Iron-catalyzed ring-opening azidation and allylation of O-heterocycles

Article abstract of DOI:10.1021/ol402511r

We have established the first catalytic C-C and C-N bond formation reactions of O-heterocycles (e.g., tetrahydrofuran, phthalane, and lactone derivatives) using iron trichloride as a catalyst in the presence of TMSN ₃ or allylsilanes accompanie

Full text of DOI:10.1021/ol402511r

ORGANIC
LETTERS
2013
Vol. 15, No. 20
5282–5285
Iron-Catalyzed Ring-Opening Azidation
and Allylation of O‑Heterocycles
Yoshinari Sawama,*,† Kyoshiro Shibata,† Yuka Sawama,‡ Masato Takubo,†
Yasunari Monguchi,† Norbert Krause,§ and Hironao Sajiki*,†
Laboratory of Organic Chemistry, Gifu Pharmaceutical University, 1-25-4
Daigaku-nishi, Gifu 501-1196, Japan, Laboratory of Pharmaceutical Physical
Chemistry, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196,
Japan, and Organic Chemistry, Dortmund University of Technology,
Otto-Hahn-Strasse 6, D-44227 Dortmund, Germany
sawama@gifu-pu.ac.jp; sajiki@gifu-pu.ac.jp
Received September 1, 2013
ABSTRACT
We have established the first catalytic CÀCandCÀN bond formation reactions of O-heterocycles (e.g., tetrahydrofuran, phthalane, and lactone derivatives)
using iron trichloride as a catalyst in the presence of TMSN3 or allylsilanes accompanied by the ring opening of O-heterocycles. The reactions smoothly
proceeded at room temperature to give the corresponding primary saturated alcohols from the 2-substituted tetrahydrofurans, ortho-substituted benzyl
alcohols from phthalanes, and saturated carboxylic acids from lactones in high yields.
The tetrahydrofuran ring represented as O-heterocycles
can be a useful organic backbone source composed of four
carbons and one oxygen atom, namely the 1-butanol unit,
by cleavage of the carbon (C)Àoxygen (O) bond of the
tetrahydrofuran ring due to the easy availability of various
tetrahydrofuran derivatives.1À5 However, a very small
number of carbon and nitrogen (N) atom introduction
reactions accompanied by the ring opening (CÀO bond
cleavage) of tetrahydrofurans have been reported in the
literature and required more than a chemical equivalent
of Lewis acids and/or harsh reaction conditions [TiCl4
(1.2 equiv) at À78 °C,6 Sc(OTf)3 (2 equiv) at 100 °C using a
microwave apparatus7] in the presence of allylslilanes
or TMSN3 as a nucleophile. We now report the efficient
and mild iron(III) chloride catalyzed CÀN and CÀC bond
formations of tetrahydrofuran derivatives (e.g., 2-aryl,2
alkenyl,3 and alkynyl2 substituents), additionally phthalanes4
and lactone5 derivatives associated with the ring-opening
reaction. The present method could afford the corresponding
highly functionalized alcohols and carboxylic acids at room
temperature.
† Laboratory of Organic Chemistry, Gifu Pharmaceutical University.
‡ Laboratory of Pharmaceutical Physical Chemistry, Gifu Pharmaceutical
University.
§ Dortmund University of Technology.
(1) Related references are cited in a recent paper; see: Mulvey, R. E.;
Blair, V. L.; Clegg, W.; Kennedy, A. R.; Klett, J.; Russo, L. Nat. Chem.
2010, 2, 588–591.
(2) For preparation of 2-aryl and -alkynyl tetrahydrofurans, see:
Brown, D. S.; Bruno, M.; Davenport, R. J.; Ley, S. V. Tetrahedron 1989,
13, 4293–4308.
(3) For preparation of 2-alkenyl tetrahydrofurans, see: (a) Jang, Y.-
J.; Shih, Y.-K.; Liu, J.-Y.; Kuo, W.-Y.; Yao, C.-F. Chem.;Eur. J. 2003,
9, 2123–2128. (b) Liu, Z.-Q.; Sun, L.; Wang, J.-G.; Han, J.; Zhao, Y.-K.;
Zhou, B. Org. Lett. 2009, 11, 1437–1439.
Wehaverecently discovered that Lewisacids, suchasthe
AuCl3 or FeCl3 catalyst, could activate the CÀO bond of
2-aryl-2,5-dihydrofuran substructure-containing substrates
to give the ring-opened intermediate, and the subsequent
(4) For preparation of phthalane derivatives, see: Yoshioka, M.;
Osawa, H.; Fukuzawa, S. Bull. Chem. Soc. Jpn. 1982, 55, 877.
(5) For preparation of lactone derivatives, see: Dohi, T.; Takenaga,
N.; Goto, A.; Maruyama, A.; Kita, Y. Org. Lett. 2007, 9, 3129–3132.
(6) Oku, A.; Homoto, Y.; Harada, T. Chem. Lett. 1986, 15, 1495–
1498.
(7) Qin, H.-L.; Lowe, J. T.; Panek, J. S. J. Am. Chem. Soc. 2007, 129,
38–39.
r
10.1021/ol402511r
Published on Web 10/01/2013
2013 American Chemical Society

