catalyzed Three-Component Domino Sequences:
Syntheses of Functionalized a-Oxy-N-acylhemiaminals and
a-Oxyimides
Fleur Drouet,a Jieping Zhu,b,* and Gꢀraldine Massona,*
a
Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles, CNRS, 91198 Gif-sur-Yvette Cedex, France
E-mail: geraldine.masson@cnrs.fr (homepage: http://www.icsn.cnrs-gif.fr/spip.php?article225)
Institute of Chemical Sciences and Engineering, Ecole Polytechnique Fꢀdꢀrale de Lausanne (EPFL), EPFL-SB-ISIC
b
LSPN, CH-1015 Lausanne, Switzerland
E-mail: jieping.zhu@epfl.ch
Received: September 18, 2013; Published online: November 27, 2013
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201300847.
Abstract: The iron
(III) chloride-multicatalyzed di-
many bioactive natural products[8] and chelating li-
gands.[9] To the best of our knowledge, there are few
methods for the synthesis of oxy-N-acylhemiaminal
motif[10] and no method for the preparation of the a-
oxyimide unit.[7,11,12] We therefore wanted to develop
a straightforward synthesis of these oxygenated motifs
based on a sequence involving the metal-catalyzed a-
oxyamination[1–3] of enamides with TEMPO 2 and
subsequent trapping of the N-acyliminium intermedi-
ate with an adequate oxygenated nucleophile such as
an alcohol or water (Scheme 1).[13,14] In addition, a-
oxyimides 5 could also be accessed by subsequent oxi-
dation of hemiaminal intermediates 4 with a suitable
oxidant.
oxygenation of enamides with TEMPO in the pres-
ence of alcohols has been developed. This multi-
component domino process affords efficient new
strategies for the synthesis of a-oxy-N-acylhemi-
ACHTUNGTRENNUNGaminals or a-oxyimides in good to excellent yields
under mild conditions.
Keywords: domino reactions; enamides; multicom-
ponent reaction; radicals; SOMO activation
Transition metal-catalyzed reactions are versatile
The main difficulties associated with the develop-
tools for carbon-oxygen bond formation. In particular, ment of such a domino MCR/oxidation sequence lie
recent advances in the transition metal-catalyzed oxy- in the complexity of the reaction mechanism as well
genation of enamines have provided a rapid access to as the presence of multiple components and inter-
a-oxyaldehydes.[1–3] For example, Sibi et al.[1,2] report- mediates sensitive to oxidation.[11b] Consequently, the
ed the first FeCl3-catalyzed enantioselective a-oxy- choice of the catalyst was expected to be crucial in
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
nism of this oxyamination and proved that the reac- synthesis of functionalized a-oxy-N-acylhemiaminals
tion proceeds via an enamine addition pathway.[5] In- 4 and a-oxyimides 5.
spired by these works[1–3] and in connection with our
recent interest in oxidative domino processes,[6] we
envisaged a one-pot procedure for the synthesis of a-
oxy-N-acylhemiaminals (ethers) 4 from readily avail-
able enamides.
The a-oxy-N-acylhemiaminal (or a-oxy-N-acyl-
ACHTUNGTRENNUNGhemiaminal ether) moiety is of great importance since
it is found as a substructure in a multitude of natural-
ly occurring and medicinally relevant substances.[7] In
addition, this subunit might serve as a convenient and
chemically stable precursor for the synthesis of the a-
Scheme 1. Rational design for an oxidative three-component
oxyimide moiety which is a privileged function in reaction of enamides, TEMPO and alcohols.
Adv. Synth. Catal. 2013, 355, 3563 – 3569
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3563

Fleur Drouet et al.
COMMUNICATIONS
Table 1. Survey of reaction conditions for the iron-catalyzed three-component process.[a]
Entry
M
Temperature [8C]
x (equiv.)
