Chromium(0) alkynylcarbene complexes as C,β-electrophilic carbene equivalents: Regioselective access to dienynes and dienediynes

Article abstract of DOI:10.1002/anie.200605197

(Chemical Equation Presented) Just one step is all that is needed for a direct, selective, and easy synthesis of different conjugated enyne frameworks from simple chromium alkynylcarbene complexes and commercially available 2-methoxyfuran (see scheme).

Full text of DOI:10.1002/anie.200605197

Communications
DOI: 10.1002/anie.200605197
Extended Enyne Structures
Chromium(0) Alkynylcarbene Complexes as Cb-Electrophilic Carbene
Equivalents: Regioselective Access to Dienynes andDienediynes**
JosØ Barluenga,* Patricia García-García, Diana de Sµa, Manuel A. Fernµndez-Rodríguez,
Ramón Bernardo de la Rffla, Alfredo Ballesteros, Enrique Aguilar, and Miguel Tomµs
The evolution of organic chemistry has been marked by the
incorporation of novel transformations and the development
of new synthetic tools, many of which are based on the
potential of transition metals in carbon–carbon and carbon–
heteroatom bond-forming reactions. A number of these
synthetic processes mediated by heteroatom-stabilized car-
bene complexes—particularly chromium and tungsten com-
plexes—have been reported in the last two decades.[1] For
instance, the reactivity of unsaturated carbene complexes
such as the alkynyl(alkoxy)carbene complexes 1 is deter-
mined by the strong electron-acceptor nature of the metal–
carbene functionality, which makes these metal species useful
Scheme 1. Nucleophilic addition to metal alkynylcarbene complexes:
the fate of intermediate A. L.G.=leaving group.
substrates for cycloaddition reactions as well as for 1,2- and
1,4-nucleophilic addition reactions. Recent advances in this
area have shown that the novel nonstabilized alkynylcarbene
complexes 2 are also readily available,[2] thus making studies
of their reactivity possible.
We report herein that alkynylcarbene complexes 1 and 2
behave as synthetic equivalents of the electrophilic propar-
gylcarbene species D (Scheme 1) in their reaction with 2-
oxyfurans 3 (2-methoxyfuran (MeOF; 3a) and 2-trimethylsi-
lyloxyfuran (TMSOF; 3b)). Although 2-oxyfurans are known
to add to electron-poor alkenes, addition to an alkyne
functionality has not been reported previously as far as we
are aware.[5–7]
We initiated this study by using nonstabilized, highly
reactive alkynylcarbene complexes 2. These complexes, which
were generated at À808C from 4 as described previously,[2]
gave the dienyne adducts 5a–c in good yields upon treatment
with MeOF (3a; 1.6 equiv) and warming the reaction mixture
to room temperature (Scheme 2).[8] This novel olefination of
It is well known that the metal alkynyl(alkoxy)carbenes 1
(Scheme 1) readily undergo conjugate nucleophilic addition
to form substituted alkenyl(alkoxy)carbenes B via the
allenylmetalate species A,[3] and that intermediates contain-
ing a metal–carbon single bond, such as metalates, have a high
tendency to expel a neutral metal pentacarbonyl fragment.[4]
This observation led us to suppose that if a leaving group is
adequately placed within the nucleophile moiety, the allenyl-
metalate A might evolve to enynes C in an overall process
that would involve olefination of an sp-hybridized carbon and
subsequent carbene rearrangement.
[*] Prof. Dr. J. Barluenga, P. García-García, D. de Sµa,
Dr. M. A. Fernµndez-Rodríguez, Dr. R. Bernardo de la Rffla,
Dr. A. Ballesteros, Dr. E. Aguilar, Prof. Dr. M. Tomµs
Instituto Universitario de Química Organometµlica “Enrique
Moles”
Unidad Asociada al C.S.I.C
Universidad de Oviedo
C/. Juliµn Clavería, 8, 33006 Oviedo (Spain)
Fax: ( +34)985-103-450
E-mail: barluenga@uniovi.es
Homepage: http://www.uniovi.es/emdes/barluenga/index.htm
[**] We are grateful to the Ministerio de Educación y Ciencia (grant CTQ
2004-08077-C02-01, predoctoral fellowships to P.G.-G. and D. deS.)
and the Principado de Asturias (project IB05-136, predoctoral
fellowship to R.B.R.) for financial support. We also thank Dr. A. L.
