First [4 + 3] annulation of alkynyl Fischer carbene complexes and azadienes. X-ray structure of a metalated zwitterionic intermediate

Full text of DOI:10.1021/ja952710o

J. Am. Chem. Soc. 1996, 118, 695-696
695
Scheme 1
First [4 + 3] Annulation of Alkynyl Fischer
Carbene Complexes and Azadienes. X-ray
Structure of a Metalated Zwitterionic Intermediate
Jose´ Barluenga,*,† Miguel Toma´s,† Eduardo Rubio,†
Jose´ A. Lo´pez-Pelegr´ın,† Santiago Garc´ıa-Granda,‡ and
Pilar Pertierra‡
Instituto UniVersitario de Qu´ımica Organometa´lica
“Enrique Moles”, Unidad Asociada al CSIC, and
Departamento de Qu´ımica F´ısica y Anal´ıtica
UniVersidad de OViedo, Julia´n ClaVer´ıa, 8
E-33071, OViedo, Spain
ReceiVed August 9, 1995
Recently, R,â-unsaturated Fischer carbene complexes have
been recognized to play an important role in transition-metal-
mediated organic synthesis.1 Although alkynyl Fischer carbene
complexes are less versatile intermediates than their alkenyl
counterparts, a number of useful reactions have been reported;
for instance, 1,2- and 1,4-nucleophilic additions2 as well as
[2 + 2],3 [3 + 2],4 [3 + 3],5 [4 + 2]6 and Pauson-Khand type7
cyclization reactions. On the other hand, the [4 + 3] cycload-
dition of alkenyl carbenes with electron-rich dienes, which may
involve a tandem cyclopropanation/Cope rearrangement, has
recently emerged as an attractive entry into seven-membered
carbocycles;8 in contrast, no examples of this type of process
involving alkynyl complexes are known, perhaps because of
the required involvement of a strained cumulene ring.9 In an
extension of this reaction we found that activated 1-azadienes,
like 4-amino-1-azadienes and N-hydroxy-1-azadienes, readily
undergo [4 + 3] annulation with alkenyl Fischer carbene
complexes leading to the azepine ring; interestingly, NMR
studies proved that the cycloaddition involves nucleophilic
addition of the imine nitrogen to the carbene carbon and
cyclization rather than consecutive [2 + 1] cycloaddition and
[3,3] rearrangement.10
On working with alkynyl carbene complexes and nitrogen-
containing substrates one can anticipate that either 1,4- or 1,2-
addition might take place and therefore different reaction
pathways should be observed.11 Reported here is the achieve-
ment of a [4 + 3] cycloaddition reaction of alkynyl Fischer
carbene complexes with R,â-unsaturated imines as well as the
isolation of an η1-azepine chromium complex intermediate.12
The reaction of azadienes 1 with pentacarbonyl methoxy
(phenylethynyl)chromium carbene complex 2 (R3 ) Ph) in
hexane at 20 °C was complete in 3 h affording a precipitate
that consisted essentially of the [4 + 3] cycloadducts 3a-c
(Scheme 1, Table 1, entries 1-3). When chromium alkynyl
complexes 2 having bulky groups at the â-carbon (R3 ) SiMe3,
tert-Bu; entries 4-6) were employed, the cyclization became
much more sluggish and therefore required the reaction to be
† Instituto Universitario de Qu´ımica Organometa´lica “Enrique Moles”.
‡ Departamento de Qu´ımica F´ısica y Anal´ıtica (X-ray service).
(1) (a) Wulff W. D. In ComprehensiVe Organic Synthesis; Trost, B. M.,
Fleming, I., Eds.; Pergamon: New York, 1991; Vol. 5, p 1065. (b) Do¨tz,
K. H. Angew. Chem., Int. Ed. Engl. 1984, 23, 587.
(2) For nitrogen nucleophiles, see, for instance: (a) Funke, F.; Duetsch,
M.; Stein, F.; Noltemeyer, M.; de Meijere, A. Chem. Ber. 1994, 127, 911.
(b) Stein, F.; Duetsch, M.; Pohl, E.; Herbst-Irmer, R.; de Meijere, A.
