Ni-catalyzed ketene cycloaddition: A system that resists the formation of decarbonylation side products

Article abstract of DOI:10.1021/ja2007627

Ni-phosphine complexes were used as catalysts for the cycloaddition of various ketenes and diynes. In general, 2,4-cyclohexadienones were formed instead of products arising from decarbonylation of the ketenes.

Full text of DOI:10.1021/ja2007627

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pubs.acs.org/JACS
Ni-Catalyzed Ketene Cycloaddition: A System That Resists the
Formation of Decarbonylation Side Products
Puneet Kumar, Dawn M. Troast, Rodrigo Cella, and Janis Louie*
Department of Chemistry, University of Utah, 315 South 1400 East, Salt Lake City, Utah 84112-8450, United States
S Supporting Information
b
ABSTRACT: Niꢀphosphine complexes were used as
catalysts for the cycloaddition of various ketenes and diynes.
In general, 2,4-cyclohexadienones were formed instead of
products arising from decarbonylation of the ketenes.
Figure 1. Modes of ketene coordination.
Scheme 1
lmost every possible unsaturated starting material (alkynes,
A
alkenes, dienes, CO2, nitriles, isocyanates, carbonyls, etc.)
has been employed as a substrate in transition-metal-catalyzed
cycloadditions.1,2 Despite this rich history of cycloaddition chemistry,
ketene substrates are notoriously absent.3 Insufficient reactivity
between potential transition-metal catalysts and ketenes is not the
problem. Ketenes easily form η2 complexes with various metals (Ni,
Pd, Pt, Co, Rh, Ir, etc.).4,5 Furthermore, two modes of coordination,
CꢀO or CꢀC binding, are available to ketenes (Figure 1). The
inability of these η2 complexes to undergo further reactions with other
unsaturated coupling partners lies in their propensity to undergo
decarbonylation and form stable, unreactive MꢀCO complexes
(Scheme 1).4ꢀ6 In addition, ketenes often undergo homodimeriza-
tion under thermal conditions.7 In view of these pitfalls, we were
surprised and delighted to discover that Niꢀphosphine catalysts
mediate the cycloaddition of ketenes and diynes to afford cyclohex-
adienones in good yields.8,9 Herein, we report these results.
We initially discovered that the combination of 10 mol % Ni-
(COD)2 and 10 mol % DPPF successfully catalyzed the cycloaddition
of diyne 1 and phenyl ethyl ketene a (eq 1). The cycloaddition
afforded a carbocyclic product (1a) resulting from the coupling of the
CꢀC bond of ketene a rather than the pyran (1a0) that would have
resulted from the coupling of the CꢀO bond.2j,k Other ligands and
conditions were evaluated in an effort to optimize the reaction
conditions (Table 1). In most cases, byproducts arising from dimer-
ization of the diyne and ketene were observed (entries 1ꢀ8).
However, we found that high yields were obtained when either DPPF
or DPPB was employed as the ligand. Ultimately, the following
optimized conditions were employed: 5 mol % catalyst loading
[Ni(COD)2 and DPPB in 1:1 ratio] at a 0.1 M reaction concentration
in toluene at 60 °C.10
Importantly, we found that ketenes other than a could be used
as substrates in the cycloaddition reaction and that a variety of
cyclohexadienones could be prepared under these optimized
reaction conditions (Table 2). For example, diyne 1 not only
reacted with ketene a but also with diaryl ketene b as well as
ketene c with increased steric hindrance (entries 1ꢀ3). Diynes
that are prone to cyclotrimerization side reactions,11 such as
phenyl-substituted diyne 2 and terminal diynes 3 and 4, were also
successfully converted to their respective cyclohexadienone
products in moderate yields (entries 4ꢀ6). In addition, cycload-
dition products could be prepared from sulfonamide diynes and
diyneꢀethers (entries 7ꢀ9).
