Chemoselective activities of Fe(III) catalysts in the hydrofunctionalization of allenes

Article abstract of DOI:10.1021/ol303021d

A range of tetrahydropyrans and piperidines were produced by Fe(III)-catalyzed intramolecular hydroalkoxylation and hydroamination reactions of allenes. Various Fe catalysts with different counterions were tested. Their activities toward allene and alkene activation depended sensitively on their counterion and reaction conditions. Mechanistic study of the reaction intermediates found a new reaction pattern involving the Fe catalysts and diene substrates.

Full text of DOI:10.1021/ol303021d

ORGANIC
LETTERS
2012
Vol. 14, No. 24
6262–6265
Chemoselective Activities of Fe(III)
Catalysts in the Hydrofunctionalization
of Allenes
Min Seok Jung, Won Sun Kim, Ye Ho Shin, Ha Jeong Jin, Young Sam Kim, and
Eun Joo Kang*
Department of Applied Chemistry, Kyung Hee University, Yongin 446-701, Korea
ejkang24@khu.ac.kr
Received November 3, 2012
ABSTRACT
A range of tetrahydropyrans and piperidines were produced by Fe(III)-catalyzed intramolecular hydroalkoxylation and hydroamination reactions
of allenes. Various Fe catalysts with different counterions were tested. Their activities toward allene and alkene activation depended sensitively on
their counterion and reaction conditions. Mechanistic study of the reaction intermediates found a new reaction pattern involving the Fe catalysts
and diene substrates.
Iron salts can efficiently catalyze organic reactions as
alternatives to traditional transition metal catalysts, show-
ing advantages of being more sustainably produced and
nontoxic. Ironꢀoxo complexes have been developed for
oxidation, and the chemistry of ironꢀporphyrins has been
broadly explored for catalysis.1 Iron halides have been
extensivelyusedasLewis acid catalysts invariousaddition,
substitution, cycloaddition and rearrangement reactions
of carbonyl and alcohol functional groups.2 In recent
years, iron complexes have been found to be potential
catalysts in the following organic reactions. The formation
of new carbonꢀcarbon bonds by cross-coupling reac-
tions can involve the use of Fe(II) or Fe(III) precatalysts
with the assistance of Grignard reagents to offer broad
utility even with alkyl halides.3 Iron salts catalyze various
hydrofunctionalization reactions by activating unsatu-
rated carbonꢀcarbon bonds to nucleophilic attack and
allowing new carbonꢀnitrogen, oxygen and phosphorus
bonds to form.4,5
Iron-catalyzed carbonꢀheteroatom bond-forming reac-
tions of unsaturated carbonꢀcarbon bonds were first
reported by Rosenblum in 1981: alkynes were hydroalk-
oxylized to vinyl ethers using CpFe(CO)2(iso-butylene)BF4.6
The exchange reaction of a cationic η2-olefin iron complex to
an η2-acetylene iron complex, yielding a competitive vinyli-
dene isomer, was provided as the mechanistic view of iron
catalyst. Iron trichloride has been used in hydroamination7
~
(4) Correa, A.; Mancheno, O. G.; Bolm., C. Chem. Soc. Rev. 2008, 37,
1108.
(5) For iron-catalyzed allylic functionalization reactions, see: (a)
ꢁ
Guerinot, A.; Serra-Muns, A.; Gnamm, C.; Bensoussan, C.; Reymond,
S.; Cossy, J. Org. Lett. 2010, 12, 1808. (b) Wang, Z.; Li, S.; Yu, B.; Wang,
Y.; Sun, X. J. Org. Chem. 2012, 77, 8615.
(6) Bates, D. J.; Rosenblum, M.; Samuels, S. B. J. Organomet. Chem.
(1) (a) Barton, D. H. R. Chem. Soc. Rev. 1996, 25, 237. (b) Goldstein,
S.; Meyerstein, D. Acc. Chem. Res. 1999, 32, 547. (c) Costas, M.; Mehn,
M. P.; Jensen, M. P.; Que, L., Jr. Chem. Rev. 2004, 104, 939. (d) Tshuva,
E. Y.; Lippard, S. J. Chem. Rev. 2004, 104, 987. (e) The Porphyrin
Handbook; Kadish, K. M., Smith, K. M., Guilard, R., Eds.; Academic Press:
San Diego, 2000.
