Fe-catalyzed allylic C-C-bond activation: Vinylcyclopropanes as versatile a1,a3,d5-synthons in traceless allylic substitutions and [3 + 2]-cycloadditions

Article abstract of DOI:10.1021/ja300294a

The low-valent iron complex Bu₄N[Fe(CO)₃(NO)] (TBAFe) catalyzes the allylic C-C-bond activation of electron-poor vinyl cyclopropanes to generate synthetically useful a1,a3,d5-synthons which are prone to undergo multiple consecutive reactions. The versatility of this approach is demonstrated by a traceless allylic substitution and a formal [3 + 2] cycloaddition to give either functionalized acyclic products or densely substituted cyclopentanes and pyrrolidines in high yields and regioselectivities.

Full text of DOI:10.1021/ja300294a

Communication
pubs.acs.org/JACS
Fe-Catalyzed Allylic C−C-Bond Activation: Vinylcyclopropanes As
Versatile a1,a3,d5-Synthons in Traceless Allylic Substitutions and [3 +
2]-Cycloadditions
Andre P. Dieskau, Michael S. Holzwarth, and Bernd Plietker*
́
Institut fur Organische Chemie, Universitat Stuttgart, Pfaffenwaldring 55, DE-70569 Stuttgart, Germany
̈
̈
S
* Supporting Information
ABSTRACT: The low-valent iron complex Bu4N[Fe-
(CO)3(NO)] (TBAFe) catalyzes the allylic C−C-bond
activation of electron-poor vinyl cyclopropanes to generate
synthetically useful a1,a3,d5-synthons which are prone to
undergo multiple consecutive reactions. The versatility of
this approach is demonstrated by a traceless allylic
substitution and a formal [3 + 2] cycloaddition to give
either functionalized acyclic products or densely sub-
stituted cyclopentanes and pyrrolidines in high yields and
regioselectivities.
ithin the past years our group and others have shown
W
that the electron-rich ferrate Bu4N[Fe(CO)3(NO)]
(TBAFe) is a versatile electron-transfer catalyst that can be
employed in various transformations like allylic substitutions,1
transesterifications,2 or hydrosilylations.3 Although the former
transformation is performed under neutral and salt-free
conditions the degree of atom economy in transition metal
catalyzed allylic substitutions in general can be improved
through the use of strained vinyl-substituted rings like
vinyloxiranes,4 vinylaziridines,5 or vinylcyclopropanes.6,7
Figure 1. Iron-catalyzed C−C bond activations.
The complementary activation of a VCP using a metal-centered
nucleophilic ferrate with generation of an intermediate allyl-Fe
complex, which might be regarded as an a1,a3,d5-synthon,
however has not been reported yet but would open up new
perspectives for synthetic applications.20
Herein we report that the nucleophilic ferrate Bu4N[Fe-
(CO)3(NO)] (TBAFe) is an efficient catalyst for this particular
allylic C−C-bond activation. The synthetic versatility of the
intermediate allyl metal complexes is demonstrated in a formal
traceless allylic substitution and a [3 + 2]-cycloaddition
(Scheme 1).
We initiated our studies by focusing on the traceless allylic
substitution reaction. The carbanion of the allyl-Fe inter-
mediate, which is formed upon Fe-mediated C−C-bond
scission, reacts as a base and generates a new nucleophilic
species which in turn attacks the allyl metal a1,a3-acceptor to
give the corresponding homologation product (Scheme 1). In
order to trigger the proton shift, a sufficient difference in the
pKa values of the primary formed carbanion and the
pronucleophile is a prerequisite. As a consequence acidic
pronucleophiles were chosen as coupling partners. After an
We envisioned this strategy to be attractive in order to push
the limits in Fe-catalyzed allylic substitution chemistry. In
particular the activation of a C−C-bond appeared to be of
interest from both a catalytic and synthetic point of view. The
selective catalytic activation of a carbon−carbon single bond is
a scientific task that has attracted considerable interest in the
past decade.8 The working catalytic systems are mainly based
on rhodium,9 ruthenium,10 nickel,11 and palladium.12 However,
systems that employ inexpensive and readily abundant metals
such as iron have only scarcely been investigated. Iron salts
were shown to act as Lewis acid catalysts13−15 leading to
stabilized carbenium ions which can be trapped in Friedel−
Craft type reactions (eqs 1 and 2, Figure 1). Furthermore, ferric
chloride catalyzes the DDQ/TMSN3 mediated formation of
