Acylamino chromium carbene complexes: Direct carbonyl insertion, formation of munchnones, and trapping with dipolarophiles [7]

Full text of DOI:10.1021/ja9934753

7398
J. Am. Chem. Soc. 2000, 122, 7398-7399
generated by the dehydration of acylated amino acids, they have
not been formed via an organometallic route to date. Mu¨nchnones
react with alkynes to form bicyclic intermediates that undergo a
cycloreversion reaction losing carbon dioxide and forming pyr-
roles. Thus, if Mu¨nchnones or Mu¨nchnone complexes could be
formed from acylamino carbene complexes, then a new class of
carbene complex plus alkyne annulation reactions leading to
pyrroles would be possible.7
Acylamino Chromium Carbene Complexes: Direct
Carbonyl Insertion, Formation of Mu1nchnones, and
Trapping with Dipolarophiles
Craig A. Merlic,* Andreas Baur, and Courtney C. Aldrich
Department of Chemistry and Biochemistry
UniVersity of California, Los Angeles
Los Angeles, California 90095-1569
As the initial test of the concept, complex 1a8 was photolyzed
under typical conditions in the presence of dimethyl acetylene-
dicarboxylate (DMAD).9 Gratifyingly, pyrrole 2a was indeed
formed as planned, but in only 41% yield. Use of the more stable
chelate complex 1b10 gave an improved 71% yield of the pyrrole.
Unfortunately, variations in the photolytic reaction conditions or
changes in the alkyne trap resulted in significantly diminished
ReceiVed September 27, 1999
Photolysis of chromium Fischer carbene complexes has become
an established synthetic method for the synthesis of a wide range
of products including â-lactams, amino acids, peptides, cyclobu-
tanones, and arenes, principally due to the extensive studies by
Hegedus and co-workers.1,2 The presumed photogenerated inter-
mediate is a chromium-complexed ketene resulting from insertion
of carbon monoxide.3 Acylamino chromium carbene complexes
in particular have been utilized as substrates for the photochemical
synthesis of products such as â-amino esters, â-lactams, and
2-aminophenols, but can demonstrate markedly different behavior
from their nonacylated analogues.4 More broadly, aminocarbene
complexes have been the subject of intense study.5 We report
herein evidence for the direct, nonphotochemical insertion of
carbon monoxide at ambient temperature and subsequent forma-
tion of Mu¨nchnones as reactive intermediates in reactions of
acylamino chromium carbene complexes and demonstrate ap-
plications to the synthesis of heterocyclic compounds.
yields. Knowing that carbene complexes react with alkynes,11
a
control reaction was performed by mixing carbene 1a and DMAD
in THF solvent, pressurizing with 30 psi carbon monoxide, and
letting it stand at room temperature in the dark. Remarkably, the
pyrrole 2a was formed in 78% yield!
Consideration of the ketene intermediate resulting from pho-
tolysis of an acylamino chromium carbene complex immediately
suggests the possibility of cyclization to a Mu¨nchnone or
Mu¨nchnone complex (eq 1). Mu¨nchnones, and related mesoionic
Carbene 1b also gave the pyrrole in high yield (90%) under
the same conditions of CO pressure in the dark. Reaction of either
1a or 1b using an initial CO purge of the solution, but no applied
CO pressure, produced pyrrole, but in lower yields. Confirmation
of the Mu¨nchnone intermediate, as opposed to a reaction pathway
involving initial alkyne insertion,7h,m was accomplished by pres-
surizing a THF solution of 1b in the absence of alkyne. The dark
brown solution changed to light yellow within 24 h and the
Mu¨nchnone, 3-methyl-2,4-diphenyl-1,3-oxazolium-5-oxide, could
be isolated by recrystallization from acetonitrile in 27% yield.
(7) Pyrroles have been formed from reactions of group six Fischer carbene
complexes, but by entirely different mechanisms: (a) Aumann, R.; Kuckert,
E.; Kru¨ger, C.; Angermund, K. Angew. Chem., Int. Ed. Engl. 1987, 26, 6,
563-564. (b) Aumann, R.; Heinen, H. J. Organomet. Chem. 1990, 389, C1-
C6. (c) Aumann, R.; Heinen, H. J. Organomet. Chem. 1990, 391, C7-C11.
