(1-Alkynyl)dicarbonylcyclopentadienyliron complexes as electron-rich alkynes in organic synthesis: BF3-mediated [2+2] cycloaddition/ring- opening providing (2-alkenyl-1-imino)iron complexes

Article abstract of DOI:10.1002/chem.201100669

Strike while the iron is hot! A BF₃-mediated formal [2+2] cycloaddition between (1-alkynyl)iron complexes and aromatic aldehyde imines occurs, which is followed by ring-opening of the initially formed azacyclobutenes to yield (2-alkenyl-1-imino)iron complexes (see scheme). The resulting iron complexes undergo deferric substitution reactions with water under oxidative conditions to afford the corresponding cinnamamides with high E selectivity.

Full text of DOI:10.1002/chem.201100669

COMMUNICATION
DOI: 10.1002/chem.201100669
(1-Alkynyl)dicarbonylcyclopentadienyliron Complexes as Electron-Rich
Alkynes in Organic Synthesis: BF3-Mediated [2+2] Cycloaddition/Ring-
Opening Providing (2-Alkenyl-1-imino)iron Complexes
Ryotaro Nakaya,[a, b] Shigeo Yasuda,[b] Hideki Yorimitsu,*[a] and Koichiro Oshima*[b, c]
Formal stepwise [2+2] cycloadditions between alkynes
and alkenes are useful for the synthesis of functionalized cy-
clobutenes.[1] Among them, combinations of electron-rich al-
kynes and electron-deficient double bonds are rather rare
because of the limited repertoire of electron-rich alkynes.
One can employ heteroatom-substituted alkynes such as
ynamides[2] and 1-alkynyl ethers,[3] sulfides,[4] and selenides[5]
or their vinylogous and phenylogous analogues. To increase
the variety of the cycloaddition, new families of electron-
rich alkynes need to be uncovered.
Iron is an exceptionally ubiquitous and safe transition-
metal and has been attracting much attention. Because of
the inherent cost efficiency of iron, development of new re-
actions by using organoiron reagents is an interesting chal-
lenge.[6] We have been interested in the unusual reactivity of
kenes such as tetracyanoethylene. Organometallic chemists
have been interested only in the basic reactivity of the alky-
nylmetal complexes; however, no applications to organic
synthesis have been reported so far.
Attempted reactions of dicarbonylcyclopentadienyl(phe-
nylethynyl)iron (1a) with a variety of electron-deficient
carbon–carbon double bonds resulted in failure. No thermal
reactions took place in the absence of any Lewis acids and
complex mixtures were obtained in the presence of the
Lewis acids. However, the reaction of 1a with N-phenylben-
zaldehyde imine (2a) occurred with the aid of an equimolar
amount of BF3·OEt2 to yield the unexpected adduct 3a in
43% yield (Scheme 1). The reaction proceeds through a
BF3-mediated formal [2+2] cycloaddition reaction followed
by ring-opening of the resulting azacyclobutenes.[14,15]
aryldicarbonylcyclopentadienyliron
complexes
[CpFe(-
CO)2Ar] (CpFe(CO)2 is abbreviated as Fp hereafter) and
developed several useful reactions with FpAr in organic syn-
thesis.[7] Along this line, we have developed an efficient
ꢀ À
method for the synthesis of the alkynyl analogues FpACTHNUTRGNEUNG(C C
R) by Sonogashira-type cross-coupling reactions of FpI with
terminal alkynes.[8]
ꢀ À
With FpACHTUNGTRENNUNG(C C R) in hand, we report herein the use of the
alkynyliron complexes as electron-rich alkynes in stepwise
[2+2] cycloaddition reactions for organic synthesis. Such al-
kynyliron complexes[9] and their Ru,[10] W,[9b,c,11] Mn,[9b,c,12]
and Ni[9b,13] analogues are known to undergo thermal step-
wise [2+2] cycloaddition reactions with highly activated al-
[a] R. Nakaya, Prof. Dr. H. Yorimitsu
Department of Chemistry, Graduate School of Science,
Kyoto University, Kitashirakawa
Scheme 1. BF3-Mediated addition of N-phenylbenzaldehyde imine (2a)
to phenylethynyliron 1a followed by ring-opening.
Sakyo-ku, Kyoto 606-8502 (Japan)
Fax : (+81)75-753-3970
E-mail: yori@kuchem.kyoto-u.ac.jp
The use of a larger amount of BF3·OEt2 (2.2 equiv) in-
creased the yield of 3a to 51% (Scheme 1). The reaction
did not proceed in a catalytic fashion; the reaction in the
presence of 10 mol% of BF3·OEt2 provided 3a in 7% yield.
BF3·OEt2 was the best Lewis acid among those tested; AlCl3
could promote the addition reaction much less efficiently to
give 3a in 21% yield and other Lewis acids such as TiCl4,
ZnCl2, MgBr2, FeCl3, and SnCl4 failed to promote the reac-
tion efficiently.
[b] R. Nakaya, Dr. S. Yasuda, Prof. Dr. K. Oshima
Department of Material Chemistry, Graduate School of Engineering
Kyoto University, Kyoto-daigaku Katsura
Nishikyo-ku, Kyoto 615-8510 (Japan)
[c] Prof. Dr. K. Oshima
Environment, Safety, and Health Organization
Kyoto University, Yoshida
Sakyo-ku, Kyoto 606-8501 (Japan)
Fax : (+81)75-753-7710
E-mail: oshima@orgrxn.mbox.media.kyoto-u.ac.jp
The substituent on the nitrogen proved to have a signifi-
cant influence on the efficiency of the reaction (Table 1).
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201100669.
Chem. Eur. J. 2011, 17, 8559 – 8561
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
8559