amides under oxidative conditions (eq 2, Figure 1).16 In the
field of photocatalysis, [Cp(CO)2FeMe] allows for a σ-bond
metathesis between alkylsilanes and alkylnitriles via the cleavage
of a C−CN bond (eq 3, Figure 1).17 The catalytic activation of
vinylcyclopropanes (VCPs) by a Lewis acid18 or nucleophilic
noble metal catalysts based on Pd,7a−e Ir,7e Rh,7f,g Ru,7h and
Ni7i,j is a literature precedent. Furstner was able to show that
̈
low-valent ferrates generated in situ by treating Fe(acac)3 with
alkyl Grignard reagents are potent catalysts for the addition of
hard nucleophiles into the π-bond of a VCP (eq 4, Figure 1).19
Received: January 11, 2012
Published: March 7, 2012
© 2012 American Chemical Society
5048
dx.doi.org/10.1021/ja300294a | J. Am. Chem. Soc. 2012, 134, 5048−5051

Journal of the American Chemical Society
Communication
Scheme 1. Fe-Catalyzed Traceless Allylic Substitution and [3
+ 2]-Cycloaddition of VCPs
Scheme 2. Sequential Fe-Catalyzed Transformations of
VCPs
optimization of solvent and ligands,21 we were pleased to find
that TBAFe and NHC-ligand L1 in THF combine to a potent
catalytic system for this transformation. The desired sub-
stitution products were obtained in good to excellent yields and
regioselectivities in favor of the linear substitution products A
(Table 1).
Table 1. Fe-Catalyzed Traceless Allylic Substitution of
a
VCPs
methyl glycinate delivered, under standard coupling con-
ditions,23 functionalized dipeptide 12 in good overall yield. In
contrast, the addition of allyl carbonate 11 to the reaction
mixture triggers a second Fe-catalyzed process leading to the
allylic substitution product 13 in good regioselectivity and a
reasonable 58% isolated yield.
We subsequently turned our attention toward the elaboration
of the second reaction manifold, the formal [3 + 2]-
cycloaddition. In this case the carbanion of the allyl-Fe
intermediate, formed upon Fe-mediated C−C-bond scission,
reacts as a d5-synthon in a Michael addition thus generating a
new carbanion that adds onto the allyl Fe-moiety to form a five-
membered ring (Scheme 1).
Performing this transformation under the conditions that
proved successful for the traceless allylic substitution gave only
moderate conversions; however, good yields of the desired
cycloaddition products were obtained using mesityl substituted
NHC-ligand L2 (Table 2).20 First the scope of vinyl-
cyclopropanes was investigated using 1,1-bis(phenylsulphonyl)-
ethylene as a Michael acceptor. To our delight different VCPs
can be employed in this cycloaddition giving rise to
vinylcyclopentanes 14−18 in good to excellent yields.
Competing side reactions like dimerization of the starting
material or formation of the corresponding seven-membered
rings were not observed. Functional groups such as esters,
nitriles, or amides on the VCPs are tolerated. Whereas a
Meldrum acid derived VCP was unreactive, barbiturate-derived
VCP gave rise to spiro compound 18 in a 90% yield. Further
studies focused on the application of different activated olefins
in the [3 + 2]-cycloaddition using malononitrile-derived VCP
as a coupling partner. A variety of Michael acceptors are
reactive, yielding densely substituted carbocycles in good to
excellent yields albeit with low diastereoselectivities (19, 21−
24) (Table 2). The transformation displays a broad functional
group tolerance. Esters, sulfones, nitriles, amides, and ketones
are successfully employed; even heterocycles such as indoles 24
are tolerated. The use of an extended Michael acceptor yields
only the 1,4-addition product 23. Interestingly, for some
unsymmetrically substituted Michael acceptors a moderate
stereoselective bias could be observed during product
formation (20, 25) generating only two out of four possible
diastereoisomers.
a
The reactions were performed on a 0.2 mmol scale, using
vinylcyclopropane (1 equiv), pronucleophile (1.5 equiv), TBAFe (10
mol %), and L1 (10 mol %) in THF (0.4 M) at 80 °C.
A variety of pronucleophiles such as malodinitrile, a
cyanophenyl ester, cyanocyclopentanone, or a phenylazlactone
were successfully employed in this transformation giving rise to
polyfunctional products in good to excellent yields. In general
E-configured double bonds were formed with high selectivity.
However, a drop in E/Z ratio was observed for azlactone 8.
