Iron in the service of chromium: The ortho-benzannulation of trans,trans-dienyl Fischer carbene complexes

Article abstract of DOI:10.1021/ja0540268

Chromium Fischer carbene complexes with trans,trans-dienyl substituents on the carbene carbon will react with diiron nonacarbonyl to give 2-alkoxycyclohexa-2,4-dienone iron tricarbonyl complexes and/or 2-alkoxyphenols in excellent yields. In the presence

Full text of DOI:10.1021/ja0540268

Published on Web 11/17/2005
Iron in the Service of Chromium: The ortho-Benzannulation of
trans,trans-Dienyl Fischer Carbene Complexes
Yiqian Lian and William D. Wulff*
Department of Chemistry, Michigan State UniVersity, East Lansing, Michigan 48824
Received June 17, 2005; E-mail: wulff@chemistry.msu.edu
Scheme 2
The synthesis of o-alkoxyphenols by the photoinduced CO inser-
tion and cyclization (ortho-benzannulation) of dienyl Fischer car-
bene complexes was originally reported from our laboratories1 and
later improved by Merlic and co-workers (Scheme 1).2 This reaction
has been explored and developed as a synthetic method and has
been utilized in the total synthesis of Carbazoquinocin C,3 a member
of a family of compounds possessing neuronal cell protecting activ-
ity, and in the total synthesis of Calphostins A-D, inhibitors of pro-
tein kinase C.4 The reaction requires that the R,â-double bond in 1
has a cis-disposition of the carbene complex and the second double
bond. As a consequence of synthetic expediency, most of the com-
plexes of the type 1 that have been examined either have the R,â-
unsaturated double bond incorporated into an aryl ring or were those
that could be directly prepared from a [4 + 2] or [2 + 2] cycloaddi-
tion onto the alkyne function of an enynyl carbene complex. In a
few rare cases where the substituents R1 and R2 were embedded into
a strained four-membered ring, the formation of o-alkoxyphenols
from complex 1 could be induced thermally.5 The corresponding car-
bonylative cyclization of trans,trans-dienyl complex 2 to o-alkoxy-
phenols is not known and has been reported to fail under photo-
chemical conditions.2
Sources of iron tricarbonyl that were successful include diiron
nonacarbonyl and benzylidene acetone iron tricarbonyl, both of
which were superior to triirondodecacarbonyl. It was of interest to
note that the yields of 5a and 7a were only slightly better under a
carbon monoxide atmosphere than under argon (Table 1). The best
solvent for this reaction was THF, which gave an 81% total yield
of 5a and 7a. The dienone complex 5a could be converted to the
o-methoxyphenol 7a in 91% yield upon stirring in Et3N/H2O at
room temperature for 5 h. The control reaction under argon without
a source of iron does produce a small amount of 7a (8% yield) but
only after 144 h. After 144 h under a CO atmosphere, a 70%
recovery of 4a is obtained, and only trace of 7a is observed. Clearly,
iron is playing the key role in this carbonylative cyclization.
Scheme 1
Table 1. Optimization with Added Iron Tricarbonyl Sources
additive
solvent
benzene
benzene
heptane
THF
CO/Ar
time, h
5a, % yield
7a, % yield
CO
Ar
CO
Ar
CO
Ar
CO
Ar
144
144
18
28
36
20
36
20
17
20
48
<0.5a
8
8
6
7
70
58
68
54
61
50
68
34
60
Fe2(CO)9
Fe2(CO)9
Fe2(CO)9
5
20
10
12
8
In the course of a control experiment for a cyclopropanation reac-
tion, we had occasion to heat the trans,trans-pentadienyl carbene
complex 4a in benzene at 80 °C under 500 psi of carbon monoxide
(Scheme 2). As expected, the pentaene 6a resulting from dimerization
of the carbene ligand was observed,6 but what was most certainly
not expected was the η4-dienyl iron complex 5a. The structure of this
product was determined by its NMR spectra, X-ray diffraction analy-
sis, mass spectra, and the presence of iron was confirmed by SEM/
EDS. The reaction was performed in a Monel Paar reactor which is
composed of 65% nickel, 33% copper, and only 2% iron and did not
look corroded. The mechanical stirrer, on the other hand, appeared
to be quite corroded and was suspected to be the source of iron.
With the mass of the stirrer rapidly diminishing, we decided to
pursue other sources of iron for this reaction. In addition, for the
purpose of convenience and to be able to maintain rigorous control
over the source of iron, conditions were sought where the reaction
could be carried out in glass under 1 atm of carbon monoxide.
CO
Ar
CO
Fe2(CO)9
Fe(CO)3(ba)b
CH3CN
benzene
7
a With 70% recovery of 4a. b Benzylideneacetone iron tricarbonyl.
In an effort to explore the scope of this reaction, a number of
different trans,trans-dienyl carbene complexes were investigated,
all of which (except 4d) were directly prepared by an aldol reaction
of the methyl carbene complex 8 with unsaturated aldehydes and
ketones (Scheme 3).7,8 For many of the substrates, THF was the
optimal solvent, and cyclization gave high to excellent yields of
dienone iron tricarbonyl complexes and/or o-methoxyphenols (Table
2). The dienone complexes could be converted to their correspond-
ing phenols by treatment with base (7a, Table 1) or by stirring
with silica gel in the presence of air (7b, Table 2). In all cases, only
a single diastereomer of the dienone iron tricarbonyl complex was
formed, and the stereochemistry of each was assigned as syn based
9
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J. AM. CHEM. SOC. 2005, 127, 17162-17163
10.1021/ja0540268 CCC: $30.25 © 2005 American Chemical Society