Table 1. Effect of the aryl group on the nitrogen and influence on the ef-
ficiency of the reaction.
alkyne termini of 1 is not influential (Table 2, entries 9–11).
However, tert-butyl-substituted 1e was less reactive proba-
bly due to steric reasons (Table 2, entry 12). The reactions
always proceeded with exclusive E selectivity, which was un-
ambiguously determined by X-ray crystallographic analysis
(see the Supporting Information). We assume that the steric
congestion around the nitrogen in the azacyclobutene skele-
ton would control the rotational direction of the ring-open-
ing (Scheme 1).
Acyliron complexes such as RCOFp are known to be con-
verted to the corresponding ester with substitution of the Fp
moiety upon treatment with N-bromosuccinimide (NBS) at
08C in an alcoholic solvent.[16] We attempted to apply this
protocol to the deferric hydrolysis of 3 in an aqueous
medium because (E)-a-arylcinnamamides are difficult to
synthesize in a stereoselective fashion.[17] Although our ini-
tial attempts indeed afforded the corresponding amide, the
hydrolysis occurred with isomerization of the double bond,
which highlighted the difficulty of synthesizing the desired
product stereoselectively. After screening of the reaction
conditions, we eventually found an optimum reaction tem-
perature and a suitable reaction medium that allowed the
hydrolysis to occur without isomerization. Specifically, treat-
ment of iron complexes 3 with NBS (3 equiv) in aqueous
THF at À408C for 12 h yielded the corresponding cinnama-
mides with retention of the stereochemistry (Table 3). A va-
riety of highly arylated a,b-unsaturated amides 4 were ob-
tained in high yields, whereas the oxidative hydrolysis of 4-
methoxyphenylimino-substituted 3b competed with oxida-
tion of the electron-rich aromatic ring to yield 4b in moder-
ate yield.
Entry
R
2
3
Yield
[%]
1
2
3
4
5
6
7
Ph
2a
2b
2c
2d
2e
2 f
2g
3a
3b
3c
3d
3e
3 f
3g
51
67
96
<5
<5
<5
<5
4-MeOC6H4
4-CF3C6H4
MeO
PhNH
Ts
n-C6H13
Aromatic substituents are essential to obtain (2-alkenyl-1-
imino)iron complexes 3 in reasonable yields (Table 1, en-
tries 1–3). In particular, imine 2c (with a 4-trifluoromethyl-
phenyl group) was found to be the best substrate and was
converted to 3c in 96% yield. The reactions of oxime ether
2d and hydrazone 2e afforded very complex mixtures
(Table 1, entries 4 and 5). The reactions of tosylimine 2 f
and alkylimine 2g yielded mixtures of several unidentified
compounds (Table 1, entries 6 and 7).
A variety of aromatic aldimines can also participate in the
reaction (Table 2, entries 1–8). The reactions of electron-de-
Table 2. Scope of the reaction.
Table 3. Oxidative hydrolysis of 3 yielding cinnamamides.
Entry
R1
1
R2
2
3
Yield
[%]
1
2
3
4
5
6
7
8