Solvent
Time [h]
Yield [%][b]
1
2
3
4
5
6
7
8
FeCl3
20
20
20
20
20
20
20
75
75
75
75
75
75
75
60
7
7
7
7
7
7
3
3
3
3
3
3
3
3
3
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
MeCN
THF
15
15
15
15
15
7
7
3
3
3
70
33
20
46
Fe
CuCl2
Cu(OTf)2
(OTf)3
A
FeCl2
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
39
82[c,d]
54[c]
86[c]
67[c]
75[c]
60[c]
80[c]
86[c,e]
88[c,f]
91[c,f]
9
10
11
12
13
14
15
DMF
3
3
3
3
1,2-DCE
toluene
toluene
toluene
3
[a]
Reaction conditions: (E)-enecarbamate (1a) (0.2 mmol), TEMPO (2) (0.4 mmol), 3a, metal salt (0.06 mmol), NaNO2
(0.06 mmol) and O2 balloon, c=0.7M.
Isolated yield after column chromatography.
[b]
[c]
[d]
[f]
With anhydrous Na2SO4 as a drying agent.
A 68% yield of 4a was isolated with 4ꢂ MS. c=0.4M or c=0.2M.
[e]
Without NaNO2-O2 as co-oxidant.
Benzyl (E)-prop-1-enylcarbamate (1a), TEMPO (2)
Varying the concentration of the reaction mixture
and ethanol (3a) were chosen as model substrates. over a given range (0.7–0.2M of 1a) had no notable
Gratefully, in the presence of FeCl3 (0.3 equiv.) and effect on the reaction yield (entry 13). Interestingly,
NaNO2 (0.3 equiv.) under an O2 atmosphere in tolu- the same result was obtained when only FeCl3 was
ene,[1,3] the three-component reaction provided the used as catalyst under an argon atmosphere, which in-
desired a-oxyaminated N-acylhemiaminal ether 4a in dicated that the presence of neither NaNO2 nor O2
70% yield as a diastereomeric mixture (ratio 1.6:1, was essential for the three-component reaction to
Table 1, entry 1). Other metal salts such as Fe
FeCl2, CuCl2 and Cu(OTf)2 were also able to catalyze obtained at 608C, these conditions were retained as
the reaction at room temperature, albeit affording the the optimum ones for further studies (entry 15).
desired product with lower yields (entries 2–5). How- To evaluate the scope of the present iron-catalyzed,
(OTf)3, take place (entry 14).[16] Finally, as similar results were
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
ever, likely due to the presence of water, yields were three-component domino process, we examined the
not reproducible. Therefore, the addition of a drying reaction of several enecarbamates with methanol
agent to the reaction mixture permitted reproducible (Table 2, entries 1–6). This transformation provided
results. Although no enhancement of the conversion good to excellent yields of a-oxyaminated N-acylhe-
was obtained in the presence of pulverized 4ꢂ molec- miaminal ethers 4 over a range of acyclic enecarba-
ular sieves, the addition of Na2SO4 afforded 4a in mates in short reaction times (3 h). Uniformly high
82% yield (entry 6). On the other hand, decreasing chemical yields were achieved with enecarbamates
the amount of ethanol to 3 equivalents resulted in a di- bearing either a linear or branched alkyl group (en-
minished yield because of competitive oxidation of tries 1–4). Interestingly, the enecarbamate geometry
the alcohol (entry 7).[11b,15] Fortunately, when the reac- had only a slight influence on this transformation
tion was carried out at 758C with 3 equivalents of 3a, since both (E)- and (Z)-1a furnished the product in
the reaction was more chemoselective and proceeded good yields (entry 6). In addition, a cyclic N-acyl(ene-
faster to give an 86% yield of 4a (entry 8). Subse- carbamate) also reacted efficiently to afford the cor-
quent solvent screening did not offer any further im- responding a-oxyaminated N-acylhemiaminal ether 4f
provement and toluene remained the best reaction in good yield as a 6:1 mixture of diastereomers
medium (entries 9–12).
(entry 5). A variety of protecting and functional
3564
asc.wiley-vch.de
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2013, 355, 3563 – 3569

Iron Chloride-Catalyzed Three-Component Domino Sequences
Table 2. Iron-catalyzed a-oxyamination of enamide derivatives.[a]
Entry
1
Product 4
Yield [%][a,b]
87
dr[c]
4b
4c
4d
4e
3:1
2
3
4
80
83
73
5.5:1[d]
4:1[d]
8:1
5
4f
82
6:1[d]
6
7
4g
4h
98/78[e]
76
2:1[d]/1:1.3[d,e]
2:1
8
9
4i
76
1.6:1[d]
4j
85
1.5:1
10
4k
74[f]
1:2.5[d]
[a]
Reaction conditions: (E)-enecarbamate (1) (0.2 mmol), TEMPO (2) (0.4 mmol), 3a (0.6 mmol), FeCl3 (0.03 mmol), c=
0.4M at 608C in toluene for 3–6 h.
