Specific synthesis of 1,2- and 1,3-dialkylidenecycloheptanes by [3+2+2] cyclization of alkenyl Fischer carbene complexes and allenes

Article abstract of DOI:10.1021/ja045459y

The 1,2- and 1,3-dialkylidenecycloheptane rings are specifically assembled from chromium alkenyl Fischer carbene complexes and allenes via [3+2+2] cyclization reactions. The former cycloadducts are obtained when the cyclization is performed in the presenc

Full text of DOI:10.1021/ja045459y

Published on Web 10/13/2004
Specific Synthesis of 1,2- and 1,3-Dialkylidenecycloheptanes by [3+2+2]
Cyclization of Alkenyl Fischer Carbene Complexes and Allenes
Jose´ Barluenga,*,† Rube´n Vicente,† Pablo Barrio,† Luis A. Lo´pez,† Miguel Toma´s,† and Javier Borge‡
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, 33071 OViedo, Spain
Received July 28, 2004; E-mail: barluenga@uniovi.es
Scheme 1. Ni(0)-Mediated [3+2+2] Cyclization of Chromium
Alkenyl Carbene Complexes 1a-d with Allene 2a
The development of new, efficient methods for the construction
of carbocycles from single acyclic blocks represents an important
ongoing challenge for synthetic organic chemists. In particular,
dialkylidenecycloalkanes are valuable building blocks for further
structural elaboration. Among these compounds, the 1,2-dialkyli-
denecycloalkanes are relatively accessible from 1,n-enynes via
transition-metal-catalyzed cycloisomerization reactions.1 In this
regard, while the cycloisomerization of 1,6-enynes to cyclopentane
derivatives has been very efficiently performed and that of 1,7-
enynes to the cyclohexane ring works fairly well, the cyclization
of 1,8-enynes to the 1,2-dialkylidenecycloheptane derivatives has
been reported to fail.2,3 Taking advantage of the chance of success
that allenes4 offer to accomplish this task, and based on our own
experience on Fischer carbene complexes,5,6 we present a new
access to 3,4- and 2,4-dialkylidenecyclohptanones by nickel(0)-
mediated and rhodium(I)-catalyzed [3+2+2] cyclization of alkenyl
carbene complexes and allenes.7
First, we found that the treatment of chromium alkenyl carbene
complexes 1a-d with 1,1-dimethylallene 2a (3 equiv) at -10 °C
in acetonitrile in the presence of [Ni(cod)2] (1 equiv), followed by
warming to room temperature over 2 h, resulted in the formation
of the [3+2+2] cycloadducts 3. Chromatographic purification of
3 led to the 3,4-diisopropylidenecycloheptanone derivatives 4 in
moderate yields (40-56% overall yield) (Scheme 1; Table 1, entries
1-4).8 It is interesting to note that not only a stereogenic center
(C6) is created along the reaction course, but axial chirality arises
from the atropisomerism about the sp2-sp2 single bond of the
butadiene unit (C3-C4) (see Figure 1 for the X-ray structure of
compound 4a; C8-C3-C4-C11 dihedral angle ) 89.5°).9,10 Also
noteworthy is the selectivity of the process: (i) three C-C bonds
are regioselectively formed; (ii) the less substituted CdC of the
allene is solely involved (head-to-head allene-allene coupling); and
(iii) only one diastereoisomer is detected.
Table 1. Cyclization of Carbene Complexes 1 and Allenes 2 to
Cycloheptane Derivatives 4 (Scheme 1) and 5 (Scheme 2) in the
Presence of Ni(0) and Rh(I)
entry
R1
R2
R3
R4
4 (%)a,b
5 (%)a
1
2
3
4
5
6
7
8
p-MeOC6H4
nBu
Ph
H
H
H
H
H
H
H
H
Me
H
Me
H
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
4a (53)
4b (40)
4c (52)
4d (56)
5a (55)
5b (61)
2-furyl
iBu
5c (70)
5d (58)
5e (60)
5f (63)
5g (71)
5h (64)
5i (55)
5j (50)
tBu
Me
ferrocenyl
Me
Me
Me
9
10
11
12
-(CH2)5-
Ph
Ph
Ph
H
Me
a Yields of isolated products. b Overall yield from carbene complex 1.
In accordance with a previous report,6d we propose that the nickel
carbene I, formed by chromium-nickel exchange, inserts a single
allene unit through the less substituted CdC bond to generate
metallacycle species II. In the present case, this intermediate does
not undergo reductive metal elimination, but the insertion of a
second allene into the more reactive C(allyl)-Ni bond takes place
to afford the species III, which in turn evolves to the observed
[3+2+2] cycloadduct by reductive metal elimination. At this point,
the crucial role of the solVent arises, as we previously found that
the [3+2] cyclization resulting from a single allene insertion occurs
exclusively if the reaction is performed in toluene.6d We argue that,
in the present case, the half-life of the species II is enhanced by
Ni-acetonitrile coordination,11 thus allowing species II to suffer
another allene insertion.
Figure 1. X-ray structures of 4a (top) and 6f (bottom) (ellipsoids at 30%
probability level).
Next, we questioned whether the [Rh(naphthalene)(cod)]+-
catalyzed [3+2] cyclization of carbenes 1 and allenes, recently
reported by us,6d could also be switched to the [3+2+2] cyclization
† Instituto Universitario de Qu´ımica Organometa´lica “Enrique Moles”.
‡ Departamento de Qu´ımica F´ısica y Anal´ıtica.
9
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J. AM. CHEM. SOC. 2004, 126, 14354-14355
10.1021/ja045459y CCC: $27.50 © 2004 American Chemical Society