(d) Dragisich, V.; Wulff, W. D. Organometallics 1990, 9, 2867-2870. (e)
Dragisich, V.; Murray, C. K.; Warner, B. P.; Wulff, W. D.; Yang, D. C. J.
Am. Chem. Soc. 1990, 112, 1251-1253. (f) Denise, B.; Goumont, R.; Parlier,
A.; Rudler, H.; Daran, J.-C.; Vaissermann, J. J. Chem. Soc., Chem. Commun.
1990, 1238-1240. (g) Aumann, R.; Heinen, H.; Goddard, R.; Kru¨ger, C. Chem.
Ber. 1991, 124, 2587-2593. (h) Grotjahn, D. B.; Kroll, F. E. K.; Scha¨fer, T.;
Harms, K.; Do¨tz, K. H. Organometallics 1992, 11, 298-310. (i) Aumann, R.
Chem. Ber. 1993, 126, 2325-2330. (j) Aumann, R.; Jasper, B.; Goddard, R.;
Kru¨ger, C. Chem. Ber. 1994, 127, 717-724. (k) Funke, K.; Duetsch, M.;
Stein, F.; Noltemeyer, M.; de Meijere, A. Chem. Ber. 1994, 127, 911-920.
(l) Danks, T. N.; Velo-Rego, D. Tetrahedron Lett. 1994, 35, 9443-9444. (m)
Parlier, A.; Rudler, M.; Rudler, H.; Goumont, R.; Daran, J.-C.; Vaissermann,
J. Organometallics 1995, 14, 2760-2774. (n) Aumann, R.; Meyer, A. G.;
Fro¨hlich, R. Organometallics 1996, 15, 5018-5027. (o) Aumann, R.; Fro¨hlich,
R.; Zippel, F. Organometallics 1997, 16, 2571-2580. (p) Aumann, R.; Yu,
Z.; Fro¨hlich, R. Organometallics 1998, 17, 2897-2905. (q) Iwasawa, N.;
Ochiai, T.; Maeyama, K. J. Org. Chem. 1998, 63, 3164-3165.
(8) Hegedus, L. S.; Schultze. L. M.; Montgomery, J. Organometallics 1989,
8, 2189-2195.
compounds, play an important role in heterocyclic synthesis due
to their participation in dipolar cycloaddition reactions.6 Usually
(1) For reviews, see: (a) Hegedus, L. S. Tetrahedron 1997, 53, 4105-
4128. (b) Hegedus, L. S. Acc. Chem. Res. 1995, 28, 299-305.
(2) For general reviews, see: (a) Do¨tz, K. H.; Fischer, H.; Hofmann, P.;
Kreissl, F. R.; Schubert, U.; Weiss, K. Transition Metal Carbene Complexes;
Verlag Chemie: Weinheim, Germany, 1983. (b) Wulff, W. D. In Compre-
hensiVe Organometallic Chemistry II; Abel, E. W., Stone, F. G. A., Wilkinson,
G., Eds; Pergamon Press: New York, 1995; Vol. 12, pp 470-547. (c) Wulff,
W. D. In ComprehensiVe Organic Synthesis; Trost, B. M., Fleming, I., Eds;
Pergamon Press: Oxford, England, 1991; Vol. 5, pp 1065-1113.
(3) Hegedus, L. S.; deWick, G.; D’Andrea, S. J. Am. Chem. Soc. 1988,
110, 2122-2126.
(4) (a) Hegedus, L. S.; Montgomery, J.; Narukawa, Y.; Snustad, D. C. J.
Am. Chem. Soc. 1991, 113, 5784-5791. (b) Hegedus, L. S.; Lastra, E.;
Narukawa, Y.; Snustad, D. C. J. Am. Chem. Soc. 1992, 114, 2991-2994. (c)
Merlic, C. A.; Xu, D.; Gladstone, B. G. J. Org. Chem. 1993, 58, 538-545.