[b]
[c]
[d]
[e]
[f]
Isolated yield after column chromatography.
1
The dr was determined by H NMR analysis of crude reaction mixtures.
Diastereomers were separated by column chromatography.
With (Z)-enecarbamate.
With FeCl3·6H2O as a metal salt and without Na2SO4.
groups, including Boc, Cbz and TBS, was compatible tention to investigating its oxidation in a one-pot
with the mild reaction conditions. The expected N- domino process. Oxidative amidation of aldehydes
carbamoylhemiaminal ethers were obtained in excel- with amines has received much attention in recent
lent yields when several primary and secondary alco- years.[17] Among various routes that have been devel-
hols were used. Gratefully, water can also be used as oped so far, iron-catalyzed aerobic oxidative amida-
a nucleophile, cleanly affording the formation of the tion could be adapted to a one-pot, three-component
desired hemiaminal products (entry 10).
synthesis of a-oxyimides 5.[17h] In our first attempts,
Having established the feasibility of the three-com- the applicability of the previously reported conditions
ponent synthesis of hemiaminal 4k, we turned our at- (FeCl3-TEMPO-NaNO2) was investigated for the
Adv. Synth. Catal. 2013, 355, 3563 – 3569
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
3565

Fleur Drouet et al.
COMMUNICATIONS
Table 3. Survey of reaction conditions for the iron-catalyzed
three-component oxyamination/water trapping/oxidation
domino reaction.[a]
Entry FeACHTUNGTRENNUNG
(III) source Temp. [8C] x [equiv.] Yield [%][b]
1
2
3
4
5
6
7
8
9
FeCl3
FeCl3
75
75
75
55
60
65
70
60
60
3
1.5
0
0
0
0
0
0
0
20
37
51
72
73
60
FeCl3·6H2O
FeCl3·6H2O
FeCl3·6H2O
FeCl3·6H2O
FeCl3·6H2O
FeCl3·6H2O
FeCl3·6H2O
54
80[c]
63[c,d]
[a]
Reaction conditions: (E)-enecarbamate (1a) (0.2 mmol),
TEMPO (2) (0.4 mmol), 3a, metal salt (0.06 mmol),
NaNO2 (0.06 mmol) and O2 balloon, c=0.7M.
Isolated yield after column chromatography.
With anhydrous Na2SO4 as a drying agent.
A 68% yield of 4a was isolated with 4ꢂ MS.
c=0.4M or c=0.2M.
Scheme 2. Scope of enamide substrates for the oxidative
three-component reaction.
[b]
[c]
[d]
[e]
[f]
Without NaNO2-O2 as co-oxidant.
three-step reaction sequence (oxyamination, water
trapping, oxidation).[11b,15] Unfortunately, incomplete
conversion to a-oxyimides 5a was observed due to
partial hydrolysis of enecarbamate 1a (Table 3).
Indeed, by carefully controlling the amount of water
(with the use of FeCl3·6H2O) and temperature, the
yield of 5a increased to 73% (entry 5, Table 3). This
demonstrated that the addition of an exact amount of
water, along with a precise temperature of 608C is
crucial for this three-component dioxygenation
domino process. The reaction of (E)-1a with 3 equiva-
lents of TEMPO afforded a-oxyimide 5a in an excel-
Scheme 3. Proposed radical mechanism.
lent yield, whereas a lower yield was observed with nent reaction to afford the corresponding adducts in
(Z)-1a (entry 9 vs. 8). Satisfied with these results, we good yields.