(2) Bolm, C.; Legros, J.; Le Paih, J.; Zani, L. Chem. Rev. 2004, 104,
6217 and references cited therein.
(3) For review articles of iron-catalyzed cross coupling reactions, see:
1981, 209, C55.
(7) (a) Komeyama, K.; Morimoto, T.; Takaki, K. Angew. Chem., Int.
Ed. 2006, 45, 2938. (b) Michaux, J.; Terrasson, V.; Marque, S.; Wehbe,
J.; Prim, D.; Campagne, J.-M. Eur. J. Org. Chem. 2007, 2601. (c) Zotto,
C. D.; Michaux, J.; Zarate-Ruiz, A.; Gayon, E.; Virieux, D.; Campagne,
J.-M.; Terrasson, V.; Pieters, G.; Prim, D. J. Organomet. Chem. 2011,
696, 296.
ꢀ
(a) Czaplik, W. M.; Mayer, M.; Cvengros, J.; Wangelin, A. J. Chem-
€
SusChem 2009, 2, 396. (b) Sherry, B. D.; Furstner, A. Acc. Chem. Res.
2008, 41, 1500.
(8) Alcaide, B.; Almendros, P.; del Campo, T. M. Chem.;Eur.
J. 2008, 14, 7756.
r
10.1021/ol303021d
Published on Web 12/10/2012
2012 American Chemical Society

and hydroalkoxylation8 of alkenes, intermolecular hydro-
aryloxylation of alkynes,9 and tandem annulation reac-
tions of ketones and alkynes.10 Other iron salts, such as
iron toluenesulfonate and iron trifluoromethylsulfonate,
have also been reported as effective catalysts for the intra-
molecular hydroalkoxylation of unactivated alkenes,11 the
intermolecular hydroalkoxylation of styrene12 and the
hydrocarboxylation and hydroalkynylation of norbornene.13
Electrogenerated Fe3þ with a strong base can catalyze hetero-
cycle formation from electron-deficient alkynes and alco-
hols.14 Regioselective double hydrophosphination of arylace-
tylenes was catalyzed by CpFe(CO)2Me.15 Despite much
research into such reactions of alkynes and alkenes, reactivities
of Fe catalysts toward allenes remain less well studied.16 This
work reports the delicate reactivities of various iron salts in the
hydrofunctionalization of allenes, which have been interesting
substrates to control stereo- and regioselectivities.17
To examine the possibility of Fe-catalyzed reactions of
allenes, various Fe(III) catalysts were tested using cyclo-
pentyl substituted allenyl alcohol (1a) in hydroalkoxyla-
tion reactions. Iron trichloride and its hydrate catalysts
smoothly promoted cyclization to afford the oxacyclic
product (Table 1, entries 1 and 2). Using allenyl alcohol
1a treated with iron tribromide led to an unexpected
mixture of products isolated with a 1:2 ratio (entry 3).
Time-dependent TLC analysis showed that the reaction
first underwent a pathway for the formation of 2a, which
then disappeared with the concurrent appearance of 3a.
The Fe(III) catalyst was therefore presumed to activate the
allene moiety in starting material 1a as well as the alkene
moiety in cyclized product 2a. Double bond isomerization
to form the more thermodynamically favored product 3a
was driven at elevated temperature over longer reaction
durations.18 Activities toward specific CꢀC multiple
bonds, such as allenes and alkenes, could be achieved by
varying the solvent and reaction temperature. Reaction in
chlorobenzene at 60 °C afforded the cyclized product 3a
with high yield (entry 7); lower temperature (ꢀ40 °C)
suppressed isomerization, resulting a sole product 2a after
48 h (entry 9). However, the use of low temperature for
long reaction times was inefficient, and further examina-
tion of the effects of counterions was carried out. Iron(III)
trifluoroacetate catalyzed a mild reaction, which was
optimized at 30 °C to yield 2a as sole product within 10 h
(entry 11). Iron(III) toluenesulfonate catalyzed the forma-
tion of 3a as sole product at low temperatures and at
q80 °C (entry 14). Iron(III) trifluoromethylsulfonate led to
poor yields and decomposition of the reaction mixture
(entry 15). These propensities of iron salts depended on
their counterion; the weaker a basicity of anion is, the
stronger a Lewis acidity of iron catalyst is. Additional
ligands such as TMEDA and dppp depleted the activity of
FeCl3 6H2O catalyst, resulting in no reaction even after
3
3 days. The activity of acid catalysts, particularly trifluoro-
acetic acid and toluenesulfonic acid,19 which may be
unintentionally generated from the iron salts, was also checked
(entries 16 and 17): low conversion was observed under
corresponding conditions, suggesting that a simple acid-
catalyzed pathway did not greatly contribute to the reaction.