functionalizations using allylTMS and TMSN3 efficiently
provided the corresponding useful unsaturated linear or
arene products.8 Our next challenge was the application of
these methodologies to the ring-opening CÀC and CÀN
bond formations using the thermodynamically more stable
tetrahydrofurans in a catalytic manner. The azidative9 ring
opening of 2-phenyltetrahydrofuran (1a) using TMSN3
(4 equiv) was first examined in the presence of 10 mol %
of a Lewis acid in CH2Cl2 at room temperature (Table 1).
Table 1. Lewis Acid Catalyzed Azidative Ring Opening of
2-Phenyltetrahydrofuran (1a)
azido
yield
(%)
entry
catalyst
source
time
HAuCl4 3H2O and AuCl3 as gold(III) catalysts, which are
3
effective catalysts for the ring opening of dihydrofurans,8a
effectively promoted the desired azidation within 5 min to
give the 4-azido-4-phenylbutan-1-ol (2a) in high yields
(entries 1 and 2).10 The use of (Ph3P)AuCl/AgSbF6 as a
1
2
3
HAuCl4 3H2O
TMSN3
TMSN3
TMSN3
5 min
5 min
1 h
81
79
38
3
AuCl3
(Ph3P)AuCl/
AgSbF6
AgOTf
4
TMSN3
TMSN3
TMSN3
TMSN3
TMSN3
TMSN3
TMSN3
TMSN3
TMSN3
NaN3
24 h
NR
trace
trace
68
Au(I) species, AgOTf, BF3 Et2O, TMSOTf, ZnCl2, and
FeCl2 4H2O as Lewis acids, and TFA as a Brønsted acid led
3
5
BF3 Et2O
24 h
3
3
6
TMSOTf
ZnCl2
24 h
to low or no reaction efficiencies (entries 3À9). It is note-
worthy that FeCl3 and FeBr3 as cheaper iron(III) catalysts
most effectively facilitated the azidative ring-opening
reaction to give 2a in efficient yields (entries 10 and 11).
Additionally, the decrement of FeCl3 (5 mol % from 10 mol
%) and TMSN3 (1.5 equiv from 4 equiv) could also retain
the reaction efficiency to give 2a in a high yield (entry 12).
The reaction using NaN3 or diphenylphosphoryl azide
(DPPA) as an azido source never proceeded (entries 13
and 14), and the use of other solvents (e.g., CHCl3, toluene,
dioxane, and THF) was less effective for promoting the
present reaction (see Supporting Information).
7
24 h
8
FeCl2 4H2O
24 h
53
3
9
TFA
24 h
trace
87
10
11
12a,b
13
14
FeCl3
FeBr3
FeCl3
FeCl3
FeCl3
5 min
5 min
15 min
24 h
88
85
NR
NR
DPPA
24 h
a 5 mol % of FeCl3 and 1.5 equiv of TMSN3 were used. b Reactions in
other solvents (e.g., CHCl3, toluene, dioxane, THF) gave inefficient
results (see Supporting Information).
give the corresponding allylic and propargyl azides (2g and
2i) (entries 6À8). It is noteworthy that the mixture of E- and
Z-alkenyl tetrahydrofurans (1h) was completely transformed
into the corresponding E-alkenyl azide (2g) (entry 7).13 The
present method was applicable to the azidative ring opening
of 2-phenyl tetrahydropyran (1j) by the addition of TMSCl
as a co-Lewis acid (entry 9).14 The reaction using 1,4-epoxy-
tetrahydronaphthalene (1k) as a substrate allowed the dou-
ble azidation at the 1 and 4 positions to give the 1,4-diazido
product (2k) in high yield (entry 10).15 Furthermore, the
present reactions could be adapted for the azidation of the
phthalane and lactone derivatives (entries 11À14). 1-Phenyl
and alkenyl phthalanes (1l and 1m) were efficiently trans-
formed into ortho-substituted benzylalcohols (2l and the
The FeCl3-catalyzed ring-opening azidation could
be adapted to various substrates (Table 2).11 While the
2-aryltetrahydrofurans (1bÀd) bearing electron-donating
and -withdrawing groups on the aromatic ring efficiently
underwent the azidative ring-opening reaction to give the
4-azidated linear primary alcohols at room temperature
(2bÀd) (Table 2, entries 1À3), the 2-alkylated tetrahydro-
furan (1e) never reacted with TMSN3 even under higher
temperature conditions (entry 4).12 The 2,2-disubstituted
tetrahydrofuran (1f) was also transformed into the tertiary
azido product (2f) regardless of the bulkiness of the sub-
strate (entry 5). Furthermore, the 2-alkenyl and alkynyl
tetrahydrofurans (1gÀi) efficiently and regioselectively
underwent the azidative ring opening at the 2 position to
(8) (a) Sawama, Y.; Sawama, Y.; Krause, N. Org. Lett. 2009, 11,
5034–5037. (b) Sawama, Y.; Kawamoto, K.; Satake, H.; Krause, N.;
Kita, Y. Synlett 2010, 14, 2151–2155. (c) Sawama, Y.; Shishido, Y.;
Yanase, T.; Kawamoto, K.; Goto, R.; Monguchi, Y.; Kita, Y.; Sajiki, H.
Angew. Chem., Int. Ed. 2013, 52, 1515–1519. (d) Sawama, Y.; Ogata, Y.;
Kawamoto, K.; Satake, H.; Shibata, K.; Monguchi, Y.; Sajiki, H.; Kita,
Y. Adv. Synth. Catal. 2013, 355, 517–528.
(13) The azidation of 1g and 1h could proceed via various intermedi-
ates (A), which undergo [3,3]-sigmatropic rearrangements of allylic azide
moieties to provide only thermodynamically stable 2g. See the related
papers: (a) Lauzon, S.; Tremblay, F.; Gagnon, D.; Godbout, C.;
ꢀ
Chabot, C.; Mercier-Shanks, C.; Perreault, S.; DeSeve, H.; Spino, C.
J. Org. Chem. 2008, 73, 6239–6250. (b) Craig, D.; Harvey, J. W.;
O’Brien, A. G.; White, A. J. P. Org. Biomol. Chem. 2011, 9, 7057–7061.
(9) An azide is easily transformed into a triazole by the Huisgen
reaction and amine by reduction, etc.; see: (a) Huisgen, R. Angew.
Chem., Int. Ed. Engl. 1963, 2, 565–598. (b) Rostovsev, V. V.; Green,
L. G.; Fokin, V. V.; Sharpless, K. B. Angew. Chem., Int. Ed. 2002, 41,
2596–2599. (c) Scriven, E. F. V. Chem. Rev. 1988, 88, 297–368.
(10) While the mixture of 4-azido-4-phenylbutan-1-ol (2a) and its
TMS ether was obtained during the reaction process, only 2a was
isolated after the deprotection of the TMS group of the TMS ether
using TBAF. Alternatively, the quench using 1 M HCl aq. instead of
TBAF gave a similar yield.
(11) The usage of FeCl3 and TMSN3 or allylsilanes was optimized for
each reaction.
(12) The ring-opening azidation of methyl tetrahydrofuran-2-car-
boxylate and 4-(2-tetrahydrofuryl)acetophenone also gave no ring-
opened products.
(14) TMS halides, such as TMSCl, were reported to activate the
Lewis acid such as InCl3; see: Onishi, Y.; Nishimoto, Y.; Yasuda, M.;
Baba, A. Org. Lett. 2011, 13, 2762–2765. In addition, we also discovered
that the AuCl3À or FeCl3ÀTMSCl combination is effective for the ring
opening of 1,4-epoxy-1,4-dihydronaphthalenes. See refs 8b and 8c.
Org. Lett., Vol. 15, No. 20, 2013
5283