Interestingly, in the presence of malodinitrile the minor isomer
2B was not isolated as the anticipated branched product, but
rather as the cyclic enamine resulting from a subsequent
cyclization.22
In order to underline the synthetic usefulness of this
transformation, vinylcyclopropane 1a was employed in two
different sequential transformations: an Fe-catalyzed traceless
allylic substitution followed by a ring opening of the azlactone
by an amino acid (eq 1, Scheme 2) and a traceless allylic
substitution followed by a standard allylic substitution (eq 2,
Scheme 2). Without isolation of intermediate 8, the addition of
5049
dx.doi.org/10.1021/ja300294a | J. Am. Chem. Soc. 2012, 134, 5048−5051

Journal of the American Chemical Society
Communication
a
functional group tolerance. The advantages of the present
catalytic system were demonstrated in sequential iron-catalyzed
transformations. Apart from the synthetic usefulness of the
multifunctional products, the activation of electron-poor allylic
C−C bonds opens up new perspectives in the field of low-
valent Fe catalysis. Future studies will focus on the activation of
other strained ring systems such as cyclobutanes as well as vinyl
oxiranes and aziridines.
Table 2. Fe-Catalyzed [3 + 2]-Cycloaddition of VCPs
ASSOCIATED CONTENT
* Supporting Information
■
S
Detailed experimental procedures and characterization of all
reported compounds. This material is available free of charge
via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
bernd.plietker@oc.uni-stuttgart.de
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Financial support by the Deutsche Forschungsgemeinschaft
and the Studienstiftung des deutschen Volkes (Ph.D. grant for
A.P.D.) is gratefully acknowledged.
REFERENCES
■
(1) (a) Dieskau, A. P.; Plietker, B. Org. Lett. 2011, 13, 5544−5547.
(b) Holzwarth, M. S.; Frey, W.; Plietker, B. Chem. Commun. 2011, 47,
11113−11115. (c) Trivedi, R.; Tunge, J. A. Org. Lett. 2009, 11, 5650−
5652. (d) Plietker, B.; Dieskau, A.; Mows, K.; Jatsch, A. Angew. Chem.,
̈
a
The reactions were performed on a 0.2 mmol scale, using
vinylcyclopropane (1 equiv), Michael acceptor (1.25 equiv), TBAFe
(10 mol %), and L2 (10 mol %) in THF at 80 °C unless noted
Int. Ed. 2008, 47, 198−201. (e) Plietker, B. Angew. Chem., Int. Ed.
2006, 45, 1469−1473.
(2) (a) Magens, S.; Ertelt, M.; Jatsch, A.; Plietker, B. Org. Lett. 2007,
10, 53−56. (b) Magens, S.; Plietker, B. Chem.Eur. J. 2011, 17,
8807−8809.
b
otherwise. Reaction run at 60 °C.
Finally, we wondered whether we could extend this method
toward electron-deficient π-bonds of imines. Whereas N-Ph and
N-Boc protected imines gave no or an undefined reaction, we
were pleased to find that N-tosyl arylimines are good coupling
partners for this transformation. In two test experiments 1b was
coupled with 26a and 26b under the standard reaction
conditions to the corresponding pyrrolidines 27 and 28 in
good yields, albeit with low diastereoselectivity (Scheme 3).
Unfortunately aldehydes were not applicable toward the
reaction conditions.
(3) Dieskau, A. P.; Begouin, J.-M.; Plietker, B. Eur. J. Org. Chem.
2011, 5291−5296.
(4) (a) Olofsson, B.; Somfai, P. Aziridines and Epoxides in Organic
Synthesis; Wiley-VCH Verlag GmbH & Co. KGaA: 2006; pp 315−347.
(b) Trost, B. M.; Crawley, M. L. Chem. Rev. 2003, 103, 2921−2944.
Some recent examples for Pd: (c) Trost, B. M.; Horne, D. B.;
Woltering, M. J. Angew. Chem., Int. Ed. 2003, 42, 5987−5990.
́
(d) Castano, A. M.; Mendez, M.; Ruano, M.; Echavarren, A. M. J. Org.
̃
Chem. 2000, 66, 589−593.
(5) (a) Ohno, H. Aziridines and Epoxides in Organic Synthesis; Wiley-
VCH Verlag GmbH & Co. KGaA: 2006; pp 37−71. Some recent
examples for Pd: (b) Lowe, M. A.; Ostovar, M.; Ferrini, S.; Chen, C.
C.; Lawrence, P. G.; Fontana, F.; Calabrese, A. A.; Aggarwal, V. K.