carried out this domino oxidation/three-component
A possible reaction sequence for this aerobic dioxy-
reaction sequence with a variety of enamide deriva- genation of enamides is shown in Scheme 3 and
tives 1 (Scheme 2). The reaction proceeded well with Scheme 4. The a-oxyamination of enamides could
linear as well as a-substituted enecarbamates. More- proceed by three different mechanisms.[1–3] One possi-
over, unsubstituted enamide derivatives worked well bility can be the formation of radical cation 8 via
to give the corresponding a-oxyimides 5e and 5g in single electron oxidation of enamide followed by trap-
good yields. Functional groups such as ester (5k), silyl ping
ether (5d) and triple bond (5h) were well tolerated. (Scheme 3).[1,2,18] The other possibilities would involve
The reaction could be applied to various carbamates enamide addition to Fe(III)-bound TEMPO species 7
and amides (Scheme 2) and no oxidation of unsaturat- or to an oxoammonium salt 11 generated in situ by
ed bonds present on enecarbamates was observed. Fi- oxidation of TEMPO with Fe
(III) (Scheme 4).[3,19–21]
with
the
oxygen
radical
TEMPO
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
nally, cyclic enecarbamates such as 5i and 5k were Although the absence of ring opening side product in
successfully engaged into this oxidative three-compo- the case of the above-mentioned reaction of 2-cyclo-
3566
asc.wiley-vch.de
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2013, 355, 3563 – 3569

Iron Chloride-Catalyzed Three-Component Domino Sequences
Scheme 4. Proposed ionic mechanism.
Scheme 6. Proposed oxidation mechanism.
In summary, we have developed an iron-catalyzed,
three-component domino sequence for the synthesis
of a variety of a-oxy-N-acylhemiaminal ethers. The
reaction is applicable to a wide range of enamides
leading to dioxygenated products in excellent yields.
In addition, an efficient one-pot method for aerobic
Scheme 5. Ring opening of 2,2-diphenylcyclopropyl radical
cation.
propylvinylcarbamate 1d with TEMPO leading to 4d oxidative amidation was also developed providing, to
suggested a non-radical pathway, it would be possible the best of our knowledge, the shortest route to a-
that the ring-opened radical intermediate underwent oxyimides. A highlight of this study is that two cata-
a rapid ring closure.[22] We therefore decided to study lytic cycles, both initiated by FeCl3 as the sole cata-
the mechanism with the enecarbamate 1l, substituted lyst, proceed successfully. This new type of multicata-
with
a 2,2-diphenylcyclopropyl as a mechanistic lytic system features high atom economy, use of easily
probe.[23] In this case a stable ring-opened radical in- available starting materials, operational simplicity and
termediate 12, less amenable to ring closing, would be good tolerance for diverse functional groups. Further
formed. Indeed, when (E)-benzyl [2-(2,2-diphenylcy- research on the development of related multicatalytic
clopropyl)vinyl]carbamate 1l was exposed to FeCl3, concepts is ongoing in our laboratories.
the cyclopropyl ring opening product 13 was isolated
in 41% yield (Scheme 5). When we ran an additional
control experiment, in which oxoammonium tetra- Experimental Section
fluoroborate salt was used instead of TEMPO, no a-
aminoxylated product was formed. Although at the General Protocol for a-Oxy-N-acylhemiaminals 4
present stage we cannot exclude the occurrence of
The reaction was carried out under an argon atmosphere in
competitive radical and non-radical pathways, we pro-
dried glassware, with magnetic stirring. Enamide
pose that the mechanism involves the one-electron
oxidation of 1 to generate radical cation 8 and Fe(II)-
TEMPO 9. Then, iminium intermediate 10 reacts with
TEMPO and undergoes a subsequent trapping by al-
1 (0.2 mmol, 1.0 equiv.) was dissolved in toluene (0.5 mL) in
a flask containing dried Na2SO4. TEMPO 2 (0.4 mmol,
2.0 equiv.), FeCl3 (0.06 mmol, 30 mol%) and alcohol
3
(0.6 mmol, 3 equiv.) were added successively and the reac-
tion mixture was heated at 608C for 3–6 h (monitored by
TLC). The reaction mixture was diluted with CH2Cl2, fil-
tered through a short pad of silica gel and eluted with
EtOAc (50 mL). Solvents were removed under vacuum and
purification by flash column chromatography (SiO2, 10–30%
EtOAc in heptane) afforded the corresponding products 4.