Table 2. Scope and Limitation of Ring-Opening Azidation
Table 3. Allylative Ring Opening
a FeCl3 (10 mol %) and allylsilane (3 equiv) were used. b FeCl3 (5 mol
%) and allylsilane (2 equiv) were used. c FeCl3 (50 mol %) and allylsilane
(2 equiv) was used. d FeCl3 (50 mol %) and allylsilane (3 equiv) were
used. e FeCl3 (10 mol %), allylsilane (3 equiv), and TMSCl (1 equiv) were
used. f FeCl3 (20 mol %) and allylsilane (4 equiv) were used. g FeCl3
(10 mol %) and allylsilane (4 equiv) were used. h The quench using TBAF
was not necessary.
mixture of 2ma and 2mb,16 entries 11 and 12),17 and also
azidated saturated carboxylic acids (2n and 2o) were effi-
ciently obtained by the use of 1-phenyl γ-butyro- and δ-
valerolactone (1n and 1o) as substrates (entries 13 and 14).17
Moreover, the allylative ring-opening reaction of var-
ious tetrahydofuran derivatives, which could construct the
highly functionalized C7 linear alcohol skeletons bearing
an olefin functionality at the opposite terminal against the
hydroxyl group, was investigated (Table 3).11 The reaction
a FeCl3 (5 mol %) and TMSN3 (1.5 equiv) were used. b FeCl3 (5 mol
%) and TMSN3 (2 equiv) were used. c FeBr3 (10 mol %) and TMSN3 (3
equiv) were used at 0 °C. d FeCl3 (10 mol %), TMSN3 (3 equiv), and
TMSCl (20 mol %) were used. e FeCl3 (10 mol %) and TMSN3 (2 equiv)
were used at À40 °C to rt. f FeCl3 (10 mol %) and TMSN3 (3 equiv) were
used. g FeCl3 (1.1 equiv) and TMSN3 (3 equiv) were used. h The quench
using TBAF was not necessary.
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Org. Lett., Vol. 15, No. 20, 2013