(5) For reviews, see: (a) de Meijere, A. Pure Appl. Chem. 1996, 68, 61-
72. (b) Grotjahn, D. B.; Do¨tz, K. H. Synlett 1991, 381-390. (c) Schwindt,
M. A.; Miller, J. R.; Hegedus, L. S. J. Organomet. Chem. 1991, 413, 143-
153. (d) Rudler, H.; Audouin, M.; Chelain, E.; Denise, B.; Goumont, R.;
Massoud, A.; Parlier, A.; Pacreau, A.; Rudler, M.; Yefsah, R.; Alvarez, C.;
Delgado-Reyes, F. Chem. Soc. ReV. 1991, 20, 503-531.
(6) For general reviews, see: (a) Stefaniak, L.; Jazwinski, J. Khim.
Geterotsikl. Soedin 1995, 1180-1199. (b) Osterhout, M. H.; Nadler, W. R.;
Padwa, A. Synthesis 1994, 123-141. (c) Kobayashi, Y.; Kumadaki, I. AdV.
Heterocycl. Chem. 1982, 31, 169-206. (d) Ollis, W. D.; Ramsden, C. A.
AdV. Heterocycl. Chem. 1976, 19, 1-122.
(9) A Pyrex pressure tube containing a solution of carbene complex and 2
equiv of alkyne in THF solvent was pressurized to 40 psi with CO. Photolysis
was performed using a 450 W Hanovia medium-pressure mercury lamp and
water cooling until the deep orange color of the carbene complex disappeared
(2.5 h).
(10) Complex 1a is an unstable red oil, but complex 1b forms stable olive-
green needles. See Supporting Information.
(11) For a recent review, see: Harvey, D. F.; Sigano, D. M. Chem. ReV.
1996, 96, 271-288.
10.1021/ja9934753 CCC: $19.00 © 2000 American Chemical Society
Published on Web 07/14/2000

Communications to the Editor
J. Am. Chem. Soc., Vol. 122, No. 30, 2000 7399
The isolated Mu¨nchnone spectroscopically matched an authentic
sample prepared independently.12 Thus, the presumed initial metal-
complexed ketene led to a metal-free Mu¨nchnone. In the presence
of alkyne trap, chromium hexacarbonyl and carbon dioxide13 were
found, in addition to pyrrole, at the end of the reaction which
supports the intermediacy of the Mu¨nchnone in pyrrole formation.
Finally, high yields of pyrrole could be formed from either 1a or
1b by first reacting the carbene complex with CO in the absence
of alkyne and then adding alkyne to the yellow Mu¨nchnone
solution.
resulted in complex 5 in 65% yield (eq 5). An important point is
that the direct nonphotochemical carbonyl insertion is critical in
Carbenes 1a and 1b reacted with other alkynes, using either
initial addition of alkyne or adding alkyne to the preformed
Mu¨nchnone, and typical results are shown in eq 3. In concert
this instance as, in general, methoxy-substituted carbene complexes
are more photochemically reactive than amino-substituted carbene
complexes.1 Using complex 5 as a substrate in our photochemical
benzannulation reaction,18 photolysis led regioselectively to indole
6 in 51% yield.
The mechanism broadly outlined in eq 1 is our working
framework for pyrrole formation. First, chelated complexes such
as 1b would be converted to the pentacarbonyl complex which
should be more reactive toward CO insertion.4c Then, direct CO
insertion, without photolysis, occurs providing a ketene complex.