C O M M U N I C A T I O N S
Scheme 3
Scheme 4
Table 2. Iron-Mediated Reactions of Dienyl Fischer Carbene
Complexesa
went spontaneous cyclization to give the cyclopentadiene 14 since
the cyclopentenone 15 was isolated from the reaction.9 In contrast,
the trans,trans-4d complex is stable and, upon treatment with Fe2-
(CO)9 at 80 °C, gave an 87% yield of 5d and 7d (Table 2).
How does this iron-assisted conversion of the dienyl chromium
carbene complexes to o-alkoxyphenols occur? In the only related
chemistry, thermolysis of 16 gives the dienone complex 17, demon-
strating that a likely iron carbene complexed intermediate can insert
CO and cyclize to a dienone (Scheme 4).10 With regard to how the
organic fragment is transferred from chromium to iron, the two
most likely possibilities are that the iron tricarbonyl unit becomes
complexed to the dienyl unit in 4 followed by loss of chromium or
there is a direct trans-metalation to give an iron carbene complex
which then undergoes internal coordination to the diene in some
fashion such that the R,â-trans-double bond is isomerized. The
transfer of the carbene ligand from chromium Fischer carbene
complexes to other metals is an active area of interest and, if it
occurs here, would be the first example to iron.6 Mechanistic and
further synthetic studies will be reported in due course.
Acknowledgment. This work was supported by the NIH (GM
33589). We acknowledge the Center for Advanced Microscopy at
MSU and Xiuni Wu for assistance with the SEM/EDS experiment.
We thank Rui Huang for the X-ray structure of 5a.
Note Added after ASAP Publication. After this paper was
published ASAP on November 17, 2005, structure 7e in Table 2
was corrected. The corrected version was published ASAP on
November 21, 2005.
Supporting Information Available: Experimental procedures and
spectral data for all new compounds including X-ray diffraction and
SEM/EDS data for 5a. This material is available free of charge via the
Internet at http://pubs.acs.org.
References
(1) Wulff, W. D. In AdVances in Metal-Organic Chemistry; Liebeskind, L.
S., Ed.; JAI Press: Greenwich, CT, 1989; Vol. 1, p 336.
(2) Merlic, C. A.; Xu, D. J. Am. Chem. Soc. 1991, 113, 7418.
(3) Rawat, M.; Wulff, W. D. Org. Lett. 2004, 6, 329.
(4) Merlic, C. A.; Aldrich, C. C.; Albaneze-Walker, J.; Saghatelian, A.;
a Unless otherwise specified, all reactions were carried out in THF at 80
°C with 1 equiv of Fe2(CO)9 under 1 atm of CO at 0.02 M in 4. b Yields
in parentheses are based on unrecovered starting material. c The crude
reaction mixture was stirred with silica gel for 2-3 days. d In benzene.
Mammen, J. J. Org. Chem. 2001, 66, 1297.
(5) Barluenga, J.; Aznar, F.; Palomero, M. A. J. Org. Chem. 2003, 68, 537.
(6) Gomez-Gallego, M.; Mancheno, M. J.; Sierra, M. A. Acc. Chem. Res.
2005, 38, 44 and references therein.
(7) Wang, H.; Hsung, R. P.; Wulff, W. D. Tetrahedron Lett. 1998, 39, 1849.
(8) Aumann, R.; Heinen, H. Chem. Ber. 1987, 120, 537.
(9) For related examples, see citations listed in ref 5.
(10) Franck-Neumann, M.; Geoffroy, P.; Winling, A. Synlett 1995, 341.
on the X-ray structure of 5a. The reaction can also be used to gener-
ate a spiro-cyclohexadienone iron tricarbonyl complex (5g, 85%).
Attempts were made to generate the cis,trans-dienyl complex
4d from cis,trans-dienyl iodide 10d; however, cis,trans-4d under-
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