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
1a
1a
1a
1a
1a
1a
1a
1a
1b
1c
1d
1e
4-MeOC6H4
4-CF3C6H4
4-FC6H4
4-ClC6H4
4-BrC6H4
4-MeO2CC6H4
4-TBSOC6H4
2-MeC6H4
Ph
2h
2i
2j
2k
2l
2m
2n
2o
2c
2c
2c
2c
3h
3i
3j
3k
3l
3m
3n
3o
3p
3q
3r
3s
91
88
93
85
91
75
50
82
73
77
72
26
Entry
3
Ar1
Ph
Ar2
Ph
Ar3
4
Yield
[%]
1
2
3
4
5
6
7
8
3a
3b
3c
3h
3i
Ph
Ph
Ph
Ph
Ph
4a
4b
4c
4h
4i
84
50
72
99
74
4-MeOC6H4 Ph
4-CF3C6H4
4-CF3C6H4
4-CF3C6H4
Ph
4-MeOC6H4
4-CF3C6H4
4-MeO2CC6H4 Ph
Ph
Ph
9
4-MeOC6H4
4-CF3C6H4
nBu
10
11
12
Ph
Ph
Ph
3m 4-CF3C6H4
3p
3q
4m 70
4-CF3C6H4
4-CF3C6H4
4-MeOC6H4 4p
4-CF3C6H4 4q
86
83
tBu
ficient imines 2i and 2m were slightly less efficient yet satis-
factory. The ester moiety of 2m was compatible with the re-
action. The tert-butyldimethylsilyl (TBS) protecting group of
2n remained intact under the reaction conditions. However,
the conversion of 2n and the yield of 3n were moderate be-
cause of the rapid consumption of 1a. The methyl group of
2o did not retard the reaction. Unfortunately, the reactions
of aliphatic aldimines prepared from aliphatic aldehydes
yielded complex mixtures. The electronic nature of the
In summary, we have developed a synthetically useful
ꢀ À
transformation of FpACTHNUGRTENUNG(C C R) complexes as electron-rich
alkynes. Specifically, boron trifluoride mediates the addition
of aromatic aldehyde imines to the alkynylirons with cleav-
age of the carbon–nitrogen double bond of the imine to
afford (2-alkenyl-1-imino)irons. The products are useful pre-
cursors of (E)-a-arylcinnamamides through deferric hydrol-
ysis.
8560
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(1-Alkynyl)dicarbonylcyclopentadienylirons as Electron-Rich Alkynes
COMMUNICATION
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chloromethane (1.0 mL) solution of [CpFe(CO)
(C CPh)] (1a, 139 mg,
0.50 mmol) and N-(4-trifluoromethylphenyl)benzaldehyde imine (2c,
137 mg, 0.55 mmol) was placed in a 20 mL reaction flask under argon.
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the same temperature. Saturated aqueous NaHCO3 was then added to
the mixture. The product was extracted with ethyl acetate (3ꢁ20 mL).
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Acknowledgements
This work was supported by Grants-in-Aid for Scientific Research and
GCOE Research from JSPS. S.Y. acknowledges JSPS for financial sup-
port. H.Y. thanks financial support from The Kurata Memorial Hitachi
Science and Technology Foundation and the Mizuho Foundation for the
Promotion of Sciences.
Keywords: amides · cleavage reactions · cycloaddition ·
iron · schiff bases
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Received: March 3, 2011
Published online: June 21, 2011
Chem. Eur. J. 2011, 17, 8559 – 8561
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
8561