cohol 3. FeACHTUNGTRENNUNG(III)-TEMPO 7 can be regenerated by the
excess of TEMPO.[24] In addition, when water was
used as a nucleophile in the presence of NaNO2 and
O2, the a-oxy-N-acylhemiACHTNUGRTNEUNG
aminal (4 with R3 =H)
would enter a second catalytic cycle resulting in oxi-
dative amidation via intramolecular hydrogen abstrac-
tion of the FeACHTUNGTRENNUNG(III)-TEMPO-hemiaminal complex 14
General Protocol for a-Oxymides 5
(Scheme 6). Meanwhile, Fe(II)-TEMPOH 15 would
be reoxidized by NaNO2 and O2.[21,25] However, again,
another mechanism based on an oxoammonium inter-
mediate cannot be excluded.[21,25]
Enamide 1 (0.2 mmol, 1.0 equiv.) was dissolved in toluene
(0.3 mL).
TEMPO
(0.6 mmol,
3.0 equiv.),
NaNO2
(0.06 mmol, 30 mol%) and FeCl3·6H2O (0.06 mmol,
Adv. Synth. Catal. 2013, 355, 3563 – 3569
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
3567

Fleur Drouet et al.
COMMUNICATIONS
30 mol%) were successively added and the reaction mixture
was immediately put under an O2 atmosphere (O2 balloon)
and heated at 608C for 15 h (monitored by TLC). The reac-
tion mixture was then diluted with CH2Cl2, filtered through
a pad of silica and eluted with EtOAc (50 mL). Solvents
were removed under vacuum and purification by flash
column chromatography (SiO2, 30% EtOAc in heptane) af-
forded the pure product 5.
natural products, see: g) B. Echinocandin, F. Benz, F.
Knuesel, J. Nuesch, H. Treichler, W. Voser, R. Nyfeler,
W. Keller-Schierlein, Helv. Chim. Acta 1974, 57, 2459;
h) H. Umezawa, S. Kondo, H. Iinuma, S. Kunimoto, Y.
Ikeda, H. Iwasawa, D. Ikeda, T. Takeuchi, J. Antibiot.
1981, 34, 1622; i) J. Tanaka, T. Higa, Tetrahedron Lett.
1996, 37, 5535.
[8] For reviews, see: a) Studies in Natural Products
Chemistry, Vol. 2 (Ed.: Atta-ur-Rahman), Elsevier,
1988, p 680; b) a-Hydroxy Acids in Enantioselective
Syntheses, (Eds.: G. M. Coppola, H. F. Schuster), VCH,
Weinheim, 1997; c) S. Masamune, W. Choy, J. S. Peters-
en, L. R. Sita, Angew. Chem. 1985, 97, 1; Angew. Chem.
Int. Ed. Engl. 1985, 24, 1; d) C. Spry, K. Kirk, K. J.
Saliba, FEMS Microbiol. Rev. 2008, 32, 56.
Acknowledgements
Financial support from CNRS and ANR are gratefully ac-
knowledged. F.D. thanks ICSN for a doctoral fellowship.
[9] Selected recent examples, see: a) G. Blay, I. Fernꢃndez,
A. Marco-Aleixandre, J. R. Pedro, J. Org. Chem. 2006,
71, 6674; b) P. Geoghegan, P. OꢄLeary, ACS Catal.
2012, 2, 573; c) G. Blay, I. Fernꢃndez, A. Marco-Aleix-
andre, J. R. Pedro, Org. Lett. 2006, 8, 1287; d) G. Blay,
I. Fernꢃndez, V. Hernꢃndez-Olmos, A. Marco-Aleixan-
dre, J. R. Pedro, Tetrahedron: Asymmetry 2005, 16,
1953; e) G. Blay, I. Fernꢃndez, V. Hernꢃndez-Olmos,
A. Marco-Aleixandre, J. R. Pedro, J. Mol. Catal. A:
Chem. 2007, 276, 235; f) G. Blay, L. Cardona, I. Fernan-
dez, A. Marco-Aleixandre, M. C. Munoz, J. R. Pedro,
Org. Biomol. Chem. 2009, 7, 4301.
[10] Example of the a-aminoxylation of a-arylated enecar-
bamates, see: M. Lu, Y. Lu, D. Zhu, X. Zeng, X. Li, G.
Zhong, Angew. Chem. 2010, 122, 8770; Angew. Chem.
Int. Ed. 2010, 49, 8588.