Angew. Chem., Int. Ed. 2011, 50, 6370−6374. (c) Trost, B. M.; Osipov,
M.; Dong, G. J. Am. Chem. Soc. 2010, 132, 15800−15807. (d) Trost, B.
M.; Fandrick, D. R.; Brodmann, T.; Stiles, D. T. Angew. Chem., Int. Ed.
2007, 46, 6123−6125.
Scheme 3. Fe-Catalyzed VCP Activation towards
Pyrrolidines
(6) (a) Rubin, M.; Rubina, M.; Gevorgyan, V. Chem. Rev. 2007, 107,
3117−3179. (b) Khusnutdinov, R. I.; Dzhemilev, U. M. J. Organomet.
Chem. 1994, 471, 1−18.
(7) For Pd, see: (a) Trost, B. M.; Morris, P. J. Angew. Chem., Int. Ed.
2011, 50, 6167−6170. (b) Goldberg, A. F. G.; Stoltz, B. M. Org. Lett.
In summary we report the allylic C−C-bond activation in the
presence of the low-valent iron (-II) complex Bu4N[Fe-
(CO)3(NO)] (TBAFe). The intermediate allyl Fe-complex
was employed as an a1,a3,d5-synthon in a traceless allylic
substitution and a [3 + 2]-cycloaddition with activated olefins
and imines giving rise to densely substituted vinylcyclopentanes
or -pyrrolidines. Both reaction manifolds display a broad
́
2011, 13, 4474−4476. (c) Sebelius, S.; Olsson, V. J.; Szabo, K. J. J. Am.
Chem. Soc. 2005, 127, 10478−10479. (d) Burgess, K. J. Org. Chem.
1987, 52, 2046−2051. (e) Sebelius, S.; Olsson, V. J.; Wallner, O. A.;
́
Szabo, K. J. J. Am. Chem. Soc. 2006, 128, 8150−8151. For Ir, see: A
fascinating Umpolung reaction of VCPs has been published recently:
(e) Moran, J.; Smith, A. G.; Carris, R. M.; Johnson, J. S.; Krische, M. J.
J. Am. Chem. Soc. 2011, 133, 18618−18621. For Rh, see: (f) Yu, Z.-X.;
Wender, P. A.; Houk, K. N. J. Am. Chem. Soc. 2004, 126, 9154−9155.
5050
dx.doi.org/10.1021/ja300294a | J. Am. Chem. Soc. 2012, 134, 5048−5051

Journal of the American Chemical Society
Communication
(g) Wender, P. A.; Husfeld, C. O.; Langkopf, E.; Love, J. A. J. Am.
Chem. Soc. 1998, 120, 1940−1941. For Ru, see: (h) Trost, B. M.;
Toste, F. D.; Shen, H. J. Am. Chem. Soc. 2000, 122, 2379−2380. For
Ni, see: (i) Sumida, Y.; Yorimitsu, H.; Oshima, K. Org. Lett. 2008, 10,
4677. (j) Bowman, R. K.; Johnson, J. S. Org. Lett. 2006, 8, 573.
(8) Jun, C.-H. Chem. Soc. Rev. 2004, 33, 610−618.
(9) (a) Seiser, T.; Cramer, N. J. Am. Chem. Soc. 2010, 132, 5340−
5341. (b) Crepin, D.; Dawick, J.; Aïssa, C. Angew. Chem., Int. Ed. 2010,
́
49, 620−623. (c) Seiser, T.; Cramer, N. Angew. Chem., Int. Ed. 2008,
47, 9294−9297. (d) Dreis, A. M.; Douglas, C. J. J. Am. Chem. Soc.
2008, 131, 412−413. (e) Nishimura, T.; Katoh, T.; Takatsu, K.;
Shintani, R.; Hayashi, T. J. Am. Chem. Soc. 2007, 129, 14158−14159.
(f) Wender, P. A.; Deschamps, N. M.; Sun, R. Angew. Chem., Int. Ed.
2006, 45, 3957−3960. (g) Taw, F. L.; Mueller, A. H.; Bergman, R. G.;
Brookhart, M. J. Am. Chem. Soc. 2003, 125, 9808−9813. (h) Bart, S.
C.; Chirik, P. J. J. Am. Chem. Soc. 2003, 125, 886−887. (i) Murakami,
M.; Takahashi, K.; Amii, H.; Ito, Y. J. Am. Chem. Soc. 1997, 119, 9307−
9308. (j) Murakami, M.; Amii, H.; Ito, Y. Nature 1994, 370, 540−541.