Organometallics 1993, 12, 2556. (c) Pipoh, R.; van Eldik, R.; Henkel, G.
Ibid. 1993, 12, 2236. (d) Pipoh, R.; van Eldik, R. Ibid. 1993, 12, 2668. (e)
Aumann, R.; Jasper, B.; La¨ge, M.; Krebs, B. ibid. 1994, 13, 3502. (f) Rahm,
A.; Wulff, W. D.; Rheingold, A. L. Ibid. 1993, 12, 597. (g) Duetsch, M.;
Lackmann, R.; Stein, F.; de Meijere, A. Synlett 1991, 324. (h) Aumann, R.
Chem. Ber. 1994, 127, 725. (i) Aumann, R.; Hinterding, P. Ibid. 1993, 126,
421. For oxygen nucleophiles, see: (j) Stein, F.; Duetsch, M.; Lackmann,
R.; Noltemeyer, M.; de Meijere, A. Angew. Chem., Int. Ed. Engl. 1991,
30, 1658. (k) Camps, F.; Llebaria, A.; Moreto´, J. M.; Ricart, S.; Vin˜as, J.
M. J. Organomet. Chem. 1991, 401, C17. (l) Aumann, R.; Jasper, B.; La¨ge,
M.; Krebs, B. Chem. Ber. 1994, 127, 2475. (m) Segundo, A.; Moreto´, J.
M.; Vin˜as, J. M.; Ricart, S.; Molins, E. Organometallics 1994, 13, 246. (n)
Aumann, R. Chem. Ber. 1992, 125, 2773. For phosphorus nucleophiles,
see: (o) Aumann, R.; Jasper, B.; Fro¨hlich, R. Organometallics 1995, 14,
231. For carbon nucleophiles, see: (p) Aumann, R.; Kosmeier, M.; Roths,
K.; Fro¨hlich, R. Synlett 1994, 1041. For the ene reaction with electron-rich
alkenes, see ref 3a.
(8) (a) Wulff, W. D.; Yang, D. C.; Murray, C. K. J. Am. Chem. Soc.
1988, 110, 2653. (b) Barluenga, J.; Aznar, F.; Mart´ın, A.; Garc´ıa-Granda,
S.; Salvado´, M. A.; Pertierra, P. J. Chem. Soc., Chem. Commun. 1993, 319.
(c) Barluenga, J.; Aznar, F.; Mart´ın, A. Organometallics 1995, 14, 1429.
(d) Barluenga, J.; Aznar, F.; Valde´s, C.; Mart´ın, A.; Garc´ıa-Granda, S.;
Mart´ın, E. J. Am. Chem. Soc. 1993, 115, 4403. (e) Harvey, D. F.; Grenzer,
M. E.; Gantzel, P. K. Ibid. 1994, 116, 6719.
(3) (a) Faron, K. L.; Wulff, W. D. J. Am. Chem. Soc. 1990, 112, 6419.
(b) Faron, K. L.; Wulff, W. D. Ibid. 1988, 110, 8727. (c) Aumann, R.;
Roths, K.; La¨ge, M.; Krebs, B. Synlett 1993, 667. (d) Pipoh, R.; van Eldik,
R.; Wang, S. L. B.; Wulff, W. D. Organometallics 1992, 11, 490. (e) Camps,
F.; Moreto´, J. M.; Ricart, S.; Vin˜as, J. M.; Molins, E.; Miravitlles, C. J.
Chem. Soc., Chem. Commun. 1989, 1560. (f) Camps, F.; Llebaria, A.;
Moreto´, J. M.; Ricart, S.; Vin˜as, J. M. Tetrahedron Lett. 1990, 31, 2479.
(4) (a) Kreissl, F. R.; Fischer, E. O.; Kreiter, C. G. J. Organomet. Chem.
1973, 57, C9. (b) Chan, K. S.; Wulff, W. D. J. Am. Chem. Soc. 1986, 108,
5229. (c) Chan, K. S.; Yeung, M. L.; Chan, W.; Wang, R.; Mak, T. C. W.