[11] a) T. Nemoto, H. Kakei, V. Gnanadesikan, S.-y. Tosaki,
T. Ohshima, M. Shibasaki, J. Am. Chem. Soc. 2002,
124, 14544; b) H. Kakei, T. Nemoto, T. Ohshima, M.
Shibasaki, Angew. Chem. 2004, 116, 321; Angew. Chem.
Int. Ed. 2004, 43, 317.
References
[1] M. P. Sibi, M. Hasegawa, J. Am. Chem. Soc. 2007, 129,
4124.
[2] a) N.-N. Bui, X.-H. Ho, S.-i. Mho, H.-Y. Jang, Eur. J.
Org. Chem. 2009, 5309; b) T. Koike, M. Akita, Chem.
Lett. 2009, 38, 166; c) T. Kano, H. Mii, K. Maruoka,
Angew. Chem. 2010, 122, 6788; Angew. Chem. Int. Ed.
2010, 49, 6638; d) K. Akagawa, T. Fujiwara, S. Sakamo-
to, K. Kudo, Org. Lett. 2010, 12, 1804; e) K. Akagawa,
K. Kudo, Org. Lett. 2011, 13, 3498.
[3] a) S. P. Simonovich, J. F. Van Humbeck, D. W. C. Mac-
Millan, Chem. Sci. 2012, 3, 58; b) J. F. Van Humbeck,
S. P. Simonovich, R. R. Knowles, D. W. C. MacMillan,
J. Am. Chem. Soc. 2010, 132, 10012.
[4] Reviews: a) T. Vogler, A. Studer, Synthesis 2008, 1979–
1993; b) L. Tebben, A. Studer, Angew. Chem. 2011,
123, 5138; Angew. Chem. Int. Ed. 2011, 50, 5034.
[5] Examples of a-aminoxylation of aldehydes via an en-
amine intermediate, see: a) G. Zhong, Angew. Chem.
2003, 115, 4379; Angew. Chem. Int. Ed. 2003, 42, 4247;
b) S. P. Brown, M. P. Brochu, C. J. Sinz, D. W. C. Mac-
Millan, J. Am. Chem. Soc. 2003, 125, 10808; c) Y. Haya-
shi, J. Yamaguchi, K. Hibino, M. Shoji, Tetrahedron
Lett. 2003, 44, 8293.
[6] a) M. Bekkaye, Y. Su, G. Masson, Eur. J. Org. Chem.
2013, 3978; b) T. Courant, G. Masson, Chem. Eur. J.
2012, 18, 423; c) J. Brioche, G. Masson, J. Zhu, Org.
Lett. 2010, 12, 1432; d) J.-M. Grassot, G. Masson, J.
Zhu, Angew. Chem. 2008, 120, 961; Angew. Chem. Int.
Ed. 2008, 47, 947; e) P. Fontaine, A. Chiaroni, G.
Masson, J. Zhu, Org. Lett. 2008, 10, 1509.
[7] For selected examples of N-acyl aminal-containing nat-
ural products, see: a) N. B. Perry, J. W. Blunt, M. H. G.
Munro, L. K. Pannell, J. Am. Chem. Soc. 1988, 110,
4850; b) S. Sakemi, T. Ichiba, S. Kohmoto, G. Saucy, T.
Higa, J. Am. Chem. Soc. 1988, 110, 4851; c) N. Fusetani,
T. Sugawara, S. Matsunaga, J. Org. Chem. 1992, 57,
3828; d) R. H. Cichewicz, F. A. Valeriote, P. Crews,
Org. Lett. 2004, 6, 1951; e) G. R. Pettit, J. P. Xu, J. C.
Chapuis, R. K. Pettit, L. P. Tackett, D. L. Doubek,
J. N. A. Hooper, J. M. Schmidt, J. Med. Chem. 2004, 47,
1149; f) J. C. Jewett, V. H. Rawal, Angew. Chem. 2007,
119, 6622; Angew. Chem. Int. Ed. 2007, 46, 6502. For
selected examples of N-acyl hemiaminal-containing
[12] M. W. Leighty, B. Shen, J. N. Johnston, J. Am. Chem.
Soc. 2012, 134, 15233.