This is an unusual step since while CO insertion readily occurs
with chromium carbene complexes lacking a heteroatom sub-
stituent directly bonded to the carbene carbon as part of the Do¨tz
reaction,2 CO insertion in heteroatom-substituted chromium
carbene complexes has been shown in general to be a photo-
chemical, and not thermal, process.1,3 The acyl substituent must
be crucial for reducing electron donation from the nitrogen atom
to the carbene carbon and thus activating CO insertion. The ketene
cyclizes to a metal-free Mu¨nchnone as evidenced by our isolation
of 3-methyl-2,4-diphenyl-1,3-oxazolium-5-oxide. The demetala-
tion is likely to be facilitated by the presence of CO. The
subsequent alkyne cycloaddition and carbon dioxide cyclorever-
sion are well established and supported by our detection of carbon
dioxide.6 This proposal is in marked contrast with one put forth
by Do¨tz and co-workers7h for pyrrole formation from an acylamino
molybdenum carbene complex wherein initial alkyne insertion
was followed by carbonyl insertion and ketene rearrangement to
a 2-alkoxy pyrrole. However, in our chromium case, carbonyl
insertion clearly precedes alkyne incorporation.
with literature precedent from the work of Huisgen,14 electron
rich or sterically demanding alkynes are not efficient traps of
Mu¨nchnones. Isolation of sensitive acylaminocarbene complexes
can be avoided entirely by using a one-pot procedure of sequential
addition of base, acid chloride, and alkyne to transform simple,
stable aminocarbene complexes directly to pyrroles (eq 4).
Complex 3b leading to pyrrole 2f also demonstrates that the
thermal CO insertion is not limited to aryl carbene complexes.
In summary, we have demonstrated the direct, nonphotochemi-
cal, insertion of carbon monoxide in acylamino chromium carbene
complexes, formation and trapping of Mu¨nchnones, and the use
of alkynyl carbene complexes as efficient and functional traps of
Mu¨nchnones for subsequent benzannulation reactions.
Since unsaturated carbene complexes are quite efficient reac-
tants in Diels Alder cycloaddition reactions15 and there have been
a few reports of participation in dipolar cycloaddition reactions,16
we tested the idea of a carbene complex as the dipolarophile to
trap the carbene-generated Mu¨nchnone.17 Reaction of complex
1b with complex 4 under 30 psi CO in the dark for just 2.25 h
Acknowledgment. We thank the National Institutes of Health and
the National Science Foundation for support of our work. C.A.M. is a
recipient of a Camille Dreyfus Teacher-Scholar (1994-1999) award. A.B.
is a recipient of a Deutsche Forschungsgemeinschaft postdoctoral
fellowship. C.C.A. is a recipient of National Institutes of Health training
grant support and support from the Rohm and Haas Company.
(12) See Supporting Information.
(13) Hexacarbonylchromium was isolated in 49% yield. Carbon dioxide
was trapped with an aqueous barium hydroxide solution as barium carbonate
in 88% yield.
(14) (a) Bayer, H. O.; Huisgen, R.; Knorr, R.; Schaefer, F. C. Chem. Ber.
1970, 103, 2581-2597. (b) Huisgen, R.; Gotthardt, H.; Bayer, H. O.; Schaefer,
F. C. Chem. Ber. 1970, 103, 2611-2624. (c) Gotthardt, H.; Huisgen, R. Chem.
Ber. 1970, 103, 2625-2638.
Supporting Information Available: Description of syntheses and
characterization data for compounds 1a-b, 2a-f, 5, 6, and 3-methyl-
2,4-diphenyl-1,3-oxazolium-5-oxide (PDF). This material is available free
of charge via the Internet at http://pubs.acs.org.
(15) Powers, T. S.; Jiang, W.; Su, J.; Wulff, W. D. J. Am. Chem. Soc.
1997, 119, 6438-6439 and references therein.
(16) For a review, see: Alcaide, B.; Casarrubios, L.; Dom´ınguez, G.; Sierra,
M. A. Curr. Org. Chem. 1998, 2, 551-574.
(17) Alkynyl carbene complexes have been reacted with preformed
mesoionic compounds: Choi, Y. H.; Kang, B. S.; Yoon, Y.-J.; Kim, J.; Shin,
S. C. Synth. Commun. 1995, 25, 2043-2050.
JA9934753
(18) (a) Merlic, C. A.; Xu, D. J. Am. Chem. Soc. 1991, 113, 7418-7420.
(b) Merlic, C. A.; Roberts, W. M. Tetrahedron Lett. 1993, 34, 7379-7382.