J. Org. Chem. 1995, 60, 1741. (d) Chan, K. S. J. Chem. Soc., Perkin Trans.
1 1991, 2602.
(5) (a) Wang, S. L. B.; Wulff, W. D. J. Am. Chem. Soc. 1990, 112, 4550.
(b) Merlic, C. A.; Xu, D. Ibid. 1991, 113, 9855. (c) Aumann, R.; Roths,
K.; Grehl, M. Synlett 1993, 669. (d) Reference 2p.
(6) (a) Wulff, W. D.; Yang, D. C. J. Am. Chem. Soc. 1984, 106, 7565.
(b) Wulff, W. D.; Yang, D. C. Ibid. 1984, 106, 7656. (c) Bao, J.; Dragisich,
V.; Wenglowsky, S.; Wulff, W. D. Ibid. 1991, 113, 9873. (d) Bao, J.; Wulff,
W. D.; Dragisich, V.; Wenglowsky, S.; Ball, R. G. Ibid. 1994, 116, 7616.
(e) Wulff, W. D.; Tang, P. C.; Chan, K. S.; McCallum, J. S.; Yang, D. C.;
Gilbertson, S. R. Tetrahedron 1985, 41, 5813. (f) Barluenga, J.; Aznar, F.;
Barluenga, S. J. Chem. Soc., Chem. Commun. 1995, 1973.
(9) For cycloheptaallenic species, see: (a) Dolbier, W. R., Jr.; Garza,
O. T.; Al-Sader, B. H. J. Am. Chem. Soc. 1975, 97, 5038. (b) Manisse, N.;
Chuche, J. Ibid. 1977, 99, 1272. (c) Manisse, N.; Chuche, J. Tetrahedron
1977, 33, 2399. (d) Chapman, O. L.; Johnson, J. W.; McMahon, R. J.; West,
P. R. J. Am. Chem. Soc. 1988, 110, 501.
(10) Barluenga, J.; Toma´s, M.; Ballesteros, A.; Santamar´ıa, J.; Lo´pez-
Ortiz, F.; Carbajo, R. J.; Garc´ıa-Granda, S.; Pertierra, P. Chem.sEur. J.
1996, 2, 180.
(11) The 1,2- and 1,4-addition of amines (see refs 2b-i) and imines (see
ref 2a) to alkynyl carbene complexes is well documented.
(12) For previous work on Fischer carbene complexes and simple
1-azadienes, see: (a) Barluenga, J.; Toma´s, M.; Lo´pez Pelegr´ın, J. A.; Rubio,
E. J. Chem. Soc., Chem. Commun. 1995, 665. (b) Danks, T. N.; Velo-
Rego, D. Tetrahedron Lett. 1994, 35, 9443.
(13) Running the reaction of azadiene 1 (R1 ) Ph; R2 ) n-Pr) with
carbene 2 (R3 ) Ph) in THF at 20 °C resulted in the formation of 3a (55%)
along with a second compound (28%) resulting from the [4 + 2]
cycloaddition of the azadiene to the alkynyl function of the carbene complex.
Unpublished results.
(14) This metal migration has been independently invoked by Fischer
and Do¨tz to rationalize the cyclodimerization of alkynyl carbenes of
chromium and tungsten that occurs on reaction with organolithium and
organozinc reagents. See: (a) Do¨tz, K. H.; Christoffers, C.; Knochel, P. J.
Organomet. Chem. 1995, 489, C84. (b) Fischer, H.; Meisner, T.; Hofmann,
J. Chem. Ber. 1990, 123, 1799.
(7) (a) Do¨tz, K. H.; Christoffers, J. J. Organomet. Chem. 1992, 426,
C58. (b) Camps, F.; Moreto´, J. M.; Ricart, S.; Vin˜as, J. M. Angew. Chem.
Int., Ed. Engl. 1991, 30, 1470.
