The first examples of a Meta-benzannulation from the reaction of Fischer carbene complexes with alkynes

Article abstract of DOI:10.1021/ja035428n

The intramolecular benzannulations of carbene complexes with alkynes are examined where the alkyne is tethered to the α-carbon of the vinyl carbene complex. These reactions are sensitive to the length of the tether and to the nature of the solvent. With a tether length of 16 methylenes, the reaction occurs in the same fashion as the intermolecular reactions to give a p-cyclophane. With intermediate tether lengths (n = 10, 13), the reaction gives an additional p-cyclophane in which the two oxygen substituents are meta on the arene ring. This type of product is unprecedented from the reaction of carbene complexes and alkynes and is quite surprising because the formation of this product requires that the carbon-carbon bond between the α- and β-carbons of the vinyl carbene complex is broken. A mechanism is proposed to account for this process which involves the crossed intramolecular [2 + 2] cycloaddition of the alkene and a ketene in a conjugated dienyl ketene to give a benzvalenone paddalane intermediate. Copyright

Full text of DOI:10.1021/ja035428n

Published on Web 07/02/2003
The First Examples of a Meta-Benzannulation from the Reaction of Fischer
Carbene Complexes with Alkynes
Huan Wang,† Jie Huang,† William D. Wulff,*,† and Arnold L. Rheingold‡
Department of Chemistry, Michigan State UniVersity, East Lansing, Michigan 48824, and Department of Chemistry,
The UniVersity of Delaware, Newark, Delaware 19716
Received April 2, 2003; E-mail: wulff@cem.msu.edu
Scheme 1
The benzannulation reaction of Fischer carbene complexes with
alkynes to give p-alkoxy phenols was first reported by Do¨tz1 and
has become one of the most synthetically valuable methods for the
synthesis of phenols and quinones.2 At first glance, it would appear
highly improbable that the reaction of a Fischer carbene complex
with an alkyne could give rise to a m-alkoxy phenol because this
would require the breaking of either the carbon-carbon bond of
the alkenyl substituent of the carbene complex (to give phenol 4)
or the carbon-carbon bond of the alkyne (to give phenol 5). Herein,
we describe the discovery of a unique pathway that can occur in
the reaction of Fischer carbene complexes with alkynes which
results in the formation of phenols of the type 4 in a process that
involves the breaking of the carbon-carbon bond connecting
substituents R1 and R2 of the carbene complex (Scheme 1).
In our ongoing studies of the intramolecular reactions of Fischer
carbene complexes with alkynes,3 we had envisioned the possibility
of preparing p-cyclophanes from the alkenyl carbene complex 6
which had an alkyne tethered to the R-position of the alkenyl
substituent. Contrary to expectation, this reaction in fact was found
to give the m-cyclophane 8 in addition to the bicyclohexenone 9.3b
The bicyclohexenone 9b could be isomerized to the m-cyclophane
8b in the presence of acid, but it was not clear if the m-cyclophane
8b was a secondary product or could be formed by some other
mechanism.
Table 1. Macrocyclizations of Complexes 6a
total
yield 7 yield 10 yield 8 yield 9 yield 11 yield
Intermolecular reactions of carbene complexes with alkynes are
sensitive to the nature of the reaction solvent,2,4 and thus it should
have not been astonishing that the intramolecular reaction would
also show the same dependence. Nonetheless, the outcome of the
intramolecular reaction of 6b in benzene was a bona fide surprise.
Not only was the originally anticipated p-cyclophane 7b the major
product of the reaction, but the reaction also produced the
completely unprecedented meta-substituted methoxy phenol 10b.
The structure of this aberrant product was confirmed by X-ray
analysis of a single crystal to have a meta-orientation of the oxygen
substituents.
entry series
n
solvent
THF
benzene
1
2
a
a
b
b
b
b
b
c
c
d
d
6
6
36
28
8
49b
37c
69
57
51
59
73
72
58
69
59
3
4
10 THF
4
17
22
22
40
5
Tr
15
24
42
11
10 CH3CN
10 CH2Cl2
10 hexane
10 benzene
13 THF
13 benzene
16 THF
16 benzene
5
5
6
17
29
21
2
<2
12
8
7
8
Tr
16
12
10
26
10
9
38
2
9
10
11
14
56
48
18
1
2
A more extensive investigation of the effect of solvent and tether
length on these reactions was undertaken, and the results are
presented in Table 1. For tether lengths of six methylenes, only
the 6,6-p-cyclophane 11a and corresponding 6,6,6-p-cyclophanes
(not shown) are observed. Several different solvents were examined
for the complex with 10 methylenes, and it was found that
coordinating solvents favor the pair of products 8b and 9b, whereas
noncoordinating solvents favor the product pair 7b and 10b (Scheme
2). This solvent dependence persists as the tether length is increased
to 13, but it disappears for the complex 6d with 16 methylenes in
the spacer where it was found that THF and benzene give essentially
the same product distribution.
a Reaction performed at 0.002 M at 100 °C for 12 h under argon. b A
13% yield of trimer was also isolated. c A 9% yield of trimer was also
isolated.
The mechanism of the reaction of Fischer carbene complexes
with alkynes is thought to begin with the formation of an η1,η3-
vinyl carbene complexed intermediate.2,5 This species is formed
with the regioselective incorporation of the alkyne such that the
larger substituent occurs at the end carbon as is the case in
intermediate 12 in Scheme 3. A migratory insertion of a carbon
monoxide ligand with concomitant coordination of the vinyl
substituent of the original carbene complex to the metal center gives
the 18 e- η6-dienyl ketene complex 13. The final two steps are the
electrocyclic ring closure of the ketene complex to give the
cyclohexadienone 16 followed by tautomerization to the phenol 7.
† Michigan State University.
‡ The University of Delaware.
9
8980
J. AM. CHEM. SOC. 2003, 125, 8980-8981
10.1021/ja035428n CCC: $25.00 © 2003 American Chemical Society