Table 1. Optimization of Hydroalkoxylation for
Tetrahydropyran Synthesisa
entry
cat.
FeCl3
solvent
temp (°C) yield (%)b 2a:3a
1
DCE
60
60
60
60
60
60
60
25
ꢀ40
0
60
75
45
14
54
63
80
68
95
60
91
93
58
89
73
38
31
58
0:1
0:1
1:2
1:0
2:1
1:1
0:1
8:1
1:0
1:0
1:0
5:1
0:1
0:1
0:1
1:5
1:0
0:1
2
FeCl3 6H2O
DCE
3
3
FeBr3
DCE
4
FeCl3 6H2O
THF
3
5
FeCl3 6H2O
MeCN
Benzene
PhCl
DCE
3
6
FeCl3 6H2O
3
7
FeCl3 6H2O
(9) Xu, X.; Liu, J.; Liang, L.; Li, H.; Li, Y. Adv. Synth. Catal. 2009,
351, 2599.
(10) Wang, Z.-Q.; Lei, Y.; Zhou, M.-B.; Chen, G.-X.; Song, R.-J.;
Xie, Y.-X.; Li, J.-H. Org. Lett. 2011, 13, 14.
(11) Komeyama, K.; Morimoto, T.; Nakayama, Y.; Takaki, K.
Tetrahedron Lett. 2007, 48, 3259.
(12) Ke, F.; Li, Z.; Xiang, H.; Zhou, X. Tetrahedron Lett. 2011, 52,
318.
(13) (a) Choi, J.-C.; Kohno, K.; Masuda, D.; Yasuda, H.; Sakakura,
T. Chem. Commun. 2008, 777. (b) Kohno, K.; Nakagawa, K.; Yahagi,
T.; Choi, J.-C.; Yasuda, H.; Sakakura, T. J. Am. Chem. Soc. 2009, 131,
2784.
(14) Li, C.-H.; Yuan, G.-Q.; Zheng, J.-H.; He, Z.-J.; Qi, C.-R.; Jiang,
H.-F. Tetrahedron 2011, 67, 4202.
(15) Kamitani, M.; Itazaki, M.; Tamiya, C.; Nakazawa, H. J. Am.
3
8
FeCl3 6H2O
3
9c
10
11
12
13
14
15d
16
17e
18e
FeCl3 6H2O DCE
3
Fe(TFA)3
Fe(TFA)3
Fe(TFA)3
Fe(OTs)3
Fe(OTs)3
Fe(OTs)3
Fe(OTf)3
TFAd
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
30
40
0
80
80
60
30
80
TsOHd
a Reactions and conditions: allenyl alcohol (0.25 mmol), catalyst
(5 mol %), solvent (0.2 M) for 10 h under N2, unless otherwise specified.
b Isolated yield after chromatographic purification. c Reaction for 48 h.
d 3 mol % of catalyst was used. e 15 mol % of acid catalyst was used.
Chem. Soc. 2012, 134, 11932.
(16) For Fe(CO)n-catalyzed reactions of allenes, see: (a) Lennon, P.;
Rosan, A. M.; Rosenblum, M. J. Am. Chem. Soc. 1977, 99, 8426. (b)
Sigman, M. S.; Eaton, B. E. J. Org. Chem. 1994, 59, 7488. (c) Oulie, P.;
Altes, L.; Milosevic, S.; Bouteille, R.; Muller-Bunz, H.; McGlinchey,
ꢁ
M. J. Organometallics 2010, 29, 676.
(17) For selected reviews on hydrofunctionalization of allenes, see:
(a) Bates, R. W.; Satcharoen, V. Chem. Soc. Rev. 2002, 31, 12. (b) Ma, S.
Aldrichimica Acta 2007, 40, 91. (c) Alcaide, B.; Almendros, P. Adv.
Synth. Catal. 2011, 353, 2561. (d) Krause, N.; Winter, C. Chem. Rev.
2011, 111, 1994.