Diynes separated by a four-atom linker instead of a three-atom
linker afforded cyclohexadienones in higher yields (entries
10ꢀ18). For example, the reaction between diyne 7 and ketene
a afforded the product in 91% yield (entry 10) versus 82% with
diyne 1 (entry 1). We found that a ketene bearing an electron-
withdrawing group at the para position (ꢀF; entry 13) enhanced
the formation of the carbocyclic product, whereas ketenes
Received: January 25, 2011
Published: April 29, 2011
r
2011 American Chemical Society
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dx.doi.org/10.1021/ja2007627 J. Am. Chem. Soc. 2011, 133, 7719–7721
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Table 1. Ni-Catalyzed Cycloaddition of Diynes and Ketenesa
Table 2. Ni-Catalyzed Cycloaddition of Diynes and Ketenesa
Entry
Ligand (Ln)
Ni:Ln
1 % Conv.b
1a % Yieldb
1
2
IPrc
SIPrc
1:2
1:2
1:2
1:2
1:2
1:2
1:1
1:1
1:1
1:1
100
63
12
3
3
PPh3
100
100
100
100
32
39
4
PCy3
20
5
MePPh2
CyPPh2
DPPE
DCPE
DPPF
DPPB
54
6
31
2
7
8
22
ꢀ
9
100
>99 (86)d
86 (86)d
10
100
a Reaction conditions: Ni catalyst (5 mol %), diyne (1 equiv, 0.05 M), and
ketene (1.2 equiv) in benzene at 60 °C for 12 h. b Analyzed by GC using
decane as an internal standard. c The catalyst solutions were equilibrated for
at least 6 h before use. d The values in parentheses are isolated yields.
bearing an electron-donating group at the para position (ꢀOMe,
ꢀMe; entries 11 and 12) had the opposite effect. Interestingly,
the cycloaddition of diyne 7 and trimethylsilyl ketene i gave a
phenolic product resulting from a facile 1,3-silyl migration
(Figure 2).12 The reaction of ketene j afforded a spirobicyclic
product in good yield (entry 17). Again, terminal diynes 8
and 9 were also found to afford carbocyclic products, as
evidenced by the formation of 8a and 9a (entries 18 and 19
respectively).13
Figure 2. Proposed intermediate.
The standard reaction conditions were applied to unsymme-
trical diyne 10. We were delighted to obtain regioisomer 10a
selectively in 66% yield (eq 2). The regiochemistry of 10a was
determined by one-dimensional nuclear Overhauser effect
(nOe) spectroscopy.
a Reaction conditions: Ni(COD)2 (5 mol %), DPPB (5 mol %), diyne
(1 equiv, 0.1 M), and ketene (1.2 equiv) in toluene at 60 °C for 5 h.
b Isolated yields. c Average of at least two runs. d Crude ketene was used.
The asymmetric formation of quaternary stereocenters re-
mains a formidable challenge for organic chemists.14 With this in
mind, we also investigated the development of an asymmetric
version of the cycloaddition reaction. Initial investigations em-
ploying (R)-BINAP as the ligand gave dismal results. That is, no
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reaction was observed under the standard reaction conditions (5
mol % catalyst and 0.1 M diyne at 60 °C in toluene). However, a
carbocyclic product was generated when the temperature was
elevated to 80 °C. Although a relatively low yield (38%) was
obtained, excellent enantioselectivity (99%) was observed (eq 3).
A higher yield was obtained when the reaction temperature
was increased to 100 °C. Gratifyingly, only a slight decrease
in enantioselectivity was observed at a higher temperature
(100 °C).
In conclusion, we have successfully incorporated ketenes in
[2 þ 2þ2] cycloaddition reactions with diynes. Decarbonylation
of the ketene starting materials was not observed. Instead, a
variety of 2,4-cyclohexadienones were formed. An enantiopure
cyclohexadienone product was obtained when (R)-BINAP was
used as the ligand. Efforts to develop a general asymmetric
catalyst system and understand the mechanistic details of this
cycloaddition chemistry are underway.
(5) For various metalꢀketene complexes, see: Ni: (a) Hoberg, H.;
Korff, J. J. Organomet. Chem. 1978, 152, 255. (b) Sugai, R.; Miyashita, A.;
Nohira, H. Chem. Lett. 1988, 17, 1403. (c) Miyashita, A.; Grubbs, R. H.
TetrahedronLett. 1981, 22, 1255. (d) Miyashita, A.; Shitara, H.; Nohira, H.
J. Chem. Soc., Chem. Commun. 1985, 850. Pt:(e) Schorpp, K.; Beck, W. Z.
Naturforsch. 1973, 28B, 738. (f) Miyashita, A.; Shitara, H.; Nohira, H.
Organometallics 1985, 4, 1463. Ti, Zr:(g) Straus, D. A.; Grubbs, R. H. J.