Suµrez-Sobrino for his assistance with the X-ray crystallographic
analysis.
Scheme 2. Formation of conjugated dienynoic acid esters 5 (yields
given in brackets)
an alkynylcarbene is stereoselective and involves a formal 1,2-
migration of the C-C triple bond that leads to an overall
regioselective olefination at Cb of the alkynylcarbene.
Next, we found that classic heteroatom-stabilized Fischer
carbenes could also be used in this reaction; they provide an
Supporting Information for this article (experimental procedures
and spectroscopic data for 5a–c, 6a–g, 7a–d, 9a–c, and 11) is
available on the WWW under http://www.angewandte.org or from
the author.
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Angewandte
Chemie
alkoxy functionality at the alkynyl appendage (Table 1).
When chromium carbene complexes of 1a–g were treated
with two equivalents of 3a (THF or 1,4-dioxane, 08C to room
Table 1: Formation of conjugated dienynoic acid derivatives 6 and 7.[a]
Entry
1
R1
3
Product
Yield [%][b,c]
1
2
1a
1b
Ph
3a
3a
6a
6b
83 (97)
91
4-MeO-C6H4
3
1c
3a
6c
86 (91)
Scheme 3. Proposed reaction pathways for the formation of 5–7.
4
1d
3a
6d
87
5
6
1e
1 f
TMS
nBu
3a
3a
6e
6 f
89
96
7
8
1g
1a
3a
3b
6g
7a
73
Ph
54 (55)
9
1c
3b
7b
44
10
11
1 f
1h
nBu
tBu
3b
3b
7c
7d
41
56
[a] All reactions were carried out with 1.0 mmol of the carbene complex
and two equivalents of the corresponding 2-oxyfuran in 10 mL of THF (or
1,4-dioxane). [b] Yields of isolated product for the reaction performed in
THF, based on 1. [c] Yields for the reaction performed in 1,4-dioxane are
given in brackets.
temperature, overnight) the expected 7-methoxy-2,4-hepta-
dien-6-ynoic acid derivatives 6a–g were produced in 73–97%
yield (Table 1, entries 1–7). The scope of this reaction is
noteworthy as both simple and functionalized R1 substituents
are tolerated (alkyl, aryl, alkenyl, trimethylsilyl (TMS),
alkynylalkyl). Moreover, the reaction of 3b with carbene
complexes 1a,c,f,h under the same reaction conditions led to
the corresponding polyunsaturated carboxylic acids 7a–d,
although in somewhat lower yield (41–56%; Table 1,
entries 8–11).
The observed results can be rationalized by Michael-type
addition of 3a to the alkynyl function of carbenes 1 and 2 to
generate the zwitterionic allenyl intermediate I (Scheme 3,
path A). Reorganization of this species by metal-elimination-
induced furan ring-opening regenerates the alkyne function
and provides the (Z)-pentadienoate moiety of adducts 5–7.
An alternative proposal would involve a 1,3-Cr(CO)5 shift to
generate the rearranged metal carbene II,[9] which would
evolve by 1,2-addition of 3 (to form intermediate III) and
metal elimination/ring-opening (Scheme 3, path B). How-
ever, the latter pathway can be ruled out, at least for metal
carbenes 1 (R = OMe), since their equilibration into carbenes
II is thermodynamically unfavorable.[2]
Scheme 4. Synthesis of linear- (9) and cross-conjugated dienynes (11;
yields given in brackets) from cross- (8) and linear-conjugated
diynecarbenes (10).
yield), whose structure was determined by X-ray diffraction
analysis.[10,11] Unsymmetrical carbenes 8b (R1 = nPr; R2 = 4-
MeO-C6H4) and 8c (R1 = Ph; R2 = iPr3Si) led exclusively to
single regioisomers 9b and 9c, respectively. These observa-
tions allowed us to estimate the ability of the R1 group to
induce the 1,3-carbene rearrangement as being in the order
alkyl > aryl > trialkylsilyl.