A range of substrates was evaluated in two standard
cyclizations using Fe(TFA)3 and Fe(OTs)3 catalysts in
(18) For Fe(CO)n-catalyzed isomerization of alkenes, see: (a) Whetton,
R. L.; Fu, K.-J.; Grant, E. R. J. Am. Chem. Soc. 1982, 104, 4270. (b) Long,
G. T.; Weitz, E. J. Am. Chem. Soc. 2000, 122, 1431.
(19) (a) Li, Z.; Zhang, J.; Brouwer, C.; Yang, C.-G.; Reich, N. W.;
He, C. Org. Lett. 2006, 8, 4175. (b) Rosenfeld, D. C.; Shekhar, S.;
Takemiya, A.; Utsunomiya, M.; Hartwig, J. F. Org. Lett. 2006, 8, 4179.
Org. Lett., Vol. 14, No. 24, 2012
6263

dichloroethane (DCE) (Table 2). The required allenyl
alcohols were prepared by allene formation reactions using
tetrahydropyranyloxy alkynols and lithium aluminum
hydride. Trialkyl substituted allenes 1a,b were hydroalk-
oxylated to afford the corresponding tetrahydropyrans 2a,
b and their isomers 3a,b in high yields. Dimethyl substi-
tuted allene 1c was transformed to 2c in 92% yield; double-
bond isomerization to generate a terminal olefin did not
occur, even at high temperature. The presence of alcohol
(1d) and benzoate (1e) was permitted in the reaction, but
these oxygen functional groups led to longer reaction time
(20 h). The reaction of allenol 1f, which has aryl and alkyl
substituents, resulted in the formation of only (E)-styryl
tetrahydropyran 2f in 85% yield.
good yields. 1H NMR analysis of the isolated tetrahydro-
pyrans showed the exclusive formation of cis-disubstituted
products, except 2j, which led to a 1:1 diastereomeric ratio.
Sterically unhindered allenols 1g and 1j were converted
more effectively into the corresponding tetrahydropyrans
rather than 1h and 1i. Allenols were recovered from the
reactions of 1h and 1i and were found to be contaminated
withsmall amountsofthe corresponding dienes, indicating
that the lower susceptibilities to cyclization may have pro-
moted isomerization of the allenes to dienes with endo-
methylene. The reactions of 1gꢀj catalyzed by Fe(OTs)3
provided 3gꢀj in high yields (79ꢀ96%).
These hydroalkoxylation results prompted assessment
of allenes’ Fe(III)-catalyzed hydroamination (Scheme 1).
Using Fe(OTf)3 in chlorobenzene at 10 °C afforded piper-
idine 5 inthe best selectivity and yield.21 Unlike the mixture
of 2 and 3, in which each isomer’s slightly different pola-
rity made them distinguishable in TLC analysis, 5 and its
isomer were not separately identifiable by TLC analysis.
Trialkyl substituted allenes 4aꢀc reacted smoothly under
the tested conditions; dialkyl or alkyl aryl substituted
allenes 4d,e required elevated temperatures to afford the
corresponding piperidines at slow rates. Diphenyl substi-
tuted allene 4f reacted more quickly and with greater
selectivity in DCE over 12 h, possibly due to the Thorpeꢀ
Ingold effect.22
Table 2. Selected Hydroalkoxylation Reactionsa
Scheme 1. Fe(OTf)3-Catalyzed Hydroaminationa
a Reactions and conditions: allenyl amide (0.25 mmol), catalyst
(5 mol %), PhCl (0.2 M) for 48 h under N2, unless otherwise specified.
Isolated yield. bRatio of exo and endo double bond. cReaction at 130 °C
for 72 h, resulting with recovered 4d (38%). dReaction at 80 °C for 72 h,
resulting with decomposedproducts. eReaction in DCE at 25 °C for 12 h.
a Reactions and conditions: allenyl alcohol (0.25 mmol), catalyst
(5 mol %), DCE (0.2 M) for 10 h under N2, unless otherwise specified.
b Isolated yield after chromatographic purification (s.m. recovered yield
in parentheses). c Reaction with Fe(OTs)3 for 20 h. d Reaction with
10 mol % of catalyst.
Overall, the observed results show that Fe(III) catalysts
were important in the activation of the allene functional
group for cyclization and the alkene functional group for
isomerization. Isomerization pathways in the presence of
Fe catalysts were further tested by reacting isolated 2b and
Incomparison, dialkylatedormonoalkylatedallenol did
not undergo cyclization.20 Secondary alcohols 1gꢀj also
underwent hydroalkoxylation resulting in moderate to
(21) Modifying other protecting groups (Ph, Bn, and Boc) proved
unsuccessful, except the reaction with ethyl carbamate derivatives. See
Tables S1 and S2 in the Supporting Information.