[13] Example of difunctionalization of C=C bonds catalyzed
by FeACTHNUTRGNE(NUG III), see: W. Liu, Y. Li, K. Liu, Z. Li, J. Am.
Chem. Soc. 2011, 133, 10756.
[14] For representative references on radical and radical-
ionic multicomponent reactions, see: a) E. Godineau,
Y. Landais, Chem. Eur. J. 2009, 15, 3044; b) M. Tojino,
I. Ryu, N. Sonoda, D. P. Curran, Chem. Rev. 1996, 96,
177; c) M. Tojino, I. Ryu, Multicomponent Reactions,
(Eds.: J. Zhu, H. Bienaymꢀ), Wiley-VCH, Weinheim,
2005, p 169.
[15] R. Liu, X. Liang, C. Dong, X. Hu, J. Am. Chem. Soc.
2004, 126, 4112.
[16] Excess of TEMPO can act as both the oxygen atom
source and the stoichiometric reoxidant for iron, see
ref.[7]
[17] a) S. C. Ghosh, J. S. Y. Ngiam, A. M. Seayad, D. T.
Tuan, C. L. L. Chai, A. Chen, J. Org. Chem. 2012, 77,
8007; b) R. Cadoni, A. Porcheddu, G. Giacomelli, L.
De Luca, Org. Lett. 2012, 14, 5014; c) S. C. Ghosh,
J. S. Y. Ngiam, C. L. L. Chai, A. M. Seayad, T. T. Dang,
A. Chen, Adv. Synth. Catal. 2012, 354, 1407; d) W. Yoo,
C. Li, J. Am. Chem. Soc. 2006, 128, 13064; e) A. Till-
ack, I. Rudloff, M. Beller, Eur. J. Org. Chem. 2001, 66,
523; f) T. Naota, S. Murahashi, Synlett 1991, 693; g) Y.
3568
asc.wiley-vch.de
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2013, 355, 3563 – 3569

Iron Chloride-Catalyzed Three-Component Domino Sequences
Tamaru, Y. Yamada, Z. Yoshida, Synthesis 1983, 474;
h) K. Nakagawa, H. Onoue, K. Minami, J. Chem. Soc.
Chem. Commun. 1966, 17; i) S. C. Ghosh, J. S. Y.
Ngiam, C. L. L. Chai, A. M. Seayad, T. T. Dang, A.
Chen, Adv. Synth. Catal. 2012, 354, 1407.
D. H. R. Barton, W. J. Motherwell, Tetrahedron Lett.
1984, 25, 603.
[21] For reviews on catalytic aerobic oxidations, see: a) T.
Mallat, A. Baiker, Chem. Rev. 2004, 104, 3037; b) I. E.
Markꢆ, P. R. Gilles, M. Tsukazaki, A. Gautier, R. Du-
meunier, K. Doda, F. Philippart, I. Chellꢀ-Regnaut, J.-
L. Mutonkole, S. M. Brown, C. J. Urch, Aerobic, Metal-
catalyzed Oxidation of Alcohols, in: Transition Metals
for Organic Synthesis, 2nd edn., Vol. 2, (Eds: M. Beller,
C. Bolm), Wiley-VCH, Weinheim, 2004, p 437; c) B.-Z.
Zhan, A. Thompson, Tetrahedron 2004, 60, 2917;
d) R. A. Sheldon, I. W. C. E. Arends, Adv. Synth. Catal.
2004, 346, 1051; e) T. Punniyamurthy, S. Velusamy, J.
Iqbal, Chem. Rev. 2005, 105, 2329; f) M. J. Schultz,
M. S. Sigman, Tetrahedron 2006, 62, 8227; g) F. Recu-
pero, C. Punta, Chem. Rev. 2007, 107, 3800; h) R. A.
Sheldon, I. W. C. E. Arends, J. Mol. Catal. A: Chem.
2006, 251, 200; i) T. Seki, A. Baiker, Chem. Rev. 2009,
109, 2409.
[22] a) T. Benkovics, J. Du, I. A. Guzie, T. P. Yoon, J. Org.
Chem. 2009, 74, 5545; b) E. L. Spence, J. Langley,
T. D. H. Bugg, J. Am. Chem. Soc. 1996, 118, 8343;
c) D. D. Tanner, J. J. Chen, C. Luelo, P. M. Peters, J.