C O M M U N I C A T I O N S
Scheme 2. Rh(I)-Catalyzed [3+2+2] Cyclization of Chromium
Alkenyl Carbene Complexes 1 with Allenes 2
and P.B. thank the Ministerio de Ciencia y Tecnolog´ıa and the
Principado de Asturias for predoctoral fellowships. We are also
grateful to Dr. Ce´sar J. Pastor (Universidad Auto´noma, Madrid)
and Dr. Alberto Soldevilla (Universidad de la Rioja) for their
assistance in the collection of the X-ray data.
Supporting Information Available: Experimental procedures and
spectral and analytical data for 4-6 (PDF); X-ray crystallographic data
for 4a and 6f (CIF). This material is available free of charge via the
Internet at http://pubs.acs.org.
Scheme 3. Proposed Mechanism for the Rh(I)-Catalyzed [3+2+2]
Cyclization of Chromium Alkenyl Carbene Complexes 1 with
Allenes 2
References
(1) (a) Trost, B. M.; Lautens, M. J. Am. Chem. Soc. 1985, 107, 1781. For a
review, see: (b) Trost, B. M.; Krische, M. J. Synlett 1998, 1.
(2) Trost, B. M. Acc. Chem. Res. 1990, 23, 34.
(3) The synthesis of dialkylidenecycloheptane derivatives in low yields
(<20%) via palladium-catalyzed cyclization-hydrosilylation of 1,8-
nonadiyne has been recently reported: Uno, T.; Wakayanagi, S.; Sonoda,
Y.; Yamamoto, K. Synlett 2003, 1997.
(4) (a) Pasto, D. J.; Huang, N.-Z. Organometallics 1985, 4, 1386. (b) Pasto,
D. J.; Huang, N.-Z.; Eigenbrot, C. W. J. Am. Chem. Soc. 1985, 107, 3160.
(c) Saito, S.; Hirayama, K.; Kabuto, C.; Yamamoto, Y. J. Am. Chem.
Soc. 2000, 122, 1076.
by modifying the catalyst. This was brought about by using
[Rh(cod)Cl]2, instead of the cationic catalyst [Rh(naphthalene)-
(cod)]+.11 When carbene complexes 1 were mixed with 1,1-
disubsituted allenes 2 (3 equiv) (CH2Cl2, 25 °C, 18-36 h) in the
presence of 10 mol % of [Rh(cod)Cl]2, 1,3-dialkylidenecycloheptene
derivatives 5a-i were obtained with total regioselectivity and in
moderate yields (55-71% after column chromatography) (Scheme
2; Table 1, entries 1, 2, 5-11). In turn, acid hydrolysis of 5a-i
produces quantitatively 2,4-dialkylidenecycloheptanones 6a-i.8 The
X-ray structure of 6f is displayed in Figure 1. The cyclization
involves regioselective formation of three C-C bonds through the
less substituted allene CdC bond (head-to-tail allene-allene
coupling). Moreover, the cycloadduct 5j (R3 ) Ph, R4 ) H; entry
12) is formed from phenylpropadiene as a sole E,E diastereoisomer
(5) Representative review on Fischer carbene complexes: Wulff, W. D. In
ComprehensiVe Organometallic Chemistry II; Abel, E. W., Stone, F. G.
A., Wilkinson, G., Eds.; Pergamon: New York, 1995; Vol. 12, p 469.
(6) (a) Ni-mediated [3+2+2] cyclization with alkynes: Barluenga, J.; Barrio,
P.; Lo´pez, L. A.; Toma´s, M.; Garc´ıa-Granda, S.; Alvarez-Ru´a, C. Angew.
Chem., Int. Ed. 2003, 42, 3008. (b) Rh-catalyzed [3+2] cyclization with
alkynes: Barluenga, J.; Vicente, R.; Lo´pez, L. A.; Rubio, E.; Toma´s, M.;
Alvarez-Ru´a, C. J. Am. Chem. Soc. 2004, 126, 470. (c) Go¨ttker-
Schnetmenn, I.; Aumann, R. Organometallics 2001, 20, 346. (d) Ni-
mediated and Rh-catalyzed [3+2] cyclization with allenes: Barluenga,
J.; Vicente, R.; Barrio, P.; Lo´pez, L. A.; Toma´s, M. J. Am. Chem. Soc.
2004, 126, 5974.
(7) Thermal reactions of Fischer carbene complexes with allenes: (a) Aumann,
R.; Uphoff, J. Angew. Chem., Int. Ed. Engl. 1987, 26, 357. (b) Aumann,
R.; Melchers, H.-D. J. Organomet. Chem. 1988, 355, 351. (c) Aumann,
R.; Trentmann, B. Chem. Ber. 1989, 122, 1977. (d) Hwu, C.-C.; Wang,