Finally, cross-conjugated dienediynes are also accessible
from linear dienylcarbenes. For instance, the reaction of the
chromium phenylbutadiynyl(ethoxy)carbene 10 with 3a
afforded the cross-conjugated dienediyne 11 (62% yield),
with complete chemoselectivity, as a result of initial nucleo-
philic attack at Cb of the diyne system.[12]
In summary, we have established a direct, flexible, and
selective route to a variety of dienynes, which may be useful as
building blocks for molecular scaffolding, including several
dienediynes bearing different conjugation patterns and func-
tionalities.[13] Importantly, the reaction reported herein
involves isomerization of the alkynyl function of an alkynyl-
carbene complex and olefination at Cb.[14] Representative
experiments show complete regioselectivity for the compet-
We also explored more complex substrates, such as linear
and cross-conjugated diynylcarbenes (Scheme 4), and were
delighted to find that the symmetrical carbene 8a (R1 = R2 =
Ph) reacts with 3a to form the linear diendiyne 9a (73%
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[7] For the chromium(0)-catalyzed olefination of diazo compounds
with 2-substituted furans, see: N. D. Hahn, M. Nieger, K. H.
Dötz, J. Organomet. Chem. 2004, 689, 2662 – 2673.
[8] The structures of the new compounds were ascertained by NMR
spectroscopic experiments, including COSY, HSQC, HMBC,
and NOESY experiments for selected compounds (see the
Supporting Information).
itive alkyne isomerization for alkyl, aryl, and silyl groups. This
new reactivity pattern for Group 6 metal alkynylcarbene
complexes could open up the possibility of designing new
reactions of the proposed propargylic-type carbene. Research
aimed at performing a twofold coupling at Cb, for instance, is
currently underway.
[9] A 1,3-metal shift in nonstabilized transition metal alkynylcar-
bene complexes is well known. See, for example: a) A. Padwa,
D. J. Austin, Y. Gareau, J. M. Kassir, S. L. Xu, J. Am. Chem. Soc.
1993, 115, 2637 – 2647; b) C. P. Casey, T. L. Dzwiniel, Organo-
metallics 2003, 22, 5285 – 5290; c) Y. Ortin, A. Sournia-Saquet, N.
Lugan, R. Mathieu, Chem. Commun. 2003, 1060 – 1061; d) E. J.
Cho, M. Kim, D. Lee, Eur. J. Org. Chem. 2006, 3074 – 3078;
e) D. J. Gorin, P. DubØ, F. D. Toste, J. Am. Chem. Soc. 2006, 128,
14480 – 14481; f) K. Ohe, M. Fujita, H. Matsumoto, Y. Tai, K.
Miki, J. Am. Chem. Soc. 2006, 128, 9270 – 9271; g) S. López, E.
Herrero-Gómez, P. PØrez-Galµn, C. Nieto-Oberhuber, A. M.
Echavarren, Angew. Chem. 2006, 118, 6175 – 6178; Angew.
Chem. Int. Ed. 2006, 45, 6029 – 6032.
Received: December 22, 2006
Published online: February 19, 2007
Keywords: carbenes · chromium · enynes · isomerization ·
.
olefination
[1] Selected recent reviews: a) J. W. Herndon, Coord. Chem. Rev.
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[10] CCDC 631762 contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge from
The Cambridge Crystallographic Data Centre via www.ccdc.
cam.ac.uk/data_request/cif.
[2] J. Barluenga, R. Bernardo de la Rffla, D. de Sµa, A. Ballesteros,
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[11] Free penta-1,4-diyn-3-ylidenes (diethynylcarbenes) have been
generated thermally or photochemically and react preferentially
through the central carbon: N. P. Bowling, R. J. Halter, J. A.
Hodges, R. A. Seburg, P. S. Thomas, C. S. Simmons, J. F. Stanton,
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[12] The configuration of the trisubstituted double bond of 11 could
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configuration as in adducts 5, 6, 7, and 9.
[4] K. Maeyama, N. Iwasawa, J. Am. Chem. Soc. 1998, 120, 1928 –
1929.
[5] 2-Oxyfurans as dienes or dienophiles: a) A. Zhou, M. Segi, T.
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Kusama, F. Shiozawa, M. Shido, N. Iwasawa, Chem. Lett. 2002,
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[13] For a recent synthesis of linear dienynes, see: a) iridium-
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[14] a) The construction of enynes by olefination with propargylic
reagents, such as phosphorus ylides and anions of propargylic
silanes and sulfones (Wittig, Peterson, and Julia methodologies,
respectively), works well for trialkylsilyl-substituted alkyne
substrates; b) for a recent review of transition-metal-catalyzed
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[6] The addition reaction of MeOF to the acetylenic esters does not
take place below 508C.
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