(k) Gozin, M.; Weisman, A.; Ben-David, Y.; Milstein, D. Nature 1993,
364, 699−701.
(10) (a) Kondo, T.; Kodoi, K.; Nishinaga, E.; Okada, T.; Morisaki,
Y.; Watanabe, Y.; Mitsudo, T.-aki J. Am. Chem. Soc. 1998, 120, 5587−
5588. (b) Shimada, T.; Yamamoto, Y. J. Am. Chem. Soc. 2003, 125,
6646−6647.
(11) (a) Watson, M. P.; Jacobsen, E. N. J. Am. Chem. Soc. 2008, 130,
12594−12595. (b) Nakao, Y.; Yukawa, T.; Hirata, Y.; Oda, S.; Satoh,
J.; Hiyama, T. J. Am. Chem. Soc. 2006, 128, 7116−7117. (c) Murakami,
M.; Ashida, S.; Matsuda, T. J. Am. Chem. Soc. 2005, 127, 6932−6933.
(d) Nakao, Y.; Oda, S.; Hiyama, T. J. Am. Chem. Soc. 2004, 126,
13904−13905.
(12) (a) Matsumura, S.; Maeda, Y.; Nishimura, T.; Uemura, S. J. Am.
Chem. Soc. 2003, 125, 8862−8869. (b) Nishimura, T.; Uemura, S. J.
Am. Chem. Soc. 2000, 122, 12049−12050. (c) Nishimura, T.; Ohe, K.;
Uemura, S. J. Am. Chem. Soc. 1999, 121, 2645−2646.
(13) (a) Huang, L.; Cheng, K.; Yao, B.; Xie, Y.; Zhang, Y. J. Org.
Chem. 2011, 76, 5732−5737. (b) Paine, T. K.; England, J.; Que, L.
Chem.Eur. J. 2007, 13, 6073−6081.
(14) (a) Rao, C. B.; Rao, D. C.; Babu, D. C.; Venkateswarlu, Y. Eur. J.
Org. Chem. 2010, 2855−2859. (b) Biswas, S.; Maiti, S.; Jana, U. Eur. J.
Org. Chem. 2010, 2861−2866.
(15) Li, H.; Li, W.; Liu, W.; He, Z.; Li, Z. Angew. Chem., Int. Ed. 2011,
50, 2975−2978.
(16) Qin, C.; Zhou, W.; Chen, F.; Ou, Y.; Jiao, N. Angew. Chem., Int.
Ed. 2011, 50, 12595−12599.
(17) Nakazawa, H.; Itazaki, M.; Kamata, K.; Ueda, K. Chem.Asian J.
2007, 2, 882−888.
(18) (a) Parsons, A. T.; Smith, A. G.; Neel, A. J.; Johnson, J. S. J. Am.
Chem. Soc. 2010, 132, 9688−9692. (b) Parsons, A. T.; Johnson, J. S. J.
Am. Chem. Soc. 2009, 131, 3122−3123. (c) Pohlhaus, P. D.; Sanders,
S. D.; Parsons, A. T.; Li, W.; Johnson, J. S. J. Am. Chem. Soc. 2008, 130,
8642−8650. (d) England, D. B.; Kuss, T. D. O.; Keddy, R. G.; Kerr,
M. A. J. Org. Chem. 2001, 66, 4704−4709.
(19) Sherry, B. D.; Furstner, A. Chem. Commun. 2009, 7116−7118.
̈
(20) For stoichiometric reactions of Fe-carbonyls with vinyl-
cyclopropanes, see: (a) Taber, D. F.; Kanai, K.; Jiang, Q.; Bui, G. J.
Am. Chem. Soc. 2000, 122, 6807−6808. (b) Johnson, B. F. G.; Lewis,
J.; Thompson, D. J.; Heil, B. J. Chem. Soc., Dalton Trans. 1975, 567−
571. (c) Eisenstadt, A. Tetrahedron Lett. 1972, 13, 2005−2008.
(d) Sarel, S.; Ben-Shoshan, R.; Kirson, B. J. Am. Chem. Soc. 1965, 87,
2517−2518.
(21) See Supporting Information for details.
(22) The branched isomer 2B cyclizes spontaneously to the
corresponding enamine:
(23) Ruble, J. C.; Fu, G. C. J. Am. Chem. Soc. 1998, 120, 11532−
11533.
5051
dx.doi.org/10.1021/ja300294a | J. Am. Chem. Soc. 2012, 134, 5048−5051