0002-7863/96/1518-0695$12.00/0 © 1996 American Chemical Society

696 J. Am. Chem. Soc., Vol. 118, No. 3, 1996
Communications to the Editor
Table 1. Azepines 3 and 4 Prepared from 1-Azadienes 1 and
Carbene Complexes 2
T, °C
(t, h) compd
yield,a
%
yield,b
%
entry R1 R2
R3
Ph nPr Ph
Ph Bn Ph
Ph iPr Ph
compd
1
2
3
4
5
6
20 (3)
20 (3)
20 (3)
3a
3b
3c
3d
90
80
85
60
4a
4b
4c
4d
4e
4f
93c
87c
90c
Me nPr SiMe3 20 (24)
Ph nPr SiMe3 20 (3)
85c (75)d
64
Ph nPr tBu
50 (36)
57
a Isolated yields (not optimized) after column chromatography
(deactivated SiO2, 2:1 hexane-ethyl acetate). b Isolated yields (not
optimized) after column chromatography (SiO2, 2:1 hexane-ethyl
acetate). c Refers to heating compounds 3 at 50 °C. d Yield obtained
by reacting azadiene 1 and carbene 2 at 50 °C for 3 h.
carried out in THF, instead of hexane, at 20-50 °C. Thus, 3d
was obtained in moderate yield, while cycloadducts 3e,f
underwent further transformation into their metal-free derivatives
4e,f under the reaction conditions.13
Figure 1. Crystal structure of 3a. Selected bond lengths (Å): N(1)-
C(2) 1.336, C(2)-O(1) 1.325, O(1)-C(11) 1.445, C(2)-C(3) 1.442,
C(3)-C(4) 1.348, Cr-C(3) 2.233, C(4)-C(5) 1.556, C(5)-C(6) 1.498,
C(6)-C(7) 1.324, C(7)-N(1) 1.419.
The unprecedented 1,2-migration of the pentacarbonylmetal
portion is rather intriguing,14 although it is well established that
the [1,3] shift of the pentacarbonylchromium and -tungsten
groups does take place when nitrogen-containing substrates are
involved.15 The formation of heterocycles 3 is thought to occur
by nucleophilic addition of the imine nitrogen of 1 to the carbene
carbon of 2 to form the zwitterionic species A followed probably
by cyclization to the η2-chromium-cumulene azepine B;16
finally, metallacyclopropane ring opening on complex B would
provide the isolated η1-complexes 3.
Scheme 2
The structure of compounds 3 was determined by an X-ray
crystal analysis of complex 3a (Figure 1).17 Although η1-
chromium complexes 3 are air-stable and withstand purification
by column chromatography, the carbon-metal σ-bond was
labile under thermal, hydrolytic, and electrophilic conditions
(Scheme 2). Thus, heating complexes 3a-d at 50 °C in either
THF or benzene followed by column chromatography resulted
in the formation of azepinones 4a-d in high yields; compounds
4e,f formed directly at 20 and 50 °C, respectively, from 1 and
2 as indicated above.18 Compounds 4a-d were also obtained
in comparable yields by stirring a THF solution of 3a-d with
H2O (20 °C, 24 h). In addition, 3b produced the deuterated
azepinone 5 (R1 ) Ph, R2 ) Bn; 90%) upon treatment with
D2O, whereas 3a reacted with iodine to furnish the 3-iodo-2-
azepinone 6 (55%; 93% estimated before column chromatog-
raphy).19
In summary, we have accomplished the first [4 + 3]
cycloaddition of alkynyl Fischer carbene complexes leading to
σ-complexed and metal-free azepines;20 a novel [1,2] shift of a
pentacarbonylmetal moiety is demonstrated and seems to be the
driving force of the cyclization. Mechanistic studies directed
to gain a better understanding of the process are currently under
way.21
(15) (a) Fischer, H.; Schlageter, A.; Bidell, W.; Fru¨h, A. Organometallics
1991, 10, 389. (b) Sleiman, H. F.; McElwee-White, L. J. Am. Chem. Soc.
1988, 110, 8700. (c) Maxey, C. T.; Sleiman, H. F.; Massey, S. T.; McElwee-
White, L. Ibid. 1992, 114, 5153. (d) Hegedus, L. S.; Lundmark, B. R. Ibid.
1989, 111, 9194.
Acknowledgment. This research was supported by the DGICYT
(Grant PB92-1005).