F. C.; Yeh, M.-C. P.; Sheu, J.-H. J. Organomet. Chem. 1994, 474, 123.
(8) Compounds 4-6 were characterized by NMR techniques (including
HMQC, HMBC, COSY, and NOESY).
1
(NOESY H NMR experiments performed on 6j).
(9) Heating 4a in toluene-d8 above 80 °C in the NMR tube affords a ca. 2:3
mixture of diasteroisomers 4a/4a′.
At this early stage, a mechanistic proposal to cycloadducts 5 is
tentatively suggested in Scheme 3. Chromium-rhodium exchange
followed by reversible metalla-[4+2] cycloaddition would produce
intermediate IV, which would evolve to the thermodynamically
more stable metallacycle V. Insertion of a second molecule of allene
would give rise to the metallacyclooctene species VI, which would
yield compounds 5 upon reductive elimination.12
In conclusion, we have found that 1,2- and 1,3-dialkylidenecy-
cloheptane13 derivatives are chemo-, regio-, and diastereoselectively
synthesized by the [3+2+2] cyclization of chromium alkenyl-
(methoxy)carbene complexes and allenes in the presence of Ni(0)
and Rh(I), respectively. The carbene nature of the nickel carbene
complexes6a accounts for the formation of metallacycle II via [2+2]
cycloaddition to allene, while the low carbene character of Fischer
rhodium carbene complexes6b must be responsible for the different
insertion mode to form the regioisomeric metallacycle IV.14 In both
cases, the stabilization of the metallacyclohexene species II, IV
seems crucial to retard the metal elimination and thus allow the
second allene insertion to occur. In terms of scope, 1-substituted
and 1,1-disubstituted allenes do work well, and a wide array of
carbene complexes 1 can be employed. This study brings to us the
belief that new ways to expand the usefulness of R,â-unsaturated
alkoxy carbene complexes can still be devised by combining them
with a diversity of transition metals and unsaturated substrates.
(10) For some examples of nonplanar conformations for 1,3-butadienes, see:
(a) Kiefer, E. F.; Levek, T. J.; Bopp, T. T. J. Am. Chem. Soc. 1972, 94,
4751. (b) Bechert, G.; Mannschreck, A. Chem. Ber. 1981, 114, 2365. (c)
Bechert, G.; Mannschreck, A. Chem. Ber. 1983, 116, 264.
(11) It is well stablished that the metal reductive elimination is retarded by
σ-donor ligands and facilitated by cationic metal complexes: Collman, J.
P.; Hegedus, L. S.; Norton, J. R.; Finke, R. G. Principles and Applications
of Organotransition Metal Chemistry; University Science Books: Mill
Valley, CA, 1987.
(12) In the case of cationic rhodium(I) catalyst, the intermediate of type IV
undergoes metal elimination faster than equilibration to intermediate of
type V (ref 6d). Conversely, when the reaction with neutral Rh(I) catalyst
is effected in the presence of a good π-acceptor ligand which favors the
metal elimination (ref 11), e.g. CO, the process actually results in the
clean formation of cyclopentene 7 (88% yield).
(13) Regarding the 1,3-dialkylidenecycloheptane ring, a SciFinder search reveals
that only the 2,7-dialkylidenecycloheptanone skeleton is known.
(14) One reviewer has pointed that a product-driven argument (Ni π-allyl
species II vs Rh vinyl species IV/V) can be taken into consideration.
Acknowledgment. This paper is dedicated to Professor Pedro
Molina on the occasion of his 60th birthday. Financial support for
this work is acknowledged (BQU2001-3853 and PR-01-GE-9). R.V.
JA045459Y
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