using 2-phenyltetrahydrofuran (1a) with various allylsi-
lane derivatives, such as allylTMS, 2-phenyl and bromo-
substituted allylsilanes, and [2-(trimethylsilyl)ethylidene]-
cyclohexane, was efficiently catalyzed by FeCl3 as the case
with the azidation togive the corresponding 6-hepten-1-ols
(3aÀd) (entries 1À4) in moderate to excellent yields. The
2-alkynyl tetrahydrofuran (1i) could be transformed into
1,5-eneyne18 products bearing a primary hydroxyl group
(3eÀg) (entries 5À7). Furthermore, the ring-opening ally-
lation of the phthalane and lactone derivatives could also
proceed to give the corresponding allylated ortho-benzy-
lalcohol (3h) and saturated carboxylic acid (3i) derivatives
(entries 8 and 9).17
tetrahydrofuran derivatives. The azidation using TMSN3
and allylation using various allylsilanes was efficiently
catalyzed by FeCl3 as a cheap and universal iron catalyst
at room temperature to afford the corresponding azidated
linear primary alcohols in excellent yields. Furthermore,
the phthalane and lactone derivatives also underwent
the FeCl3-catalyzed ring-opening allylation and azidation
to give the corresponding ortho-substituted benzylalcohols
and the saturated carboxylic acids. These azidated and
allylated products can be valuable as small synthetic
precursors for a wide variety of functional materials.
Acknowledgment. This work was partially supported
by a Grant-in-Aid for Young Scientists (B) from the Japan
Society for the Promotion of Science (JSPS).
In conclusion, we have established the first catalytic
CÀC and CÀN bond formations associated with the
ring-opening reaction of the thermodynamically stable
Supporting Information Available. The details of opti-
mization of reaction conditions and the spectroscopic
(15) Benzyl TMS ether generated by the first azidation of 1k was
efficiently transformed into the diazido product (2k). We have also
established the direct azidation of benzyl TMS ether using the TMSN3
and FeCl3 combination; see: Sawama, Y.; Nagata, S.; Yabe, Y.; Morita,
K.; Monguchi, Y.; Sajiki, H. Chem.;Eur. J. 2012, 18, 16608–16611.
1
data of new products such as H and 13C NMR and IR
were depicted. This material is available free of charge via
the Internet at http://pubs.acs.org.
(18) 1,5-Eneynes are important precursors to construct complicated
cyclic compounds. For selected references, see: (a) Luzung, M. R.;
Markham, J. P.; Toste, F. D. J. Am. Chem. Soc. 2004, 126, 10858–
10859. (b) Bruneau, C. Angew. Chem., Int. Ed. 2005, 44, 2328–2334. (c)
Sun, J.; Conley, M. P.; Zhang, L.; Kozmin, S. A. J. Am. Chem. Soc. 2006,
128, 9705–9710. (d) Reeds, J. P.; Whitwood, A. C.; Healy, M. P.;
Fairlamb, I. J. S. Chem. Commun. 2010, 46, 2046–2048.
(16) 2ma and 2mb could not be separated. Each product (2ma and
2mb) was smoothly isomerized during the isolation to the corresponding
isomer by the rapid rearrangement of the allylic azido functions.
(17) These are the first examples of the ring-opening azidation and
allylation of the phthalane and lactone derivatives.
The authors declare no competing financial interest.
Org. Lett., Vol. 15, No. 20, 2013
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