(16) Intermolecular electrophilic induced rearrangement of η1-propargyl
tungsten complexes leading to η2-tungsten-allene intermediates has been
recently proposed: Chen, C. C.; Fan, J. S.; Lee, G. H.; Peng, S. M.; Wang,
S. L.; Liu, R. S. J. Am. Chem. Soc. 1995, 117, 2933.
Supporting Information Available: Synthetic procedures and
characterization data for 3-6 and X-ray crystallographic data for 3a
including tables of atomic coordinates, bond lengths, and bond angles
(22 pages). This material is contained in many libraries on microfiche,
immediately follows this article in the microfilm version of the journal,
can be ordered from the ACS, and can be downloaded from the Internet;
see any current masthead page for ordering information and Internet
access instructions.
(17) Crystal data for 3a: C27H23CrNO6, Mr ) 509.46, monoclinic, space
group P21/n, a ) 12.322(7) Å, b ) 10.170(3) Å, c ) 20.820(7) Å, â )
99.07(4)°, V ) 2546(2) Å3, Z ) 4, rcalc ) 1.31 Mg m-3, F(000) ) 1056,
λ(Mo KR) ) 0.710 73 Å, µ ) 0.484 cm-1, T ) 293 K. Colorless crystal
(0.30 × 0.30 × 0.26 mm).
(18) We have not been able yet to ascertain where the hydrogen atom
replacing the metal group is coming from. In fact, heating either the
2-methoxyazepine 3b in C6D6 or its 2-trideuteriomethoxy analogue in C6H6
did not lead to the deuterated azepinone 5, but 4b was the sole product
detected.
JA952710O
(21) Following the suggestions of one reviewer, attempts were made to
tune the electronic factors governing the process. We found that amino
carbene derivatives, e.g., pentacarbonyl pyrrolidinyl (phenylethynyl)-
chromium carbene, were unreactive, the starting materials being recovered
after prolonged heating at 80 °C. Complexes (CO)4(PR3)Cr(OMe)(CtCPh)
(R ) Ph, Bu) could not be tested because we were unable to prepare them.
Finally, pentacarbonyl methoxy (phenylethynyl)tungsten carbene led almost
exclusively to the corresponding [4 + 2] cycloadduct.22
(22) The preference for the [4 + 2] cycloaddition of tungsten carbenes
compared with chromium carbenes has been reported: (a) Wulff, W. D.;
Bauta, W. E.; Kaesler, R. W.; Lankford, P. J.; Miller, R. A.; Murray, C.
K.; Yang, D. C. J. Am. Chem. Soc. 1990, 112, 3642. (b) Barluenga, J.;
Aznar, F.; Mart´ın, A.; Barluenga, S.; Garc´ıa-Granda, S.; Paneque-Quevedo,
A. A. J. Chem. Soc., Chem. Commun. 1994, 843.
(19) The iodination of anionic η1-alkenyl chromium complex species is
known: Herndon, J. W.; Reid, M. D. J. Am. Chem. Soc. 1994, 116, 383.
(20) Reviews on azepines: (a) Evans, P. A.; Holmes, A. B. Tetrahedron
1991, 47, 9131. (b) Hassenru¨ck, K.; Martin, H. D. Synthesis 1988, 569. (c)
Smalley, R. K. In ComprehensiVe Heterocyclic Chemistry; Lwowski, W.,
Ed.; Pergamon: Oxford, 1984; Vol. 7, p 491. For recent syntheses of
2-azepinones, see: (d) Robl, J. A.; Cimarusti, M. P. Tetrahedron Lett. 1994,
35, 1393. (e) Robl, J. A.; Cimarusti, M. P.; Simpkins, L. M.; Weller, H.
N.; Pan, Y. Y.; Malley, M.; DiMarco, J. D. J. Am. Chem. Soc. 1994, 116,
2348. (f) Evans, P. A.; Holmes, A. B.; Russell, K. J. Chem. Soc., Perkin
Trans. 1 1994, 3397. (g) Evans, P. A.; Holmes, A. B. Tetrahedron 1991,
47, 9131.