C O MMU N I C A T I O N S
Scheme 2
case here, where the olefin is in conjugation with the vinyl ketene
complex.6 The benzvalenone intermediate 18 should be activated
toward ring-opening by protonation or perhaps by a Lewis acidic
chromium species.6b The resulting cation would be expected to be
nonclassical and have significant contributions from the cyclobutyl
cation 19 and the cyclopropyl carbinyl cations 20 and 21. Cleavage
of the internal cyclopropane bond in intermediate 21 would give
the cyclohexadienyl cation 23 that could lose a proton to give the
cyclophane 10. Cleavage of the internal cyclopropane bond in the
intermediate 20 would give intermediate 22 and, upon proton loss,
would give an alternative pathway to the p-cyclophane 7.
We had previously proposed that the bicyclo[3.1.0]hexenone
product 9 is formed from an s-trans-conformation of the vinyl
ketene complex via a reductive cyclization leading to the chroma-
hexenone intermediate 15 and then reductive elimination.3b The data
in Table 1 suggest that the formation of the bicyclohexenone 9
and the cyclophane 8 is enhanced in coordinating solvents, and
this could be accounted for as indicated in Scheme 3. The η1,η3-
vinyl carbene complex 12 is an 18 e- intermediate, and upon carbon
monoxide insertion the resultant vinyl ketene complex is only an
18 e- complex if, simultaneous with the CO insertion, there is a
coordination of the chromium to the vinyl group derived from the
original carbene complex. In the presence of coordinating solvents,
the alkenyl substituent could be displaced by a molecule of solvent
to give the η4-vinyl ketene complex 14 in which the tethered alkenyl
group could adopt an s-trans-conformation to relieve strain and
thus set up the cyclization to 15. Apparently, these solvent effects
are only revealed for those macrocyclic intermediates that are most
sensitive to ring strain (n ) 10, 13). This is evidenced from the
complex with n ) 16 where the expected p-cyclophane 7d is the
major product in either THF or benzene as a solvent.
Scheme 3
Acknowledgment. This work was supported by the National
Science Foundation. This was partly performed at the University
of Chicago.
Supporting Information Available: Experimental procedures and
spectral data for all new compounds and X-ray data for 10b (PDF and
CIF). This material is available free of charge via the Internet at http://
pubs.acs.org.
References
(1) Do¨tz, K. H. Angew. Chem., Int. Ed. Engl. 1975, 14, 644.
(2) For recent reviews on carbene complexes in organic chemistry, see: (a)
Wulff, W. D. In ComprehensiVe Organometallic Chemistry II; Abel, E.
W., Stone, R. G. A., Wilkinson, G., Eds.; Pergemon Press: Elmsford,
NY, 1995; Vol. 12, p 469. (b) Hegedus, L. S. Tetrahedron 1997, 53, 4105.
(c) de Meijer, A.; Schirmer, H.; Duetsch, M. Angew. Chem., Int. Ed. 2000,
39, 3964. (d) Do¨tz, K. H.; Tomuschatt, P. Chem. Soc. ReV. 1999, 28 187.
(e) Herndon, J. W. Coord. Chem. ReV. 1999, 181, 177. (f) Do¨rwald, F. Z.
Metal Carbenes in Organic Synthesis; Wiley-VCH: New York, 1999.
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126 and references therein.
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We propose that the p-cyclophane 10 with the meta-orientation
of the two oxygen substituents is the result of a crossed [2 + 2]
cycloaddition of the ketene function in 17 with the alkenyl group
to give the bicyclo[2.1.1]hexenone core of the paddalane intermedi-
ate 18 which contains a benzvalenone core. This type of [2 + 2]
cycloaddition of a ketene metal complex and an olefin has been
observed before in an intramolecular reaction, but not, as is the
(6) (a) Jiang, W.; Fuertes, M. J.; Wulff, W. D. Tetrahedron 2000, 56, 2183.
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