Am. Chem. Soc. 1982, 104, 5499. Ir:(h) Lo, H. C.; Grotjahn, D. B. J. Am.
Chem. Soc. 1997, 119, 2958. (i) Grotjahn, D. B.; Bikzhanova, G. A.;
Collins, L. S. B.; Concolino, T.; Lam, K.-C; Rheingold, A. L. J. Am. Chem.
Soc. 2000, 122, 5222. (j) Grotjahn, D. B.; Collins, L. S. B.; Wolpert, M.;
Bikzhanova, G. A.; Lo, H. C.; Combs, D.; Hubbard, J. L. J. Am. Chem. Soc.
2001, 123, 8260. (k) Grotjahn, D. B.; Hoerter, J. M.; Hubbard, J. L. J. Am.
Chem. Soc. 2004, 126, 8866. Rh:(l) Grotjahn, D. B.; Hoerter, J. M.;
Hubbard, J. L. Organometallics 1999, 18, 5614. (m) Werner, H.; Bleuel, E.
Angew. Chem., Int. Ed. 2001, 40, 145.
(6) For decarbonylation of ketene complexes, see: (a) Hofman, P.;
Perez-Moya, L. A.; Steigelman, O.; Riede, J. Organometallics 1992,
11, 1167. Co:(b) Young, D. A. Inorg. Chem. 1973, 12, 482. (c) Hong,
P.; Sonogashira, K.; Hagihara, N. Tetrahedron Lett. 1971, 12, 1105. Pd:
(d) Mitsudo, T.; Kadokura, M.; Watanabe, Y. J. Org. Chem. 1987,
52, 1695. (e) Mitsudo, T.; Kadokura, M.; Watanabe, Y. J. Org. Chem.
1987, 52, 3186. (f) Mitsudo, T.; Kadokura, M.; Watanabe, Y. Tetra-
hedron Lett. 1985, 26, 3697. (g) Goll, J. M.; Fillion, E. Organometallics
2008, 27, 3622. Fe:(h) Mills, O. S.; Redhouse, A. D. J. Chem. Soc., Chem.
Commun. 1966, 444. Os:(i) Arce, A. J.; Deeming, A. J. J. Chem. Soc.,
Chem. Commun. 1982, 364. Pt:(j) Miyashita, A.; Shitara, H.; Nohira, H.
Organometallics 1985, 4, 1463. Rh:(k) Hong, P.; Nishii, N.; Sonogashira,
K.; Hagihara, N. J. Chem. Soc., Chem. Commun. 1972, 993. (l) Kondo, T.;
Tokoro, Y.; Ura, Y.; Wada, K.; Mitsudo, T. ChemCatChem 2009, 1, 82.
Ir:(m) Grotjahn, D. B.; Bikzhanova, G. A.; Collins, L. S. B.; Concolino,
T.; Lam, K.-C.; Rheingold, A. L. J. Am. Chem. Soc. 2000, 122, 5222. (n)
Urtel, H.; Bikzhanova, G. A.; Grotjahn, D. B.; Hofmann, P. Organome-
tallics 2001, 20, 3938 .
’ ASSOCIATED CONTENT
S
Supporting Information. Detailed experimental proce-
b
dures and compound characterization data. This material is
available free of charge via the Internet at http://pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
louie@chem.utah.edu
’ ACKNOWLEDGMENT
We gratefully acknowledge the DOE, the NSF, and the
NIGMS (5R01GM076125) for support of this research. R.C.
thanks CNPq-Brasil (#201732/2008-4) for a postdoctoral fel-
lowship. We thank Professor Sigman at the University of Utah for
the use of a chiral GC instrument.
(7) Tidwell, T. T. In Ketenes; Wiley-Interscience: New York, 1995.
(8) For a complementary approach to cyclohexadienones and
phenols, see: (a) Tang, P. C.; Wulff, W. D. J. Am. Chem. Soc. 1984,
106, 1132. (b) Ming-Yuan, L.; Madhushaw, R. J.; Liu, R.-S. J. Org. Chem.
2004, 69, 7700.