Am. Chem. Soc. 1992, 114, 713; see Ref.[8] or Ref.[9]
[23] O. N. Burchak, G. Masson, S. Py, Synlett 2010, 1623,
and references cited therein.
[18] For selected examples of monooxidation of enamines,
see : a) N. N. Bui, X.-H. Ho, S. I. Mho, H.-Y. Jang, Eur.
J. Org. Chem. 2009, 5309; b) J. Cossy, A. Bouzide, C.
Leblanc, J. Org. Chem. 2000, 65, 7257; c) K. Narasaka,
T. Okauchi, K. Tanaka, M. Murakami, Chem. Lett.
1992, 2, 2099. For the enantioselective transformation,
see: d) A. Mastracchio, A. A. Warkentin, A. M. Walji,
D. W. C. MacMillan, Proc. Natl. Acad. Sci. USA 2010,
107, 20648; e) K. Akagawa, T. Fujiwara, S. Sakamoto,
K. Kudo, Org. Lett. 2010, 12, 1804; f) S. Rendler,
D. W. C. MacMillan, J. Am. Chem. Soc. 2010, 132, 5027;
g) N. T. Jui, E. C. Y. Lee, D. W. C. MacMillan, J. Am.
Chem. Soc. 2010, 132, 10015; h) J. M. Um, O. Gutier-
rez, F. Schoenebeck, K. N. Houk, D. W. C. MacMillan,
J. Am. Chem. Soc. 2010, 132, 6001; i) M. Amatore, T. D.
Beeson, S. P. Brown, D. W. C. MacMillan, Angew.
Chem. 2009, 121, 5223; Angew. Chem. Int. Ed. 2009, 48,
5121; j) J. C. Conrad, J. Kong, B. N. Laforteza, D. W. C.
MacMillan, J. Am. Chem. Soc. 2009, 131, 11640; k) H.
Kim, D. W. C. MacMillan, J. Am. Chem. Soc. 2008, 130,
398; l) T. H. Graham, C. M. Jones, N. T. Jui, D. W. C.
MacMillan, J. Am. Chem. Soc. 2008, 130, 16494; m) H.-
Y. Jang, J.-B. Hong, D. W. C. MacMillan, J. Am. Chem.
Soc. 2007, 129, 7004; n) T. D. Beeson, A. Mastracchio,
J.-B. Hong, K. Ashton, D. W. C. MacMillan, Science
2007, 316, 582.
[24] The lower amount of TEMPO depressed the reaction
efficiency.
[25] For a mechanistic discussion on the aerobic oxidation,
see: a) M. F. Semmelhack, C. R. Schmidt, D. A. Cortꢀs,
C. S. Chou, J. Am. Chem. Soc. 1984, 106, 3374; b) M. F.
Semmelhack, C. R. Schmidt, D. A. Cortes, Tetrahedron
Lett. 1986, 27, 1119; c) A. Dijiksman, I. W. C. E.
Arends, R. A. Sheldon, Org. Biomol. Chem. 2003, 1,
3232; d) for a review, see: C. Galli, P. Gentili, O. Lanza-
lunga, Angew. Chem. 2008, 120, 4868; Angew. Chem.
Int. Ed. 2008, 47, 4790; e) J. J. Scepaniak, A. M. Wright,
R. A. Lewis, G. Wu, T. W. Hayton, J. Am. Chem. Soc.
2012, 134, 19350.
ˇ
[19] E. Dinca, P. Hartmann, J. Smrcek, I. Dix, P. G. Jones,
U. Jahn, Eur. J. Org. Chem. 2012, 4461.
[20] a-Aminoxylation of enols or enolates with TEMPO via
N-oxoammonium salts generated in situ by oxidation,
see: a) M. Schꢅmann, H. J. Schꢅfer, Synlett 2004, 1601;
b) S. Weik, G. Nicholson, G. Jung, J. Rademann,
Angew. Chem. 2001, 113, 1489; Angew. Chem. Int. Ed.
2001, 40, 1436; c) U. Jahn, P. Hartmann, I. Dix, P. G.
Jones, Eur. J. Org. Chem. 2001, 3333; d) D. H. Hunter,
Adv. Synth. Catal. 2013, 355, 3563 – 3569
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
3569