(20) The structures of unsuccessful allene substrates are given in the
Supporting Information.
(22) Liu, G.-Q.; Li, W.; Wang, Y.-M.; Ding, Z.-Y.; Li, Y.-M.
Tetrahedron Lett. 2012, 53, 4393.
6264
Org. Lett., Vol. 14, No. 24, 2012

Scheme 2. Double Bond Isomerization and
Hydrofunctionalization of Dienes
Scheme 3. Mechanism for Fe-Catalyzed Reactions of Allenes
than that of 3b, and 2b underwent olefin isomerization to
afford 3b during a longer reaction.
Overall, these results suggest the mechanism for the
Fe-catalyzed reactions of allenes shown in Scheme 3.
Hydrofunctionalization involved traditional coordina-
tion, nucleophilic addition and proto-demetalation, simi-
lar to previous observations of allenes in reactions. The
cyclized product can then undergo isomerization depend-
ing on the Fe(III) catalyst and reaction conditions. For the
cyclization reactions of dienes, dieneꢀiron complexes may
lead to cycloisomerization products.25
In conclusion, a highly efficient catalytic system is pre-
sented for the hydrofunctionalization of allenyl alcohols
and amides. Fe(III) salts, FeCl3, Fe(TFA)3, Fe(OTs)3 and
Fe(OTf)3, allowed efficient cycloisomerization reactions
under mild conditions. They are inexpensive and naturally
abundant, which lendstotheir wide industrial applicability
for such reactions. Further study of Fe-catalyzed cyclo-
isomerization using various accumulated multiple bond
systems is underway.
5b separately in the presence of Fe(OTs)3 or Fe(OTf)3
(5 mol %) in DCE (Scheme 2, eq 1 and 2); double bond
isomerization from exo-methylene to endo-methylene
occurred in high yield. However, an alternative route for
the direct transformation of 1b to 3b is also possible:
isomerization of allenes to dienes followed by the hydro-
functionalization of corresponding dienes.23,24 Therefore,
the hydroalkoxylation of diene 7 was examined in the
presence of the Fe(OTs)3 in DCE at room temperature
(eq 3). After 6 h, a mixture of unreacted diene 7 (59%) and
exo-methylene product 2b (41%) was observed, whereas
the reaction at 80 °C afforded 3b as a major product with a
small amount of 7 and 2b. The hydroamination of diene 8
also afforded a mixture of exo-methylene product 5b
(19%) and endo-methylene product 6b (45%). If diene 7
or 8 hydrofunctionalized through alkene activation by the
Fe catalyst without any function of conjugated diene
system, 3b or 6b would be expected as sole products.
However, the initial rate of formation of 2b was faster
Acknowledgment. This study was supported by the
National Research Foundation Grant funded by the Min-
istry of Education, Science and Technology (2011-0003298
and 2011-0004015).
Supporting Information Available. Detailed experimen-
tal procedures and characterization of all new com-
pounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
(23) For iron-catalyzed reactions of dienes, see: (a) Wu, J. Y.;
Moreau, B.; Ritter, T. J. Am. Chem. Soc. 2009, 131, 12915. (b) Moreau,
ꢁ ꢂ
ꢁ
B.; Wu, J. Y.; Ritter, T. Org. Lett. 2009, 11, 337. (c) Denes, F.; Perez-
Luna, A.; Chemla, F. Chem. Rev. 2010, 110, 2366.
(25) Trace amounts of dienes were observed after longer and hotter
reactions, suggesting that the isomerization of allenes to dienes pro-
ceeded slowly.
(24) For hydrofunctionalization reactions of dienyl alcohols, see: (a)
Kanno, O.; Kuriyama, W.; Wang, Z. J.; Toste, F. D. Angew. Chem., Int.
Ed. 2011, 50, 9919. (b) Chandrasekhar, B.; Ryu, J.-S. Tetrahedron 2012,
68, 4805. (c) Yamamoto, H.; Sasaki, I.; Shiomi, S.; Yamasaki, N.;
Imagawa, H. Org. Lett. 2012, 14, 2266.
The authors declare no competing financial interest.
Org. Lett., Vol. 14, No. 24, 2012
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