(9) For natural products containing
a 2,4-cyclohexadienone
core, see: (a) Kaouadji, M. J. Nat. Prod. 1986, 49, 500. (b) Kuo, Y.; Li,
S.; Huang, R.; Wu, M.; Huang, H.; Lee, K. J. Nat. Prod. 2001, 64, 487. (c)
Shen, Y.; Cheng, Y.; Liaw, C.; Liou, S.; Khalil, A. J. Nat. Prod. 2007,
70, 1139. (d) Quideau, S.; Pouysegu, L.; Deffieux, D. Synlett 2008, 467.
(10) When DPPF was employed as the ligand in the cycloaddition of
other substrates, such as diynes 5 and 7 with a, a complex mixture of
products that included diyne dimer, ketene dimer, and cycloadduct was
formed, hampering purification. In general, reactions run with DPPB
were cleaner. Therefore, our optimized conditions employed DPPB as
the ligand of choice.
(11) Wender, P. A.; Christy, J. P. J. Am. Chem. Soc. 2007, 129, 13402.
(12) (a) Larson, G. L.; Hernandez, D.; Lopez-Cepreo, I. M. D.;
Torres, L. E. J. Org. Chem. 1985, 50, 5267. (b) Matsuda, I.; Sato, S.;
Hattori, M.; Izumi, Y. Tetrahedron Lett. 1985, 26, 3215.
(13) When 3-hexyne and phenyl ethyl ketene (a) were subjected to
the optimized conditions, the cycloaddition product was not obtained.
Instead, only ketene dimerization was observed by GC.
’ REFERENCES
(1) (a) Leb!uf, D.; Gandon, V.; Malacria, M. In Handbook of
Cyclization Reactions; Ma, S., Ed.; Wiley-VCH: Weinheim, Germany,
2009; Vol. 1, pp 367ꢀ406. (b) Lautens, M.; Klute, W.; Tam, W. Chem.
Rev. 1996, 96, 49. (c) Chopade, P.; Louie, J. Adv. Synth. Catal. 2006,
348, 2307. (d) Louie, J. Curr. Org. Chem. 2005, 9, 605.(e) Domínguez,
G.; Pꢀerez-Castells, J. Chem. Soc. Rev. [Online early access]. DOI:
10.1039/C1CS15029D. Published Online: March 23, 2011.
(2) (a) Sato, Y.; Nishimata, T.; Mori, M. J. Org. Chem. 1994,
59, 6133. (b) Ikeda, S.; Watanabe, H.; Sato, Y. J. Org. Chem. 1998,
63, 702. (c) Wender, P. A.; Jenkins, T. E. J. Am. Chem. Soc. 1989,
111, 6432. (d) Ni, Y.; Montgomery, J. J. Am. Chem. Soc. 2004,
126, 11162. (e) Louie, J.; Gibby, J. E.; Farnworth, M. V.; Tekavec,
T. N. J. Am. Chem. Soc. 2002, 124, 15188. (f) McCormick, M. M.;
Duong, H. A.; Zuo, G; Louie, J. J. Am. Chem. Soc. 2005, 127, 5030. (g)
Duong, H. A.; Cross, M. J.; Louie, J. J. Am. Chem. Soc. 2004, 126, 11438.
(h) Tanaka, K.; Wada, A.; Noguchii, K. Org. Lett. 2005, 7, 4737. (i)
Oberg, K. M.; Lee, E. E.; Rovis, T. Tetrahedron 2009, 65, 5056. (j)
Tekavec, T. N.; Louie, J. Org. Lett. 2005, 7, 4037. (k) Tekavec, T. N.;
Louie, J. J. Org. Chem. 2008, 73, 2641.
(14) (a) Corey, E. J.; Guzman-Perez, A. Angew. Chem., Int. Ed. 1998,
37, 391.(b) Challenges and Solutions for Organic Synthesis; Christoffers, J.,
Ed.; Wiley-VCH: Weinheim, Germany, 2005. (c) Douglas, C. J.; Over-
man, L. E. Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 5363.
(3) Ketenes were coupled with alkynes using a Rh catalyst. However,
products arising from a β-hydride elimination step were obtained. See:
Kondo, T.; Niimi, M.; Yoshida, Y.; Wada, K.; Mitsudo, T.; Kimura, Y.;
Toshimitsu, A. Molecules 2010, 15, 4189.
(4) For an excellent review of the interactions of ketenes with various
metals, see: Geoffery, G. L.; Bassner, S. L. Adv. Organomet. Chem. 1988,
28, 1.
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